APPENDIX 1 CAM DATA .................................................................................................................... 4
APPENDIX 1.1 SEARCH SUMMARY INFORMATION .................................................................................. 4
APPENDIX 1.2 - AVAILABLE DATASET FOR ALL HERBAL MEDICINES AND ESSENTIAL OILS CONSIDERED
AND THEIR ACTIVE CONSTITUENTS ........................................................................................................ 7
BILOBALIDE .......................................................................................................................................... 9
GINKGOLIDE A .................................................................................................................................... 11
GINKGOLIDE B .................................................................................................................................... 13
GINKGOLIDE C .................................................................................................................................... 15
QUERCETIN ......................................................................................................................................... 17
ST JOHN’S WORT (HYPERICUM EXTRACT) ........................................................................................... 19
HYPERICIN .......................................................................................................................................... 21
GINSENG ............................................................................................................................................. 23
GINSENOSIDE RB1 ............................................................................................................................... 25
GINSENOSIDE RB2 ............................................................................................................................... 27
GINSENOSIDE RG1 ............................................................................................................................... 29
GINSENOSIDE RH2 ............................................................................................................................... 31
GARLIC OIL ......................................................................................................................................... 33
ALLICIN............................................................................................................................................... 35
ECHINACEA ......................................................................................................................................... 37
ECHINACEIN ........................................................................................................................................ 39
VALERIAN ROOT.................................................................................................................................. 41
VALTRATE........................................................................................................................................... 43
BLACK COHOSH EXTRACT ................................................................................................................... 45
ACTEIN ................................................................................................................................................ 47
FORMONONETIN .................................................................................................................................. 49
27-DEOXYACTEIN ................................................................................................................................ 51
MA-HUANG/EPHEDRA ......................................................................................................................... 53
EPHEDRINE .......................................................................................................................................... 55
PSEUDOPHEDRINE ............................................................................................................................... 58
FEVERFEW ........................................................................................................................................... 60
PARTHENOLIDE ................................................................................................................................... 62
EVENING PRIMROSE OIL....................................................................................................................... 64
LINOLEIC ACID .................................................................................................................................... 66
Γ-LINOLEIC ACID ................................................................................................................................. 69
TYLOPHORA INDICA ............................................................................................................................ 71
TYLOPHORINE ..................................................................................................................................... 73
GLUCOSAMINE .................................................................................................................................... 75
GLUCOSAMINE SULPHATE AND HYDROCHLORIDE ............................................................................... 77
LAVENDER ESSENTIAL OIL .................................................................................................................. 80
LINALYL ACETATE .............................................................................................................................. 82
PINENE ................................................................................................................................................ 84
TEA TREE OIL ..................................................................................................................................... 87
CINEOLE .............................................................................................................................................. 89
TERPINEN-4-OL ................................................................................................................................... 91
ORANGE ESSENTIAL OIL ...................................................................................................................... 93
D-LIMONENE ....................................................................................................................................... 95
L-LIMONENE ....................................................................................................................................... 99
CITRAL .............................................................................................................................................. 103
LINALOOL ......................................................................................................................................... 105
PEPPERMINT OIL ................................................................................................................................ 107
MENTHOL.......................................................................................................................................... 109
MENTHONE ....................................................................................................................................... 111
MENTHYL ACETATE .......................................................................................................................... 113
THYME ESSENTIAL OIL ...................................................................................................................... 116
THYMOL ............................................................................................................................................ 118
CARVACROL ...................................................................................................................................... 121
BORNEOL .......................................................................................................................................... 123
CAMPHOR.......................................................................................................................................... 125
WORMWOOD ..................................................................................................................................... 127
ABSINTHIN ........................................................................................................................................ 129
Α-SANTONIN...................................................................................................................................... 131
Α-THUJONE ....................................................................................................................................... 133
Β-THUJONE ........................................................................................................................................ 135
APPENDIX 1.3 SUMMARY OF FINDINGS FOR INDIVIDUAL HERBAL REMEDIES .................................. 137
1. Black Cohosh ............................................................................................................................ 137
2. Camphor ................................................................................................................................... 137
3. Echinacea ................................................................................................................................. 138
4. Evening Primrose Oil ............................................................................................................... 138
5. Feverfew ................................................................................................................................... 139
6. Garlic........................................................................................................................................ 140
7. Ginkgo biloba extract ............................................................................................................... 140
8. Ginseng ..................................................................................................................................... 142
9. Glucosamine ............................................................................................................................. 143
10. Ma huang ................................................................................................................................ 144
11. St John’s Wort ........................................................................................................................ 146
12. Valerian .................................................................................................................................. 148
APPENDIX 1.4 – SUMMARY OF FINDINGS FOR INDIVIDUAL ESSENTIAL OILS ..................................... 150
1. Lavender Oil ............................................................................................................................. 150
2. Orange Essential Oil ................................................................................................................ 152
3. Peppermint Essential Oil .......................................................................................................... 153
4. Tea Tree oil .............................................................................................................................. 155
5. Thyme essential oil ................................................................................................................... 155
6. Wormwood................................................................................................................................ 157
APPENDIX 1.5 GLOSSARY AND LIST OF ABBREVIATIONS ................................................................... 159
APPENDIX 2 PESTICIDE/BIOCIDES DATA .................. ERROR! BOOKMARK NOT DEFINED.
APPENDIX 2.1: REGULATORY REQUIREMENTS FOR APPROVAL OF PESTICIDES PERMITTED IN EU
ORGANIC REGULATIONS IN VARIOUS EU MEMBER STATES. ......... ERROR! BOOKMARK NOT DEFINED.
APPENDIX 2.2 USAGE, PROPERTIES, ECOTOXICITY AND HAZARD CLASSIFICATION FOR MAJOR
SYNTHETIC PESTICIDES .................................................................. ERROR! BOOKMARK NOT DEFINED.
APPENDIX 2.3 UK POLICY CONTEXT – TIMETABLE ....................... ERROR! BOOKMARK NOT DEFINED.
APPENDIX 2.4 APPROVED COMMODITY SUBSTANCES ................... ERROR! BOOKMARK NOT DEFINED.
APPENDIX 2.5 EPA BIOPESTICIDE FACT SHEETS............................ ERROR! BOOKMARK NOT DEFINED.
APPENDIX 2.6 AVAILABLE DATASET FOR ALL PESTICIDES/BIOCIDES ............. ERROR! BOOKMARK NOT
DEFINED.
NATURAL ORGANIC PESTICIDES ................................................ Error! Bookmark not defined.
ABAMECTIN ................................................................................ ERROR! BOOKMARK NOT DEFINED.
4-ALLYL-2-METHOXYPHENOL ................................................. ERROR! BOOKMARK NOT DEFINED.
AMINOETHOXYVINYLGLYCINE ................................................ ERROR! BOOKMARK NOT DEFINED.
AZADIRACHTIN .......................................................................... ERROR! BOOKMARK NOT DEFINED.
6-BENZYLAMINOPURINE........................................................... ERROR! BOOKMARK NOT DEFINED.
BILANAFOS ................................................................................. ERROR! BOOKMARK NOT DEFINED.
BLASTICIDIN-S ........................................................................... ERROR! BOOKMARK NOT DEFINED.
3-[N-BUTYL-N-ACETYL]-AMINOPROPRIONIC ACID, ETHYL ESTER ..... ERROR! BOOKMARK NOT
DEFINED.
CANOLA OIL................................................................................ ERROR! BOOKMARK NOT DEFINED.
CAPSAICIN .................................................................................. ERROR! BOOKMARK NOT DEFINED.
CITRONELLA ............................................................................... ERROR! BOOKMARK NOT DEFINED.
CYTOKININS................................................................................ ERROR! BOOKMARK NOT DEFINED.
DIHYDROAZADIRACHTIN .......................................................... ERROR! BOOKMARK NOT DEFINED.
DMDP ......................................................................................... ERROR! BOOKMARK NOT DEFINED.
EMAMECTIN BENZOATE ............................................................ ERROR! BOOKMARK NOT DEFINED.
OLEIC ACID (FATTY ACIDS) ...................................................... ERROR! BOOKMARK NOT DEFINED.
GARLIC EXTRACT .......................................................................... ERROR! BOOKMARK NOT DEFINED.
GIBBERELLIC ACID ........................................................................ ERROR! BOOKMARK NOT DEFINED.
L-GLUTAMIC ACID PLUS GAMMA-AMINOBUTYRIC ACID ...... ERROR! BOOKMARK NOT DEFINED.
HARPIN PROTEIN ........................................................................ ERROR! BOOKMARK NOT DEFINED.
INDOL-3-YLACETIC ACID .......................................................... ERROR! BOOKMARK NOT DEFINED.
JOJOBA OIL .................................................................................. ERROR! BOOKMARK NOT DEFINED.
KASUGAMYCIN .......................................................................... ERROR! BOOKMARK NOT DEFINED.
MAPLE LACTONE ....................................................................... ERROR! BOOKMARK NOT DEFINED.
P-MENTHANE-3,8-DIOL............................................................. ERROR! BOOKMARK NOT DEFINED.
MILBEMECTIN ............................................................................ ERROR! BOOKMARK NOT DEFINED.
MILDIOMYCIN ............................................................................ ERROR! BOOKMARK NOT DEFINED.
MILSANA, REYNOUTRIA SACHALINENSIS EXTRACT ................. ERROR! BOOKMARK NOT DEFINED.
NATAMYCIN ............................................................................... ERROR! BOOKMARK NOT DEFINED.
NICOTINE .................................................................................... ERROR! BOOKMARK NOT DEFINED.
1-OCTEN-3-OL ............................................................................ ERROR! BOOKMARK NOT DEFINED.
OXYTETRACYCLINE................................................................... ERROR! BOOKMARK NOT DEFINED.
PELARGONIC ACID ..................................................................... ERROR! BOOKMARK NOT DEFINED.
PLANT-DERIVED PORPHYRIN-DERIVATIVES........................... ERROR! BOOKMARK NOT DEFINED.
POLY-D-GLUCOSAIME............................................................... ERROR! BOOKMARK NOT DEFINED.
POLYNACTINS ............................................................................. ERROR! BOOKMARK NOT DEFINED.
POLYOXIN B ............................................................................... ERROR! BOOKMARK NOT DEFINED.
PYRETHRINS ............................................................................... ERROR! BOOKMARK NOT DEFINED.
ROTENONE .................................................................................. ERROR! BOOKMARK NOT DEFINED.
RYANIA EXTRACTS .................................................................... ERROR! BOOKMARK NOT DEFINED.
SABADILLA ................................................................................. ERROR! BOOKMARK NOT DEFINED.
SOFT SOAP ................................................................................... ERROR! BOOKMARK NOT DEFINED.
SPINOSAD .................................................................................... ERROR! BOOKMARK NOT DEFINED.
STREPTOMYCIN .......................................................................... ERROR! BOOKMARK NOT DEFINED.
VALIDAMYCIN ............................................................................ ERROR! BOOKMARK NOT DEFINED.
NATURAL INORGANIC PESTICIDES ............................................ Error! Bookmark not defined.
BORAX ......................................................................................... ERROR! BOOKMARK NOT DEFINED.
BORDEAUX MIXTURE ................................................................ ERROR! BOOKMARK NOT DEFINED.
CALCIUM POLYSULPHIDE ......................................................... ERROR! BOOKMARK NOT DEFINED.
COPPER HYDROXIDE .................................................................. ERROR! BOOKMARK NOT DEFINED.
COPPER OXYCHLORIDE............................................................. ERROR! BOOKMARK NOT DEFINED.
COPPER OCTANAOTE................................................................. ERROR! BOOKMARK NOT DEFINED.
COPPER SULPHATE ..................................................................... ERROR! BOOKMARK NOT DEFINED.
MERCURIC CHLORIDE ............................................................... ERROR! BOOKMARK NOT DEFINED.
MERCURIC OXIDE ...................................................................... ERROR! BOOKMARK NOT DEFINED.
MERCUROUS CHLORIDE ............................................................ ERROR! BOOKMARK NOT DEFINED.
PETROLEUM OILS ....................................................................... ERROR! BOOKMARK NOT DEFINED.
SULPHUR ..................................................................................... ERROR! BOOKMARK NOT DEFINED.
SULPHURIC ACID ........................................................................ ERROR! BOOKMARK NOT DEFINED.
APPENDIX 3 WORKSHOP INFORMATION .................. ERROR! BOOKMARK NOT DEFINED.
ATTENDEES ................................................................................... ERROR! BOOKMARK NOT DEFINED.
AGENDA ........................................................................................ ERROR! BOOKMARK NOT DEFINED.
APPENDIX 4 DATA GENERATED FROM MODELS ... ERROR! BOOKMARK NOT DEFINED.
APPENDIX 4.1 PREDICTED PROPERTIES AND PERSISTENCE OF IDENTIFIED NON-SYNTHETIC CHEMICALS
...................................................................................................... ERROR! BOOKMARK NOT DEFINED.
APPENDIX 4.2 PREDICTED ECOTOXICITY VALUES FOR THE IDENTIFIED CHEMICALS ...................ERROR!
BOOKMARK NOT DEFINED.
APPENDIX 4.3 PBT HAZARD CLASSIFICATION CRITERIA ............... ERROR! BOOKMARK NOT DEFINED.
APPENDIX 4.4 ADDITIONAL CAM DATA ....................................... ERROR! BOOKMARK NOT DEFINED.
Appendix 1 CAM data
Appendix 1.1 Search summary information
Search summary
Search term
Operator
Search term or subheading
Alternative medicine.ti,ab.
Complementary medicine.ti,ab.
Herbal medicine.ti,ab.
Plants medicinal#
Plant preparations#
Neutraceutical$1.ti,ab.
Aromatherapy.de.
With
Subheading – veterinary.de.
And
Veterinary drugs#
Veterinary medicine#
Toxicity search database summary
Database
Database producer
Coverage
Medline
National Library of Medicine
1
1951-present
ToxFile
Dialog Corporation AG
1965-present
Embase
Elsevier B.V.
1974-present
Biosis
Biosis
1969-present
Summary of toxicity terms
1
Medline - Set 1
Medline - Set 2
Health adj effect$1.ti,ab,de.
Adverse adj effect$1.ti,ab.
Toxicology#
Toxicity-tests#
Toxic$8.ti,ab.
Carcinogen$5.ti,de,ab.
Teratogen$5.ti,de,ab.
Mutagen$5.ti,de,ab.
Neurotoxic$8.ti,de,ab.
Cytotoxic$8.ti,de,ab.
Genotoxic$8.ti,de,ab.
Poison$3.ti,de,ab.
Toxicokinetics$1.ti,ab.
Metabolism#
Tolerable adj daily intake$1.ti,de,ab.
TDI.ti,ab.
ADI.ti,ab.
Allowable adj daily adj intake$1.ti,de,ab.
Reference adj dose$1.ti,ab.
Reference-values#
Guidelines#
Toxicity.de.
Adverse adj effect$1.de.
Metabolism.de.
Urine.de.
Embase - Set 1
Embase – Set 2
Health adj effect$1.ti,de,ab.
Adverse adj effect$1.ti,de,ab.
Toxic$8.ti,de,ab.
Toxicity#
Toxicity-testing#
Drug adj toxicity.de.
Pharmacokinetics.de.
using data provided by the National Library of Medicine
Carcinogen$5.ti,de,ab.
Mutagen$5.ti,de,ab.
Teratogen$5.ti,de,ab.
Neurotoxic$8.ti,de,ab.
Cytotoxic$8.ti,de,ab.
Genotoxic$8.ti,de,ab.
Poison$3.ti,de,ab.
Toxicokinetic$1.ti,de,ab.
Tolerable adj daily adj intake.ti,de,ab.
TDI.ti,de,ab.
Acceptable adj daily adj intake$1.ti,de,ab.
ADI.ti,de,ab.
Reference adj dose$1.ti,de,ab.
Guideline adj value$1.ti,de,ab.
Toxicology#
Pharmacokinetics#
Biosis
Health adj effect$1.ti,de,ab.
Adverse adj effect$1.ti,de,ab.
225#2
toxic$8.ti,de,ab.
Carcinogen$5.ti,de,ab.
Teratogen$5.ti,de,ab.
Mutagen$5.ti,de,ab.
Neurotoxic$8.ti,de,ab.
Cytotoxic$8.ti,de,ab.
Genotoxic$8.ti,de,ab.
Poison$3.ti,de,ab.
Toxicokinetic$1.ti,de,ab.
Tolerable adj daily adj intake.ti,de,ab.
TDI.ti,de,ab.
Acceptable adj daily adj intake.ti,de,ab.
ADI.ti,de,ab.
Reference adj dose$1.ti,de,ab.
Reference adj value$1.ti,de,ab.
Guideline adj value$1.ti,de,ab.
Pharmacokinetic$1.ti,de,ab.
2
Concept code for toxicity
Fate and behaviour search terms
3
Set 1
Set 2
Operator
Set 3
Absorbance Bioaccumulation
Bioconcentration
Biodegradation
Compartmentalisation or
compartmentalization
Magnification
Photodegradation
Volatilisation or volatilization
Halflife or (half (w) life)
Kow
Octanol (w) water (w) co (w) efficient
Octanol (w) water (w) coefficient
Body (w) (load or burden)
Accumulation
Behaviour or behavior
Concentration
Deposition
Distribution
Dispersal
Exposure
Fate
Level
Load
5N3
Environment?
Water
Air
Food
Sediment
Soil
operator used on the host Dialog to search for terms within 5 words of each other in any order.
Appendix 1.2 - Available dataset for all herbal medicines and essential
oils considered and their active constituents
Parameter
Preferred units/format
Supporting information
Preparation/chemical name
Ginkgo biloba extract
Therapeutic activity
Chemical structure
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Used in traditional medicine
for asthma and vascular
disease. Nootropic: used in
treatment of vascular
insufficiency.4
Herbal/dietary supplement.5
An extract of the leaves has
been used in cerebrovascular
and peripheral vascular
disorders. It has also been
investigated in Alzheimer’s
disease and multi-infarct
dementia.6
N/A
N/A
90045-36-6
N/A
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
5
National Toxicology Program Executive Summary, available [April 2004] at: http://ntpserver.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/Ginkgo.html
6
Sweetman SC (2002) Martindale. The Complete Drug Reference. Thirty-third edition. London, UK, Pharmaceutical Press.
4
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mouse (oral) LD50 7.73g kg-1
7
Standardised extract
corresponding to 2.3 g
kg-1 of active
ingredients, 1.9 g kg-1
of flavone glycosides,
and 464 mg kg-1 of
terpene lactones
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
7
http://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/Ginkgo.html viewed April 2004
Parameter
Preferred units/format
Supporting
information
-
Preparation/chemical name
Bilobalide
Therapeutic activity
Chemical structure
(Beilstein, 2004)
O
O
O
O
O
O
O
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water
partition coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
9-tert-butyl-8,9-dihydroxydihydro-furo[2,3b]furo[3’,2’:2,3]cyclopental[1,2c]furan-2,4,7-trione
33570-04-6
C15H18O8
326.3 g mol-1
(Beilstein, 2004)
-
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Parameter
Preferred units/format
Supporting
information
Preparation/chemical name
Ginkgolide A
Therapeutic activity
Chemical structure
O
O
O
H
O
O
O
O
O
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition
coefficient (Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water
partition coefficient (Kp)
Organic carbon normalised
soil/sediment water
partition coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
8
15291-75-5
C20H24O9
408.40 g mol-1
Decomposes at ~300°C8
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Parameter
Preferred units/format
Supporting
information
-
Preparation/chemical name
Ginkgolide B
Therapeutic activity
Chemical structure
(Beilstein, 2004)
H
O
O
O
O
O
O
O
O
O
O
H
H
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition
coefficient (Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water
partition coefficient (Kp)
Organic carbon normalised
soil/sediment water
partition coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
9
(1β)-1-Hydroxyginkgolide A
15291-77-7
C20H24O10
424.40 g mol-1
Decomposes at ~300°C9
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other
aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Parameter
Preparation/chemical name
Therapeutic activity
Preferred units/format
Supporting information
Ginkgolide C
Used in treatment of severe
sepsis.a
Chemical structure
O
O
O
O
O
H
O
O
O
H
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
10
O
O
(1α,7β)-1,7-Dihydroxyginkgolide
15291-76-6
C20H24O11
440.40 g mol-1
Decomposes at ~300°C10
N/A
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Parameter
Preparation/chemical
name
Therapeutic activity
Chemical structure
Preferred units/format
Supporting
information
-
Quercetin
O
-
O
O
O
O
O
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission
rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition
coefficient (Kow, P)
Solubility in water
Acid dissociation
constant (pKa)
3,3’,4’,5,7-Pentahydroxyflavone
117-39-5
C15H10O7
302.24 g mol-1
Vapour pressure
Henry’s Law Constant
Soil/sediment water
partition coefficient
(Kp)
Organic carbon
normalised
soil/sediment water
partition coefficient
(Koc)
3.74 x 10-12 Pa 14
6.68 x 10-16 Pa m3 mol-1 15
11
-
316.5 °C11
Sublimes a
2.0412
0.16 g L-1 13
pKa1: 7.03
pKa2: 9.15 b
Determined at 16°C
Determined at 25°C
using a
spectrophotometric
method
Estimated at 25°C
Estimated at 25°C
IARC (1999) IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Some Chemicals that Caus Tumours of
the Kidney or Urinary Bladder in Rodents and Some Other Substances. Volume 73. Lyon, France, International Agency for
Research on Cancer
12
Beilstein database (2004)
13
Seidell (1941) cited in SRC PhysProp Database
14
Neely WB & Blau GE (1985) cited in SRC PhysProp Database
15
Meylan WM & Howard PH (1991) cited in SRC Phys Prop Database
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates
from above studies
Fate in the field
Bioconcentration factor
62–105 days b
Sludge from
municipal
wastewater.
