Control of Substances Hazardous to
Health Regulations 1999
Proposals for Maximum Exposure Limits
and Occupational Exposure Standards
This consultative document is issued by the Health and Safety Commission in compliance with
its duty to consult, under Sections 16(2) and 50(3) of the Health and Safety at Work etc Act 1974.
Comments should be sent to:
Laura Whitford
Health and Safety Executive
Health Directorate, Chemicals Policy Division
6th Floor, South Wing, Rose Court
2 Southwark Bridge
London SE1 9HS
Tel: 020 7717 6375 Fax: 020 7717 6299
e-mail: [email protected]
to reach her no later than 7 June 2002
The Commission tries to make its consultation procedure as thorough and open as possible. Responses to
this consultation document will be lodged in the Health and Safety Executive's Information Centres after the
close of the consultation period where they can be inspected by members of the public or be copied to them
on payment of the appropriate fee to cover costs.
Responses to this consultation document are invited on the basis that anyone submitting them agrees to their
being dealt with in this way. Responses, or part of them, will be withheld from the Information Centres only
at the express request of the person making them (Under the Code of Practice on Access to Government
Information; Environmental Information Regulations 1992 and the Data Protection Act 1998). In such
cases a note will be put in the index to the responses identifying those who have commented and have asked
that their views, or part of them, be treated as confidential.
Many business e-mail systems now automatically append a paragraph stating the message is confidential. If
you are responding to this CD by e-mail and you are content for your responses to be made publicly
available, please make clear in the body of your response that you do not wish any standard confidentiality
statement to apply.
CONSULTATIVE
DOCUMENT
Further single copies of this document may be obtained from HSE Books – see back cover
Control of Substances Hazardous to Health Regulations 1999
Proposals for Maximum Exposure Limits and Occupational Exposure Standards
CONSULTATIVE DOCUMENT
Contents
SUMMARY
WHAT ARE EXPOSURE LIMITS
HOW ARE OELS SET
REGULATORY IMPACT/COST BENEFITS ASSESSMENTS
PROPOSALS FOR CHANGES TO THE LIST OF MAXIMUM
EXPOSURE LIMITS
Proposal for chloroethane
Proposal for hydroquinone
Proposal for manganese
PROPOSALS FOR CHANGES TO THE LIST OF OCCUPATIONAL
EXPOSURE STANDARDS
Proposal for removal of OES for subtilisins
Proposal for removal of OES for sulphuric acid
Proposal for removal of OESs for 2,3-epoxypropyl ethers
(glycidyl ethers)
Proposal to retain existing OES for para-phenylenediamine but
to add ‘sk’ notation
Proposal to change definition of what is covered by an OES for
mineral oil mists
INVITATION TO COMMENT
Annexes
Annex 1
Annex 2
Annex 3
Annex 4
Annex 5
Annex 6
Annex 7
Summary criteria for occupational exposure limits:
Chloroethane
Hydroquinone
Manganese
Para-phenylenediamine
Subtilisins
Explanatory note - Cost Benefit Assessment methodology for
Regulatory Impact Assessment and application to Occupational
Exposure Limits: an overview
MEL proposals: Summary comparison of costs and benefits
Metal Working Fluids - summary of ACTS/WATCH position
Sulphuric acid CHAN
The Health and Safety Commission's position on
implementation of Indicative Occupational Exposure Limit
Values (IOELVs)
Response form
Page
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ii
SUMMARY
The Health and Safety Commission would like your comments on proposals for occupational
exposure limits (OELs) for chemical substances. A form is included at the back of this
booklet to help you do this. It repeats the questions set out at appropriate points in the text
below.
This consultative document contains proposals on 8 different substances or groups of
substances. These are:
Ÿ
three new Maximum Exposure Limits (MELs) for substances formerly assigned
Occupational Exposure Standards (OESs): chloroethane, hydroquinone and
manganese and its inorganic compounds(1);
Ÿ
withdrawal of five OESs for: glycidyl ethers (2,3-epoxypropyl ethers);
Ÿ
withdrawal of an OES for subtilisins (proteolytic enzymes as 100% pure
crystalline enzyme);
Ÿ
withdrawal of an OES for sulphuric acid;
Ÿ
no change to OES for para-phenylenediamine, but introduction of a skin
notation for this substance; and
Ÿ
narrowing of the criteria for applying one OES: mineral oil mists in order to
exclude metal working fluids (for which separate HSE guidance is planned).
These proposals have already been discussed by a panel of scientific experts but you may
have views or further information of which they were not aware. For example you may have
data relating to whether a limit can reasonably be achieved in the workplace. Please do take a
few minutes to fill in the response form at the back of this booklet.
The Health and Safety Commission seeks to inform its decision-making by consulting a wide
range of interested bodies. In the light of your comments, the Health and Safety Commission
will approve the new list of MELs and OESs as appropriate. The agreed limits will then come
into force on the publication of the 2003 issue of HSE’s booklet ‘EH40 - occupational
exposure limits’.
Please feel free to copy this consultative document more widely. Further copies are available
from the address on the back cover and on the Internet on the HSE home page at:
http://www.hse.gov.uk/condocs/live.htm
1
For the purpose of this document any reference to manganese includes all inorganic
compounds of manganese (including manganese fume and trimanganese tetraoxide).
1
BACKGROUND - WHAT ARE EXPOSURE LIMITS ?
1.
Substances which may cause harm to health are subject to the Control of Substances
Hazardous to Health Regulations 1999 (COSHH). These Regulations require employers to
prevent, or if this is not reasonably practicable, adequately control, employees’ exposure to
hazardous substances. To help protect workers against ill-health HSE has set occupational
exposure limits (OELs).
2.
There are two types of limit - Maximum Exposure Limits (MELs) and
Occupational Exposure Standards (OESs). These are expressed as concentrations of a
hazardous substance in the air, averaged over a specified period of time referred to as a time
weighted average (TWA). Two time periods are used: 8 hour (based on an average shift); and
15 minute short term exposure limits (STELs) which are set to help prevent effects, such as
eye irritation, which may occur after just a few minutes’ exposure.
3.
MELs and OESs are legally binding as they are approved by the Health and Safety
Commission. MELs were formerly listed in Schedule 1 of the COSHH Regulations and were
approved by the Minister responsible for the Health and Safety Commission/Executive.
Following consultation in 1998, the Minister agreed that the Commission should in future
approve MELs in the same way as OESs, thus retaining their legal status but removing the
need to make annual revisions to the COSHH Regulations. COSHH was amended
accordingly in March 1999. Both types of limit are defined in COSHH and retain their legal
status when published in EH40.
4.
A MEL is set for substances which may cause the most serious health effects, such as
cancer and occupational asthma: health effects for which no 'safe' levels of exposure can be
determined or for which safe levels may exist but at a concentration that is not yet routinely
achievable in the workplace. To comply with COSHH, exposure should be reduced as far
below the MEL as is reasonably practicable and should not exceed the MEL when averaged
over the specified reference period. For substances given a short term MEL (15 minute
reference period), the level of exposure should never be exceeded.
5.
An OES is set at a level at which (based on current scientific knowledge) there is no
indication of risk to the health of workers who breathe it in day after day. If exposure to a
substance that has an OES is reduced at least to that level, then adequate control has been
2
achieved. If this level is exceeded, the reason must be identified and measures to reduce
exposure to the OES limit set out in EH40 put into action as soon as is reasonably practicable.
6.
For some toxic substances, biological monitoring may also be appropriate as a means
of assessing whether exposure is being properly controlled. This allows an employer to check
how much of a substance is being taken into the body by breathing or through the skin.
Measurements of substances (or their by-products) in blood, urine or expired air are
commonly used. Biological monitoring guidance values (BMGVs) are set to help
employers, safety representatives and employees to interpret biological monitoring results but BMGVs are provided purely as guidance and have no legal status.
7.
For more information on employers duties under COSHH, see HSE’s leaflet COSHH
- a brief guide to the regulations (IND136 (rev1)).
HOW ARE OELS SET ?
8.
MELs, OESs and BMGVs are set on the recommendations of the Health and Safety
Commission's (HSC) Advisory Committee on Toxic Substances (ACTS) and its
subcommittee the Working Group on the Assessment of
Toxic Chemicals (WATCH).
Information on ACTS and WATCH, the agendas and summaries of their meetings are
available on the Internet on the HSE home page at:
http://www.hse.gov.uk/foi/openacts.htm
ACTS and WATCH papers are also available from HSE’s public information points (see
back cover).
9.
WATCH is an independent committee consisting of toxicologists, occupational
hygienists and other scientific experts. WATCH makes a thorough critical assessment of the
available information, presented to them by HSE specialists, on the human health hazards for
specific substances, on the extent of occupational exposure to these substances and on the
risks associated with their use in workplaces. Using this information WATCH determines
whether an OES or a MEL would be more appropriate, but it can only make firm
recommendations in respect of OESs.
3
10.
WATCH’s recommendations are then passed to ACTS for discussion. ACTS is an
independent tripartite committee which advises the Commission on matters relating to the
prevention, control and management of hazards and risks to the health and safety of persons
arising from the supply or use of toxic substances at work. In setting a MEL, ACTS will also
take socio-economic factors into account. A short description of this process is included in
paragraphs 11-13 and in Annex 2 for information.
11.
Summaries of the much more extensive and detailed risk assessment considered by
WATCH, and the criteria used by WATCH and ACTS when proposing an occupational
exposure limit are published in HSE’s EH64: Summary criteria for occupational exposure
limits (available from HSE Books). This consultative document includes a copy of the
proposed summary criteria for chloroethane, hydroquinone and manganese to help you
understand the reason why the limits are being proposed. There is also a summary for
subtilisins to help set out the reason why the OES is being withdrawn and an updated
summary for para-phenylenediamine which includes the proposed ‘skin’ notation. No
summary has been prepared for glycidyl ethers because these substances are no longer widely
used; or for metal working fluids because separate guidance is being prepared. Also, no
summary has yet been prepared for sulphuric acid but this is because we are proposing to
submit new information to the European Scientific Committee on Exposure Limits (SCOEL)
so that a European OEL can be developed. Meanwhile, a Chemical Hazard Alert Notice
(CHAN No. 25) is attached at Annex 5. Copies of the full WATCH documentation for each
substance under discussion (except sulphuric acid, which has been discussed by ACTS) are
available through HSE public information centres (see back cover).
REGULATORY IMPACT/COST BENEFIT ASSESSMENTS
12.