Anaerobic
degradation at 37°C.
?
Test species and
method
Test method and
species
Biota-sediment/soil
?
accumulation factor
Mammalian oral toxicity Mouse (oral) LD50 159 mg kg-1
Rat (oral) LD50 161 mg kg-1 16
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other
aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
16
Material Safety Datasheet at https://fscimage.fishersci.com/msds/56284.htm
Parameter
Preparation/chemical name
Therapeutic activity
Chemical structure
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
17
Preferred units/format
Supporting information
St John’s Wort
(hypericum extract)
Antidepressant17
Used, frequently for selfmedication, in the treatment
of depression. Such
preparations are also
promoted for the treatment of
other nervous disorders such
as insomnia and anxiety,
particularly if associated with
the menopause.18
N/A
68917-49-7
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
18
Sweetman SC (2002) Martindale. The Complete Drug Reference. Thirty-third edition. London, UK, Pharmaceutical Press.
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Rats, mice: NOEL > 5000 mg
kg-1 (Hammerness et al.,
2003)
Parameter
Preferred units/format
Supporting
information
Preparation/chemical name
Therapeutic activity
Hypericin
Antidepressant19
Hypericin oil has been used as
an astringent.20
Chemical structure
O
O
O
O
O
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water
partition coefficient (Kp)
Organic carbon normalised
soil/sediment water
19
O
O
1,3,4,6,8,13-Hexahydroxy10,11-dimethylphenanthro[1,10,9,8opqra]perylene-7,14-dione
548-04-9
C30H16O8
504.45 g mol-1
320 °C 21
3.43 b
8.78 22
0.04 g L-1 b
Estimated
Determined at 30°C
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
20
Sweetman SC (2002) Martindale. The Complete Drug Reference. Thirty-third edition. London, UK, Pharmaceutical Press.
21
Beilstein, 2004
22
Meylan WM & Howard PH (1995) cited in SRC PhysProp Database
partition coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Parameter
Preparation/chemical name
Therapeutic activity
Chemical structure
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
23
Preferred units/format
Supporting information
Ginseng
Tonic23
Reported to enhance the
natural resistance and
recuperative power of the
body and to reduce fatigue.24
N/A
50647-08-0
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
24
Sweetman SC (2002) Martindale. The Complete Drug Reference. Thirty-third edition. London, UK, Pharmaceutical Press.
Mammalian oral toxicity
Rat (oral) LD50 750 mg kg-1
Mouse (oral) LD50 200 mg
kg-1 25
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
25
http://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/Ginseng.html
Panax ginseng
Parameter
Preferred units/format
Supporting
information
Preparation/chemical
Ginsenoside Rb1
name
Therapeutic activity
Chemical structure
O
O
O
O
O
O
O
O
O
O
H
H
O
O
O
H
O
O
O
H
O
O
O
O
O
O
O
Chemical name
2-O-β-Glucopyranosyl-(3β,12β)-20-((6-O-β-Dglucopyranosyl-β-D-glucopyranosyl)oxy-12hydroxydammar-24-en-3-yl-β-D-glycopyranoside
41753-43-9
C54H92O23
1109.31 g mol-1
CAS no
Molecular formula
Molecular weight
Major emission
routes
Application/emission
rates
Proportion
metabolised
Identity of
metabolites
Density
Melting point
205–207°C 26
Boiling point
Octanol-partition
coefficient (Kow, P)
Solubility in water
Acid dissociation
26
Beilstein database (2004)
constant (pKa)
Vapour pressure
Henry’s Law
Constant
Soil/sediment water
partition coefficient
(Kp)
Organic carbon
normalised
soil/sediment water
partition coefficient
(Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in
activated sludge
Persistence in soil
Persistence in
sediment
Identity of
degradates from
above studies
Fate in the field
Bioconcentration
factor
Biota-sediment/soil
accumulation factor
Mammalian oral
toxicity
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian
inhalation toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity
(Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other
aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Parameter
Preparation/chemical
name
Therapeutic activity
Chemical structure
Preferred units/format
Supporting
information
Ginsenoside Rb2
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission
rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition
coefficient (Kow, P)
Solubility in water
Acid dissociation
constant (pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water
partition coefficient
(Kp)
Organic carbon
normalised
soil/sediment water
partition coefficient
(Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
27
Beilstein database (2004)
20-((6-O-α-L-Arabinopyranosl-β-Dglucopyranosyl)oxy)-12βhydroxydammar-24-en-3β-yl-2-O-β-Dglucopyranosyl-β-D-glucopyranoside
11021-13-9
C53H90O22
1079.28 g mol-1
201°C 27
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates
from above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral
toxicity
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other
aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Parameter
Preferred units/format
Supporting
information
Preparation/chemical
Ginsenoside Rg1
name
Therapeutic activity
Chemical structure
O
O
O
O
O
H
H
O
O
H
O
H
O
O
O
O
O
O
Chemical name
(3β,6α,12β)-3,12-Dihydroxydammar-24-ene-6,20diylbis(β-D-glucopyranoside)
22427-39-0
C42H72O14
801.02 g mol-1
CAS no
Molecular formula
Molecular weight
Major emission
routes
Application/emission
rates
Proportion
metabolised
Identity of
metabolites
Density
Melting point
202–205°C 28
Boiling point
Octanol-partition
coefficient (Kow, P)
Solubility in water
Acid dissociation
constant (pKa)
Vapour pressure
Henry’s Law
Constant
Soil/sediment water
partition coefficient
28
Beilstein database (2004)
(Kp)
Organic carbon
normalised
soil/sediment water
partition coefficient
(Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in
activated sludge
Persistence in soil
Persistence in
sediment
Identity of
degradates from
above studies
Fate in the field
Bioconcentration
factor
Biota-sediment/soil
accumulation factor
Mammalian oral
toxicity
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian
inhalation toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity
(Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other
aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Parameter
Preferred units/format
Supporting
information
Preparation/chemical
Ginsenoside Rh2
name
Therapeutic activity
Chemical structure
O
O
H
H
O
O
O
H
O
O
H
O
Chemical name
(3β,12β)-12,20-dihydroxydammar-24-en-3-yl-(β-Dglucopyranoside)
78214-33-2
C36H62O8
622.88 g mol-1
CAS no
Molecular formula
Molecular weight
Major emission
routes
Application/emission
rates
Proportion
metabolised
Identity of
metabolites
Density
Melting point
220–225°C 29
Boiling point
Octanol-partition
coefficient (Kow, P)
Solubility in water
Acid dissociation
constant (pKa)
Vapour pressure
Henry’s Law
Constant
Soil/sediment water
partition coefficient
(Kp)
Organic carbon
normalised
soil/sediment water
partition coefficient
29
Beilstein database (2004)
Solvent
methanol
(Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in
activated sludge
Persistence in soil
Persistence in
sediment
Identity of
degradates from
above studies
Fate in the field
Bioconcentration
factor
Biota-sediment/soil
accumulation factor
Mammalian oral
toxicity
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian
inhalation toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity
(Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other
aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Parameter
Preparation/Chemical name
Data
Supporting info.
-
Garlic oil
Therapeutic activity
Chemical structure
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
Treatment of hypertension
and hyperlipidemia30.
Expectorant, diaphoretic,
disinfectant and diuretic
properties31 and recently
investigated for antimicrobial,
antihypertensive, lipid
lowering, fibrinolytic,
antiplatelet and cancer
protective effects.
8000-78-0
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
-
Density
Melting Point
Boiling Point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
1.04 - 1.09 (25 °C)32
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
-
30
-
Test method
-
Test method
Test method
-
Test method
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
characteristics
-
-
Merck Index (2001) [Garlic, entry 4384]
Martindale (2002) [Garlic, p1614]
32
MSDS [Garlic Oil] viewed on-line at http://www.thegoodscentscompany.com; April 2004
31
e.g. to STP; application
to soil
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
Test method
Test method
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
-
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
-
-
Test method
Test method; aerobic
anaerobic
Test method; soil type
Test method
Test method
Test species and
method
Test method and
species
Parameter
Preparation/Chemical name
Data
Supporting info.
-
Allicin
Therapeutic activity
Constituent of garlic1,4.
Treatment of hypertension
and hyperlipidemia (as per
garlic oil)1.
Chemical structure
O
S
S
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
Prop-2-ene-1-sulphinothioic
acid S-2-propenyl ester
539-86-6
C6H10OS2
162.2833
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem
draw file
Density (RD)
Melting Point
Boiling Point
1.112
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
33
e.g. to STP; application
to soil
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
Decomposes on distilling1;
134ºC34
1.87 (est)35
Test method
25 g/l1 (pH 6.5)
-
Test method
Test method
-
Test method
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
-
Merck Index (2001) [Allicin, entry 257]
Bielstein Database [Allicin]; accessed April 2004
35
SRC PhysProp Database viewed on-line at http://esc.syrres.com/interkow/physdemo.htm; April 2004
4
Martindale (2002) [Garlic, p 1614]
34
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
characteristics
-
36
Beilstein Database, 2004.
Test method
Test species and
method
Test method and
species
LD50 in mice: 60 mg/kg (iv);
120 mg/kg (sc)1
LC 50 at 24,48,72 & 96 hrs
6.34, 5.45, 4.48, 3.64 mg L-1
36
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Test method
Test method
Test method
Test method; aerobic
anaerobic
Test method; soil type
Test method
-
Toxicity to aquatic
invertebrates
Parameter
Data
Preparation/Chemical
Echinacea
name
Therapeutic activity
Treatment of respiratory infections, e.g. colds
(immunostimulant)37.
Used in herbal preparations for prophylaxis of
bacterial and viral infections38.
Chemical structure
Chemical name
CAS no
Echinacea angustifolia, ext. (84696-11-7)
Echinacea purpurea, ext. (90028-20-9)
Echinacea pallida, ext. (97281-15-7)
Echinacea angustifolia tincture (129677-89-0)
Molecular formula
Molecular weight
Major emission routs -
Supporting
info.
-
-
e.g. to STP;
application to
soil
-
Application/emission
rates
Proportion
metabolised
Identity of
metabolites
e.g. kg ha-1; dose (mg kg-1)
Density
Melting Point
Boiling Point
Octanol-partition
coefficient (Kow, P)
Solubility in water
Acid dissociation
constant (pKa)
Vapour pressure
Henry’s Law
Constant
Soil/sediment water
partition coefficient
(Kp)
Organic carbon
-
Test method
-
Test method
Test method
-
Test method
Test method;
temperature
Soil/sediment
characteristics
37
38
Amount produced; Chem draw file
-
-
Merck Index (2001)
Martindale (2002) [Echinacea, p 1606]
Test method
and species
Would be
nice if all this
info. Could
also be
obtained for
the
metabolites
Soil/sediment
normalised
soil/sediment water
partition coefficient
(Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in
activated sludge
characteristics
Persistence in soil
-
Persistence in
sediment
Identity of degradates
from above studies
Fate in the field
Bioconcentration
factor
Biota-sediment/soil
accumulation factor
Mammalian oral
toxicity
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian
inhalation toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity
(Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other
aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
-
Test method
Test method
Test method
Test method;
aerobic
anaerobic
Test method;
soil type
Test method
-
-
-
Test method
Test species
and method
Test method
and species
39
-
Rat (oral) LD50 >15000 mg kg-1
Mouse (oral) LD50 >30000 mg kg-1 39
http://ntp-server.niehs.nih.gov./htdocs/Chem_Background/ExecSumm/Echinacea.html viewed, April 2004
Parameter
Data
Supporting
info.
-
Preparation/Chemical
name
Therapeutic activity
Chemical structure
Echinacein
Constituent of Echinacea2
Echinacein
-
O
N
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
Dodeca-2,6,8,10-tetraenoic acid isobutyl
amide
Echinacein (504-97-2, 10076-00-3, 1343038-1, 119719-30-1)40
C16H25NO
247.381
-0
Application/emission
rates
Proportion
metabolised
Identity of metabolites
e.g. kg ha-1; dose (mg kg-1)
Density
Melting Point
Boiling Point
Octanol-partition
coefficient (Kow, P)
Solubility in water
Acid dissociation
constant (pKa)
Vapour pressure
Henry’s Law Constant
69-70ºC1
Soil/sediment water
partition coefficient
(Kp)
Organic carbon
normalised
soil/sediment water
partition coefficient
(Koc)
-
40
2
Amount produced; Chem draw file
e.g. to STP;
application to
soil
Test method
and species
Would be nice
if all this info.
Could also be
obtained for
the metabolites
-
Test method
-
Test method
Test method
-
Test method
Test method;
temperature
Soil/sediment
characteristics
-
Beilstein Database 2004 [Echinacein]; accessed April 2004
[Echinacea] viewed on-line at http://www.naturalproducts.org April 2004
Soil/sediment
characteristics
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in
activated sludge
-
Persistence in soil
-
Persistence in
sediment
Identity of degradates
from above studies
Fate in the field
Bioconcentration
factor
Biota-sediment/soil
accumulation factor
Mammalian oral
toxicity
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian
inhalation toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other
aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
-
Test method
Test method
Test method
Test method;
aerobic
anaerobic
Test method;
soil type
Test method
-
-
-
Test method
Test species
and method
Test method
and species
-
Parameter
Preparation/Chemical name
Data
Chemical structure
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
Valerian root
Sedative41
Valerian has sedative
properties and is used to treat
anxiety states; it has also been
used as a carminative42
8057-49-6
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem
draw file
Density
Melting Point
Boiling Point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
-
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
-
Therapeutic activity
41
42
Merck Index (2001) [Valerian, entry 9969]
Martindale (2002) [Valerian, p 1678]
Supporting info.
-
e.g. to STP; application
to soil
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
Unitless
Test method
-
Test method
Test method
-
Test method
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
characteristics
-
-
Test method
Test method
Test method
Test method; aerobic
anaerobic
Test method; soil type
Test method
-
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
-
Daily dose not to exceed
1800mg 43
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
43
http://tangcenter.uchicago.edu/herbal_resources/valerian.shtml
Test method
Test species and
method
Test method and
species
Short-term use only
Parameter
Data
Supporting
info.
-
Preparation/Chemical
name
Therapeutic activity
Chemical structure
Valtrate
Constituent of valerian44,45
-
O
O
O
O
O
H
O
O
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
Valtrate
18296-44-1 (22173-55-3)
C22H30O8
422.471
-0
Application/emission
rates
Proportion
metabolised
Identity of metabolites
e.g. kg ha-1; dose (mg kg-1)
Density
Melting Point
Boiling Point
Octanol-partition
coefficient (Kow, P)
Solubility in water
Acid dissociation
constant (pKa)
Vapour pressure
Henry’s Law Constant
-
Soil/sediment water
-
44
Amount produced; Chem draw file
e.g. to STP;
application to
soil
Test method
and species
Would be nice
if all this info.
Could also be
obtained for the
metabolites
-
Test method
-
Test method
Test method
-
Test method
Test method;
temperature
Soil/sediment
Beilstein Database [Valtrate]; accessed April 2004
The valepotriates valtrate/isovaltrate and dihydrovaltrate are considered to be the main tranquilizing constituents of drugs
derived from the roots of several Valerianaceae (von der Hude et al, 1986)
45
partition coefficient
(Kp)
Organic carbon
normalised
soil/sediment water
partition coefficient
(Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in
activated sludge
characteristics
-
Soil/sediment
characteristics
-
Persistence in soil
-
Persistence in
sediment
Identity of degradates
from above studies
Fate in the field
Bioconcentration
factor
Biota-sediment/soil
accumulation factor
Mammalian oral
toxicity
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian
inhalation toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other
aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
-
Test method
Test method
Test method
Test method;
aerobic
anaerobic
Test method;
soil type
Test method
-
-
-
Test method
Test species
and method
Test method
and species
-
Parameter
Preparation/Chemical name
Data
Supporting info.
-
Black cohosh extract
Therapeutic activity
Chemical structure
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
Treatment of symptoms
associated with premenstrual
syndrome (PMS),
dysmenorrhea, and
menopause46.
84776-26-1
-
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem
draw file
Density
Melting Point
Boiling Point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
-
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
-
46
e.g. to STP; application
to soil
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
-
Test method
-
Test method
Test method
-
Test method
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
characteristics
-
-
NTP summary [Black Cohosh] viewed on-line at http://ntpserver.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/blackcohosh.html April 2004
Test method
Test method
Test method
Test method; aerobic
anaerobic
Test method; soil type
Test method
-
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
-
Test method
Test species and
method
Test method and
species
Parameter
Data
Preparation/Chemical
Actein
name
Therapeutic activity
Constituent of Black Cohosh47.
Chemical structure
O
O
O
O
O
O
O
O
O
O
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
Application/emission
rates
Proportion
metabolised
Identity of
metabolites
Density
Melting Point
Boiling Point
Octanol-partition
coefficient (Kow, P)
Solubility in water
Acid dissociation
constant (pKa)
Vapour pressure
Henry’s Law
Constant
Soil/sediment water
partition coefficient
(Kp)
Organic carbon
normalised
soil/sediment water
partition coefficient
(Koc)
47
Actein
18642-44-9
C37H56O11
676.8448
-0
e.g. kg ha-1; dose (mg kg-1)
Amount produced; Chem draw file
-
-
-
NTP summary [Black Cohosh] viewed on-line at http://ntpserver.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/blackcohosh.html April 2004
48
Beinstein Database [Actein]; accessed April 2004
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in
activated sludge
Persistence in soil
Persistence in
sediment
Identity of degradates
from above studies
Fate in the field
Bioconcentration
factor
Biota-sediment/soil
accumulation factor
Mammalian oral
toxicity
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian
inhalation toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity
(Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other
aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
-
Parameter
Preparation/Chemical name
Data
Supporting info.
-
Formononetin
Therapeutic activity
Treatment of menopausal
symptoms.
Constituent of Black
Cohosh49 and major
oestrogenic factor in clover
species50
Chemical structure
-
O
O
O
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
7-hydroxy-3-(4-methoxyphenyl)-4-benzopyrone
485-72-3
C16H12O4
268.2751
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem
draw file
Density
Melting Point
Boiling Point
Octanol-partition coefficient
(Kow, P)
Solubility in water
256.5ºC52; 258ºC2
49
e.g. to STP; application
to soil
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
3.11 (est)4
Test method
-
Test method
NTP summary [Balck Cohosh] viewed on-line at at http://ntpserver.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/blackcohosh.html April 2004
50
Merck Index (2001) [Formononetin, entry 4268]
51
Beilstein Database [Formononetin]; accessed April 2004
52
SRC PhysProp Database viewed on-line at http://esc.syrres.com/interkow/physdemo.htm; April 2004
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
-
Test method
-
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
-
Test method
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
characteristics
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
-
37-95% degraded in 1-3
weeks (from 5 mg/l);
30-60% degraded in 10-15 d3
-
Test method
Test method
Test method
Test method; aerobic
anaerobic
Test method; soil type
Test method
Test method
Test species and
method
Test method and
species
Parameter
Data
Preparation/Chemical
27-deoxyactein
name
Therapeutic activity
Constituent of Black Cohosh53.
Chemical structure
O
O
O
O
O
O
O
O
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
Application/emission
rates
Proportion
metabolised
Identity of
metabolites
Density
Melting Point
Boiling Point
Octanol-partition
coefficient (Kow, P)
Solubility in water
Acid dissociation
constant (pKa)
Vapour pressure
Henry’s Law
Constant
Soil/sediment water
partition coefficient
(Kp)
Organic carbon
normalised
soil/sediment water
partition coefficient
(Koc)
Photolysis half life
53
27-deoxyacetylacetol-O-D-xylopyranoside
660.84
-0
e.g. kg ha-1; dose (mg kg-1)
Amount produced; Chem draw file
-
-
-
-
NTP summary [Black Cohosh] viewed on-line at http://ntpserver.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/blackcohosh.html April 2004
O
Hydrolysis half life
Persistence in air
Persistence in
activated sludge
Persistence in soil
Persistence in
sediment
Identity of degradates
from above studies
Fate in the field
Bioconcentration
factor
Biota-sediment/soil
accumulation factor
Mammalian oral
toxicity
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian
inhalation toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity
(Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other
aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
-
Parameter
Preparation/Chemical name
Data
Supporting info.