Before any new piece of legislation can be introduced the Health and Safety
Commission is obliged to carry out an assessment of the costs it would impose on industry
and the benefits it is expected to bring. Since October 1998, this assessment has been
included in the Regulatory Impact Assessment (RIA). Annex 2 of this document gives a
description of the methodology behind the formulation of cost benefit assessments (CBAs)
for RIAs and a general statement on their application.
4
13.
HSE has examined what costs and benefits will result from these proposals. The OES
proposals in this document are expected to have negligible financial implications for industry
since WATCH and ACTS, as part of the review process, considered the available evidence on
usage, exposure levels and controls currently in place in industry. It is anticipated that
increased costs to industry will occur for the MEL proposals as a result of having to introduce
controls on exposure to chloroethane, hydroquinone and manganese.
14.
Summaries of the RIAs for chloroethane, hydroquinone and manganese are outlined at
Annex 3. A copy of the detailed RIA for each substance is available free of charge from:
Laura Whitford at Health Directorate, Health and Safety Executive, 6th Floor, Rose
Court, 2 Southwark Bridge Road, London, SE1 9HS. If you have any comments on any
of the RIAs we would welcome these also.
5
PROPOSALS FOR CHANGES TO THE LIST OF MAXIMUM EXPOSURE LIMITS
15.
Summary criteria documents explaining the rationale behind the proposed
occupational exposure limits for chloroethane, hydroquinone and manganese are enclosed at
Annex 1. To help you a response form is included at the back of this booklet repeating the
questions set out in bold in the text below and giving space for your comments.
16.
It is proposed that the following three substances be added to the list of MELs. HSE
has issued a Chemical Hazard Alert Notices (CHANs) for these substances in the interim.
These are available on HSE's web site at: http://www.hse.gov.uk/pubns/chindex.htm
New MEL proposal for chloroethane
Reference Periods
Substance
Chloroethane
17.
CAS
Number
75-00-3
Notes
-
Long-term exposure limit
(8-hour TWA reference
period)
ppm
mg.m-3
50
135
Short-term exposure limit
(15 minute reference period)
ppm
mg.m-3
-
-
WATCH considered chloroethane in January 2000 and concluded that the criteria for
setting an OES could not be met. WATCH advised that in view of concerns over the cancer
risk to humans it was appropriate to set a MEL (8-hour TWA). WATCH also concluded that
neither a STEL nor an ‘Sk’ or ‘Sen’ notation were appropriate. As a result HSC withdrew the
OES for chloroethane with effect from 14 May 2001 with the publication of EH40/2001.
18.
At its meeting in November 2001 ACTS considered setting a MEL for chloroethane.
Further details are given in the ‘Basis for the limit’ section of the summary criteria document
at Annex 1.
19.
Chloroethane is also included in a proposal for a second Indicative Occupational
Exposure Limit Value (IOELV) Directive. IOELVs are European Community limits which
are health based. There is a requirement under European law to take account of the IOELV
(where one is set) when setting a national limit. HSC has considered this requirement and
come up with five separate criteria (set out at Annex 6) where a higher national limit could be
set. The proposed IOELV for chloroethane is 100 ppm as an 8-hour time weighted average
(TWA). No short-term exposure limit (STEL) is proposed. It is HSE's view that the proposal
6
in this CD fully implements the proposed IOELV for chloroethane. If you do not agree with
the proposal and think that a limit higher than the IOELV should be set you will need to
provide evidence to show which of the criteria in Annex 6 are met. Further IOELV proposals
for other substances in the draft second IOELV Directive will be included in a separate
consultation exercise planned for summer 2002.
Question 1:
Do you agree with the 8 hour TWA MEL proposal for chloroethane?
If you disagree, please explain why.
If you think a limit higher than the IOELV should be set, please explain
which of the criteria in Annex 6 are met and provide any relevant
evidence.
New MEL proposal for hydroquinone
Reference Periods
Substance
Hydroquinone
19.
CAS
Number
123-31-9
Notes
Long-term exposure limit
(8-hour TWA reference
period)
ppm
mg.m-3
-
-
0.5
Short-term exposure limit
(15 minute reference period)
ppm
mg.m-3
-
-
Hydroquinone has been in the ACTS/WATCH review programme since 1992. A key
issue of mutagenicity took some time to resolve because of the need to acquire new scientific
information. WATCH considered hydroquinone in January 2000 and concluded that it would
not be appropriate to recommend a revised OES and that because the potential health effects
are serious consideration of a MEL (8-hour TWA) was warranted. WATCH also concluded
that neither a STEL nor an ‘Sk’ or ‘Sen’ notation were appropriate. HSC withdrew the
existing OES for hydroquinone with effect from 14 May 2001 with the publication of
EH40/2001.
20.
At its meeting in November 2001 ACTS considered setting a MEL for hydroquinone.
Further details are given in the ‘Basis for the limit’ section of the summary criteria document
at Annex 1.
Question 2:
Do you agree with the 8 hour TWA MEL proposal for hydroquinone?
If you disagree, please explain why.
7
New MEL proposal for manganese and its inorganic compounds
Reference Periods
Substance
Manganese and
its inorganic
compounds
21.
CAS
Number
7439-96-5
7785-87-7
1313-13-9
1344-43-0
7722-64-7
Notes
Long-term exposure limit
(8-hour TWA reference
period)
ppm
mg.m-3
-
-
0.5
Short-term exposure limit
(15 minute reference period)
ppm
mg.m-3
-
-
At its meeting in January 2000 WATCH concluded that the criteria for setting an OES
could not be met and that in view of the neurological effects of manganese it was appropriate
to set a MEL (8-hour TWA). WATCH also concluded that the toxicological characteristics of
manganese were such that neither a STEL nor an ‘Sk’ or ‘Sen’ notation were appropriate; and
that it was not possible to derive a biological monitoring guidance value (BMGV). As a result
HSC withdrew the OES for manganese and all its inorganic compounds (which include
manganese fume and trimanganese tetraoxide) with effect from 14 May 2001 with the
publication of EH40/2001.
22.
At its meeting in November 2001 ACTS considered setting one MEL for all of these
substances. Further details are given in the ‘Basis for the limit’ section of the summary
criteria document at Annex 1.
Question 3:
Do you agree with the 8 hour TWA MEL proposal for manganese and its
inorganic compounds?
If you disagree, please explain why.
8
PROPOSALS FOR CHANGES TO THE LIST OF OCCUPATIONAL EXPOSURE
STANDARDS
23.
A summary criteria document explaining the rationale behind the withdrawal of the
occupational exposure standard for subtilisins is included at Annex 1. No summary is
attached for withdrawal of OESs for glycidyl ethers because these substances are no longer
widely used. A revised summary for para-phenylenediamine which includes the skin notation
is also at Annex 1.
24.
No summary has yet been prepared for withdrawal of the OES for sulphuric acid
because we are proposing to submit new information to the European Scientific Committee
on Exposure Limits (SCOEL) so that a European OEL can be developed. This change in
approach reflects ACTS and HSC's recent thinking on developing European limits. Interim
guidance in the form of a Chemical Hazard Alert Notice (CHAN) is included at Annex 5.
Proposals for removal of the OESs for subtilisins
25.
It is proposed to remove the following OESs from the current EH40 List:
Reference Periods
Substance
Subtilisins
(proteolytic enzymes
as 100% pure
crystalline enzyme)
26.
CAS
Number
-
Long-term exposure limit
(8-hour TWA reference
period)
ppm
mg.m-3
Notes
-
-
0.00006
Short-term exposure
limit (15 minute
reference period)
ppm
mg.m-3
-
0.00006
WATCH considered subtilisins at its meeting in September 2000 and concluded that
they met the criteria for the establishment of a MEL (8-hour TWA and STEL). The summary
criteria document at Annex 1 gives more detail. WATCH also concluded that the current
OESs were not scientifically sustainable.
27.
The MEL setting process is underway. In the interim HSE has issued a CHAN for
subtilisins which is available on HSE's web site at: http://www.hse.gov.uk/pubns/chan24.htm
Question 4:
Do you agree with the proposal to remove the current OES for
subtilisins?
If you disagree, please explain why.
9
Proposals for removal of the OES for sulphuric acid
Reference Periods
Substance
CAS
Number
7664-93-9
Sulphuric acid
28.
Notes
Long-term exposure limit
(8-hour TWA reference
period)
ppm
mg.m-3
-
-
1
Short-term exposure
limit (15 minute
reference period)
ppm
mg.m-3
-
-
As part of an initiative by the International Council of Chemical Associations (ICCA)
the European Sulphuric Acid Association (ESA) commissioned a new toxicity study on
sulphuric acid. The results showed inflammation of the larynx, which is the same site at
which cancers have been seen in workers exposed to strong mists containing sulphuric acid.
As a result of the study a British industry association has recommended that the occupational
exposure level should be voluntarily reduced below 0.3 mg.m-3.
29.
ACTS discussed sulphuric acid at its meeting in July 2001 and recommended that
HSC consults on the withdrawal of the current OES. ACTS also recommended that HSE
prepare documentation for submission to the European Commission so that the European
Scientific Committee on Exposure Limits (SCOEL) can develop a European OEL and this
has now been done. In the interim, HSE has issued a CHAN for sulphuric acid which is
attached at Annex 5.
Question 5:
Do you agree with the proposal to remove the current OES for sulphuric
acid?
If you disagree, please explain why.
10
Proposals for removal of the OESs for 2,3-epoxypropyl ethers (glycidyl ethers)
30.
We are also proposing to remove the OESs for one group of substances from the
current EH40 list. 2,3-epoxypropyl ethers (or glycidyl ethers) are currently assigned the
following OESs (the compound names are those used in table 2 of EH40):
Reference Periods
Substance
Allyl-2,3epoxypropyl ether
Bis(2,3epoxypropyl) ether
n-Butyl glycidyl
ether (BGE)
2,3-Epoxypropyl
isopropyl ether
Phenyl-2,3-epoxy
propyl ether
31.
CAS
Number
106-92-3
Notes
Long-term exposure limit
(8-hour TWA reference
period)
ppm
mg.m-3
Short-term exposure limit
(15 minute reference
period)
ppm
mg.m-3
-
5
24
10
47
2238-07-5
-
0.1
0.54
-
-
2426-08-6
-
25
135
-
-
4016-14-2
-
50
241
75
362
122-60-1
-
1
6.2
-
-
WATCH reviewed glycidyl ethers in 1997, in relation to OEL and classification
concerns. The possibility of taking a common approach to all glycidyl ethers was discussed,
in view of their common structural feature, the glycidyl (i.e. 2,3-epoxypropyl) group.
WATCH concluded that although a fully identical classification position for members of the
group could not be justified, on the basis of the toxicological information for the five glycidyl
ethers, their OES status did not appear to be sustainable. The toxicological concerns included
carcinogenicity, mutagenicity and impairment of fertility. Further investigation by HSE
suggests that these substances are no longer used in the UK except possibly on a laboratory
scale, since less hazardous alternatives are available. Therefore, HSE is not planning to
develop MEL proposals for glycidyl ethers.
Question 6:
Do you agree with the proposals to remove the current OESs for
2,3-epoxypropyl ethers (glycidyl ethers)?
If you disagree, please explain why.
Question 7:
Is there any residual significant use of 2,3-epoxypropyl ethers (glycidyl
ethers) in the UK?
If so, please give details.
11
Proposal to retain the existing OES for p-phenylenediamine but add a ‘Skin’ notation
Reference Periods
Substance
p-Phenylenediamine
32.
CAS
Number
106-50-3
Notes
Long-term exposure limit
(8-hour TWA reference
period)
ppm
mg.m-3
Sk
-
0.1
Short-term exposure limit
(15 minute reference
period)
ppm
mg.m-3
-
-
WATCH reviewed p-phenylenediamine (PPD) in January 2001 and concluded that
although there were gaps in the toxicological package, the current OES of 0.1 mg.m-3 was
judged to fulfill the OES criteria. The toxicological data did not indicate the need for a STEL
OES. WATCH considered that it was appropriate for a ‘Skin’ notation to be assigned for
PPD, however, it was not considered appropriate for a ‘Sen’ notation nor for HSE to develop
a BMGV.
Question 8:
Do you agree with the proposal to retain the current OESs for
p-phenylenediamine and introduce a ‘Skin’ notation?
If you disagree, please explain why.
Proposals to change definition of what is covered by the OES for mineral oil mists
33.
At its meetings of March and July 2000 ACTS proposed to revise what is covered by
the mineral oil mists OES currently listed in EH40. The entry in table 2 will not change.
However, the definition of oil mists, mineral given in paragraphs 13 & 14 on page 32 of
EH40/2002 will need to be reworded. The suggested rewording will effectively exclude metal
working fluids from the definition of mineral oils and mists. Revised paragraphs 13 and 14
are given below:
13 The OES is applicable only to mists from highly refined mineral oils. In
those applications where such mineral oils are present as part of a
formulation or may be contaminated during use, the OES may no longer be
applicable. In particular, the OES does not apply to oil mists from used
engine oils (which are defined as carcinogens in Schedule 1 of COSHH),
mineral-oil metalworking fluids, oil-based drilling muds or textile fly in
12
weaving sheds. Employers should consider the extent and type of
contamination and the applicability of the limit as part of their assessment
under the COSHH regulations.
14 Guidance on metal working fluids will be available from HSE Books
mid 2002 - HSG### - Metal working fluids good practice manual, which
will include guidance on appropriate levels of airborne mist control in
different circumstances. Two guidance notes on mist and mineral oils are
also available - EH58: The carcinogenicity of mineral oils, and EH49:
Nitrosamines in synthetic metal cutting and grinding fluids. See also HSE’s
series of guidance booklets giving advice on various aspects of metal
working fluids (INDG 165, INDG 167, INDG 168 and INDG169L).
34.
There is currently no summary criteria document for metal working fluids so no
revised document has been included. Metal working fluids will be covered by the separate
HSE guidance (referred to above) which is currently being prepared. If you wish to comment
on this guidance, please contact Martin Stear, Health and Safety Executive, Room 319
Magdalen House, Stanley Precinct, Bootle, Merseyside L20 3QZ by mid March 2002. We
hope to publish this guidance in August/September 2002. In the meantime, a summary of the
ACTS/WATCH position on this issue is at Annex 4 by way of background.
Question 9:
Do you agree with the proposal to exclude metal working fluids from the
OES for mineral oil mists, and to include the revised text for EH40
defining the scope of the OES?
If you disagree, please explain why.
13
INVITATION TO COMMENT
35.
The Health and Safety Commission would welcome comments on proposals set out in
this consultative document. For convenience, all the questions are repeated in a form
(Annex 7) set out at the back of the document which you may find helpful to use for your
reply. We will acknowledge receipt of all comments sent to us and will give careful
consideration to all comments received in developing our proposals. We may contact you, for
example, if we have a query.
36.
If you reply to this consultative document in a personal capacity, rather than as a
postholder of an organisation, you should be aware that information you provide may
constitute “personal data” in the terms of the Data Protection Act 1998. For the purposes of
this Act, HSE is the “data controller” and will process the data for health and safety and
environmental purposes. HSE may disclose these data to any person or organisation for the
purposes for which it was collected, or where the Act allows disclosure. You have the right to
ask for a copy of the data and to ask for inaccurate data to be corrected. Please note all replies
will be made public unless you specifically state you wish yours to be made confidential.
37.
The Health and Safety Commission/Executive would also like to know what you think
about this consultation, both the content and layout. Your views may help to improve further
consultations. If you are not satisfied with the way in which this consultation exercise has
been conducted you can complain by contacting:
Mr C Rowe
Health and Safety Executive
Room 602
Rose Court
2 Southwark Bridge Road
London
SE1 9HS.
14
ANNEX 1
Summary criteria for occupational exposure limits
15
MEL PROPOSAL
series of closed reaction vessels where it is reacted
with lead/sodium alloy to produce the tetraethyl lead.
CHLOROETHANE
It has not been used as a refrigerant or general
anaesthetic in the UK for almost 30 years. It is used
as a ‘local’ anaesthetic in the UK. That use is
widespread by general practitioners, accident and
emergency clinics, dentists, chiropodists and
veterinary practices. The substance is imported in
prepackaged spray vials, containing 50-100 ml of
pressurised chloroethane liquid. It is also used during
tattooing and body piercing, but against the advice of
the relevant enforcing authorities.
Maximum exposure limit
8-hour TWA: 50 ppm
(subject to consultation)
IDENTITY AND PROPERTIES
CAS No:
75-00-3
EXPOSURE
EEC No:
602-009-00-0
Formula:
C2H5Cl
Synonyms:
Aethylis, ethyl chloride,
monochloroethane, muriatic ether
Gas pressure:
133.3 kPa at 20oC
Gas density:
2.22 (air = 1)
Boiling point:
12.3oC
During the manufacture of tetraethyl lead 50-100
employees may be potentially exposed to the gas. The
company indicates that significant exposure to
chloroethane is only likely to occur in the event of an
accident on the plant or during maintenance
operations. In such situations the operatives would
wear self contained breathing apparatus and actual
exposure would be minimal.
Melting point:
-138.3oC
Some exposure is predicted during the breach of
containment for transfer of liquid from tankers. The
Estimation and Assessment of Substance Exposure
(EASE) model predicts that with non-dispersive use
and control within a local exhaust system short-term
peaks of 100-200 ppm could be produced. However it
is assumed that 8-hour time-weighted average (TWA)
exposures would be less than 10 ppm.
Conversion factor: 1 ppm = 2.7 mg.m-3 at 20oC and
760 mmHg.
Chloroethane is a colourless, flammable vapour in air.
The odour is variously described as ethereal with an
odour threshold of 3.7 - 4.4 ppm.
Chloroethane is classified under the Chemicals
(Hazard Information and Packaging for Supply)
Regulations 1994 (CHIP) as a carcinogen category 3,
extremely flammable and as dangerous for the
environment. It is labeled with the R-phrases:
During subsequent use, manufacturing processes are
within closed systems. However, the Estimation and
Assessment of Substance Exposure (EASE) model
predicts that with non-dispersive use and control
within a closed system, long-term inhalation exposure
will be between 0 and 0.1 ppm.
R40: Possible risk of irreversible effects(1)
R12: Extremely flammable
There is some exposure, to low concentrations of
vapour and from skin contact associated with
application of liquid chloroethane to skin in use as a
‘local’ anaesthetic. Typically volumes applied would
be 1.5-2 ml per test. No quantitative data exist
indicating exposure concentrations. Many thousands
of people are potentially exposed and user estimates
indicate exposure concentrations are less than 10 ppm
8-hour TWA. Calculations under assumed conditions
of use suggest vapour concentrations could be 30 ppm
for brief periods.
R52/53: Harmful to aquatic organisms, may cause
long-term adverse effects in the aquatic environment.
OCCURRENCE AND USE
Chloroethane is not a naturally occurring substance. It
may be produced adventitiously during the burning of
industrial and domestic waste.
In the United Kingdom (UK), chloroethane is not now
produced. It is imported and used in the production of
tetraethyl lead or as a local anaesthetic.
There may be potential exposure to chloroethane
during the incineration of industrial and domestic
waste products. The number of workers potentially
exposed to the gas may be thousands. Industry
believes however, that any exposure is expected to be
negligible.
The sole use of chloroethane in chemical
manufacturing in the UK is in the production of
tetraethyl lead. The vapour is fed under controlled
pressure from one of three bulk storage spheres into a
1
Subject to change in 2002 with proposed new CHIP regulations to "limited evidence of a carcinogenic effect".
HSE REVIEW 2001
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MEL PROPOSAL
MEASUREMENT
A limited metabolic study in rats and mice
demonstrated that chloroethane is metabolised by
glutathione (GSH) conjugation followed by further
metabolic processing by the mercapturic acid pathway
to a range of metabolites4. Chloroethane was also
found to be metabolised to a much lesser extent by
P450 oxidation. Several metabolites common to both
species were observed although there was some
evidence for the production of a metabolite in the
mouse which was not evident in the rat which suggests
that there may be species differences in metabolism.
Following inhalation exposure, a significant
proportion of chloroethane is exhaled unchanged in
breath. The main route of excretion for the observed
metabolites is via the urine.
Air monitoring
Personal exposure to chloroethane vapour can be
measured using pumped sampling onto two charcoal
tubes in series and analysis by solvent desorption and
gas chromatography according to method NIOSH
25191. Users need to be aware of the limited capacity
of the sorbent at high concentrations. A maximum
sample volume of 4L at 0.05 L/min on 400 mg
charcoal is recommended. The method meets the
requirements of EN 10762 with respect to desorption
efficiency and humidity effects at concentrations
500-2000 ppm.