-
Ma-huang/Ephedra
Therapeutic activity
Chemical structure
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
Herbal cold relief. Action of
ephedra is due to the presence
of ephedrine and
pseudoephedrine54.
Used in traditional Chinese
medicine as a diaphoretic,
stimulant and antiasthmatic55.
Has also been used to aid
weight loss56.
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem
draw file
Density
Melting Point
Boiling Point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
-
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
-
54
e.g. to STP; application
to soil
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
-
Test method
-
Test method
Test method
-
Test method
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
characteristics
-
-
Test method
Test method
Martindale (2002) [Ephedra, p 1090]
Merck Index (2001) [Ephedra, entry 3638]
56
Ephedra and Ephedrine for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy and Side Effects. Viewed
on-line at http://www.ahrq.gov/clinic/epcsums/ephedsum.htm April 2004
55
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
-
Biota-sediment/soil
accumulation factor
-
Mammalian oral toxicity
Rat (oral) 600mg kg-1
Probable oral lethal dose
(human) 5-50mg kg-157
-
Test method
Test method; aerobic
anaerobic
Test method; soil type
Test method
Test method
Test species and
method
Test method and
species
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
57
Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/
Parameter
Preparation/Chemical name
Supporting info.
-
Data
Ephedrine
Therapeutic activity
Major active constituent of
Ephedra; also prepared
synthetically – used as an
expectorant and nasal
decongestant4.
Bronchodilator. Also used for
veterinary purposes as a
bronchodilator and to treat
urinary incontinence1.
Chemical structure
N
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
(1R,2S)-2-methylamino-1phenyl-propan-1-ol
299-42-3
C10H15NO
165.2358
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem
draw file
Density
Melting Point
g cm-3
34 ºC1,59
37-39 ºC60
36 ºC (anhydrous form,
hemihydrate melts at 42 ºC)5
255 ºC2
260 ºC (745 mmHg)1
1.132
0.9361
Boiling Point
Octanol-partition coefficient
(Kow, P)
58
e.g. to STP; application
to soil
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
Test method
Merck Index (2001) [Ephedrine, entry 3639]
SRC PhysProp Database viewed on-line at http://esc.syrres.com/interkow/physdemo.htm; April 2004
60
Chemfinder viewed on-line at http://chemfinder.cambridgesoft.com
4
Martindale (2002) [Ephedra, Ephedrine p 1090]
59
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
63.6 g/l (30 ºC)2
10.3 (0 ºC)2
9.662
0.11 Pa (est)2
9 x 10-6 Pa m3 mol-1 (est)2
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
-
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
-
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
62
-
-
Rat (oral) LD50 600mg kg-1 63
90-180 mg 65
Test method
Test method
Test method
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
characteristics
Test method
Test method
Test method
Test method; aerobic
anaerobic
Test method; soil type
Test method
Test method
Test species and
method
Test method and
species
LDLO (human) 9mg
kg-1
(route unreported)64
Treatment of diabetic
neuropathic oedema
LD50 (oral) 562 mg kg-1 66
[Ephedrine, PIM 209] viewed on-line via Inchem at http://www.inchem.org/documents/pims/pharm/pim209.htm April 2004
http://ptcl.chem.ox.ac.uk/MSDS/EP/(-)-ephedrine_anhydrous.html viewed April 2004
64
Material Safety Datasheet at http://physchem.ox.ac.uk/MSDS/ viewed April 2004
65
Martindale (2002) [Ephedrine, p 1090]
66
Material Safety Datasheet viewed at http://www.sigmaaldrich.com Product number: 134910, viewed April 2004
63
Parameter
Preparation/Chemical name
Data
Supporting info.
-
Pseudophedrine
Therapeutic activity
Active constituent of
Ephedra/Ma huang; similar
action to ephedrine – used for
relief of cough and cold
symptoms5.
Nasal decongestant1
Chemical structure
Chemical name
-
H
O
N
H
CAS no
Molecular formula
Molecular weight
Major emission routs
(1S,2S)-2-methylamino-1phenyl-propan-1-ol
90-82-4
C10H15NO
165.2367
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem
draw file
Density
Melting Point
1.12 g cm-3 68
118-119 ºC 1,69
117 ºC 70
0.893
Boiling Point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
67
106 g/l (est at 25 ºC)3
Sparingly soluble in water1
10.3 (0 ºC)2
e.g. to STP; application
to soil
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
Test method
Test method
Test method
Merck Index (2001) [Pseudoephedrine, entry 8007]
Beilstein Database (2004)
69
SRC PhysProp Database viewed on-line at http://esc.syrres.com/interkow/physdemo.htm; April 2004
70
Chemfinder viewed on-line at http://esc.syrres.com/interkow/physdemo.htm; April 2004
5
Martindale (2002) [Pseudoephedrine, p 1099]
68
Vapour pressure
Henry’s Law Constant
0.11 Pa (est)2
9 x 10-6 Pa m3 mol-1 (est)2
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
-
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
-
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
71
-
-
Test method
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
characteristics
Test method
Test method
Test method
Test method; aerobic
anaerobic
Test method; soil type
Test method
Test method
Test species and
method
Test method and
species
Rat (oral) LD50 660mg kg-1
Mouse (oral) LD50 500mg
kg-1 71
Irritating to skin and eyes 72
Harmful by inhalation 73
Material Safety Datasheet at http://ptcl.chem.ox.ac.uk/MSDS/PS/(+)-pseudoephedrine.html viewed April 2004
Material Safety Datasheet at http://ptcl.chem.ox.ac.uk/MSDS/PS/(+)-pseudoephedrine.html viewed April 2004
73
Material Safety Datasheet at http://ptcl.chem.ox.ac.uk/MSDS/PS/(+)-pseudoephedrine.html viewed April 2004
72
Parameter
Preparation/chemical name
Preferred units/format
Feverfew
Therapeutic activity
Supporting information
Featherfew, featherful,
midsummer daisy,
Tanacetum parthenium
Herbal remedy used in the
prophylactic treatment of
migraine and arthritis.74
Chemical structure
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
74
Sweetman SC (2002) Martindale. The Complete Drug Reference. Thirty-third edition. London, UK, Pharmaceutical Press.
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Parameter
Preparation/chemical name
Preferred units/format
Supporting information
Parthenolide
Therapeutic activity
Chemical structure
O
O
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
75
IUPAC format
20554-84-1
C15H20O3
248.32 g mol-1
115–116°C75
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Parameter
Preparation/chemical name
Preferred units/format
Supporting information
Evening primrose oil
Therapeutic activity
Chemical structure
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
76
In treatment of atopic eczema
and mastalgia; dietary
supplement76
Used for symptomatic relief
of atopic eczema and
mastalgia. Also investigated
in a variety of other disorders
including multiple sclerosis,
rheumatoid arthritis and the
premenstrual syndrome.77
90028-66-3
0.9283 g cm-3
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
77
Sweetman SC (2002) Martindale. The Complete Drug Reference. Thirty-third edition. London, UK, Pharmaceutical Press.
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Parameter
Preferred units/format
Supporting
information
Preparation/chemical
Linoleic acid
name
Therapeutic activity Nutrient (essential fatty acid)78
Chemical structure
O
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission
routes
Application/emission
rates
Proportion
metabolised
Identity of
metabolites
Density
Octadeca-9,12-dienoic acid
60-33-3
C18H32O2
280.45 g mol-1
Melting point
Boiling point
-5°C81
230°C a
Octanol-partition
coefficient (Kow, P)
Solubility in water
7.0582
Acid dissociation
constant (pKa)
Vapour pressure
4.7784
Henry’s Law
Constant
Soil/sediment water
0.51 Pa m3 mol-1 86
78
Estimated European per captia intake (eaters
only): 133 µg/day79
0.9022 g cm-3 80
0.000139 g L-1 83
1.16 x 10-4 Pa 85
Determined
at 20°C
Determined
at 16 mm Hg
Estimated at
25°C
Determined
at 25°C
Extrapolated
from data at
25°C
Estimated at
25°C
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
79
IPCS (1999) Satefy Evaluation of Certain Food Additives. WHO Food Additives Series: 42. Genva, Switzerland, World Health
Organisation
80
Lide DR (1997) cited in Hazardous Substances Database (HSBD), available [April 2004] at http://toxnet.nlm.nih.gov/
81
Beilstien Database (2004)
82
Sangster (1993) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
83
Meylan WM et al. (1996) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
84
Serjeant EP & Dempsey B (1979) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com
85
Daubert TE & Danner RP (1991) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com
86
Meylan WM & Howard PH (1991) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com
partition coefficient
(Kp)
Organic carbon
normalised
soil/sediment water
partition coefficient
(Koc)
Photolysis half life
Hydrolysis half life
1.6 x 10+5 87
Persistence in air
0.05–0.125 days89
Persistence in
activated sludge
1.25 days at 20°C90
Persistence in soil
Persistence in
sediment
Identity of
degradates from
above studies
Degradation products identified from anaerobic
digester sludge study included:
O
O
acetic acid
O
O
hexadecanoic acid
87
Hazardous Substances Database (HSBD), available [April 2004] at http://toxnet.nlm.nih.gov/
Hazardous Substances Database (HSBD), available [April 2004] at: http://toxnet.nlm.nih.gov/
89
Hazardous Substances Database (HSBD), available [April 2004] at: http://toxnet.nlm.nih.gov/
90
Novak JT & Jruas DL (1973) cited in Hazardous Substances Database (HSBD), available [April 2004] at:
http://toxnet.nlm.nih.gov/
88
Estimated
from
measured log
Kow.
Not expected
to under
hydrolysis
due to lack of
hydrolyzable
functional
groups88
Based on
estimated
half-lives for
reaction with
hydroxyl
radicals and
ozone,
respectively.
Unacclimated
activated
sludge
inoculum
(an/aerobic
not specified)
O
O
tetradecanoic acid
Fate in the field
Bioconcentration
factor
Biota-sediment/soil
accumulation factor
Mammalian oral
toxicity
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian
inhalation toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity
(Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other
aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
1.3 x 10+591
Estimated for
aquatic
organisms
based on
measured log
Kow
Mouse (oral) LD50 >50 g kg-1 92
91
Hazardous Substances Database (HSBD), available [April 2004] at http://toxnet.nlm.nih.gov/
92
Material Safety Datasheet at https://fscimage.fishersci.com/msds/70654.htm viewed April, 2004
Parameter
Preferred units/format
Supporting
information
Preparation/chemical
γ-Linoleic acid
name
Therapeutic activity In treatment of atopic eczema93
Chemical structure
O
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission
routes
Application/emission
rates
Proportion
metabolised
Identity of
metabolites
Density
Melting point
Boiling point
Octanol-partition
coefficient (Kow, P)
Solubility in water
Acid dissociation
constant (pKa)
Vapour pressure
Henry’s Law
Constant
Soil/sediment water
partition coefficient
(Kp)
Organic carbon
normalised
soil/sediment water
partition coefficient
(Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in
activated sludge
Persistence in soil
93
Octadeca-6,9,12-trienoic acid
506-26-3
C18H30O2
278.43 g mol-1
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
Persistence in
sediment
Identity of
degradates from
above studies
Fate in the field
Bioconcentration
factor
Biota-sediment/soil
accumulation factor
Mammalian oral
toxicity
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian
inhalation toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity
(Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other
aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
94
Reduced mean survival time at conc 9 – 24 mg l-1 94
Beilstein database [-linoleic acid 1712253] accessed April 2004.
Parameter
Preparation/chemical name
Preferred units/format
Tylophora indica
Therapeutic activity
Supporting information
(aka Tylophora
astmatica)
Inconclusive evidence for
treatment of asthma.95
Chemical structure
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
95
Huntley A & Ernst E (2000) Herbal medicines for asthma: a systematic review. Thorax, 55, 925–929
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Parameter
Preferred units/format
Supporting
information
Preparation/chemical name
Tylophorine
Therapeutic activity
Chemical structure
O
O
H
N
O
O
Chemical name
2,3,6,7-Tetramethoxy9,10,11,12,12a,13-hexahydro9a-azacylcopenta[b]triphenylene
482-20-2
C24H27NO4
393.48 g mol-1
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
282–284°C 96
Boiling point
Octanol-partition coefficient 4.40 97
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water
partition coefficient (Kp)
Organic carbon normalised
soil/sediment water
partition coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
96
Decomposes
Estimated
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
97
Meylan WM & Howard PH (1995) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Parameter
Preparation/Chemical name
Data
Supporting info.
-
Glucosamine
Therapeutic activity
Antiarthritic98.
Used for treatment of
rheumatic disorders including
osteoarthritis. It is isolated
from chitin or prepared
synthetically4.
Chemical structure
-
O
H
N
O
H
H
O
H
O
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
2-Amino-2-deoxy-D-glucose
3416-24-8 (28905-11-5 for α
form & 28905-10-4 for β)
C6H13NO51
179.171
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem
draw file
Density
Melting Point
88˚C (α form)1; β decomposes
at 110˚C
-4.23 (est)99
Test method
Boiling Point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
98
β form very soluble in water1
6.47 at 20˚C
(potentiometric)100
-
e.g. to STP; application
to soil
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
Test method
Test method
Test method
Merck Index (2001) [Glucosamine, entry 4471]
SRC PhysProp Database [Glucosamine 3416-24-8] Viewed online at http://esc.syrres.com/interkow/physdemo.htm April 2004
100
Beilstein Database 2004 [Glucosamine 3416-24-8] accessed April 2004
4
Martindale (2002) [Glucosamine, p 1616]
99
Henry’s Law Constant
-
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
-
‘Turnover time’ of 303.4 h-1
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
characteristics
Test method
Test method
Test method
Test method; aerobic
anaerobic
Test method; soil type
101
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
-
Test method
-
-
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
-
Test method
Test species and
method
Test method and
species
101
Swindoll et al (1988) Aerobic biodegradation of natural and xenobiotic organic compounds by subsurface microbial
communities. Environmental Toxicology and Chemistry, Vol 7: 291-299
Parameter
Preparation/Chemical name
Data
Supporting info.
-
Glucosamine sulphate and
hydrochloride
Therapeutic activity
Antiarthritic102.
Glucosamine salts are given in
the treatment of rheumatic
disorders, including
osteoarthritis6.
Chemical structure
-
O
O
S
O
O
O
O
O
O
N
O
Glucosamine sulphate
O
C
l
H
H
N
O
H
H
O
H
O
O
Glucosamine hydrochloride
Chemical name
Major emission routs
2-Amino-2-deoxy-D-glucose;
sulphate &
2-Amino-2-deoxy-D-glucose;
hydrochloride
29031-19-4 (sulphate)
66-84-2 (hydrochloride)
2C6H13NO5.H2O4S (sulphate)103
C6H13NO5.ClH
(hydrochloride)104
179.17 + 98.07 (sulphate)2
179.17 + 36.46 (hydrochloride)3
-0
Application/emission rates
e.g. kg ha-1; dose (mg kg-1)
CAS no
Molecular formula
Molecular weight
102
Merck Index (2001)
Beilstein Database 2004 [Glucosamine sulphate 29031-19-4] April 2004
104
Beilstein Database 2004 [Glucosamine hydrochloride 66-84-2] April 2004
103
-
-
e.g. to STP;
application to soil
-
Proportion metabolised
-
Identity of metabolites
Amount produced; Chem draw
file
Density
Melting Point
Hydrochloride 190-194˚C
(decomposes)105;
300˚C106
-
Test method
100 g/l (hydrochloride)5
-
Test method
Test method
-
Test method
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
characteristics
Boiling Point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
-
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
-
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity:
-
Mammalian oral toxicity:
-
-
-
Test method and
species
Would be nice if all
this info. Could also
be obtained for the
metabolites
Test method
Test method
Test method
Test method;
aerobic anaerobic
Test method; soil
type
Test method
Test method
Test species and
method
Test method and
species
Hydrochloride Mouse (oral) 15
g kg-1 107
Sulphate Mouse (oral) > 5 g kg-1
108
105
Material Safety Datasheet viewed on-line at http://physchem.ox.ac.uk/MSDS/ April 2004
NTP Glucosamine Data Summary, viewed on-line at http://ntpserver.niehs.nih.gov/htdocs/Chem_Background/ExSumPdf/glucosamine.pdf
6
Martindale (2002) [Glucosamine, p 1616]
107
http://www.sigmaaldrich.com Glucosamine Hydrochloride, product code G2206, viewed April 2004
108
NTP Glucosamine Data Summary, viewed on-line at http://ntpserver.niehs.nih.gov/htdocs/Chem_Background/ExSumPdf/glucosamine.pdf
106
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Parameter
Preparation/Chemical name
Data
Supporting info.
-
Lavender essential oil
Chemical structure
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
Sleep aid and carminative109
Insecticide110
Used in herbal head lice
shampoo, in conjunction with
Tea Tree Oil.
8000-28-0
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem
draw file
Density
0.93 (at 20˚C)111
0.875-0.888 (sg at 25˚C)112
Therapeutic activity
Melting Point
Boiling Point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
109
e.g. to STP; application
to soil
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
-
Test method
‘Insoluble in water’3
-
Test method
Test method
-
Test method
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
characteristics
-
-
Test method
Test method
Test method
Test method; aerobic
anaerobic
Martindale (2002)
PAN Pesticides Database, viewed on-line at http://www.pesticideinfo.org/Index.html April 2004
111
Chemfinder [Oil of lavender], viewed on-line at http://chemfinder.cambridgesoft.com/ April 2004
112
Essential oil information viewed on-line at http://www.perfumersworld.com/essoil/oilotm.htm April 2004
110
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
-
Test method; soil type
Test method
-
-
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
-
Test method
Test species and
method
Test method and
species
-
-
Parameter
Preparation/Chemical name
Data
Supporting info.
-
Linalyl acetate
Therapeutic activity
Chemical structure
Constituent of lavender oil1
O
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
3,7-Dimethyl-1,6-octadien-3ol
115-95-7
C12H20O2
196.28113
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem
draw file
Density
0.895 (at 20 ˚C)1
0.901114
<25 ˚C115
220 ˚C1,2,3
3.933
Test method
8.2 mg/l (est)3
-
Test method
Test method
Melting Point
Boiling Point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
113
e.g. to STP; application
to soil
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
14.8 Pa at 25 ˚C (ext)3
Test method
3
-1
3
176 Pa m mol (est at 25 ˚C) Test method;
temperature
-1
L kg
Soil/sediment
characteristics
116
5800 (est from log Kow)
Soil/sediment
characteristics
Half life (d)
170 d to 4.8 yr (est at pH 7
and 8, respectively)4
0.14 dd
Test method
Test method
Test method
Merck Index (2001) [Linalyl acetate, entry 5518]
Chemfinder [Linalyl acetate] viewed on-line at http://chemfinder.cambridgesoft.com/ April 2004
115
SRC PhysProp Database [Linalyl acetate] viewed on-line at http://esc.syrres.com/interkow/physdemo.htm April 2004
116
HSDB [Linalyl acetate] viewed on-line via TOXNET at http://toxnet.nlm.nih.gov/ April 2004
114
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Thought to be readily
degradable4
see above
see above
-
Test method; aerobic
anaerobic
Test method; soil type
Test method
-
1300 (est)4
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
-
Test method
Test species and
method
Test method and
species
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
117
118
LD50 rat oral 14.55 g/kg
(13.35 g/kg mouse)4
Rabbit: severe irritant
Guinea pig: moderate
irritant117
0-0.5 mg/kg bw118
100mg for 24hrs
100mg for 24hrs
Material Safety Datasheet at http://sigmaalrich.com Product number L2807 viewed April 2004
JECFA (1998) Linalyl acetate, viewed on-line at http://www.inchem.org/documents/jecfa/jeceval/jec_931.htm April 2004
Parameter
Preparation/Chemical name
Data
Supporting info.