Although the method was not
validated at concentrations below 100 ppm, no
problems are expected in meeting the EN 1076
requirements in the range 5-50 ppm. No colorimetric
gas detector tubes are available specifically for the
measurement of chloroethane but Gastec tube 138
(methylene chloride) can be used. Instrumental
methods can be used for real time background and
personal concentration measurements provided
account is taken of potential interferences.
There is no information on the metabolism of
chloroethane in humans. However, GSH conjugation
is also active in humans and so this metabolic pathway
may also be relevant to humans.
HEALTH EFFECTS
Animal studies
Biological monitoring
Chloroethane has low acute toxicity. No overt signs of
toxicity were observed in F344 rats or B6C3F1 mice
exposed to 19,000 ppm chloroethane by inhalation for
4 hours5. Chloroethane does not cause skin, eye or
respiratory tract irritation and there is no evidence that
it is a sensitiser.
There have been no reported occupational exposure
studies or volunteer studies using biological
monitoring for chloroethane and consequently there
are no data to suggest a biological monitoring
guidance value.
Biological monitoring may be
possible by analysis of chloroethane in blood and
breath or the analysis of its mercapturic acid
metabolite in urine.
A good quality study investigated the toxicity of
chloroethane in mice and rats5. Chloroethane did not
cause any significant toxicity in animals exposed to
19,000 ppm for 90 days.
TOXICOKINETICS
The toxicokinetics of chloroethane have been very
poorly characterised. However, the rapid induction of
anaesthesia in humans and animals following
inhalation indicates that chloroethane is rapidly
absorbed through the lungs.
Chloroethane is a mutagen in standard in vitro systems
with or without metabolic activation, giving positive
responses in bacterial mutagenicity tests and in a
mammalian cell gene mutation test3. There was no
evidence of micronuclei formation or induction of
liver UDS in B6C3F1 mice exposed to 25,000 ppm
chloroethane6. However, the negative micronuclei
findings must be interpreted with caution since this
test has been shown to be weakly sensitive to the in
vivo genotoxicity of several other halogenated
hydrocarbons which are known to have genotoxic
activity in vivo7. Overall, chloroethane is clearly
genotoxic in vitro but its genotoxic potential in vivo is
unclear.
There are no data relating to oral or dermal
absorption, but given that chloroethane is a gas,
absorption via these routes would be expected to be
minimal, in comparison with inhalation.
A limited rabbit study investigating the distribution of
chloroethane
following
inhalation
exposure
demonstrated that chloroethane was distributed widely
but appeared to accumulate in perirenal fat3.
Following exposure to 15,000 ppm (the only
concentration tested) chloroethane for 2 years there
was a marked increased in the incidence of uterine
tumours in female mice, and equivocal evidence for
the induction of astrocytomas in female rats5. The
mechanism
of
chloroethane-induced
uterine
carcinogenesis and the dose-response characteristics at
There is no information on the ability of chloroethane
or its metabolites to cross the placenta or enter the
breast milk.
HSE REVIEW 2001
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MEL PROPOSAL
BASIS FOR THE LIMIT
lower doses are unknown. A study testing the
hypothesis that the mechanism involves disruption of
the normal hormonal control of the oestrus cycle did
not demonstrate any significant changes in the oestrus
cycle following exposure to chloroethane, although
the study did demonstrate slight changes in the levels
of circulating sex hormones, particularly progesterone,
during exposure8.
The structural analogue
bromoethane also produces uterine tumours in mice at
substantially lower concentrations (down to at least
100 ppm).
There is unequivocal evidence that chloroethane is
carcinogenic in female mice at the one high exposure
concentration that has been tested. In light of this and
the uncertainties regarding the dose-response
relationship and whether the underlying mechanism of
carcinogenicity is genotoxic or non-genotoxic, the
relevance of the animal carcinogenicity findings to
humans cannot be discounted. It is significant that the
structural analogue bromoethane also produces such
tumours in mice at substantially lower concentrations.
On this basis, criterion 1 for establishing a
health-based OES cannot be satisfied.
No studies have specifically investigated the potential
effects of chloroethane on fertility but long-term
studies in rats and mice have not demonstrated any
adverse effects on the gonads, suggesting that
chloroethane is unlikely to affect fertility. A single
study has demonstrated that chloroethane did not
cause developmental effects in mice exposed during
gestation to 5000 ppm9.
The occupational use of this substance in
manufacturing is very limited and confined to
enclosed systems with occasional breaches of those
systems for repair, maintenance or unloading.
Exposure from modelled data would be low. There is
widespread use of the substance in local anaesthesia
but that use involves small quantities and brief
exposure durations.
Human data
Human data relates almost exclusively to the use of
chloroethane as a general anaesthetic pre-1960.
Information from the secondary literature indicates
that inhalation exposure to 40,000 ppm chloroethane
causes rapid anaesthesia and 60,000 ppm is lethal.
Apart from effects on the CNS, chloroethane appeared
to be of relatively low acute toxicity, although there is
some evidence that it may cause depression of cardiac
function and arrhythmias and possibly liver damage at
the high concentrations used in anaesthesia3.
WATCH concluded that the criteria for the
assignment of an OES were not met and that a MEL
should be considered.
In the light of concerns about carcinogenicity, and the
exposures to chloroethane in industrial and clinical
use, ACTS considered that it should be reasonably
practicable to achieve 8-hr TWA concentrations of 50
ppm or lower, and has recommended a MEL at this
value.
There is no reliable evidence that chloroethane
produces sensitisation. From consideration of its
structure and absence of evidence for interaction with
plasma proteins, chloroethane is not considered to
have sensitisation potential.
The available data suggest that dermal absorption of
chloroethane is minimal and that it does not have
sensitising properties. It was the view of WATCH
that 'Sk' and 'Sen' notations would not be required.
In view of the poor potential for skin absorption and
the small numbers regularly exposed, the role for
biological monitoring is limited. Consequently, the
criteria for establishing a Biological Monitoring
Guidance Value are not met.
There are no human data in relation to genotoxicity or
carcinogenicity. However, on the basis of positive
findings from a well conducted carcinogenicity study
in animals and the lack of any information on the
mode of action, it is uncertain whether or not
chloroethane may pose a carcinogenic hazard to
humans.
This substance was originally included in a proposal
for the first EU Indicative Limit Occupational
Exposure Limit Values (IOELV) Directive, but was
not included in the finally adopted Directive. It is
included in a current proposal for a second IOELV
Directive. ACTS and WATCH took into account the
limit value included in the proposed Directive and the
supporting evidence3,10 in their deliberations on limit
values for this substance.
There are no human data available in relation to
reproductive toxicity. However, given the negative
findings in animals for developmental effects and the
lack of concern for systemic toxicity, except at high
exposure levels, it is considered unlikely that there
would be any concern for reproductive effects at
occupational exposure levels.
HSE REVIEW 2001
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MEL PROPOSAL
REFERENCES
1. NIOSH Manual of Analytical Methods, Method
2519 (1994), Ethyl Chloride, 4th Ed, National
Institute of Occupational Safety and Health,
Cincinnati, Ohio, USA.
2. British Standards Institution, Workplace
atmospheres - Pumped solvent tubes for the
determination of gases and vapours, European
Standard BS EN 1076:1997, ISBN 0 580 28358 5.
3. Commission of the European Communities (1992).
Occupational Exposure Limits, Criteria document for
monochloroethane,
EUR
14241,
ISBN
92-826-4242-9.
4. Fedtke, N., Certa, H., Ebert, R. and Wiegand, H-J.
(1994) Species differences in the biotransformation of
ethyl chloride. I-Cytochrome P450-dependent
metabolism,
II-GSH-dependent
metabolism.
Arch.Toxicol., 68, 158-166 and 217-223.
5. National Toxicology Programme (1989),
Toxicology
and
carcinogenesis
studies
of
chloroethane in F344/N rats and B6C3F1 mice. NIH
Publication No.90-2801, NTP TR 346.
6. Ebert, R., Fedtke, N., Certa, H., Wiegand, H-J,
Regnier, J-F, Marshall, R. and Dean, S.W. (1994)
Genotoxicity studies with chloroethane. Mut.Res.,
322, 33-44.
7. Crebelli, R., Carere, A., Leopardi, P., Conti, L.,
Fassio, F., Raiteri, F., Barone, D., Ciliutti, P., Cinelli,
S. and Vericat, J.A. (1999) Evaluation of 10 aliphatic
halogenated hydrocarbons in the mouse bone marrow
micronucleus test. Mutagenesis, 14, 207-215.
8. Bucher, J.R., Morgan, D.L., Adkins, B., Travlos,
G.S., Davis, B.J., Morris, R. and Elwell, M.R. (1995)
Early changes in sex hormones are not evident in mice
exposed to the uterine carcinogens chloroethane or
bromoethane. Tox.Appl.Pharm., 130, 169-173.
9. Hanley, T.R., Scortichini, B.H., Johnson, K.A. and
Momany-Pfruender, J.J. (1987) Effects of inhaled
ethyl chloride on fetal development in CF1 mice.
Toxicologist, 7, 189.
10. Commission of the European Communities
(1999),
Occupational
Exposure
Limits,
Recommendation of the Scientific Committee on
Occupational Exposure Limits for chloroethane
SCOEL/SUM/23 final, in EUR 18216, ISBN
92-828-4270-3.
HSE REVIEW 2001
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MEL PROPOSAL
OCCURRENCE AND USE
HYDROQUINONE
Hydroquinone use in Great Britain has declined from
around 6000 tonnes in 1992 to approximately 3000
tonnes in 1999. Just under half of current use is in
photographic developing reagents. It is also used as a
polymerisation inhibitor and intermediate in a number
of processes, such as the manufacture of photographic
developers, agrochemicals, methyl methacrylate,
resins, acrylonitrile and thermoplastic monomer.
Exposure may occur during use of products containing
relatively low concentrations of hydroquinone, such as
printing plate-making, film development, printing
inks, paints and surface coatings. The number of
workers potentially exposed may be up to 5000, but of
these, the number exposed by inhalation is estimated
to be about 1000.