-
Pinene
Therapeutic activity
Constituent of many volatile
oils obtained from plants,
including lavender oil
Chemical structure
-
α pinene (dl-racemate)
Molecular formula
Molecular weight
Major emission routs
β pinene (dl-racemate)
2,6,6Trimethylbicyclo[3.1.1]hept-2ene (α pinene)
6,6-Dimethy-2methylenebicyclo[3.1.1]heptane
(β pinene)
80-56-8 (α pinene)
127-91-3 (β pinene)
C10H16
136.23119
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem draw
file
Density
0.8591, 0.857120 (α pinene)
0.877, 0.866 (β pinene)
-64 ˚C121, -62.5 ˚C122 (α pinene)
-61.5 ˚C123 (β pinene)
Chemical name
CAS no
Melting Point
119
-
e.g. to STP;
application to soil
Test method and
species
Would be nice if all
this info. Could also
be obtained for the
metabolites
Merck Index (2001) [α-pinene entry 7527, β-pinene entry 7528]
Chemfinder [alpha Pinene] viewed on-line at http://chemfinder.cambridgesoft.com/ April 2004
121
SRC PhysProp Database [Alpha-Pinene] viewed on-line at http://esc.syrres.com/interkow/physdemo.htm April 2004
122
HSDB Profiles [Alpha-Pinene], [Beta-Pinene] viewed on-line via TOXNET at http://toxnet.nlm.nih.gov/ April 2004
123
SRC PhysProp Database [Beta-Pinene] viewed on-line at http://esc.syrres.com/interkow/physdemo.htm April 2004
120
Boiling Point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
155-156 ˚C (α pinene)1,3
162-166˚C (β pinene)5,124
4.83 (α pinene at 25 ˚C) 3
4.16 (β pinene)5
2.49 mg/l2 (α pinene)
4.89 mg/l5 (est, β pinene)
-
633 Pa (α pinene at 25 ˚C)3
391 Pa (β pinene at 25 ˚C)5
Henry’s Law Constant
3x104 Pa m3 mol-1 (α pinene,
est: VP/sol)3
1.6x104 Pa m3 mol-1 (β pinene,
est)5
Soil/sediment water
2451L kg-1 (calculated for α
partition coefficient (Kp)
pinene based on estimated
Kom)125
Organic carbon normalised
1200 (est from log Kow, α, β
soil/sediment water partition pinene)4
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
0.17 d (est α pinene)4
0.2 d (est β pinene)4
Persistence in activated
Half life (d); ready/non-ready
sludge
Persistence in soil
Rapid biodegradation:
‘removal’ in ~250 hr’ (α pinene
)4
α pinene ‘readily degraded’:
observed biodegradation rate of
1.1-2.1 ug g-1 h-1 in soil slurrya
Biodegradation also
‘anticipated’ for β pinene4
Persistence in sediment
Half life (d)
Identity of degradates from
Amount produced; ChemDraw
above studies
structure
Fate in the field
Dissipation half life (d);
Measured concs (mg kg-1; mg l1
)
Bioconcentration factor
2800 (est, α pinene)4
440 (est, β pinene)4
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
LD50 rat oral 3.7 g/kg (α
124
Test method
Test method
Test method
Test method
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
characteristics
Test method
Test method
Test method
Test method; aerobic
anaerobic
Test method; soil type
Test method
Test method
Test species and
method
Test method and
species
Merck Index (2001) [β Pinene]
Chemfinder [beta-Pinene] viewed on-line at http://chemfinder.cambridgesoft.com/ April 2004
125
Misra & Pavlostathis (1997) Biodegradation kinetics of monoterpenes in liquid and soil-slurry systems. Appl Microbiol
Biotechnol, 47: 572-577
7
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian inhalation
toxicity
pinene)4126
Irritating to the skin, eyes and
respiratory system127
LCLO rat inhalation 625g m-3
( pinene)
LCLO guinea pig 527g m-3 (
pinene)
LCLO mouse 364g m-3 (
pinene)128
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
126
Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/
Material Safety Datasheet at http://ptcl.chem.ox.ac.uk/MSDS/PI/alpha-pinene.html viewed April 2004
128
Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/
127
Parameter
Preparation/Chemical name
Data
Supporting info.
-
Tea Tree Oil
Chemical structure
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
Antiseptic129.
Considered to have anti-viral,
anti-bacterial and anti-fungal
properties. It is used for the
treatment of candida and other
infections, ringworm and
athlete’s foot130.
Used in shampoo for
treatment of headlice.
68647-73-4
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem
draw file
Density
0.895-0.905 at 15 ˚C1
0.89131
-
Test method
-
Test method
Test method
-
Test method
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
characteristics
Therapeutic activity
Melting Point
Boiling Point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
129
-
-
e.g. to STP; application
to soil
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
Test method
Test method
Merck Index (2001) [Tea Tree Oil 68647-73-4]
Worwood VA (1991) The Fragrant Pharmacy: a complete guide to aromatherapy and essential oils
131
Chemfinder [Tea-tree oils] viewed on-line at http://chemfinder.cambridgesoft.com/ April 2004
130
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
-
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
-
-
Test method
Test method; aerobic
anaerobic
Test method; soil type
Test method
Test method
Test species and
method
Test method and
species
Rat (oral) LD50 1900 mg kg1132
Mammalian skin/eye toxicity
Rabbit (skin) LD50 5000 mg
kg-1 133
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
132
Material Safety Datasheet at http://www.sigmaaldrich.com/ Product number W390208
133
Material Safety Datasheet at http://www.sigmaaldrich.com/ Product number W39020
Parameter
Preparation/Chemical name
Supporting info.
-
Data
Cineole
Therapeutic activity
Constituent of Tea Tree Oil1
(and numerous other plants)
Chemical structure
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane
470-82-6
C10H18O
154.25134
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem
draw file
Density
0.922135
0.9267 g/cm3 (20 ˚C)4
1.5 ˚C136
176.4 ˚C3,137
174-176.4 ˚C1
2.743,4
Test method
3.5 g/l3, 3.24 g/l1
-
Test method
Test method
253 Pa (25 ˚C)3,4
11 Pa m3 mol-1 (est at 25 ˚C)3
Test method
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
characteristics
Melting Point
Boiling Point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
134
-
-
e.g. to STP; application
to soil
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
Test method
Beilstein Database [cineole] accessed April 2004
Chemfinder [1,8-Cineole] viewed on-line at http://chemfinder.cambridgesoft.com/ April 2004
136
SRC PhysProp Database [1,8-Cineole] viewed on-line at http://esc.syrres.com/interkow/physdemo.htm April 2004
137
HSDB [Cineole] viewed on-line via TOXNET at http://toxnet.nlm.nih.gov/ April 2004
135
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
-
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
-
-
Test method
Test method
Test method; aerobic
anaerobic
Test method; soil type
Test method
Test method
Test species and
method
Test method and
species
Rat (oral) LD50 2480 mg kg-1
138
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
LD50 Artemia salina
737ppm139
Brine shrimp
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
138
139
Material Safety Datasheet viewed at http://www.sigmaaldrich.com/ Product number C8144 viewed April 2004
Beilstein Database, May 2004
Parameter
Supporting info.
Data
Preparation/Chemical name
Terpinen-4-ol
Therapeutic activity
Chemical structure
Constituent of Tea Tree Oil140
-
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
4-methyl-1-(1-methylethyl)-3cyclohexen-1-ol
562-74-3
C10H18O
154.25141
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem
draw file
Density
Melting Point
Boiling Point
0.933142
209 ˚C143
210-214 ˚C (at 760 mmHg)2
3.264
Test method
g L-1
-
Test method
Test method
Pa
Pa m3 mol-1
Test method
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
characteristics
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
140
L kg-1
L Kg-1
Half life (d)
e.g. to STP; application
to soil
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
Test method
Merck Index (2001) [Tea Tree Oil 68647-73-4]
Beilstein Database [562-74-3]
142
Chemfinder [terpinen-4-ol] viewed on-line at http://chemfinder.cambridgesoft.com/ April 2004
143
SRC PhysProp Database [562-74-3] viewed on-line at http://esc.syrres.com/interkow/physdemo.htm April 2004
141
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Half life (d)
Half life (d)
Half life (d); ready/non-ready
Half life (d)
Half life (d)
Amount produced;
ChemDraw structure
Dissipation half life (d);
Measured concs (mg kg-1; mg
l-1)
-
Test method
Test method
Test method; aerobic
anaerobic
Test method; soil type
Test method
Test method
Test species and
method
Test method and
species
Rat (oral) LD50 1300 mg kg-1
144
Mammalian skin/eye toxicity
Rabbit (skin) >2500 mg kg-1
Rabbit skin: moderate irritant
145
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
144
145
Material Safety Datasheet at http://www.fisher.co.uk/ Catalogue number 27043-1000
Material Safety Datasheet at http://www.fisher.co.uk/ Catalogue number 12515-0000
Draize test, 500mg / 24
hr
Parameter
Preparation/chemical name
Preferred units/format
Supporting information
Orange essential oil
Therapeutic activity
Chemical structure
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
146
Expectorant146
Used as a flavour and in
perfumery.147
Used as a flavour and
perfume.
8008-57-9
2600 µg/day 148
Estimated European
per captia intake
0.844–0.847 g cm-3
At 20/20°C
Slightly soluble in water a
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
147
Sweetman SC (2002) Martindale. The Complete Drug Reference. Thirty-third edition. London, UK, Pharmaceutical Press.
148
IPCS (1999) Safety Evaluation of Certain Food Additives. WHO Food Additives Series: 42. Aliphatic, Acyclic and Alicyclic
Terpenoid Tertiary Alcohols and Structuraaly Related Substances. Geneva, Switzerland, World Health Organization
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Rat (oral) LD50 >5g kg-1 149
Rabbit (skin) LD50 >5g kg-1
150
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
149
150
Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/
Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/
Parameter
Preparation/chemical name
Preferred units/format
Supporting information
d-Limonene
Therapeutic activity
Chemical structure
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
151
4-Isopropenyl-1-methylcyclohexene
5989-27-5
C10H16
136.24 g mol-1
0.8482 g cm-3 151
-73.97°C 152
175.5–176°C 153
Determined at 4/20°C
Determined at 101725
Pa
4.57154
0.0204 g L-1 155
Determined at 25°C
213 Pa156
2604 Pa m3 mol-1 157
1501L kg-1 (calculated, based
on estimated Kom)158
1030–4780159
Determined at 25°C
Estimated at 25°C
0.096–0.108160
Based on experimental
rates constants for the
gas-phase reaction
with photochemically
Estimated soil
adsorption coefficients
Beilstein database (2004)
Beilstein database (2004)
153
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
154
Li J & Purdue EM (1995) cited in SRC PhysProp Database, avaialble [April 2004) at: http://esc.syrres.com/
155
Beilstein database (2004)
156
Beilstein database (2004)
157
VP/WSOL cited in SRC PhysProp Database, avaialble [April 2004] at: http://esc.syrres.com/
158
Misra & Pavlostathis (1997) Biodegradation kinetics of monoterpenes in liquid and soil-slurry systems. Appl Microbiol
Biotechnol, 47: 572-577
159
Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/
160
Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/
152
produced hydroxyl
radicals
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
0.008–0.033 days161
Estimated atmospheric
lifetime depending on
hydroxyl and ozone
conc
‘Readily degraded’: observed
biodegradation rate of 0.9-1.9
ug g-1 h-1 in soil slurryh
Photolysis of d-limonene in
the presence of nitrogen
oxides produces:162
-
O
formaldehyde
O
H
O
formic acid
(
I
I
)
C
O
carbon monoxide
O
O
carbon dioxide
O
acetaldehyde
O
O
O
O
N
O
peroxyacetyl nitrate
O
acetone
161
162
Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/
Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/
Degradation products of
hydrolysis of limonene
include:
O
formaldehyde
O
O
acetic acid
O
H
O
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
formic acid
e
246–262163
Estimated for aquatic
organisms based on
water solubility and
estimated log Kow
Rat (oral) LD50 4.4g kg-1
Mouse (oral) LD50 5.6g kg-1
164
Mammalian skin/eye toxicity
Rabbit (skin) LD50 >5g kg-1
165
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
0.1 mg kg-1 bw day-1 166
EC50 0.4mg l-1 167
Earthworm Eisenia fetida
(Savigny) LD50 6.0ppm 168
Cutaneous exposure
Environmental fate
Fate (Animals)
163
Hazardous Substances Data Bank (HSDB) available, [April 2004] at: http://toxnet.nlm.nih.gov/
http://ptcl.chem.ox.ac.uk/MSDS/LI/(R)-(+)-limonene.html viewed April 2004
165
http://ptcl.chem.ox.ac.uk/MSDS/LI/(R)-(+)-limonene.html viewed April 2004
166
Concise International Chemical Assessment Document, viewed April 2004 at
http://www.inchem.org/documents/cicads/cicads/cicad05.htm
167
CICAD entry http://www.inchem.org/documents/cicads/cicads/cicad05.htm#PartNumber:9 viewed May 2004
168
Hazardous Substances Data Bank (HSDB) available, [April 2004] at: http://toxnet.nlm.nih.gov/
164
Fate (Plants)
Parameter
Preparation/chemical name
Preferred units/format
Supporting information
L-Limonene
Therapeutic activity
Chemical structure
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa174)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
169
4-Isopropenyl-1-methylcyclohexene
5989-54-8
C10H16
136.24 g mol-1
0.8407 g cm-3 169
-73.95°C 170
175.5–176.5°C 171
Determined at 4/21°C
Determined at 101725
Pa
4.38172
0.00315 g L-1 173
Estimated at 25°C
191.98 Pa
38503.5 Pa m3 mol-1 175
1501L kg-1 (calculated, based
on estimated Kom)176
1030–4780177
Determined at 25°C
Estimated at 25°C
Estimated soil
adsorption coefficients
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
170
Beilstein database (2004)
171
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
172
Griffin S et al. (1999) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
173
Meylan WM et al. (1996) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
174
Nadais MH & Bernardo-Gil MG (1993) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
175
Meylan WM & Howard PH (1991) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
176
Misra & Pavlostathis (1997) Biodegradation kinetics of monoterpenes in liquid and soil-slurry systems. Appl Microbiol
Biotechnol, 47: 572-577
177
Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/
coefficient (Koc)
Photolysis half life
0.108 days178
Half-life based on
experimental rate
constant for the gasphase reaction of
limonene with
photochemically
produced hydroxyl
radicals.
Hydrolysis half life
Persistence in air
0.008–0.033 days179
Estimated atmospheric
lifetime depending on
hydroxyl and ozone
conc
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
‘Readily degraded’: observed
biodegradation rate of 0.9-1.9
ug g-1 h-1 in soil slurryh
Photolysis of d-limonene in
the presence of nitrogen
oxides produces:180
O
formaldehyde
O
H
O
formic acid
(
C
I
I
)
O
carbon monoxide
O
O
carbon dioxide
O
acetaldehyde
178
Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/
Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/
180
Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/
179
O
O
O
O
N
O
peroxyacetyl nitrate
O
acetone
Degradation products of
hydrolysis of limonene
include:
O
formaldehyde
O
O
acetic acid
O
H
O
formic acid
Fate in the field
Bioconcentration factor
246–262181
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Rat (oral) LD50 5000 mg kg-1
Estimated for aquatic
organisms based on
water solubility and
estimated log Kow
182
Mammalian skin/eye toxicity
Rabbit (skin) LD50 >5000 mg
kg-1 183
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
181
Hazardous Substances Data Bank (HSDB) available, [April 2004] at: http://toxnet.nlm.nih.gov/
Material Safety Datasheet at http://www.sigmaalrich.com Product number 218367
183
Material Safety Datasheet at http://www.sigmaalrich.com Product number 218367
182
Ecotoxicity (Algae)
Green alga, LCIC >100mol/l Lowest complete
inhibition
Blue-green alga, LCIC >
184
concentration, rapid
100mol/l
microplate assay
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
184
Beilstein Database, viewed April 2004, Beilstein Registry number 2323991
Parameter
Preparation/chemical name
Preferred units/format
Supporting information
Citral
Therapeutic activity
Chemical structure
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
3,7-Dimethyl-2,6-octadienal
5392-40-5
C10H16O
152.23 g mol-1
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
L kg-1
185
0.885–0.891 g cm-3 185
<-10°C186
226–228°C 187
3.45188
Determined at 25/25°C
0.5785 g L-1 189
Determined at 25°C
12.17 Pa190
4.41 Pa m3 mol-1 191
Estimated at 25°C
Estimated at 25°C
using a fragment
constant method
Soil/sediment
characteristics
Estimated based on
molecular connectivity
indexes.
150 c
0.03–0.12 days c
Estimated
Based on rate constant
for vapour-phase
reaction with ozone
and hydroxyl radicals,
respectively
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
186
SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
187
Hazardous Substances Data Bank (HSDB), available [April 2004] at: http://toxnet.nlm.nih.gov/
188
Meylan WM & Howard PH (1995) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
189
Beilstein database (2004)
190
Neely WB & Blau GE (1985) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
191
Meylan WM & Howard PH (1993) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
250192
Estimated for aquatic
organisms from an
estimated log Kow.
Rat (oral) LD50 4.96 g kg-1
Mouse (oral) LD50 6 g kg-1
193
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
192
Irritating to skin and eyes 194
Human 500 g kg-1 195
Hazardous Substances Data Bank, available [April 2004] at: http://toxnet.nlm.nih.gov/
Material Safety Datasheet at http://ptcl.chem.ox.ac.uk/MSDS/CI/citral.html viewed April 2004
194
Material Safety Datasheet at http://ptcl.chem.ox.ac.uk/MSDS/CI/citral.html viewed April 2004
195
Hazardous Substances Data Bank, available [April 2004] at: http://toxnet.nlm.nih.gov/
193
Parameter
Preparation/chemical name
Preferred units/format
Supporting information
Linalool
Therapeutic activity
Chemical structure
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
3,7-Dimethyl-octa-1,6-dien-3ol
78-70-6
C10H18O
154.25 g mol-1
e.g. kg ha-1; dose (mg kg-1)
-
0.8685 g cm-3 196
<25°C 197
198°C198
Determined at 4/20°C
Determined at 101 325
Pa
2.97199
1.56 g L-1 200
Determined at 25°C
21.33 Pa 201
2.18 Pa m3 mol-1 202
Determined at 25°C
Test method;
temperature
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
75203
Photolysis half life
0.033–0.067 days204
Determined from an
experimental water
solubility and a
recommended
regression-derived
equation
Photooxidation at
21.9°C in 135L. 2m
long reaction chamber
196
197
198
199
200
201
202
203
204
Beilstein database (2004)
SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
Beilstein database (2004)
Li J & Perdue EM (1995) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
Beilstein database (2004)
Li J & Perdue EM (1995) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
Altschuh J et al. (1999) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
Hazardous Substances Data Bank (HSDB), avaialble [April 2004] at: http://toxnet.nlm.nih.gov/
Beilstein database (2004)
Hydrolysis half life
Persistence in air
0.03–0.13 days 205
Based on estimated
vapour phase reaction
rate constants in air
with ozone and
hydroxyl radicals,
respectively.
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
106 206
Estimated for aquatic
organisms from an
experimental log Kow
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
205
Mouse (oral) LD50 3g kg-1
(oily solution)
Mouse (oral) LD50 1.7g kg-1
(10% aqueous arabic gum
solution)
Rat (oral) LD50 2.79g kg-1 207
Rabbit (skin) 5.61g kg-1
Rat (skin) 5.61g kg-1
Rabbit (eye) moderate irritant
at 100% 208
0-0.5 mg kg-1 bw 209
Hazardous Substances Data Bank (HSDB), avaialble [April 2004] at: http://toxnet.nlm.nih.gov/
Hazardous Substances Data Bank (HSDB), avaialble [April 2004] at: http://toxnet.nlm.nih.gov/
207
Hazardous Substances Data Bank (HSDB), avaialble [April 2004] at: http://toxnet.nlm.nih.gov/
208
Material Safety Datasheet at http://www.fisher.co.uk/ Catalogue number 12515-0000
209
JECFA (1998) http://www.inchem.org/documents/jecfa/jecmono/v042je17.htm viewed April 2004
206
Parameter
Preparation/chemical name
Therapeutic activity
Chemical structure
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Preferred units/format
Supporting information
-
Peppermint oil
Carminative210
Aromatic carminative which
relaxes gastrointestinal
smooth muscle and relieves
flatulence and colic. Entericcoated capsules containing
peppermint oil are used for
the relief of symptoms of the
irritable bowel syndrome or
gastrointestinal spasm
secondary to other disorders.
Also used as a flavour and
with other volatile agents in
preparations for respiratorytract disorders.211
8006-90-4
e.g. kg ha-1; dose (mg kg-1)
-
0.896–0.908 g cm-3 212
Determined at 25/25°C
Very slightly soluble in
water213
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
210
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
211
Sweetman SC (2002) Martindale. The Complete Drug Reference. Thirty-third edition. London, UK, Pharmaceutical Press.