Maximum exposure limit
8-hour TWA: 0.5 mg m-3
(subject to consultation)
IDENTITY AND PROPERTIES
Chemical name:
Hydroquinone
CAS No:
000123-31-9
EINECS No:
204-617-8
Empirical formula: C6 H6 O2
EXPOSURE
Synonyms:
1,4 benzenediol,
1,4 dihydroxybenzene,
4 hydroxyphenol, benzonquinol,
betaquinol, hydroquinol,
alpha-hydroquinone,
benzohydroquinone,
p-benzenediol,
p-dihydroxybenzene
Exposure to hydroquinone occurs during the handling
of hydroquinone as a raw material in product
manufacture.
The main types of product are:
photographic and imaging; polymerisation inhibitor in
bulk chemicals; fine chemicals, rubber, thermoplastic
polymers, etc; resins for surface coatings and inks.
The main use by tonnage is as a photographic
developer.
Boiling point:
287oC
Vapour Pressure:
2.4 x 10-3 Pa at 25oC
Exposure to hydroquinone may also occur due to its
inclusion as an ingredient in the following types of
process medium: imaging solutions (plate-making and
film development); printing inks; paint and
surface-coating products.
Hydroquinone has three crystalline states. The stable
form is obtained as white needles. It is a weak acid
and forms mono- and di-salts in solutions of alkaline
hydroxides or carbonates. It has a very low vapour
pressure but can easily be oxidised in the presence of
moisture to quinone (more volatile than
hydroquinone).
The main source of exposure by inhalation occurs in
the product manufacturing sectors, and is related to
tasks carried out during the charging of
reaction/mixing vessels. Personal sampling data from
industry indicated that where the crystalline form (as
opposed to a powdered form used in some
applications) and local exhaust ventilation were used
(the majority of cases) exposures could be maintained
below 0.5 mg.m-3 8-hour TWA and 2 mg.m-3
15-minute STEL. The largest potential for exposure
during end use is in photographic developing.
Exposure in this sector can also be maintained below
0.5 mg.m-3 8-hour TWA and 2 mg.m-3 15-minute
STEL.
Hydroquinone is classified under the Chemicals
(Hazard Information and Packaging for Supply)
Regulations 1994 (CHIP) as Carcinogenic Category 3,
Mutagenic Category 3, Harmful, Irritant, Sensitising
and Dangerous for the environment, to be labelled
with the following R-phrases:
R40 Possible risk of irreversible effects(1)
R22 Harmful if swallowed
MEASUREMENT
R41 Risk of serious damage to eyes
Workplace air monitoring
R43 May cause sensitisation by skin contact
Hydroquinone in air is present as both vapour and
particulate fraction.
The proportion of total
hydroquinone captured by particulate filters is
strongly temperature-dependent in the range 10-30oC,
so measurement methods must take the vapour
R50 Very toxic to aquatic organisms
1
Subject to change in 2002 with proposed new CHIP regulations to "limited evidence of a carcinogenic effect".
HSE REVIEW 2001
20
MEL PROPOSAL
hydroquinone bioaccumulates.
There is no
information in relation to transfer of hydroquinone
across the placenta, nor whether or not it can be
transferred to the offspring via the breast milk.
fraction into account. They should also be capable of
distinguishing
between
hydroquinone
and
benzoquinone formed by oxidation of hydroquinone in
the presence of water. Published methods include
several variations of filter, impinger or sorbent tube
collection followed by liquid chromatography (HPLC)
or gas chromatography (GC). The potential sensitivity
of most procedures is reportedly 0.05 mg.m-3 or better.
However, actual validation for workplace air is not
usually reported below 1 mg.m-3. The HPLC method
of Scobbie and Groves1 complies with the BS EN
482:1994 standard on overall uncertainty in the range
0.05-1 mg.m-3 (8-hour sample) and with MDHS 14/3
recommendations on sampling particulates. For a
15-minute sample, the quantitation limit of this
method is about 0.05 mg.m-3.
HEALTH EFFECTS9,10
Animal studies
Hydroquinone is of moderate acute toxicity via the
oral route. Typical oral LD50 values in rats, mice,
rabbits, dogs and guinea pigs range from 300 to
550 mg/kg. Clinical signs of toxicity included violent
tremors, twitching and convulsions.
No acute
inhalation data and no useful dermal data were
available.
No conventional skin or eye irritation studies were
available. A single application of a dilute solution
(2%) was not irritating to rabbit skin, but repeat
application was irritating to rabbit (2% solution) or
guinea pig skin (0.1% solution). The limited eye
irritation data available indicated that hydroquinone
can cause severe ocular damage in animals. No
information on respiratory tract irritation is available.
Hydroquinone has been clearly shown to have skin
sensitising potential.
Biological monitoring
Biological monitoring of workers exposed to
hydroquinone may be possible by the analysis of
hydroquinone in urine. Biological monitoring may be
able to detect occupational exposure to hydroquinone
at or above an airborne concentration of 2 mg.m-3
(8-hour TWA). However, the background levels of
hydroquinone in urine produced from dietary and
environmental sources may make detection and
interpretation of low levels of exposure difficult.
There are no data in the literature on which to base a
biological monitoring guidance value.
The only repeated exposure inhalation study available
(in rats) was inadequately reported and the
significance of the results is therefore uncertain.
Corneal opacities, evidence for loss of circulating
erythrocytes and liver degeneration were seen at
10 mg.m-3, 4 hours per day for 4 months. Evidence
for erythrocyte loss was also seen at 5 mg.m-3. No
adverse effects were reported at 1 mg.m-3.
Analytical methods for the determination of
hydroquinone in urine are based on the
acid-hydrolysis of glucuronide conjugates followed by
solvent extraction. Chromatography can be via HPLC
with UV detection4, HPLC with fluorescence
detection5, GC of the trimethylsilyl derivatives with
flame ionisation detection6, GCMS detection7 or GC
of the heptafluorobutyryl derivatives with electron
capture detection8. The HPLC-UV method4 lacks
sensitivity and specificity compared to the others. The
most sensitive is the HPLC-fluoresence method5, with
a detection limit of 0.03 mg.l-1 and a coefficient of
variation of 3% within day and 6% day to day. There
are no international quality assurance schemes for
urinary hydroquinone at present.
A no observed adverse effect level was not identified
for long term exposure by the oral route. At dose
levels of 25 mg/kg/day and above, kidney toxicity was
observed; it was apparent that male rats of the F344
strain were more sensitive to this effect than female
F344 rats, Sprague Dawley rats or mice. At levels of
50 mg/kg/day and above there were adverse effects in
the liver and thyroid.
Haematological changes
occurred in some studies at dose levels of
100 mg/kg/day and above. Treatment levels of
200 mg/kg/day and above were associated with
tremors or convulsions, indicative of neurotoxicity.
Other effects elicited at doses of 200 mg/kg/day and
above included gastric mucosal lesions, death and
(observed in old, poorly reported studies) decreased
bone marrow cellularity and aplastic anaemia.
TOXICOKINETICS9,10
Absorption and elimination by the inhalation and oral
routes is rapid. Absorption by the dermal route is
poor, except when an alcohol vehicle is used.
Distribution studies indicate that the highest
concentration of hydroquinone occurs in the liver and
kidney. Metabolism occurs mainly via conjugation.
The primary urinary metabolites are the glucuronide
and sulphate conjugates of hydroquinone. Small
quantities of unchanged hydroquinone, mercapturate
acid conjugates and p-benzoquinone have also been
detected in the urine. There is no evidence that
HSE REVIEW 2001
No evidence of toxicity was seen in rat and mouse
repeat dose dermal toxicity studies using dose levels
of up to 3840 mg/kg/day.
21
MEL PROPOSAL
workers handling photographic developing solutions
containing 0.6% or 7% or hydroquinone.
An
association between the long term use of
hydroquinone-containing skin lightening products and
ochronosis has also been demonstrated.
Although giving negative results in standard Ames
tests, hydroquinone is clearly mutagenic in eukaryotic
cells in vitro. Mutagenicity was observed both in the
presence and absence of an exogenous metabolic
system. Chromosome aberration and micronucleus
tests clearly demonstrated that hydroquinone is also an
in vivo mutagen in somatic cells following exposure
by the oral, intraperitoneal and subcutaneous routes.
Several studies, both in vitro and in vivo, have
provided evidence that hydroquinone also has the
potential to induce aneuploidy. In vivo tests involving
germ cell have provided no clear evidence of
mutagenic activity.
Several studies and cases provided clear evidence that
hydroquinone can elicit skin sensitisation reactions in
some individuals.
Ocular lesions, which included conjunctival and
corneal pigmentation, corneal pitting, erosion,
thinning and opacities, wrinkling of Descemet's
membrane and, in the most severe cases, loss of vision
have been found in persons exposed to benzoquinone
vapour and hydroquinone dust in a hydroquinone
production plant. Exposure levels of up to 3.2 ppm
benzoquinone vapour and 20 - 35 mg.m-3 of
hydroquinone dust were reported. A correlation
between the severity of lesions and duration of
employment was determined but, because no
individual exposure data was available, a relationship
with exposure levels could not be established. It was
unclear what the relative contributions of
benzoquinone vapour and hydroquinone dust were to
formation of the lesions.
The Department of Health Committee on
Mutagenicity
has
considered
the
available
mutagenicity data for hydroquinone and concluded
that "occupational exposure to phenol is associated
with a risk of mutagenicity, but it is not possible to
quantify this risk. Overall, there is insufficient
evidence to support a threshold approach to risk
assessment with respect to inhalation or dermal
exposure".
Evidence of carcinogenic potential was apparent in
two oral carcinogenicity studies, both using F344
strain rats and B6C3F1 strain mice. This was observed
as the presence of kidney adenomas in male rats in
both studies and an increased incidence of
hepatocellular neoplasms, mainly adenomas, in female
mice in one study and male mice in the other. It is
possible that these findings are species or strain
specific, calling into question their relevance to
humans, and that a "non-genotxic" mechanism,
involving chronic tissue damage, was responsible.
However, with the available data the mechanism(s) of
tumour formation in experimental animals cannot
clearly be identified and consequently it is difficult to
judge its relevance to humans or, in view of the
positive genotoxicity findings, that "non-genotoxic"
mechanisms were involved in the tumour production.
No abnormal findings were reported following oral
administration to volunteers of 300-500 mg
hydroquinone/day (4-7 mg/kg/day) for up to
five months. Only limited data relating to systemic
effects in occupationally exposed persons are
available. Among hydroquinone production plant
workers, no systemic abnormalities were detected by
physical examination and haematological analysis,
following exposure at levels sufficient to cause eye
lesions, although a role for hydroquinone was
indicated.