212
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
213
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Rat (oral) LD50 2.4g kg-1
Mouse (oral) LD50 2.5g kg-1
214
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
214
Hazardous Substances Data Bank (HSDB), avaialble [April 2004] at: http://toxnet.nlm.nih.gov/
Parameter
Preparation/chemical name
Therapeutic activity
Chemical structure
Preferred units/format
Supporting information
Menthol
Antipruritic (topical)
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
2-Isopropyl-5-methylcyclohexanol
89-78-1
C10H20O
156.27 g mol-1
18 000 µg/day215
Proportion metabolised
-
Identity of metabolites
Amount produced; Chem
draw file
Density
Melting point
Boiling point
0.9 g cm-3 216
41–43°C 217
212–212.5°C 218
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
3.40219
Henry’s Law Constant
1.54 Pa m3 mol-1 222
215
Estimated European
per capita intake
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
Determined at 4/20°C
Determined at 101325
Pa
0.456 g L-1 220
Determined at 25°C
14.67 Pa 221
Extrapolated from data
at 25°C
Estimated at 25°C
ICPS (1999) Safety Evaluation of Certain Food Additives. WHO Food Additives Series: 42. Substances Structurally Related
to Menthol. Geneva, Switzerland, World Health Organization
216
Beilstein database (2004)
217
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
218
Beilstein database (2004)
219
Griffin S et al. (1999) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
220
Yalkowsky SH & Dannenfelser RM (1992) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
221
Jordan TE (1954) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
222
Meylan WM & Howard PH (1993) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Rat (oral) LD50 3180 mg kg-1
223
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
223
224
0 – 4 mg kg-1 bw 224
Hazardous substances Database viewed at http://toxnet.nlm.nih.gov/ April 2004
JECFA, 1998 viewed http://www.inchem.org/documents/jecfa/jecmono/v042je04.htm April 2004
Parameter
Preparation/chemical name
Therapeutic activity
Preferred units/format
Supporting information
Menthone
Used in perfume and flavour
compositions225
Chemical structure
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
2-Isopropyl-5-methylcyclohexanone
10458-14-7
C10H18O
154.23 g mol-1
1000 µg/day 226
Estimated European
per capita intake
0.8924 g cm-3 227
-6°C228
202°C 229
Determined at 4/20°C
0.7 g L-1 230
Determined at 20°C
13332.2–101325 Pa 231
Determined at 138–
209°C
Determined at 101325
Pa
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
225
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
226
ICPS (1999) Safety Evaluation of Certain Food Additives. WHO Food Additives Series: 42. Substances Structurally Related
to Menthol. Geneva, Switzerland, World Health Organization
227
Beilstein database (2004)
228
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
229
Beilstein database (2004)
230
Beilstein database (2004)
231
Beilstein database (2004)
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Parameter
Preparation/chemical name
Therapeutic activity
Chemical structure
Preferred units/format
Supporting information
Menthyl acetate
Used in perfumery232
O
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
5-Methyl-2-(1methylehtyl)cyclohexanol
acetate
89-48-5
C12H22O2
198.30 g mol-1
420 µg/day 233
Proportion metabolised
-
Identity of metabolites
Amount produced; Chem
draw file
Density
Melting point
Boiling point
0.9185 g cm-3 234
27°C 235
227–228°C 236
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
4.39237
232
Estimated European
per capita intake
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
Determined at 4/20°C
Determined at 101325
Pa
Estimated
Slightly soluble in water238
13.33 Pa 239
84.10 Pa m3 mol-1 240
At 25°C
Estimated using a
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
233
ICPS (1999) Safety Evaluation of Certain Food Additives. WHO Food Additives Series: 42. Substances Structurally Related
to Menthol. Geneva, Switzerland, World Health Organization
234
Beilstein database (2004)
235
Beilstein database (2004)
236
Beilstein database (2004)
237
Meylan WM & Howard PH (1995) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/
238
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
239
Hazardous Substances Data Bank (HSDB), available [April 2004] at: http://toxnet.nlm.nih.gov/
fragment constant
estimation method
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
5800241
0.875 days 242
270–2666.33 days 243
Persistence in air
0.875 days 244
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
1300245
Determined from an
estimated log Kow and
a regression equation
Based on an estimated
base-catalyzed secondorder hydrolysis rate
constant, using a
structure estimation
method. Half-lives
correspond to pH 8 and
7, respectively.
Based on estimated
half-life for
photochemically
produced hydroxyl
radicals
Estimated for aquatic
organisms from an
estimated log Kow
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
240
241
242
243
244
245
Hazardous Substances Data Bank (HSDB), available [April 2004] at: http://toxnet.nlm.nih.gov/
Hazardous Substances Data Bank (HSDB), available [April 2004] at: http://toxnet.nlm.nih.gov/
Hazardous Substances Data Bank (HSDB), available [April 2004] at: http://toxnet.nlm.nih.gov/
Hazardous Substances Data Bank (HSDB), available [April 2004] at: http://toxnet.nlm.nih.gov/
Hazardous Substances Data Bank (HSDB), available [April 2004] at: http://toxnet.nlm.nih.gov/
Hazardous Substances Data Bank (HSDB), available [April 2004] at: http://toxnet.nlm.nih.gov/
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Parameter
Preparation/Chemical name
Data
Supporting info.
-
Thyme essential oil
Therapeutic activity
Chemical structure
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
Similarly to thyme, thyme oil
has carminative, antiseptic,
antitussive, and expectorant
properties and is used chiefly
in preparations for
respiratory-tract disorders.246
8007-46-3
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem
draw file
Density
0.915-0.935 (sg at 25 ˚C)247
Melting Point
Boiling Point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
246
247
e.g. to STP; application
to soil
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
-
Test method
-
Test method
Test method
-
Test method
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
characteristics
-
-
Test method
Test method
Test method
Test method; aerobic
anaerobic
Martindale (2002) [Thyme, Thyme Oil]
The Good Scent Company [Thyme Oil Red, White] viewed on-line at http://www.thegoodscentscompany.com April 2004
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
-
Test method; soil type
Test method
-
-
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
-
Test method
Test species and
method
Test method and
species
Rat (oral) LD50 2840 mg kg-1
248
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Rabbit (skin) LD50 >5000 mg
kg-1 249
LC50 20.5 mg l-1 (coho
salmon)
LC50 16.1 mg l-1 (rainbow
trout) (Stroh et al., 1998)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
248
249
Material Safety Datasheet http://ptcl.chem.ox.ac.uk/MSDS/TH/thyme_oil.html
Material Safety Datasheet http://ptcl.chem.ox.ac.uk/MSDS/TH/thyme_oil.html
96hrs, static acute
toxicity in moderately
hard fresh water
Parameter
Preparation/Chemical name
Data
Supporting info.
-
Thymol
Therapeutic activity
Chemical structure
Chemical name
Topical application as an
antiseptic and as an
antihelmintic.
Veterinary use as an
antihelmintic, and as an
antiseptic, external and
internal.250
Antifungal and reduces
gingivitis251
O
CAS no
Molecular formula
Molecular weight
Major emission routs
5-Methyl-2-(1methylethyl)phenol
89-83-8
C10H14O
150.221
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem
draw file
Density
Melting Point
0.9699 (at 25 ˚C)1
51.5 ˚C1,252
52 ˚C2
~233 ˚C1,253
232.53
3.302,3
3.89 (at 25 ˚C)254
~1 g/l1
900 mg/l (at 25 ˚C)3
10.6 (at 20 ˚C)3
10.622
9.9 (spectrophotometric at
Boiling Point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
250
-
e.g. to STP; application
to soil
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
Test method
Test method
Test method
Merck Index (2001) [Thymol, entry 89-93-8]
HSDB [Thymol] viewed on-line via TOXNET at http://toxnet.nlm.nih.gov/ April 2004
252
SRC PhysProp Database [Thymol] viewed on-line at http://esc.syrres.com/interkow/physdemo.htm April 2004
253
Chemfinder [Thymol] viewed on-line at http://chemfinder.cambridgesoft.com/ April 2004
254
Beilstein Database [89-83-8] accessed April 2004
251
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
24.9 ˚C ) & 10.49 (at 25 ˚C)5
0.29 Pa (at 25 ˚C)2,3
0.05 Pa m3 mol-1 (est at 25
˚C)3
-
Rat (oral) LD50 980mg kg-1
255
Mouse (oral) LD50 1.8g kg-1
Test method
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
characteristics
Test method
Test method
Test method
Test method; aerobic
anaerobic
Test method; soil type
Test method
Test method
Test species and
method
Test method and
species
? Query mouse oral tox
LD50 on sigma msds
640mg kg-1
256
Guinea pig (oral) LD50
880mg kg-1257
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
LC50 3.2 – 4.2 mg l-1 258
EC50 1.7 – 3.2 mg l-1 259
LC50 10.71 mg l-1 260
Toxic to aquatic organisms
May cause long-term adverse
255
96 hr
Pimephales promelas
96 hr
Acute toxicity to
Lymnaea acuminata
(snail) measured at 96
hrs
Material Safety Datasheet at http://physchem.ox.ac.uk/MSDS/ viewed April 2004
Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/
257
Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/
258
Material Safety Datasheet at http://www.sigmaaldrich.com/ Product code 112097 viewed April 2004
259
Material Safety Datasheet at http://www.sigmaaldrich.com/ Product code 112097 viewed April 2004
260
Beilstein Database, viewed April 2004
256
effects in the aquatic
environment 261
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
261
Material Safety Datasheet at http://physchem.ox.ac.uk/MSDS/ viewed April 2004
Parameter
Preparation/Chemical name
Data
Supporting info.
-
Carvacrol
Therapeutic activity
Constituent of Thyme oil.
Used as an anti-infective and
as antihelminthic262.
Chemical structure
O
-
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
IUPAC format
499-75-2
C10H14O
150.221
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem
draw file
Density
Melting Point
0.976 (at 20 ˚C)1,3
~0 ˚C1
1 ˚C263,264
237-238 ˚C1
237.7 ˚C2
3.492
Test method
1.25 g/l (at 25 ˚C)2
10.35 (at 25 ˚C)265
Test method
Test method
-
Test method
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
characteristics
Boiling Point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
262
-
e.g. to STP; application
to soil
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
Merck Index (2001) [Carvacrol, entry 1887]
SRC PhysProp Database [499-75-2] viewed on-line at http://esc.syrres.com/interkow/physdemo.htm April 2004
264
HSDB [Carvacrol] viewed on-line via TOXNET at http://toxnet.nlm.nih.gov/ April 2004
265
Beilsten Database [499-75-2] accessed April 2004
263
Parameter
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Data
-
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
-
Amount produced;
ChemDraw structure
-
Supporting info.
Test method
Test method
Test method
Test method; aerobic
anaerobic
Test method; soil type
Test method
Test method
Test species and
method
Test method and
species
Rat (oral) LD50 810mg kg1266
Mammalian skin/eye toxicity
Rabbit (skin) severe irritant
500mg 24 hr
267
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
266
Material Safety Datasheet at http://ptcl.chem.ox.ac.uk/MSDS/ME/2-methyl-5-(1-methylethyl)phenol.html viewed April
2004
267
Material Safety Datasheet http://www.sigmaaldrich.com/ Product code 282197 viewed April 2004
Parameter
Preparation/Chemical name
Data
Supporting info.
-
Borneol
Therapeutic activity
Constituent of thyme and
valerian.
Free or esterified borneol
identified in 250 distillates
from plants, herbs, leaves etc.4
Chemical structure
O
CAS no
Molecular formula
Molecular weight
Major emission routs
(dl enantiomers. Natural
borneol can be d or l but
v.seldom racemic)4
endo-1,7,7-Trimethylbicyclo[2.2.1]heptan-2-ol
507-70-0
C10H18O
154.25268
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem draw
file
Density
Melting Point
Boiling Point
1.011 (d-form)1
206-207 ˚C (dl form)1a
212 ˚C (d-form)1
210 ˚C269
2.69270
Test method
738 mg/l (at 25 ˚C)3
-
Test method
Test method
4.7 Pa (est at 25 ˚C)3
0.7 Pa m3 mol-1(est at 25 ˚C)3
Test method
Test method;
temperature
Soil/sediment
characteristics
Chemical name
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
268
L kg-1
e.g. to STP;
application to soil
Test method and
species
Would be nice if all
this info. Could also
be obtained for the
metabolites
Merck Index (2001) [Borneol, entry 1328]. 1a Mpt: 208 ˚C for d-form and 204 ˚C for l-form.
Chemfinder [borneol] viewed on-line at http://chemfinder.cambridgesoft.com/ April 2004
270
SRC PhysProp Database [507-70-0] viewed on-line at http://esc.syrres.com/interkow/physdemo.htm April 2004
4
HSDB [Borneol] viewed on-line via TOXNET at http://toxnet.nlm.nih.gov/ April 2004
269
Parameter
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Data
-
Supporting info.
Soil/sediment
characteristics
-
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
-
Test method
Test method
Test method
Test method; aerobic
anaerobic
Test method; soil
type
Test method
-
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
-
-
-
Test method
Test species and
method
Test method and
species
Parameter
Preparation/Chemical name
Data
Supporting info.
-
Camphor
Therapeutic activity
Topical analgesic and
antipruritic. Veterinary use
internally as carminative,
externally as an antipruritic,
counterirritant and antiseptic1.
Also used as a steam inhalant
– popular in respiratory
diseases of horse and poultry3.
Chemical structure
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routs
(d/l enantiomers:
natural form is d-camphor,
synthetic form is racemic)
IUPAC format
76-22-2
C10H16O
152.23271
-0
Application/emission rates
Proportion metabolised
e.g. kg ha-1; dose (mg kg-1)
-
Identity of metabolites
Amount produced; Chem
draw file
Density
Melting Point
0.992 g/cm3 (at 25 ˚C)1
179 ˚C1
180 ˚C272
d-Camphor sublimes at 204
˚C1
2.382
Boiling Point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
271
e.g. to STP; application
to soil
Test method and
species
Would be nice if all
this info. Could also be
obtained for the
metabolites
Test method
1.25 g/l (at 25 ˚C)1
1.6 g/l (at 25 ˚C)2
2.04 g/l (at 25 ˚C)273
-
Test method
87 Pa (at 25 ˚C)2,274
Test method
Test method
Merck Index (2001) [Camphor, entry 1739]
SRC PhysProp Database [76-22-2] viewed on-line at http://esc.syrres.com/interkow/physdemo.htm April 2004
273
Beilstein Database [Camphor]
272
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
8.2 Pa m3 mol-1 (est at 25 ˚C,
VP/WSOL)2
-
-
Test method;
temperature
Soil/sediment
characteristics
Soil/sediment
characteristics
Test method
Test method
Test method
Test method; aerobic
anaerobic
Test method; soil type
Test method
Test method
Test species and
method
Test method and
species
Rabbit LDLO 2g kg-1
Mouse LD50 1.31g kg-1275
Human lethal dose 50-500 mg
kg-1 (Gibson et al., 2004)
Mild skin, eye or respiratory
irritant
Typical TLV/TWA 2ppm
Typical STEL 3ppm276
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
274
HSDB [Camphor] viewed on-line via TOXNET at http://toxnet.nlm.nih.gov/ April 2004
Material Safety Datasheet viewed at http://physchem.ox.ac.uk/MSDS/CA/camphor.html April 2004
276
Material Safety Datasheet viewed at http://physchem.ox.ac.uk/MSDS/CA/camphor.html April 2004
275
Parameter
Preparation/chemical name
Therapeutic activity
Preferred units/format
Supporting information
Absinthium
Wormwood
Antihelminthic277
As flavouring in alcoholic
beverages (e.g. vermouth)278
Used as a bitter. Has been
used in homeopathic
medicine279
Chemical structure
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
277
Personal communication
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
279
Sweetman SC (2002) Martindale. The Complete Drug Reference. Thirty-third edition. London, UK, Pharmaceutical Press
278
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Rat oral LD50 960mg kg-1 280
Rabbit dermal LD50 > 5g kg-1 Not irritant in 48 hour
281
patch test in humans
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
280
281
WHO Food Additives Series viewed online at http://www.inchem.org/documents/jecfa/jecmono/v16je25.htm , May 2004
WHO Food Additives Series viewed online at http://www.inchem.org/documents/jecfa/jecmono/v16je25.htm, May 2004
Parameter
Preferred units/format
Supporting
information
-
Preparation/chemical
Absinthin
name
Therapeutic activity
Chemical structure
-
O
H
H
O
H
H
H
H
H
H
H
O
O
O
O
Chemical name
[3S-(3α,3a α,6β,6aα,6bβ,7α,7aβ,8 α,10aβ,11β,13a α,13b α,13cβ,14bβ)]3,3a,4,5,6a,6b,7,7a,8,9,10,10a,13a,13c,14bHexadecahydro-6,8-dihydroxy-3,6,8,11,14,15hexamethyl-2H-7,13bethenopentaleno[1”,2”:6,7;5”,4”:6’,7’]dicyclohepta[1,2b:1’,2’-b’]difuran-2,12(11H)-dione
1362-42-1
C30H40O6
496.63 g mol-1
CAS no
Molecular formula
Molecular weight
Major emission
routes
Application/emission
rates
Proportion
metabolised
Identity of
metabolites
Density
Melting point
179–180°C
Boiling point
Octanol-partition
coefficient (Kow, P)
Solubility in water
Acid dissociation
constant (pKa)
Vapour pressure
Henry’s Law
Constant
Soil/sediment water
partition coefficient
(Kp)
Organic carbon
normalised
soil/sediment water
Decomposes
partition coefficient
(Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in
activated sludge
Persistence in soil
Persistence in
sediment
Identity of
degradates from
above studies
Fate in the field
Bioconcentration
factor
Biota-sediment/soil
accumulation factor
Mammalian oral
toxicity
Mammalian skin/eye
toxicity
Mammalian ADI
Mammalian
inhalation toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity
(Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other
aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
Parameter
Preparation/chemical name
Therapeutic activity
Preferred units/format
Supporting information
α-Santonin
Anthelminthic (Nematodes)282
Formerly used as an
anthelminthic in the treatment
of roundworm infection, but
has been superseded by other
less toxic anthelminthics.
Used as a flavour in food.283
Chemical structure
O
O
H
O
H
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
282
3,5a,9-Trimethyl-3a,5,5a,9btetrahydro-3H,4Hnaphthol[1,2-b]furan-2,8dione
481-06-1
C15H18O3
246.3 g mol-1
1.187 g cm-3 284
175°C 285
1.78 286
Estimated
0.2 g L-1 287
Experimental
determination
0.000371 Pa 288
0.0053 Pa m3 mol-1 289
Estimated at 25°C
Estimated at 25°C
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
283
Sweetman SC (2002) Martindale. The Complete Drug Reference. Thirty-third edition. London, UK, Pharmaceutical Press
284
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
285
SRC PhysProp Database available [May 2004] at: http://esc.syrres.com/
286
Meylan WM & Howard PH (1995) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/
287
Yalkowsky SH & Dannenfelser RM (1992) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/
288
Neely WB & Blau GE (1985) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/
289
Meylan WM & Howard PH (1991) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mouse oral LD50 900mg kg-1
290
Mammalian skin/eye toxicity
Mammalian ADI
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
290
Material Safety Datasheet viewed online at http://www.sigmaaldrich.com Product number 223085, May 2004
Parameter
Preparation/chemical name
Preferred units/format
Supporting information
α-Thujone
Therapeutic activity
Chemical structure
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
Boiling point
Octanol-partition coefficient
(Kow, P)
Solubility in water
Acid dissociation constant
(pKa)
Vapour pressure
Henry’s Law Constant
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
Hydrolysis half life
Persistence in air
291
1-isopropyl-4methylbicyclo(3.1.0)hexan-3one
546-80-5
C10H16O
152.24 g mol-1
0.9101 g cm-3 291
<25°C 292
203°C 293
Determined at 4/25°C
2.65294
Pressure at which
determination made
not specified
Estimated
0.408 g L-1 295
Estimated at 25°C
54.93 Pa 296
0.0093 Pa m3 mol-1 297
Extrapolated to 25°C
Estimated at 25°C
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
292
SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/
293
SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/
294
Meylan WM & Howard PH (1995) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/
295
Meylan WM & Howard PH (1995) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/
296
Perry RH & Green D (1984) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/
297
Meylan WM & Howard PH (1993) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
Mouse oral LD50 250mg kg-1
Guinea pig oral LD50 396 mg isomer not specified
kg-1 298
Rat oral LD50 500 mg kg-1 299
Not possible to establish on
the data availablea
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
298
299
WHO Food Additives Series viewed at http://www.inchem.org/documents/jecfa/jecmono/v16je25.htm May 2004
Material Safety Datasheet viewed at http://www.sigmaaldrich.com Product number 89231, May 2004
Parameter
Preparation/chemical name
Preferred units/format
Supporting information
β-thujone
Therapeutic activity
Chemical structure
H
O
Chemical name
CAS no
Molecular formula
Molecular weight
Major emission routes
Application/emission rates
Proportion metabolised
Identity of metabolites
Density
Melting point
1-isopropyl-4methylbicyclo(3.1.0)hexan-3one
471-15-8
C10H16O
152.24 g mol-1
0.9135 g cm-3 300
<25°C 301
Boiling point
203°C 302
Octanol-partition coefficient
(Kow, P)
Solubility in water
2.65303
0.408 g L-1 304
Acid dissociation constant
(pKa)
Vapour pressure
54.93 Pa 305
Henry’s Law Constant
0.0093 Pa m3 mol-1 306
Determined at 4/25°C
Melting point for
thujone
Boiling point for αthujone
Estimated for αthujone
Estimated at 25°C for
α-thujone
Extrapolated to 25°C
for α-thujone
Estimated at 25°C for
α-thujone
Soil/sediment water partition
coefficient (Kp)
Organic carbon normalised
soil/sediment water partition
coefficient (Koc)
Photolysis half life
300
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals.
Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
301
SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/
302
SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/
303
Meylan MW & Howard PH (1995) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/
304
Meylan WM & Howard PH (1995) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/
305
Perry RH & Green D (1984) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/
306
Meylan WM & Howard PH (1993) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/
Hydrolysis half life
Persistence in air
Persistence in activated
sludge
Persistence in soil
Persistence in sediment
Identity of degradates from
above studies
Fate in the field
Bioconcentration factor
Biota-sediment/soil
accumulation factor
Mammalian oral toxicity
Mammalian skin/eye toxicity
Mammalian ADI
Dog oral LD50 250mg kg-1 307
Not possible to establish on
the data available1
Mammalian inhalation
toxicity
Ecotoxicity (Bird)
Ecotoxicity (Fish)
Ecotoxicity (Daphnia)
Ecotoxicity (Algae)
Ecotoxicity (Other aquatics)
Ecotoxicity (Bees)
Ecotoxicity (Worms)
Environmental fate
Fate (Animals)
Fate (Plants)
307
WHO Food Additives Series viewed online at http://www.inchem.org/documents/jecfa/jecmono/v16je25.htm , May 2004
Appendix 1.3 Summary of Findings for Individual Herbal Remedies
1. Black Cohosh
Dried preparations of the root of the Black cohosh plant, Cimicifugia racemosa, are
used primarily for the treatment of symptoms of the menopause (Sweetman, 1999). In
addition, the herb has been included in some cough preparations. The maximum daily
dose recommended for Black cohosh preparations available in the UK ranges between
50 and 500 mg/day. In conventional medicine, the symptoms of menopause are
managed by synthetic hormone replacement therapy (BMA, 2004).
The mechanism of action (if any) of Black cohosh for improvement of menopausal
symptoms is unclear (Huntley & Ernst, 2003). Only limited data are available with
regard to the tolerability of Black cohosh, but in general it would appear to be safe,
with a small risk of minor adverse effects such as rash and gastrointestinal
disturbance.
Black cohosh has little oestrogen receptor binding activity or oestrogenic activity in
vitro (Zava et al., 1998). Difficulties occur in extrapolating in vitro data to the in vivo
situation because of variations in absorption, activation/inactivation, metabolic
disposition and bioavailability to target tissues.
A number of active constituents have been identified in Black cohosh preparations,
but no pharmacological or toxicological data were identified by our search strategies.
2. Camphor
Camphor is used as a rubefacient and mild analgesic for conditions such as neuralgia.
It is also contained in nasal decongestant preparations for inhalation (Sweetman,
1999). Due to potentially serious toxicity, Camphor concentration should not exceed
11% in preparations for external use. Treatments for neuralgia and muscle pain in
conventional medicine include topical non-steroidal anti-inflammatory preparations
(BMA, 2004).
Toxicokinetics
The toxicokinetic data presented here are summarised from the Hazardous Substances
Databank entry for Camphor.308 Absorption of Camphor from the skin,
gastrointestinal and respiratory systems readily and occurs rapidly, and toxic levels
can be reached within minutes of ingestion. Camphor is removed from the
bloodstream by the liver. On metabolism, Camphor is partially oxidised and partially
conjugated to glucuronic acid. In addition, Camphor is hydroxylated by rat and rabbit
liver microsomes in vitro. The majority is eliminated as oxidised camphorol in the
urine, with less excreted in breath, sweat and faeces.
Toxicity Profile
Acute toxicity
Notable adverse effects include nausea, vomiting, colic, headache, dizziness,
delirium, muscle twitching, epileptiform convulsions, CNS depression and coma
(Sweetman, 1999). Infant collapse following local application of Camphor to the
nostrils has also been reported.
Camphor (as used as a rubefacient) has been shown to cause abnormal liver function
and encephalopathy (Stedman, 2002). Topical use of Camphor has caused
erythematous and papulous oedematous skin reactions (Ernst, 2000).
308
Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/ April 2004
Camphor when ingested is extremely toxic, with a rapid onset of action (between 5
and 90 minutes) (Gibson et al., 2004). As little as 1g as been fatal in a 19 month old
child. Camphor accumulates in fatty tissues and there is no antidote.
Acute toxicity data are summarised on a Material Safety Datasheet.309 In mice the oral
LD50 for Camphor was 1310mg kg-1. The lowest published lethal concentration
(LDLO) is 2000mg kg-1 in rabbits. Intraperitoneal injection of Camphor in mice gave
a LD50 of 3000mg kg-1. Typical threshold limit values/time weighted average
(TLV/TWA) are 2ppm, with the short term exposure limit (STEL) set at 3ppm.
Repeat dose toxicity
Chronic ingestion may cause granulomatous hepatitis or fatty metamorphosis.
Carcinogenicity and Mutagenicity
Camphor is non-classifiable as a human carcinogen.310
Reproductive and Developmental Toxicity
Evidence compiled in DART/ETIC (Developmental and Reproductive Toxicology)308
database suggests from studies in animals that Camphor does not affect fetal growth,
viability or morphological development at doses causing minor maternal toxicity.
3. Echinacea
Dried aerial parts of the Echinacea purpera plant is used to boost the immune
system311, and for the prevention of viral upper respiratory tract infections
(Sweetman, 1999). The maximum recommended daily dose for preparations available
in the UK ranges between 500 and 2500 mg/day. No conventional medicines are
licensed for prophylaxis of viral infections.
Toxicity Profile
Acute toxicity
Contact sensitisation has been reported for Echinacea purpera (Paulsen, 2002), with
the pollen identified as the responsible component.
Acute oral toxicity LD50 values are >15000 and >30000 mg kg-1 for rats and mice
respectively.312
Carcinogenicity and Mutagencity
A commercial preparation of Echinacea purpera has been tested for mutagenicity in
Salmonella typhimurium, with and without metabolic activation, and has been shown
to be negative in the majority of tests.2 In addition, Echinacea extract produced no
significant induction of chromosomal aberrations in human lymphocytes, nor did it
increase the number of micronucleated polychromatic erythrocytes in mouse bone
marrow. Some tumour inhibition has been shown for Echinacea in vitro.
4. Evening Primrose Oil
The major uses for Evening Primrose Oil are in the treatment of premenstrual
syndrome and mastalgia, menopausal symptoms and eczema (Sweetman, 1999).
Other conditions for which it is used include multiple sclerosis and rheumatoid
arthritis. Maximum recommended daily does for preparations available in the UK
range between 1000 and 3000 mg/day. In conventional medicine, bromocriptine is
licensed for use in moderate to severe cyclical breast pain (BMA, 2004).
4.1 Active constituents
309
Material Safety Datasheet viewed at http://physchem.ox.ac.uk/MSDS/CA/camphor.html
Hazardous Substances Databank entry viewed at http://toxnet.nlm.nih.gov/ April 2004
311
http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/100980.shtml, May 2004
312
http://ntp-server.niehs.nih.gov./htdocs/Chem_Background/ExecSumm/Echinacea.html viewed,
April 2004
310
The constituents of Evening Primrose Oil thought to be responsible for its biological
effects are linoleic acid and -linoleic acid. Toxicological data are available for
linoleic acid and are detailed below.
Linoleic acid
Toxicokinetics
Linoleic acid is a long chain carboxylic acid and is absorbed as micelle aggregates,
esterified with glycerol in chylomicrons and very low density lipoproteins, and
transported via the lymphatic system313 It is readily metabolised in the  oxidation
fatty acid metabolism pathway, and consumption presents no safety concern.
Toxicity Profile
Acute toxicity
Linoleic acid is classed as practically non-toxic, with a probable oral lethal does of >
15 g kg-1 in humans.314
Carcinogenicity and Mutagenicity
Studies of oleic acid, a chemically related compound, are considered relevant for
linoleic acid. Oleic acid was found to be negative in a large number of tests for
mutagenicity. 315 Linoleic acid is not listed by ACGIH, IARC, NIOSH, NTP or
OSHA.
5. Feverfew
Feverfew, Tanacetum parthenium, is a herbal remedy used in prophylactic treatment
of migraine (Sweetman, 1999). The maximum recommended daily dose for Feverfew
preparations available in the UK lies between 380 and 760 mg/day. Conventional
medications used for migraine prophylaxis include pizotifin, beta-blockers and tricyclic anti-depressants (BMA, 2004).
5.1 Active constituent
The constituent thought to be responsible for the biological activity of Feverfew is
parthenolide, for which limited toxicological data are available.
Parthenolide
Toxicokinetics
Pharmacological effects ascribed to parthenolide include decreased prostaglandin
synthesis and decreased platelet aggregation and serotonin secretion (Robles et al.,
1995). These effects serve to relieve inflammatory conditions such as arthritis, and to
act as anti-migraine therapy.
Toxicity Profile
Acute toxicity
Contact sensitisation has been reported for Feverfew (Paulsen, 2002), with
parthenolide identified as the component responsible.
Carcinogenicity and Mutagenicity
In vitro tests using mammalian cells have shown mutagenic activity for
parthenolide.316
313
WHO Food additives series viewed online at
http://www.inchem.org/documents/jecfa/jecmono/v042je16.htm April 2004
314
Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/ April 2004
315
WHO Food additives series viewed online at
http://www.inchem.org/documents/jecfa/jecmono/v042je16.htm April 2004
316
Material Safety Datasheet viewed at http://www.sigmaaldrich.com Apr 04, product number 384283
6. Garlic
Garlic is reported to be of value in lowering blood pressure and blood cholesterol
levels.317 In addition, expectorant, diaphoretic, diuretic and disinfectant properties
have been attributed to Garlic (Sweetman, 1999). The maximum recommended dose
for Garlic preparations available in the UK is between 170 and 670 mg/day for Garlic
extract and 2 and 10 mg/day for Garlic oil. Hypertension and hypercholesterolemia
are treated in conventional medicine with anti-hypertensives and statins respectively
(BMA, 2004).
Garlic and Garlic oil are licensed for veterinary use (NOAH, 2004). These
preparations are intended for use in dogs and cats for the symptomatic relief of
respiratory and digestive complaints, as well as skin infections. The maximum
recommended daily dose range between 390 mg/day Garlic extract (equivalent 1.1
mg/day Garlic oil), and 1555 mg/day Garlic extract (equivalent to 4.5 mg/day Garlic
oil).
Garlic is considered to be a type I and type IV allergen (Jappe et al., 1999). A number
of herb-drug interactions have been reported for Garlic (Izzo & Ernst, 2001). Two
case reports show an interaction between Garlic and warfarin leading to an increase in
INR (international normalised ratio), and clinical trial data suggest that Garlic can
change some of the pharmacokinetic properties of paracetamol via an unknown
mechanism. Use of Garlic can increase the risk of post-operative bleeding and can
have hypoglycaemic effects.
Adverse effects reported include nausea and gastrointestinal problems (Ernst, 2003a).
Dermatological effects following oral administration of Garlic have been reported to
include urticaria and angioedema (Ernst, 2000). Systematic review of Garlic-induced
adverse effects showed that causality is well established for allergic reactions, and
that the most serious reported adverse effects are those affecting platelet adhesiveness,
prothrombin time and partial thromboplastin time (Morbidoni et al., 2001).
7. Ginkgo biloba extract
Ginkgo biloba extract is used to improve circulation to the brain and muscles, and
also for tinnitus.318 This herbal remedy is also reputed to be of use in Alzheimer’s
disease and multi-infarct dementia (Sweetman, 1999). The maximum recommended
dose for Ginkgo biloba preparations available in the UK range between 60 and 120
mg/day and up to 1000 mg/day. Betahistidine is a drug licensed in the UK for the
treatment of tinnitus (BMA, 2004).
Toxicokinetics319
Ginkgo biloba extract (standard extract eGb761) is composed of numerous active
constituents, among which are quercetin, Ginkgolides A & B, and bilobalide.
Information available for any of these are of pertinence to the whole extract.
Following oral administration of eGb761 (80mg), the bioavailabilities of Ginkgolides
A & B with plasma half lives of 4 and 6 hours respectively, are approximately 80%.
Bioavailability of Ginkgolide C is very low. The bioavailability of bilobalide is 70%
with a plasma half life of 3 hours following oral administration of 120mg 3Gb761.
Excretion is via the urine, accounting for 70%, 50% and 30% for Ginkgolides A & B
and bilobalide respectively.
317
http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101190.shtml, May 2004
http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101240.shtml, May 2004
319
The data presented herein is summarised from information obtained from the National Toxicology
Program of the US, viewed online at http://ntpserver.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/Ginkgo.html
318
Adverse effects of Ginkgo biloba extract include dizziness, palpitations,
gastrointestinal disturbances, bleeding disorders and skin hypersensitivity reactions
(Sweetman, 1999).
Toxicity Profile2
Acute toxicity
Standardised extract eGb761 administered orally to rats shows an LD50 of 7.73 g kg1
.
Repeat dose toxicity
In a 27 week study in rats and mice, no evidence of renal or hepatic damage was
observed following oral administration of doses ranging from 100 to 1600 mg kg-1.
Carcinogenicity and Mutagenicity
No carcinogenicity studies have been performed using standardised Ginkgo biloba
extract, but studies performed on quercetin are relevant.320
Reproductive and Developmental Toxicity
In general, no teratogenic effects for Ginkgo biloba have been reported (Jurgens,
2003). This article does, however, cite one report of decreased chick viability in a
study using a high dose.
Herb-Drug Interactions
Ginkgolides and bilobalides have anti-platelet activity through their action as PAF
antagonists (Izzo & Ernst, 2001). Two case reports exist of severe spontaneous
bleeding in patients taking warfarin or aspirin following self-medication with Ginkgo
biloba at recommended doses. Spontaneous bilateral subdural haematomas have been
reported in cases of long-term Ginkgo biloba use. Although Ginkgo biloba is a
peripheral vasodilator, it has led to a further increase in blood pressure in a patient
prescribed a thiazide diuretic for hypertension. Combination of trazodone and Ginkgo
biloba in a patient with Alzheimer’s disease led to coma, due to Ginkgo biloba induced increase in production of an active metabolite of trazodone (MCPP) causing
release of the inhibitory neurotransmitter GABA.
Adverse effects following use of Ginkgo biloba include four reported cases of
subdural and parietal haematoma and subarachnoid haemorrhage (Ernst, 2003b).
7.1 Active constituents
Ginkgo biloba extract contains a number of active constituents, including ginkgolides,
bilobalide and quercetin. Of these, the toxicology of quercetin in best characterised.
Quercetin
Toxicokinetics
Following oral administration in rats, quercetin is rapidly excreted into bile and urine
within 48 hours as the glucuronide and sulphate conjugates, 3’-O-monomethyl
quercetin and 4-monomethyl quercetin.321 As a glycoside, quercetin is hydrolysed to
the corresponding aglycone, which is then metabolised by scission of the heterocyclic
ring at the 1,2 and 3,4 bonds to yield homoprotocatechuic acid, which is further
metabolised by -oxidation of the acyl-side chain, O-methylation and demethylation
and aromatic dehydroxylation.
Pharmacokinetic studies in man suggest that quercetin is quickly eliminated with a
half life of less than 2 hours (Graefe et al., 1999). Distribution in a typical 70kg man
has been estimated at 0.003-0.012 molkg-1 from daily oral administration of 25-50
mg.322 Oral administration in man of a Ginkgo biloba extract dose containing 6.8 mg
quercetin, has a mean value of 2.17 hours for half life for elimination and 1.51 hours
320
See below section 7.1
Hazardous Substances Databank viewed at http://toxnet.nlm.nih.gov/ Apr 04
322
http://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/Ginkgo.html - chemid
321
for half life for absorption, demonstrating that the absorption and elimination are
rapid (Wang et al., 2003). Bioavailability was low, with cumulative urinary excretion
was 0.17%, where quercetin was detected as the sulphate and glucuronic acid
conjugates. The low bioavailability was thought to be due to the lack of enzymes
capable of cleaving glycosidic bonds in the gut. However, reports from randomised
clinical trial in ileostomy patients, subsequently confirmed in healthy subjects,
suggested that the presence of the glycoside residue facilitated the intestinal
absorption (Ross & Kasum, 2002).
The volume of distribution varies among studies, but has important implications for
interpreting the pharmacodynamic effects. Due to current technical limitations, there
are insufficient data available to determine beyond doubt the mechanism underlying
the observed link between consumption of high dietary flavonoids such as quercetin,
and decreased risk of coronary heart disease.
Toxicity Profile
Acute toxicity
Acute oral toxicity LD50 value for mice and rats is 160gmg kg-1 323.
Carcinogenicity and Mutagenicity
Full details of mutagenicity testing are available on the Chemical Carcinogenesis
Research Information System324. Briefly, quercetin has produced positive results in
the majority of designs of Salmonella typhimurium tests for mutagenicity. However,
quercetin has been extensively tested for carcinogenicity and although it has shown
positive results in some studies, it was negative in the majority.2 The efficient
metabolism and excretion of this compound may explain the lack of carcinogenicity
in vivo.
8. Ginseng
Ginseng (Panax ginseng) is reported to enhance resistance to infection, aid
recuperation and to reduce fatigue (Sweetman, 1999). It is used to promote general
well-being. Maximum recommended daily dose for Ginseng preparations available in
the UK range between 1500 and 3000 mg/day. There is no analogous class of
conventional medicines.
Toxicokinetics325
The chemical constituents responsible for the pharmacological activities of Ginseng
extract are the triterpene saponins, termed ginsenosides. These ginsenosides fall into
two classes based on the structure of the cognate aglycone, namely protopanaxadiol
and protopanaxatriol. The fate of administered ginsenosides is dependant on their
class. Ginsenoside Rg1 (protopanaxatriol) has a half life of 27 minutes following
intravenous administration to minipigs. In contrast, the protopanaxadiol ginsenoside
Rb1 has a half life of 16 hours in the  phase, due to high plasma protein binding.
Information on absorption and metabolism is available for ginsenoside Rg1, showing
that this constituent is rapidly absorbed and metabolised after oral administration,
with very low concentrations of the intact molecule detected in urine or faeces.
Ginsenoside Rg1 is distributed to the blood, liver, bile, subcutis and epithelia of
323
324
Material Safety Datasheet at https://fscimage.fishersci.com/msds/56284.htm
Chemical Carcinogenesis Research Information System viewed at http://toxnet.nlm.nih.gov/ Apr
04
Details of the toxicokinetics of Ginseng are included in a document entitled “Getting to the root of
ginseng” viewed online at the ACS Publications division
http://pubs.acs.org/hotartcl/chemtech/98/apr/get.html
325
oesophagus and the oral and nasal cavities. The concentrations detected in muscle,
endocrine organs and brain are low.
Adverse effects, termed “Ginseng abuse syndrome”, include morning diarrhoea, skin
eruptions, sleeplessness, nervousness, hypertension, euphoria and oedema (Sweetman,
1999).
Toxicity Profile
Acute toxicity326
Oral administration of Ginseng to mice and rats show LD50 of 750 and 200 mg kg-1
respectively.
Repeat dose toxicity
Information from subacute/subchronic toxicity studies is available for rats and dogs;
no evidence for Ginseng toxicity has been observed in either species.2
Carcinogenicity and Mutagenicity
Ginseng has tested negative for mutagenicity in the mouse lymphoma model with and
without S9 and aroclor 1254 metabolic activation. 327
Herb-Drug Interactions
Incidences of interaction of Ginseng with prescription drugs are summarised by Izzo
and Ernst (2001). Ginseng is reported to interact with the monoamine oxidase
inhibitor (MAOI), phenylzine (Ernst, 2003b) and warfarin. Ginsenosides inhibit
cAMP phosphodiesterase leading to an increase in cAMP, which may explain in part
the psychoactive central effect of Ginseng both alone and in combination with
MAOIs. Use of Ginseng reduces blood alcohol concentration, with induction of the
essential components of the microsomal alcohol oxidising system suggested as the
underlying mechanism.
Adverse effects following Ginseng ingestion include nausea, vomiting, arteritis,
deterioration of schizophrenia and mania (Ernst, 2003b).
9. Glucosamine
Glucosamine supplements have been reported to be of use in the treatment of
osteoarthritis.328 Maximum recommended dose for Glucosamine preparations
available in the UK range between 1000 and 2000 mg/day. In conventional medicine,
non-steroidal anti-inflammatory drugs (NSAIDs) are routinely prescribed for
osteoarthritis (BMA, 2004).
9.1 Active constituents
Glucosamine preparations contain the active ingredients Glucosamine hydrochloride
and Glucosamine sulphate. The toxicokinetics of Glucosamine sulphate in man are
well described (see below).