In an epidemiology study involving more than 800
workers at a hydroquinone production plant, exposure
to this substances was not associated with an increased
cancer risk. In three other epidemiological studies
investigating the long term health of chemical plant
workers exposed to a variety of chemicals, including
hydroquinone, no adverse effects on mortality rates or
health attributable to hydroquinone exposure were
detected.
No evidence of adverse effects on male or female
fertility were observed in a conventional study.
Although negative in tests using conventional
regulatory protocols, clear evidence of developmental
toxicity was observed in an unconventional study in
which pregnant rats received single oral doses of 333,
667 or 1000 mg/kg hydroquinone on day 11 of
gestation.
Malformations considered to be
treatment-related included hind limb paralysis, short
or kinky tail, missing kidney and missing or fused
digits. A NOAEL was not determined in this study.
BASIS FOR THE LIMIT
The lead health effect of concern is genotoxicity. A
level of exposure below which there would be no
concerns for this endpoint cannot be identified.
Therefore, the OES criteria are not met. Given the
serious health concerns associated with genotoxicity.
WATCH has recommended that a MEL (8-hour
TWA) be considered.
Human data
Evidence of skin irritation was seen following
exposure to a 1% aqueous solution of hydroquinone.
Reports of skin problems following occupational
exposure are limited to two cases of vitiligo in
HSE REVIEW 2001
22
MEL PROPOSAL
10. DeCaprio AP (1999) The Toxicology of
Hydroquinone - Relevance to Occupational and
Environmental Exposure. Crit Rev Toxicol 29,
283-330
After considering current and reasonably practicable
levels of control, ACTS recommends establishment of
an 8-hour TWA MEL at 0.5 mg m-3. No STEL is
proposed.
A ‘Skin’ notation is not required because
hydroquinone is poorly absorbed across the skin.
There is no evidence that hydroquinone is a
respiratory sensitiser, so a ‘Sen’ notation is not
applicable.
Biological monitoring of workers may be possible by
analysis of hydroquinone in urine. However, the
presence of background levels of hydroquinone in
urine from dietary and environmental sources would
make the interpretation of such analyses difficult.
REFERENCES
1. Scobbie E and Groves J A, Determination of
hydroquinone in air by high performance liquid
chromatography. Annal Occup Hyg (1999) 43,
131-141.
2. British Standards Institution
Workplace
atmospheres - General requirements for the
performance of procedures for the measurement of
chemical agents,
European Standard
BS EN
482:1994, ISBN 0 580 23644 7.
3. Health and Safety Executive, General methods for
sampling and gravimetric analysis of respirable and
inhalable dust, MDHS 14/3, HSE Books 2000, ISBN
0 7176 1749 1.
4. Inoue O, Seiji K, Kasahara M, Nakatsuka H,
Watanabe T, Yin S-G, LI G-L, Cai SX, Jin C, Ikeda
M (1988) Determination of catechol and quinol in
urine of workers exposed to benzene. Br J Ind Med
45, 487-492
5. Lee BL, Ong HY, Shi CY, Ong CN (1993)
Simultaneous determination of hydroquinone, catechol
and phenol in urine using high-performance liquid
chromatography with fluorimetric detection J Crom
(Biomed Appl) 619, 259-26
6. Hotz P, Carbonnelle Haufroid V, Tschopp A,
Buchet JP, Lauwreys R (1997) Biological monitoring
of vehicle mechanics and other workers exposed to
low concentrations of benzene. Int Arc Occup
Environ Health 70, 29-40
7. Health and Safety Laboratory. Unpublished method
8. Deisinger PJ, Hill TS, English C (1996) Human
exposure to naturally occurring hydroquinone. J
Toxicol Environ Health 47, 31-46
9. World Health Organization (1994) Environmental
Health Criteria 157: Hydroquinone
HSE REVIEW 2001
23
MEL PROPOSAL
EINECS No:
Formula:
Synonyms
MANGANESE AND ITS
INORGANIC COMPOUNDS
Melting point:
Water solubility:
Maximum exposure limit
8-hour TWA: 0.5 mg.m-3
231-760-3
KMnO4
chameleon mineral, Condy’s
crystals
decomposes at less than 240ºC
6.38g/100ml
A number of individual manganese compounds are
currently classified as Harmful under the Chemicals
(Hazard Information and Packaging for Supply)
Regulations (1994) and labelled as follows:
(subject to consultation)
IDENTITY AND PROPERTIES
Manganese dioxide
R20/22: Harmful by inhalation and if swallowed
Chemical name:
CAS No:
EINECS No:
Formula:
Melting point:
Boiling point:
Water solubility:
Manganese
7439-96-5
231-105-1
Mn
12440C
19620C
insoluble
Manganese sulphate
R48/20/22: Danger of serious damage to health by
prolonged exposure through inhalation and if
swallowed
Potassium permanganate
R22: Harmful if swallowed
(Also classified as oxidising with R8: Contact with
combustible material may cause fire)
There are a number of inorganic forms of manganese.
The most commonly used are:
However, in the light of this review it is considered
that manganese and all of its inorganic compounds
meet the criteria for classification as Toxic, to be
labelled with the risk phrase:
Chemical name: Manganese sulphate
CAS No:
7785-87-7
EINECS No:
232-089-9
Formula:
MnSO4
Synonyms:
manganous sulphate
sulphuric acid, manganese salt
Melting point:
7000C
Boiling point:
decomposes at 8500C
Water solubility: 52g/100ml
R48/23 Danger of serious damage to health by
prolonged exposure through inhalation.
This is based on human evidence for the CNS effects
of inorganic manganese compounds.
It is possible that the UK will submit a proposal to the
relevant European Working Group with a view to
getting these compounds reclassified as Toxic.
Chemical name: Manganese dioxide
CAS No:
1313-13-9
EINECS No:
215-206-6
Formula:
MnO2
Synonyms:
black manganese oxide
manganese peroxide
Melting point:
decomposes at 535ºC
Water solubility: insoluble
OCCURRENCE AND USE
Manganese metal is made from the electrolysis of
manganese sulphate solution, which is prepared by
dissolving manganous oxide in sulphuric acid.
Manganous oxide is made from manganese dioxide
ores by reductive roasting.
Ferromanganese is
prepared from ferruginous manganese ores in smelting
furnaces. The main sources of these ores are
Australia, Brazil, Gabon, South Africa and Ukraine.
Silicomanganese is prepared by adding quartz to the
furnace charge during ferromanganese production.
Chemical name: Manganese oxide
CAS No:
1344-43-0
EINECS No:
215-695-8
Formula:
MnO
Synonyms
manganous oxide, manganese
green
Melting point:
heating coverts to Mn3O4 and
Mn2O3
Water solubility: insoluble
Chemical name:
CAS No:
HSE REVIEW 2001
The major uses of manganese and its compounds are
in steelmaking, preparing animal feed supplements
and trace element fertilisers and manufacturing
welding consumables. Other uses include pigments,
paint driers and catalysts. The uses of permanganate
salts include metal cleaning, printed circuit board
production, chemical synthesis and water treatment.
Potassium permanganate
7722-64-7
24
MEL PROPOSAL
EXPOSURE
made up of very fine (submicron) particles condensed
from the vapour phase, and manganese-containing
dust. If manganese fume and manganese-containing
dust are both present in the air, and measurement of
manganese fume is required, it is suggested that a
respirable sampler is used to collect samples. This
will exclude the larger particles that would be
collected using an inhalable sampler.
It is estimated that there are at least 100,000 people
exposed to manganese in Great Britain. Their
exposure is either to dust or fume containing
manganese.
Manganese dust concentrations during steelmaking
can approach 8 mg.m-3 for a few individuals. Some of
these exposures can be reduced to below 0.5 mg.m-3
by using ventilated cabs. Mean fume exposures of 0.7
mg.m-3 were found for furnace operators. At one plant
8% of the results were between 2.5 and 5 mg.m-3.
With good practice, furnace operator’s manganese
fume exposure should not exceed 3 mg.m-3.
Biological monitoring
The role for biological monitoring in the assessment
of occupational exposures to manganese is unclear.
A measurable increase in both blood and urine manganese has been reported following exposure to manganese dust and fumes. However, due to the large
variation in the levels of manganese in biological
fluids from healthy unexposed individuals, the
measurement of manganese in blood and urine may
only be a useful indicator of exposure on a group
basis.
There are similar patterns of exposure and control
during the manufacture of animal feed supplement
premixes and trace element fertilisers containing
manganese. Eighty three per cent of the manganese
dust concentration results during fertiliser manufacture
were less than 1.7 mg.m-3. The range of results greater
than 1.7 mg.m-3 was 4.0 to 23.6 mg.m-3. With good
practice, exposure to manganese dust during the
manufacture of premixes and fertilisers containing
manganese should not exceed 2.5 mg.m-3.
Manganese may be quantitatively determined directly
in blood and urine matrices using electrothermal
atomic absorption spectrophotometry.18
There are numerous other industries where people are
exposed to manganese dust and fume. The greatest
numbers are in welding and metal finishing
operations. With good practice, exposures during all
of these processes should not exceed 2 mg.m-3.
TOXICOKINETICS
No toxicokinetic studies have been conducted with
manganese (Mn) metal. However, following
inhalation of metal particles, one would expect some
solubilisation and absorption to eventually occur from
the lung. In addition, it is predicted that if the metal
enters the GI tract, it would react with stomach acids
to produce the divalent ion. These ions would
subsequently be absorbed, distributed and eliminated
in a similar manner to the ions derived from inorganic
salts.
MEASUREMENT
Workplace air monitoring
A number of generic methods are available for
determination of metals in workplace air. These are
all suitable for measuring manganese and its inorganic
compounds.
Inorganic compounds of Mn are well absorbed from
the lungs, with absorption being more rapid for the
more soluble forms.
The Health and Safety Executive (HSE) has published
an X-ray fluorescence (XRF) method for metals and
metalloids in workplace air in its Methods for
Determination of Hazardous Substances (MDHS)
series14. In addition, the United States Occupational
Safety and Health Administration (OSHA) has
published an atomic absorption spectrometry (AAS)
method15 and an inductively coupled plasma atomic
emission spectrometry (ICP-AES) method16 for metal
and metalloid particulates in workplace atmospheres,
and the United States National Institute for
Occupational Safety and Health (NIOSH) has
published an ICP-AES method for elements in air17.