Glucosamine sulphate
Toxicokinetics
The toxicokinetics of Glucosamine sulphate in man has been reported recently
(Setnikar & Rovati, 2001). Following oral administration, free Glucosamine sulphate
in blood was below the limit of quantification. After 1.5 hours, Glucosamine sulphate
appeared incorporated in plasma globulins, with a peak at 9 hours, and was eliminated
326
Summarised from information obtained from the National Toxicology Program of the US, viewed
online at
http://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/Ginseng.html
327
Chemical Carcinogenesis Research Information System (CCRIS) viewed online at
http://toxnet.nlm.nih.gov/, April 2004
328
http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101260.shtml, May 2004
with a half life of 58 hours. Gastrointestinal absorption is approximately 90%, but oral
bioavailability is only 44% due to the hepatic first pass metabolism effect.
Incorporation into plasma proteins occurs with all routes of administration, with the
liver being the site of incorporation. Glucosamine sulphate is covalently bound to
plasma globulins (predominantly -globulins) and is transported to peripheral tissues
where it is enzymatically released and made available for local use. Urinary excretion
following oral administration is 8% of the administered dose, with faecal excretion
11.4%. Respiratory excretion accounts for the majority (60%), highlighting the effect
of hepatic first pass metabolism.
Following oral administration, Glucosamine sulphate is largely distributed to the
stomach walls and contents. Concentrations of Glucosamine sulphate in the liver peak
at 2 hours and decrease slowly thereafter. There is also rapid uptake in articular
cartilage.
In a study of dogs administered Glucosamine sulphate in a mixture of purified
chondroitin sulphate and manganese ascorbate, minor but not clinically important
changes in haematological and haemostatic variables were observed (McNamara et
al., 1996). These changes included a decrease in median haematocrit and a decreased
neutrophil count.
Toxicity profile
Acute Toxicity
Both Glucosamine sulphate and Glucosamine hydrochloride are in the slightly toxic
range, with acute oral toxicity in mice > 5 g kg-1 329 and 15 g kg-1 330 respectively.
10. Ma huang
In traditional Chinese Medicine, Ma Huang is used in mild respiratory disorders
including asthma. 331,332 Maximum recommended daily dose for the treatment of
bronchial asthma range between 45 and 90 mg (Bielory & Lupoli, 1999). In addition,
it has been reported to be used as a stimulant and to boost athletic performance and
weight loss.333 The maximum daily dose recommended for Ma huang contained in a
training supplement available in the UK is 1000 mg/day (80 mg/day ephedrine).334
Asthma is treated conventionally using inhaled corticosteroids and selective beta2
agonists. 335
Three incidences of hepatotoxic events associated with the use of Ma Huang have
been reported (Pittler & Ernst, 2003). The adverse effects noted included nausea,
vomiting, abdominal discomfort, jaundice, fatigue, cough, chest pain and
haemoptysis. Where liver biopsies were performed, diffuse hepatic necrosis,
polymorphonuclear neutrophil (PMN) infiltrates and fibrosis were observed.
However, the evidence for hepatotoxicity related to use of Ma huang was said to be
anecdotal, therefore it is difficult to define precise incidence figures.
329
http://www.sigmaaldrich.com Glucosamine Hydrochloride, product code G2206, viewed April
2004
330
NTP Glucosamine Data Summary, viewed on-line at http://ntpserver.niehs.nih.gov/htdocs/Chem_Background/ExSumPdf/glucosamine.pdf
331
http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101040.shtml, May 2004
332
Merck Index (2001) [Ephedra, entry 3638]
333
Ephedra and Ephedrine for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy
and Side Effects. Viewed on-line at http://www.ahrq.gov/clinic/epcsums/ephedsum.htm April 2004
334
Product information for “Thermogen XS” available, May 2004, at
http://www.creatinestore.co.uk/products/Thermogen_XS.asp?details=1
335
BNF (2004) British National Formulary 47, viewed online at http://www.bnf.org/ May 2004
One active component of Ma huang, ephedrine, is absorbed more slowly from
powdered herbal preparation than from either ephedrine tablet or oral solution forms
(White et al., 1997). However, despite this, onset of effect and absorption are the
same. Ephedrine content varies between Ephedra species.
Additional adverse effects of Ma huang use include hallucination, stroke, acute
dysphoric disorder, and seizures (Ernst, 2003b). Ma huang may interact with other
CNS stimulants, -blockers, monoamine oxidase inhibitors, phenothiazines and
theophylline (Ernst, 2003a). Reports exist of acute autoimmune hepatitis, with
massive necrosis (disproportionate severity for clinical picture) observed on biopsy
(Stedman, 2002).
10.1 Active Constituents
The alkaloids L-ephedrine and pseudoephedrine are the constituents of Ma huang that
have been identified to have pharmacological activity.
10.1.1 L-Ephedrine
Toxicokinetics
In rats, L-ephedrine is converted to L-norephedrine and 4-hydroxy-L-ephedrine. In
rabbits, L-norephedrine is also produced on metabolism of ephedrine, as well as
phenylgycol. L-ephedrine is rapidly absorbed after oral, intramuscular and subcutaneous administration (species not specified), with a plasma half life of 6 hours.
Elimination of L-ephedrine is via the urine, where it is detected largely as the
unchanged drug. 336
The fraction of ephedrine eliminated by N-demethylation to norephedrine is 8-20%
following oral administration. Norephedrine is excreted in urine, largely unchanged,
with approximately 4% biotransformation to 4-hydroxynorephedrine and hippuric
acid (Haller et al., 2002).
Among the most serious adverse effects reported are tachycardia, anxiety, restlessness
and insomnia, increased blood pressure and cardiac arrhythmia (Sweetman, 1999). Lephedrine interacts with a number of other drugs including halothane and other
general anaesthetics, theophylline and monoamine oxidase inhibitors. L-ephedrine can
antagonise anti-hypertensive therapy.
Ephedrine acts as 1-, 1- and 2- adrenergic agonist and promotes release
noradrenaline and dopamine. Ephedrine is a more potent vasopressor and cerebral
stimulant than pseudoephedrine (Berlin et al., 2001).
Toxicity Profile
Acute toxicity
L-ephedrine is classed as extremely toxic, with a probable oral lethal dose between 5
and 50 mg kg-1 in humans.337 Acute oral toxicity has been measured with an LD50 of
600 mg kg-1 and 689 mg kg-1 for rats338 and mice339 respectively. Toxicity is
dependant on the route of administration, with LD50 values decreasing with route in
the following order: intraperitoneal, parenteral and intravenous.
Carcinogenicity and Mutagenicity
When tested using four standard strains of Salmonella typhimurium, with or without
metabolic activation, no evidence of L-ephedrine mutagenicity was observed. In
addition, no evidence of chromosomal aberrations or sister chromatid exchange was
336
Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/, April 2004.
Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/, April 2004.
338
Material Safety Datasheet viewed at http://physchem.ox.ac.uk/MSDS/EP/(-)ephedrine_anhydrous.html, April 2004
339
Material Safety Datasheet viewed at http://www.sigmaaldrich.com, April 2004
337
detected. In a two year carcinogenicity study, no evidence of carcinogenicity was
observed in either F344 rats of B6C3F1 mice.
Reproductive and Developmental Toxicity
No animal reproduction studies have been performed,1 and it is not known whether Lephedrine can have adverse effects on the fetus when administered to pregnant
humans.
10.1.2 Pseudoephedrine
Toxicokinetics340
Following oral administration of pseudoephedrine hydrochloride, the pharmacological
effect (nasal decongestion) is observed within 30 minutes, and lasts for 4-6 hours.
Although sufficient evidence is lacking, pseudoephedrine is presumed to cross the
placenta and into the CSF. Pseudoephedrine has a short half life, and elimination of
the drug is renal, with 55-75% excreted unchanged. In rabbits, D-pseudoephedrine
yields D-norpseudoephedrine and L-pseudoephedrine yields L-norpseudoephedrine.
Norpseudoephedrine is classified as a schedule IV controlled substance (Haller et al.,
2002).
Pseudoephedrine is less potent than ephedrine with respect to pressor, cardiac,
mydriatic and CNS stimulant actions.
Adverse effects include tachycardia, anxiety, restlessness, insomnia, skin rashes,
urinary retention, and rarely hallucinations especially in children (Sweetman, 1999).
11. St John’s Wort
St John’s Wort is used as a herbal remedy for the treatment of anxiety and mild to
moderate depression (Sweetman, 1999). Other reported minor uses include treatment
of skin inflammation, wounds and burns.341 The maximum daily dose recommended
for preparations available in the UK (standardised to hypericin content) range
between 900 and 2700 g/day hypericin (450-900 mg/day dried St John’s Wort
extract).342,343 In conventional medicine, tricyclic and SSRI (selective serotonin
reuptake inhibitor) antidepressants are used in the treatment of depression, while
anxiety is treated with anxiolytics such as benzodiazepines.344
Toxicokinetics
The pharmacodynamics and kinetics of St John’s Wort have been described recently
(Hammerness et al., 2003). The absorption of hypericin and pseudohypericin is 14
and 21% respectively following oral administration. The time to peak is between 2
and 6 hours, with a dose-dependant half-life of 24 to 36 hours. Steady state is
achieved within 4 days. St John’s Wort exerts multiple effects on the cytochrome
P450 enzyme complex and activates P-glycoprotein.
Numerous pharmacological effects have been described for St John’s Wort that may
underlie its anti-depressant action (Hammerness et al., 2003). These include inhibition
of MAO (monoamine oxidase inhibitor) A &B and COMT (catechol-O-methyl
transferase) enzymes, decrease in serotonin, dopamine, and noradrenaline reuptake,
and increases in serotonin receptor density. Actions at benzodiazepine, adenosine,
inositol trisphosphate, glutamate (NMDA) and cholinergic receptors may contribute
to the psychotropic effects.
340
Summarised from information contained in the Hazardous Substances Databank entry for
pseudoephedrine viewed at http://toxnet.nlm.nih.gov/ Apr 04
341
http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/102670.shtml, May 2004
342
Holland and Barrett product information leaflet, available at http://www.hollandandbarrett.co.uk/
343
Lichtwer Pharma UK product information leaflet, available at http://www.lichtwer.co.uk/ May 2004
344
BNF (2004) British National Formulary 47, viewed online at http://www.bnf.org/ May 2004
Although St John’s Wort is generally well tolerated, adverse effects have been
documented. These include gastrointestinal symptoms, skin reactions, fatigue and
sedation, restlessness and anxiety, dizziness, headache and dry mouth. Phototoxicity
has also been reported for St John’s Wort (Mantle et al., 2001). A report on a
European drug monitoring study (3250 individuals) showed a 2.4% rate of adverse
drug reaction, that were generally mild, transient and similar to placebo (Greeson et
al., 2001).
Toxicity Profile
Acute toxicity
An acute NOEL value of >5000 mg kg-1 in mice and rats has been published
(Hammerness et al., 2003).
Repeat dose toxicity
A study of long-term effects of St John’s Wort was conducted in dogs, and only nonspecific symptoms were reported (Hammerness et al., 2003).
Carcinogenicity and Mutagenicity
No significant mutagenic properties have been ascribed to St John’s Wort; one study
of genotoxicity in Salmonella typhimurium found that the mutagenicity observed was
quercetin-mediated (Hammerness et al., 2003).
Reproductive and Developmental Toxicity
No adverse reproductive effects have been ascribed to use of St John’s Wort (Jurgens,
2003).
Herb-Drug Interactions
St John’s Wort extract interacts with drugs metabolised by cytochrome P450
monoxygenase enzyme system and with selective serotonin reuptake inhibitors
(SSRIs) (Izzo & Ernst, 2001). Four clinical studies showed an increase or a tendency
to increase the metabolic capacity of CYP450 enzymes. In addition, St John’s Wort
can increase the activity of P-glycoprotein. Due to a combination of these
mechanisms, use of St John’s Wort can lead to reduced plasma concentrations of
warfarin, phenprocoumon, oral contraceptives, cyclosporin, amitriptyline,
theophylline and indinavir. The concentration of digoxin is also likely to be
decreased. Concomitant use of St John’s Wort and SSRIs can lead to symptoms of
serotonin excess, “serotonin syndrome” (Ernst, 2003b).
An important herb-drug interaction occurs between St John’s Wort and cyclosporin,
where concomitant use leads to reduced plasma levels of the anti-rejection drug due to
St John’s Wort-mediated induction of CYP3A/3A4. This has led to severe acute
transplant rejection documented in a patient following liver transplantation
(Hammerness et al., 2003).
St John’s Wort has effects on numerous components of the cytochrome P450
complex, including CYP1A2, CYP2C9, CYP2D6.
11.1 Active Constituents
The pharmacologically active constituents of St John’s Wort have been identified as
quercetin,345 hypericin, and hyperforin. Limited pharmacological and toxicological
information is available for these compounds, described below.
11.1.1 Hypericin
Toxicokinetics
Hypericin is thought to be the constituent of Hypericum extract (St John’s Wort)
responsible for the photosensitivity reactions observed in some individuals
(Sweetman, 1999).
345
see Annex 1, section 7.1: Ginkgo biloba extract, active constituent
Investigations of the pharmacodynamics and pharmacokinetics of hypericin, with a
view to exploitation of its potential chemotherapeutic effects, have shown a two
compartment model for its pharmacokinetics in primates, with a terminal elimination
half life of 26 hours (Fox et al., 2001). 2 mg kg-1 was sufficient to maintain an
effective cytotoxic plasma concentration for up to 12 hours post-administration.
Metabolism of hypericin is poorly defined, with no free hypericin detected in urine,
with or without glucuronidase or sulphatase. However, based on its chemical structure
and molecular size, metabolism is predicted to be via glucuronic acid conjugation and
biliary excretion (Fox et al., 2001).
Toxicity Profile
Acute toxicity
In non-human primates, dose-limiting toxicity was skin reactions at 5 mg kg-1, and socalled “hypericinism,” symptoms of which include anorexia, increased liver
transaminases and evolution of a skin rash in light-exposed areas (Fox et al., 2001).
Carcinogenicity and Mutagenicity
Hypericin has been found to be negative in mutagenicity tests using two standard
strains of Salmonella typhimurium, with and without metabolic activation. 346
11.1.2 Hyperforin
Toxicokinetics
The pharmacodynamics and pharmacokinetics of hyperforin have been reported
(Biber et al., 1998). Hyperforin, administered as hypericum extract and therefore in
the presence of other active constituents, is orally bioavailable and is not quickly
metabolised or decomposed in the gut. Elimination half lives and plasma retention
times are long, but it does not accumulate in plasma following once daily
administration in human volunteers. After administration of a therapeutic dose,
plasma levels increased only after a 1 hour lag, and reached the maximum at 3 hours.
Mean Cmax and area under the time concentration curve did not increase with highest
doses, but elimination half life was unchanged, implying that loss of bioavailability
was due to high lipophilicity of the agent or some other interaction in the
gastrointestinal tract. No serious adverse effects were noted, even at the maximum
dose administered (5mg hyperforin).
12. Valerian
Valerian has sedative properties and is used for treatment of stress and anxiety
(Sweetman, 1999) and insomnia.347 The maximum recommended dose for
preparations available in the UK ranges between 300 and 900 mg/day. In
conventional medicine, stress and anxiety are treated with anxiolytics such as
benzodiazepines (BMA, 2004).
Valerian is licensed for veterinary use (NOAH, 2004), in a preparation combining
other active ingredients for the treatment of nervous disorders, shyness or overexcitement in dogs and cats. The maximum recommended daily dose ranges between
194 mg/day and 1555 mg/day, dependent on animal size.
Toxicity Profile
Reproductive and Developmental Toxicity
No fetotoxicity or external malformations have been observed in rats (Jurgens, 2003).
However, an increase in the number of fetuses with retarded ossification was reported.
12.1 Active constituent
346
Chemical Carcinogenesis Research Information System viewed online at
http://toxnet.nlm.nih.gov/ April 2004.
347
http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/102830.shtml May 2004
A number of active constituents have been identified in extracts of Valerian root. Of
these, toxicological data are available for borneol.
Borneol
Toxicokinetics
Absorption, distribution, metabolism and excretion are as described for Camphor348.
Toxicity Profile
Acute toxicity
Acute toxicity of borneol is indistinguishable from Camphor. Laboratory animals are
much less susceptible to borneol toxicity than man (as is the case for Camphor).
Borneol is classified as Very Toxic, with a probable oral lethal dose in man of
between 50 and 500 mg kg-1.349
Carcinogenicity and Mutagenicity
Borneol has been shown to be non-mutagenic in the Ames test, using three strains of
Salmonella typhimurium, with and without metabolic activation. 350
348
see Annex 2, section 2: Camphor
Hazardous Substances Databank viewed at http://toxnet.nlm.nih.gov April 2004
350
Chemical Carcinogenesis Research Information System viewed at http://toxnet.nlm.nih.gov April
2004
349
Appendix 1.4 – Summary of Findings for Individual Essential Oils
1. Lavender Oil
Lavender oil is used as a carminative and as a flavouring ingredient. In addition, it is
occasionally topically applied as an insect repellant (Sweetman, 1999). Additional
suggested uses include aromatherapy for appetite loss, insomnia and nervousness.351
Recommended quantities range from 1-4 drops of essential oil in a carrier1, to topical
application of neat oil.352
Topical administration of Lavender oil has been reported to cause allergic contact
dermatitis (Ernst, 2000). Traces of linalool and linalyl acetate are detected in the
blood within 5 minutes of dermal application of Lavender oil (Bickers et al., 2003),
with the maximum concentration reached at 19 minutes.
1.1 Active Constituents
Active constituents identified in Lavender essential oil include -pinene and linalool
and its ester linalyl acetate.
1.1.1-Pinene
Toxicokinetics
The toxicokinetics of -pinene have been studied in man and are summarised in the
Hazardous Substances Databank.353 Exposure was by inhalation, and uptake was 59%
of the exposure concentration. The concentration of -pinene in the blood rose
sharply, then tapered off, and was linearly related to the exposure concentration.
Elimination from blood was shown to be triphasic, with half lives of 4.8, 39 and 695
minutes for each phase.
-pinene is absorbed from skin, lungs and intestines, and is readily metabolised with
elimination of unchanged -pinene very low. Urinary excretion of verbenols after pinene inhalation is complete 20 hours following a 2 hour exposure. In primary
cultures of chick embryo liver cells, -pinene was shown to be porphyrogenic.
Toxicity Profile
Acute toxicity
The fatal dose in man is approximately 180g as turpentine (58-65% -pinene). Acute
oral toxicity LD50 value is 3700 mg kg-1 in rats. By inhalation, LCLO (lowest
published lethal concentration) values for rats, mice and guinea pigs are 625, 364 and
572 gm-3 respectively. 354
Carcinogenicity and Mutagenicity
-pinene is not listed by IARC, but there is a documented increased risk of
developing respiratory cancer if duration of occupational exposure to turpentine is
greater than five years.1
No evidence of mutagenicity was observed using four standard strains of Salmonella
typhimurium, with or without metabolic activation.355
1.1.2 Linalool and Linalyl acetate
Toxicokinetics
351
http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101680.shtml, May 2004
http://hcd2.bupa.co.uk/fact_sheets/html/aromatherapy.html May 2004
353
Viewed at http://toxnet.nlm.nih.gov/ Apr 04
354
Hazardous Substances Databank viewed at http://toxnet.nlm.nih.gov/ Apr 04
355
Chemical Carcinogenesis Research Information System viewed at http://toxnet.nlm.nih.gov/ Apr
04
352
Linalool is representative of a number of tertiary alcohols and their related esters used
as flavouring agents, and therefore its metabolism in mammals is well
characterised.356 In rats, following a single oral dose of radioactively labelled linalool,
55% of the radioactivity was excreted in the urine as the glucuronic acid conjugate
and 23% as expired CO2. Of the remainder, 15% was excreted within 72 hours in the
faeces, with minor amounts (0.5, 0.6, 0.8 and 1.2%) in the liver, gut, skin and skeletal
muscle respectively.
Linalyl acetate, an ester of linalool, is metabolised by hydrolysis to yield linalool and
the corresponding aliphatic carboxylic acid (acetic acid).357 Metabolism proceeds as
for linalool.
The biological half-life for both linalool and linalyl acetate is 14 minutes (Bickers et
al., 2003).
Toxicity Profile
Acute toxicity
Acute oral toxicity LD50 values for linalool are 3000 mg kg-1 for mice and 2790 mg
kg-1 for rats.358 LD50 value following application to skin in rabbits and rats is
5610 mg kg-1 in both species.
Acute oral toxicity LD50 values are 14.55 g kg-1 and 13.36 g kg-1 for rats and mice
respectively.359
Repeat dose toxicity
A 20 day study1 in rats showed that cytochrome P450 (CYP450)-induced allylic
oxidation becomes important on repeated dosing, yielding urinary metabolites such as
8-hydroxylinalool and 8-carboxylinalool. A transient rise in liver microsome CYP450
activity was observed.