However, if a US method is used it is necessary to
apply the sampling procedure for respirable and total
inhalable dust described by HSE.
Following oral dosing, Mn compounds undergo a
relatively low extent of absorption.1 The uptake of Mn
from the gut appears to share the same active transport
mechanism as for iron. Under normal dietary
conditions man absorbs approximately 3% of
available Mn from the intestine, although individuals
vary considerably dependent on levels of iron in the
body.
No toxicokinetic studies have been conducted using
the dermal route. However, it is predicted that, like
other metal salts, absorption via this route would be
low for Mn metal and inorganic salts.
Recent studies in rodents with radiolabelled Mn
compounds suggest there may be absorption directly
across the olfactory epithelium followed by transport
directly to the brain via neuronal transport
mechanisms.13
The methods described by HSE, OSHA and NIOSH
cannot distinguish between manganese fume, which is
HSE REVIEW 2001
25
MEL PROPOSAL
oxidizer and is likely to be corrosive at high
concentrations.
Once absorbed into the bloodstream, Mn is bound to
plasma proteins; the trivalent ion to transferrin and the
divalent ion to α-macroglobulin, or is transported as
free divalent Mn. In humans, Mn can also be bound
to β1-globulin transport protein.
MnCl2 did not demonstrate sensitisation potential in a
well conducted mouse local lymph node assay.5 No
studies are available investigating the sensitisation
potential of other Mn compounds.
Mn is widely distributed to all organs and tissues, with
animal studies indicating increased levels in the liver,
kidney and brain following absorption.
Few studies have investigated the effects of repeated
inhalation exposure to Mn compounds and there are
no long-term inhalation studies in rodents which have
followed standard protocols. From the rodent studies
which are available, there is no evidence for the ability
of Mn compounds to induce CNS changes by any
exposure route, and rodents do not appear to be an
appropriate animal model for investigating the
neurological effects of Mn (see below). Although
there is evidence for neurological changes in
non-human primates exposed to Mn compounds, the
majority of studies have employed parenteral routes of
exposure, and there are inadequate data in such
species to characterise the exposure-response
relationships for neurological effects following
inhalation.
Repeated oral dosing or intra-tracheal instillations of
MnO2 and MnCl2 in the monkey lead to accumulation
of Mn in the brain, with particular accumulation noted
in the caudate, lenticular nuclei (putamen and globus
pallidus), substantia nigra and pituitary gland.3
There is evidence from studies in rodents for transfer
of Mn across the placenta and via the breastmilk. The
chemical fate of Mn compounds in the body has not
been investigated in detail. However, the alkaline
conditions of the small intestine facilitate oxidation of
the divalent ion to the trivalent ion. Oxidation of the
divalent to trivalent ions has also been observed in
plasma in vitro. The percentage of ions in each
valency state in vivo under any particular experimental
conditions has not been quantified. The principle
route of elimination for absorbed Mn is in the faeces,
via the bile, with evidence for enterohepatic
recirculation.4
In monkeys (group size = 8) exposed continuously for
9 months to aerosols of Mn3O4 (MMAD 0.1 µm), a
NOAEL of 1 mg.m-3 Mn was identified. At this
concentration, no effects on pulmonary function or
histology, or on limb tremor or electromyographic
responses were reported. There are no other reliable
data in non-human primates repeatedly exposed by
inhalation to Mn compounds. In rats continuously
exposed for 9 months to Mn3O4, a NOAEL of 1
mg.m-3 Mn was identified2. In rabbits exposed for up
to 6 weeks (6 hrs/day) to up to 4 mg.m-3 Mn (as
MnCl2) no pulmonary histopathology (the focus of the
study) was induced.2 A 2-week exposure (5 hrs/day) to
43 mg.m-3 Mn (as MnO2) produced severe lung
damage in rats with marked pulmonary oedema.2
Overall, in relation to the pulmonary effects of inhaled
inorganic Mn compounds some useful data on
individual compounds is available, but insufficient
data are available to permit a reliable comparison of
different Mn compounds of differing solubilities,
valency states and particle sizes, or to compare
possible differences in species response.
Following inhalation exposure to MnO2 or Mn2O3 in
humans, 60% of the estimated initial lung burden was
eliminated in the faeces by 4 days post-exposure. In
humans renal elimination into the urine accounts for
only 0.1-1.3% of the administered dose, with traces
also being eliminated in sweat, tears and nails.
HEALTH EFFECTS
Animal studies
No animal toxicity studies have been conducted with
elemental Mn.
No single exposure inhalation studies for Mn
compounds are available. Oral LD50 values for the
oxides of Mn have not been determined. MnCl2 is
moderately toxic by the oral route with LD50 values of
250-810 mg kg-1 in rodents. However, these data
derive from early reports of uncertain reliability.
KMnO4 is also moderately toxic by this route with an
LD50 of 750 mg kg-1 in rodents.4 No further details are
available. No single exposure dermal toxicity studies
are available. However, no systemic toxicity would be
expected via the dermal route.
In relation to oral dosing, the most useful data derive
from a 2-year study in rats and mice exposed to up to
15000 ppm Mn (broadly equivalent to 665 mg/kg/day
in rats and 2000 mg/kg/day in mice) MnSO4 in the
diet.2 In this study, survival in top dose male rats was
not affected up to 93 weeks, but thereafter, survival
was reduced by 70% compared to controls. Survival
was not affected in female rats or in mice of either
sex. Reductions in survival in top dose male rats were
ascribed to the observation of an increase in the
severity, but not the incidence, of chronic
nephropathy; there was a high background incidence
No studies are available addressing skin or eye
irritation for Mn compounds. However, it is unlikely
that elemental Mn or its oxides would cause skin or
eye irritation. In contrast, KMnO4 is a powerful
HSE REVIEW 2001
26
MEL PROPOSAL
exposures up to 15000 ppm of MnSO4 in the diet. In
another study in female rats exposed to 1004 ppm Mn
(as MnSO4) in the diet from weaning, there were no
effects on fertility. No effects on the reproductive
organs were reported in any of the repeated inhalation
exposure studies conducted with Mn oxides. These
observations indicate a lack of effect of Mn on the
reproductive organs or fertility. In contrast, a number
of studies report testicular toxicity in rats and rabbits
at doses of Mn which produce no other toxicological
effects; these findings emanate from poorly reported
studies of doubtful reliability, and in view of the
evidence for lack of effects on the male gonads in
more reliable studies, no credence can be attached to
these reports. Overall, although fertility has not been
systematically investigated in standard studies, the
available evidence suggests that Mn does not affect
fertility in experimental animals.
of chronic nephropathy in the male rats in this study.
Reductions in hepatic iron (15-30%) were seen in all
Mn-exposed animals reflecting the fact that iron and
Mn compete for the same active transport mechanism
for absorption from the gut. However, no
haematological changes were observed in either
species.
No
other
clear
treatment-related
non-tumourigenic findings were observed (the tumour
findings are given below).
There are no studies of the repeated dose toxicity of
Mn or its compounds via the dermal route. However,
no systemic toxicity would be predicted following
dermal exposure.
The potential mutagenicity of elemental Mn and its
inorganic compounds has not been adequately
investigated. Under certain experimental conditions,
Mn compounds are mutagenic in bacteria. In addition,
positive results have been reported in a variety of
mammalian cell assays conducted in vitro using the
divalent Mn2+ ion. The positive in vitro results arise
as a secondary consequence of the substitution of
magnesium ions by divalent Mn ions in DNA
polymerases, which reduces the fidelity of DNA
replication. No reliable in vivo data are available.
However, no treatment-related tumours were observed
in a well conducted carcinogenicity study (see below),
offering some evidence for an absence of genotoxic
carcinogenicity.
The potential developmental toxicity of inorganic Mn
compounds has been reasonably well investigated in a
range of animal species.6 The investigations carried
out include standard measures of developmental toxicity as well as specific studies of potential neurodevelopmental effects. No developmental effects (including neurobehavioural) were seen in offspring of
female mice exposed pre-mating and throughout
gestation via inhalation to high airborne levels of
MnO2 (85 mg.m-3 Mn). Standard developmental
studies in mice, rats, hamsters and rabbits given oral
gavage doses of MnSO4 showed no evidence for
developmental toxicity. The top doses tested in these
studies ranged between 78 - 136 mg/kg/day; these
appeared to be maternally non-toxic doses in that they
produced no effects on maternal weight gain. Detailed
recent studies in rats exposed pre- and post-natally to
MnCl2 either via the drinking water (up to 10 mg/l) or
by oral gavage (150 mg/kg/day), again showed no
evidence for developmental effects of Mn, including
effects on neurobehaviour and CNS morphology.
Overall, the available evidence in animals suggests
that inorganic Mn compounds are not developmental
toxicants.
The carcinogenic potential of Mn compounds has not
been thoroughly investigated; in particular, there are
no inhalation studies available. In a well conducted
oral study in rat and mouse, no treatment-related
tumours were observed in rats exposed to up to 15000
ppm MnSO4 in the diet. In mice at the top dose of
15000 ppm an increase in thyroid follicular adenomas
was noted in both sexes. The incidence in the top dose
group was close to the maximum of the historical
control range for this species. Given that the thyroid
has not been a target organ of toxicity in repeated dose
studies with Mn salts in any of the animal species
tested, the increase in thyroid tumours in this study is
considered to be most likely a chance finding,
particularly in the absence of any mechanistic
evidence to support a possible causal role for Mn.
Overall, the evidence from rats and mice suggests a
lack of carcinogenic potential for orally administered
soluble Mn salts.
Human data
Reports of single exposure are few and principally
involve ingestion of unknown doses of KMnO4. This
has resulted in death, with pathological findings of
severe irritation of oral and GI tract mucosa, as well as
changes in liver, kidney and heart being noted.2
Although no standard fertility studies have been
conducted with elemental Mn or its inorganic
compounds, there are a number of studies which
provide relevant information concerning the potential
effects of Mn on the reproductive organs and on fertility outcome.6 These studies yield a variable pattern of
results. No effects on male fertility were seen in mice
given single intraperitoneal doses of 100 mg/kg MnCl2
in a dominant lethal study. In a 2-year study in rats
and mice, no effects on the weight or histology of the
reproductive organs were seen in either species with
HSE REVIEW 2001
There are no reports of skin or eye irritation for
inorganic Mn compounds. As KMnO4 is a powerful
oxidising agent it is predicted to possess corrosive
properties. There are no reports of skin sensitisation or
occupational asthma associated with Mn metal or
compounds. Given the widespread industrial use of
inorganic Mn compounds, the absence of such reports
suggests that Mn ions are likely to lack sensitising
properties.