A 29 day study of dermal application of linalool has been conducted in rats (Bickers
et al., 2003). Lethargy, ataxia and moderate to severe erythema were observed at all
doses. The toxic signs and dermal irritation were dose-related. At necropsy,
abnormalities were detected in the treated skin area, as well as gross liver, kidney and
intestinal abnormalities. Histopathology revealed very slight to slight changes in liver
and kidneys, but these were not related to treatment. In a 90 day study, linalool
treatment led to a decrease in body weight and increased in liver and kidney weight.
Haematology, clinical chemistry and urinalysis were normal.
Carcinogenicity and Mutagenicity
Linalool has been tested for mutagenicity in a series of standard tests,360,361 and was
not found be mutagenic in the majority. However, weak positive results were detected
one design of the mouse lymphoma and Bacillus subtilis H17 (rec+) and M45 (rec-)
tests.
Linalyl acetate was negative for mutagenicity in five strains of Salmonella
typhimurium, with and without metabolic activation. Neither linalool nor linalyl
acetate caused chromosomal aberrations or unscheduled DNA synthesis (Bickers et
al., 2003).
Reproductive and Developmental Toxicity
356
WHO Food Additives series viewed online at
http://www.inchem.org/documents/jecfa/jecmono/v042je17.htm, April 2004
357
Hazardous Substances Databank viewed at http://toxnet.nlm.nih.gov/ Apr 04
358
Material Safety Datasheet viewed online at http://www.fisher.co.uk/ Product number 12515-1000
359
Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/, April 2004.
360
WHO Food Additives series viewed online at
http://www.inchem.org/documents/jecfa/jecmono/v042je17.htm, April 2004
361
Chemical Carcinogenesis Research Information System viewed online at http://toxnet.nlm.nih.gov/,
April 2004
Studies of coriander oil in rats in mice have concluded that linalool does not affect
reproductive performance or subsequent growth and survival of offspring except
where there is maternal toxicity (Bickers et al., 2003). No developmental toxicity data
were available.
2. Orange Essential Oil
Orange essential oil is used as a flavour and in perfumery (Sweetman, 1999).
2.1 Active constituents
The natural oil contains a number of active constituents, including linalool and its
ester linalyl acetate362, citral, and d-limonene.
2.1.1 Citral
Toxicokinetics
Detailed information on the absorption, distribution, metabolism and excretion are
contained in the Hazardous Substances Databank entry for citral.363 Citral is a
naturally occurring aliphatic aldehyde, and undergoes detoxification in a manner
expected for aldehydes. Two routes for aldehyde detoxification exist, firstly oxidation
to yield readily metabolised acids (fatty acid oxidation pathways and the Krebs cycle),
and secondly, inactivation by reaction with sulphydryl groups e.g., glutathione. In
experimental animals, citral is converted in part to the “Hildebrandt acid”, where a
double omega oxidation reaction has taken place. In rats and mice, absorption from
the gastrointestinal tract is rapid, and excretion is via the urine, with no evidence for
long-term storage. Metabolism is rapid; urinary metabolites include several acids and
a biliary glucuronide.
Toxicity Profile
Acute toxicity
Acute toxicity data are summarised in a Material Safety Datasheet364. Acute oral
toxicity studies in rats showed an LD50 value of 4960 mg kg-1, while the value in
mice was 6000 mg kg-1. Citral was more toxic when administered via
intraperitoneally in rats, with an LD50 460 mg kg-1 for this route. No human toxic
dose has been established. 365
Citral is an irritant, causing contact or allergic dermatitis and irritation of the
membranes of the nose and throat.
Repeat dose toxicity
A repeated dose toxicity test in mice showed that on percutaneous absorption, citral
caused an increase in lymph node weight compared to untreated controls 366
Carcinogenicity and Mutagenicity
Citral showed no evidence of mutagenicity when tested using 4 strains of Salmonella
typhymurium, with and without S9 metabolic inactivation.367
Reproductive and Developmental Toxicity
Citral has been shown to be teratogenic in animals but not in humans,368 causing
craniofacial abnormalities in chick embryos. In rats, citral caused a decrease in both
362
see section 1.1.2 linalool and linalyl acetate
Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/, April 2004
364
Material Safety Datasheet viewed http://physchem.ox.ac.uk/MSDS/CI/citral.html April 2004
365
Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/, April 2004
366
Beilstein database, viewed May 2004
367
Chemical Carcinogenesis Research Information System viewed online at
363
http://toxnet.nlm.nih.gov/
368
Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/, April 2004.
the number of follicles per section and in implantation number and litter size. In
addition, an increase in post-implantation fetal death was observed. The no observed
adverse effect level (NOAEL) for embryofetotoxicity was < 60 mg kg-1 by oral
administration in rats. However, no developmental toxicity was observed in rats
following inhalation of citral up to the maternally toxic dose.
2.1.2 D-limonene
Toxicokinetics
Data for absorption and metabolism of D-limonene is available for humans.3 In
humans following oral administration, 75-95% was excreted in urine and <10%
excreted in faeces within 2-3 days. A relative pulmonary uptake for D-limonene was
determined to be 70% of the amount supplied. D-limonene is readily metabolised and
accumulates in adipose tissue (long half life in blood in the slow elimination phase).
The major metabolite in urine following oral administration is perillic acid 8,-9 diol in
rats and rabbits, perillyl--D-glucopyranosiduronic acid in hamster, P-menth-1-ene8,-9 diol in dogs, and 8-hydroxy-P-menth-1-en-9-yl--D-glucopyranosiduronic acid
in guinea pigs and man.
Toxicity Profile
Acute toxicity
Orally administered D-limonene has an LD50 of 4400 mg kg-1 in rats and
5600 mg kg-1 in mice.369 Intravenous administration in rats results in a much lower
LD50 value of 110 mg kg-1.
Carcinogenicity and Mutagenicity
The IARC classification370 of D-limonene is Group 3 (not classifiable as to its
carcinogenicity to humans). National Toxicology Program studies371 in rats and mice
showed no evidence for carcinogenicity of D-limonene. D-limonene has been tested
in a number of short-term tests and has been shown to be non-genotoxic.
The nephropathy and renal tumour-induction observed in male rats is due to 2microglobulin, a male rat specific protein, and is not relevant to human
carcinogenesis. When combined, the lack of evidence for a genotoxic mechanism and
the demonstration of a plausible epigenetic mechanism (accumulation of 2microglobulin) implies a species-specific mechanism for d-limonene carcinogenesis
(Whysner & Williams, 1996).
Reproductive and Developmental Toxicity
No evidence for embryotoxicity or teratogenicity has been observed in the absence of
maternal toxicity.372
3. Peppermint Essential Oil
Peppermint essential oil is used as a carminative and relaxes gastric smooth muscle,
and is used in the management of irritable bowel syndrome (IBS) (Sweetman, 1999).
Recommended dose for Peppermint essential oil is 0.6-1.2 ml/day for up to 3 months
(Sweetman, 1999). Conventional treatments for IBS symptoms include antispasmodics, anti-motility drugs and laxatives. However, Peppermint oil is also
prescribed for IBS in conventional medicine.
369
Material Safety Datasheet viewed online at http://ptcl.chem.ox.ac.uk/MSDS/LI/(R)-(+)limonene.html, April 2004
370
IARC classification viewed online at http://www.inchem.org/documents/iarc/vol73/73-11.html,
April 2004
371
http://ntp-server.niehs.nih.gov/htdocs/Results_Status/Resstatl/10071-T.Html
372
Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/ April 2004.
Peppermint oil is licensed for veterinary use (NOAH, 2004), for the treatment of
digestive disorders and motion sickness in cats and dogs. The maximum
recommended daily dose ranges between 0.001 ml/day and 0.004 ml/day, dependent
on animal size.
3.1 Active constituents
Menthol and the related compound menthyl acetate are the active constituents of
Peppermint essential oil.
Menthol & Menthyl acetate
Toxicokinetics
Adverse effects include hypersensitivity, abdominal pain, nausea, vomiting, vertigo,
ataxia, drowsiness and coma (Sweetman, 1999). Application of decongestants
containing menthol to the nostrils of infants and children may lead to acute respiratory
distress with cyanosis and respiratory arrest.
In humans, menthol is readily absorbed (100%) and metabolised, with approximately
80% of an oral dose eliminated as the glucuronic acid conjugate in the urine within 6
hours.373 Menthol ingestion in animals has been shown to have a number of enzyme
effects. Elevation of glucuronidase activity was observed in mice. Menthol caused
elevation of hepatic microsomal cytochrome c and NADPH-cytochrome P450
reductase in rats while two other CYP450 complexes were unchanged.
As an ester of menthol, menthyl acetate is presumed to be hydrolysed in the
gastrointestinal tract to yield menthol and acetic acid, and metabolism is assumed to
proceed as for menthol.
Toxicity Profile
Acute toxicity
Menthol is classed as very toxic, with a probable oral lethal dose of between 50 and
500 mg kg-1 in humans.374 However, the published oral toxicity LD50 values are of
the order 3000 mg kg-1 for rats and mice.2
Repeat dose toxicity
Menthol produced no toxicity in either mice or rats in a 103 week study.2
Carcinogenicity and Mutagenicity
Long-term studies of menthol in mice and rats produced no evidence for
carcinogenicity.2,375 Neither menthol nor its metabolites have been shown to be
genotoxic in vitro or in vivo.
Reproductive and Developmental Toxicity
No developmental toxicity or teratogenicity have been noted for menthol.2
373
WHO Food Additives series, viewed at
http://www.inchem.org/documents/jecfa/jecmono/v042je04.htm Apr 04
374
Hazardous Substances Databank viewed at http://toxnet.nlm.nih.gov/ Apr 04
375
Chemical Carcinogenesis Research Information System viewed at http://toxnet.nlm.nih.gov/ Apr
04
4. Tea Tree oil
Tea Tree oil is used as an antiseptic and disinfectant. 376 It can be applied neat to the
skin.377
4.1 Active constituent
Cineole has been identified as an active constituent of Tea Tree oil, and for which
toxicological data are available.
Cineole
Toxicokinetics
Oral administration of cineole (also known as Eucalyptol) to bushtailed possums led
to the detection of 19 metabolites in urine and faeces,378 among which were p-cresol,
9-hydroxycineole and cineol-9-oic acid.
Following oral administration in Swiss albino mice, cineole was found to reduce
significantly the hepatic necrosis caused by GalN/LPS. In vitro tests have shown
cineole to act as an inhibitor of cyclooxygenase 2, and to reduce lipid peroxidation.
Investigation of the effects of cineole on cytochrome P450 enzymes, measured in rat
liver microsomes, showed no effect on total CYP450 content, with elevation of the
levels of 2B1 and 3A2 isoforms.
Toxicity Profile
Acute toxicity
Cineole is listed as Very Toxic, that is, the probable lethal dose in humans is between
50 and 500 mg kg-1. 379 Adverse effects such as nausea, vomiting, vertigo, ataxia,
muscle weakness, stupor, pallor and sometimes cyanosis have been reported. Acute
toxicity data are summarised in a Material Safety Datasheet.380 Acute oral toxicity
measured in rats gave LD50 of 2480 mg kg-1. Behavioural effects observed were
somnolence and coma. LD50 values measured in mice were 1000 mg kg-1 for the
intramuscular route and 1070 mg kg-1 for subcutaneous administration.
Repeat dose toxicity
Subcutaneous cineole (2450mg kg-1, cumulative in 10 days) showed no evidence of
effects on liver regeneration.
Carcinogenicity and Mutagenicity
Cineole (12 g kg-1 for 8 weeks) was not positive for tumour induction in a mouse
primary lung tumour model.381 In mutagenicity tests, cineole gave negative results in
tests using four standard strains of Salmonella typhimurium, with and without S9
metabolic activation.1
5. Thyme essential oil
Thyme essential oil has carminative, antiseptic, antitussive and expectorant properties
and is used chiefly in preparations for respiratory-tract disorders (Sweetman, 1999).
Thyme EO is recommended for use at no more than 2% in a suitable carrier.382
5.1 Active constituents
376
http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/102757.shtml, May 2004
http://hcd2.bupa.co.uk/fact_sheets/html/aromatherapy.html May 2004
378
Beilstein Database [cineole] accessed May 2004
379
Hazardous Substances Databank record viewed at http://toxnet.nlm.nih.gov/ April 2004
380
Material Safety Datasheet viewed at http://www.sigmaaldrich.com product number C8144, April
2004
381
Beilstein Database [cineole] accessed May 2004
382
http://www.naturedirect2u.com/Essential%20oils/thyme.htm May 2004
377
Thyme EO has been shown to contain a number of compounds for which biological
activity has been shown. Of these, toxicological data are available for borneol,383
carvacrol and thymol.
5.1.1 Carvacrol
Toxicokinetics
Carvacrol384 is slowly absorbed from the gastrointestinal tract in rabbits, with 30% of
the administered dose remaining in the intestine 22 hours post administration. It is
metabolised by conjugation to glucuronic acid and sulphate. No absorption of
carvacrol applied to intact mouse skin was observed after 2 hours.
Toxicity Profile
Acute toxicity
Carvacrol is listed as very toxic, with probable oral lethal dose between 50 and 500
mg kg-1 in humans.4 When applied to intact or abraded rabbit skin, neat carvacrol was
shown to be a severe irritant. Acute toxicity values are summarised in a Material
Safety Datasheet.385 The oral LD50 was shown to be 810 mg kg-1 in rats, and a
number of behavioural effects were also observed; these included somnolence and
convulsions or effect on seizure threshold. Additional acute toxicity data are available
for mice, where intraperitoneal injection of carvacrol resulted in LD50 of 73.3 mg kg1
, intravenous administration gave an LD50 value of 80 mg kg-1, and subcutaneous
administration gave an LD50 of 680 mg kg-1. The behavioural effects observed in
mice were similar to those observed in rats.
Carcinogenicity and Mutagenicity
Carvacrol was negative in Ames tests for mutagenicity.386
5.1.2 Thymol
Applied topically, thymol is used as an antiseptic and as an antihelmintic. Veterinary
uses as an antihelmintic, and as an external and internal antiseptic, have also been
described .387
Toxicokinetics
Substituted monophenols such as thymol are conjugated with glucuronic acid and
sulphate.388
The systematic availability following oral administration of thymol in humans has
been studied (Kohlert et al., 2002). The sulphate conjugate of thymol but not free
thymol was detected in plasma. The glucuronic acid and sulphate conjugates of
thymol but not free thymol were detected in urine. Thymol was quickly absorbed,
with significant plasma levels observed at 20 minutes and Cmax achieved at 2 hours.
The bioavailability was 16%.
Toxicity Profile
Acute toxicity
Thymol is a mild local irritant and its toxicity is classified as borderline between
moderately and very toxic. Ingestion can cause gastric pain, nausea, vomiting, central
hyperactivity, occasional convulsions, and cardiac and respiratory collapse. Acute oral
383
See Annex 2, section 12.1: Valerian, active constituent Borneol
Hazardous Substances Databank viewed at http://toxnet.nlm.nih.gov/ April 2004.
385
Material Safety Datasheet downloaded from https://www.sigmaaldrich.com Product number 282197,
Apr 04
386
Chemical Carcinogenesis Research Information System (CCRIS) database viewed at
http://toxnet.nlm.nih.gov/ Apr 04.
387
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals,
Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc. [Thymol, entry 8993-8]
388
Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/, April 2004.
384
toxicity LD50 values for mice, rats and guinea pigs are 1800, 980 and 880 mg kg-1
respectively.
Carcinogenicity and Mutagenicity
The IARC classification389 for thymol is Group 3, that is, not classifiable as to its
carcinogenicity to humans. Thymol gave negative results in Salmonella typhimurium
tests for mutagenicity390, and was also negative for the induction of chromosome
aberration.391
6. Wormwood
The essential oil of Artemisia absinthium, Wormwood EO, has been used as
flavouring in alcoholic beverages (e.g. vermouth)2, as a bitter and in homoeopathic
medicine (Sweetman, 1999). Acute toxicity data for Wormwood EO shows an LD50
value of 960 mg kg-1 by oral administration in rats.392 Details on the use of
Wormwood (among other plants) as de-worming preparations in Nordic countries are
available (Waller et al., 2001). However, this information is historical and/or
anecdotal in nature, and serves to detail the plants used, the target organism and the
livestock species.
6.1 Active constituents
Wormwood EO contains a number of active constituents, including absinthin, santonin, and - and - thujone. Significant toxicological data is available only for and - thujone.
6.1.1 -santonin
Acute toxicity testing of -santonin shows LD50 value of 900 mg kg-1 following oral
administration in mice.393 In addition, anti-helminthic activity has been ascribed to santonin.394
6.1.2 -/- thujone
Toxicokinetics
Data on metabolism of  or - thujone is lacking, as is information on long-term
and/or reproductive effects.395
Thujone administration can lead to convulsions that are epileptiform in nature and are
preceded by vasodilation, fall in blood pressure and slowing of cardiac rhythm.
Toxicity Profile
Acute toxicity
Acute oral toxicity for thujone isomers is complicated by the use of mixtures of
isomers, or the isomer is not specified in some acute tests. However, it is clear that the
acute oral LD50 value of -thujone in rats and mice is 250 and 500396 mg kg-1
respectively. -thujone has LD50 for oral toxicity of 250 mg kg-1 in dogs.
389
390
http://www.inchem.org/documents/iarc/vol71/027-phenol.html
Chemical Carcinogenesis Research Information System viewed at http://toxnet.nlm.nih.gov/ Apr
04
391
Genetox database viewed at http://toxnet.nlm.nih.gov/ Apr 04
WHO Food Additives Series viewed online at
http://www.inchem.org/documents/jecfa/jecmono/v16je25.htm , May 2004
393
Material Safety Datasheet viewed online at http://www.sigmaaldrich.com Product number 223085,
May 2004
394
O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals,
Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.
395
WHO food additives series viewed online at
http://www.inchem.org/documents/jecfa/jecmono/v16je25.htm, May 2004.
396
Material Safety Datasheet viewed online at http://www.sigmaaldrich.com Product number 89231,
May 2004
392
Repeat dose toxicity
A 14 week study in rats demonstrated no significant differences in weight gain,
haematology, or heart, liver, kidney, spleen or adrenal gland weights following
thujone treatment (isomer not specified). NOEL values for female and male rats were
calculated to be 5 mg kg-1 per day and 10 mg kg-1 per day respectively.
Carcinogenicity and Mutagenicity
-thujone was found to be negative for mutagenicity using five standard strains of
Salmonella typhimurium.397
397
Chemical Carcinogenesis Research Information System viewed online at
http://toxnet.nlm.nih.gov/, May 2004
Appendix 1.5 Glossary and list of abbreviations
Glossary398
Antitussive
a drug that suppresses coughing
Carminative
a drug that relieves flatulence, used to treat gastric discomfort and colic
Diaphoretic
a drug that causes an increase in sweating which stimulates the sweat glands directly
Dysphoria (dysphoric)
a feeling of uneasiness, discomfort, anxiety, or anguish
in vitro
taking place in a living organism
in vivo
taking place in a test tube, culture dish, or elsewhere outside a living organism
Rubefacient
an agent that causes reddening and warming of the skin. Rubefacients are often used
as counterirritants for the relief of muscular pain
Statin
any one of a class of drugs that inhibit the action of hydroxymethylglutaryl coenzyme
A reductase (HMG-CoA reductase), an enzyme that is involved in the liver's
production of cholesterol.
Abbreviations
ACGIH: American Conference of Governmental Industrial Hygienists
CAM: Complementary and Alternative Medicine
CCRIS: Chemical Carcinogenesis Research Information System
COMT: Catechol-O-methyl transferase
CYP450: Cytochrome P450
EO: Essential Oil
HRT: Hormone Replacement Therapy
HSDB: Hazardous Substances Databank
IARC: International Agency for Research on Cancer
LCLO: Lowest published Lethal Concentration
LD50: Dose estimated to kill 50% of the animals dosed
MAOI: Monoamine Oxidase Inhibitor
MSDS: Material Safety Datasheet
NIOSH: National Institute for Occupational Safety and Health
NOEL/NOAEL: No Obseved (Adverse) Effect Level
NSAID: Non-Steroidal Anti-Inflammatory Drug
NTP: National Toxicology Program
OSHA: Occupational Safety and Health Administration
PAF: Platelet Activating Factor
QSAR: Quantitative Structure-Activity Relationships
QSDR: Quantitative Structure-Degradability Relationships
QSPR: Quantitative Structure-Property Relationships
SSRI: Selective Serotonin Re-Uptake Inhibitor
TCM: Traditional Chinese Medicine
398
definitions obtained from The Oxford Concise Medical Dictionary, available at Oxford Reference
Online