27
MEL PROPOSAL
Historically, effects on male fertility (impotence) have
been reported in workers suffering from severe
neurological disease due to unstated, but certainly
relatively high exposures to Mn. In view of the
animal evidence, it is likely that these effects were
mediated via CNS changes rather than direct effects
on the male reproductive organs. Only two studies
have investigated male fertility in workers under
contemporary exposure conditions. In one study,
fewer children were born to Mn-exposed male
workers compared with a control group.9 However,
no information was obtained from the wives of the
men concerning their medical and sexual history, and
use of contraception. Hence, no conclusions can be
drawn regarding the possible causes of the results.
Furthermore, in a subsequent study by the same
workers employing similar investigative methods (a
questionnaire), no reductions in male fertility were
found.10 Overall, neither of these studies provides any
definitive evidence concerning the effects of Mn on
male fertility. Based on the findings in animals, it
seems reasonable to conclude that Mn is unlikely to
directly affect male fertility in humans, although
sexual problems could arise as a secondary
consequence of impaired neurological function. No
reliable data concerning the developmental effects of
Mn in humans have been identified
The key health hazards historically associated with
repeated occupational exposure to inorganic Mn
compounds are pulmonary toxicity and a neurological
syndrome (manganism). The pulmonary effects of Mn
compounds have not been widely investigated in
contemporary epidemiological studies. However, from
the limited evidence available, it appears that there are
no effects on lung function or respiratory symptoms
with exposures to total inhalable MnO2 dust below
about 1 mg.m-3 Mn.2 The exposure concentrations at
which respiratory effects would begin to occur are not
known, nor is anything known about possible differences in the pulmonary effects of different Mn
compounds.
The signs and symptoms of the neurological disease
syndrome produced by Mn compounds show similarities to those of Parkinsonism, with gait disturbance
and effects on motor coordination being the key clinical features. However, manganism and Parkinsonism
are medically distinct conditions. There are a large
number of contemporary epidemiological studies,
chiefly cross-sectional in design, which have investigated the neurobehavioural effects of occupational
exposure to inorganic Mn compounds. The results of
these studies show a consistent pattern of poorer
performance in neurological tests, notably in relation
to motor function, in Mn-exposed workers compared
to appropriately matched controls. A number of
studies also report effects on cognitive performance
and mood, but there is no clear consistency in the
findings reported in relation to these aspects.
BASIS FOR SETTING THE LIMIT
From a large number of recent epidemiological studies
it can be seen that the key health hazard associated
with occupational exposure to inorganic Mn
compounds is a disturbance of motor function, leading
to loss of fine control of intentional movements.
Exposure data in these studies typically reveal mean
8-hour TWA concentrations of 0.25 - 1.6 mg.m-3 Mn
within the total inhalable dust. There is a single study
in which no neurological findings were detected in Mn
workers exposed to 0.18 mg.m-3 Mn, 8-hour TWA7.
However, given that this finding derives from only a
single study, and has not been confirmed in other
studies, it cannot be confidently identified as a level of
exposure at which no neurological effects of Mn
would be predicted to occur. Overall, there is insufficient information to allow any firm conclusions to be
drawn concerning the exposure-response relationship
for the effects of Mn on the CNS, nor are there any
data to allow conclusions to be drawn concerning
possible
differences
between
different
Mn
compounds, or between Mn dust and fume.
Typically, the mean occupational exposure levels at
which motor effects have been reported in relatively
recent studies range from 0.25 - 1.6 mg.m-3 Mn
(8-hour TWA) for Mn in total inhalable dust.
However, the precise exposure-response relationship
for the effects of manganese on neurological function
has not been clearly characterised and a clear
threshold level of exposure for the development of
neurological effects cannot be reliably identified.
Occupational hygiene information for UK industry
shows that with good practice exposures in the range
0.1-3.0 mg.m-3 Mn (8-hour TWA) are achievable
depending on the industry. The upper end of this
exposure range exceeds the levels at which changes in
motor function have been observed in performance
testing across a range of industry sectors. Such motor
changes are judged to be of a serious nature as they
would impair the ability of workers to control fine
muscular movements. Overall, taking into account the
occupational exposure data available for Mn, and the
exposure conditions at which effects on motor
function have been reported, it is evident that the
indicative criteria for the establishment of an OES are
not met and that setting a MEL should be considered.
There are no studies of the potential mutagenic effects
of elemental Mn or its compounds in humans.
There is only one study which has investigated the
potential carcinogenicity of Mn compounds in
humans;8 this was a cancer incidence study in
ferroalloy workers (n=3961) exposed to Mn
compounds for at least 18 months in Norway with a
follow-up time of a minimum of 12 years. The results
showed no increase in cancer (total or site specific)
incidence.
HSE REVIEW 2001
28
MEL PROPOSAL
4. WHO (1981). IPCS Environmental Health Criteria.
17, Manganese. ISBN 92 4 154077 X
In relation to the setting of an OEL for Mn inorganic
compounds, any limit which is established should be
applied to elemental manganese and all of its
inorganic compounds, whether is the form of dust or
fume. There are both toxicological and pragmatic
reasons for this. Toxicologically, inorganic manganese
compounds are well absorbed from the lungs
regardless of their solubility, which suggests the
potential for similarity in their systemic toxicity.
Pragmatically, air monitoring methods are based on
measurements of manganese and do not distinguish
between different compounds or between dust and
fume. As there are no grounds to predict acute health
effects from short-term peak exposures, there would
be no need for a STEL for elemental manganese and
its inorganic compounds.
5. Ikarashi Y, Tsuchiya T, Nakamura A (1992).
Detection of contact sensitivity of metal salts using the
murine local lymph node assay. Toxicology letters
62: 53-61
6. Barlow SM and Sullivan FM (1982). Manganese
and its compounds. In: Reproductive hazards of
Industrial chemicals. Academic Press, New York.
370-385
7. Gibbs JP, Crump KS, Houck DP et al. (1999).
Focused medical surveillance: A search for subclinical
movement disorders in a cohort of U.S. workers
exposed to low levels of manganese dust.
NeuroToxicology 20(2-3): 299-314
8. Kjuus H, Andersen A, Langard S, Knudsen KE.
(1986). Cancer incidence among workers in the
Norwegian ferro-alloy industry. Br J Ind Med 43:
227-236
As Mn compounds are not likely to be significantly
absorbed across the skin, a "Sk" notation is not
required. As there is no evidence for the potential to
cause asthma, a "Sen" notation is not required. In
relation to biological monitoring, a large body of
evidence from occupational studies indicates that
there is no clear correlation between biological
monitoring values and either airborne levels of
manganese or health effects. Given that no significant
dermal absorption of inorganic manganese compounds
is predicted, it is unlikely that skin exposure could
account for this lack of correlation. Instead, to some
extent at least, the lack of correlation may be due to
variable dietary intake and uptake of manganese; in
this context, uptake from the gastrointestinal tract is
thought to be affected by iron status, which will in
itself be variable between individuals. Overall
therefore, the establishment of a BMGV is not
proposed. The above has been endorsed by WATCH.
9. Lauwerys R, Roels H, Genet P et al (1985) Fertility
of male workers exposed to mercury vapour or to
manganese dust: a questionnaire study. Am J Ind Med
7:171-176
10. Gennart JP, Buchet JP, Roels H et al. (1992)
Fertility of male workers exposed to cadmium, lead or
manganese. Am J Epidemiology 135 (11):1208-1219
11. Crump KS and Rousseau P. (1999). Results from
eleven years of neurological health surveillance at a
manganese oxide and salt producing plant.
NeuroToxicology 20(2-3): 273-286
12. Roels H, Ortega Eslava MI, Ceulemans E et al.
(1999). Prospective study on the reversibility of
neurobehavioural effects in workers exposed to
manganese dioxide.
NeuroToxicology
20(2-3):
255-272
After considering current and reasonably practicable
levels of control, the Advisory Committee on Toxic
Substances recommended that an 8-hour TWA of 0.5
mg.m-3 was appropriate.
13. Henriksson J, Tallkvist J, Tjalve H (1999). Transport of manganese via the olfactory pathway in rats.
Toxicol Appl Pharmacol 156: 119-128
14. Health and Safety Executive Methods for the
Determination of Hazardous Substances MDHS 91
HSE Books 1998 ISBN 0 7176 1557 X
15. U.S. Occupational Safety and Health
Administration OSHA Analytical Methods Manual
2nd Edition Method ID-121. USDOL/OSHA Salt
Lake City
1991 http://www.osha-slc.gov/SLTC/
analytical_methods/html-methods/inorganic/id_121/
id_121.html
16. U.S. Occupational Safety and Health
Administration OSHA Analytical Methods Manual
2nd Edition Method ID-125G USDOL/OSHA Salt
Lake City 1991 http://www.osha-slc.gov/SLTC/
analytical_methods/html-methods/inorganic/id_125g/
id_125g.html
REFERENCES
1. Roels H, Meiers G, Delos M et al. (1997).
Influence on the route of administration and chemical
form on the absorption and cerebral distribution of
manganese in rats. Arch Toxicol 71: 223-230
2. DFG (1999). Occupational toxicants: Critical data
evaluation for MAK values (references up to July
1994). Vol 12. ISBN 0944 - 4459
3. Newland MC, Ceckler TL, Kordower JH et al.
(1989). Visualising manganese in the primate basal
ganglia with magnetic resonance imaging.
Exp
Neurology 106: 251-258
HSE REVIEW 2001
29
MEL PROPOSAL
17. U.S. National Institute for Occupational Safety
and Health NIOSH Manual of Analytical Methods 4th
Edition Method 7300. Publication 94-113 1994
NTIS PB 85-179018
18. White MA, Sabbioni E (1998) Trace element
reference values in tissues from inhabitants of the
European Union. X. A study of 13 elements in blood
and urine of a United Kingdom population. Sci .Total
Environ. 216: 253-270
HSE REVIEW 2001
30
PROPOSAL TO RETAIN OES AND ADD SKIN NOTATION
EXPOSURE
The total number of workers in the chemical process
industry who may be exposed to PPD is estimated to
be less than 50. Such exposures are generally less than
0.1 mg⋅m-3 (8-hour TWA). Dermal exposures in the
chemical process industry are expected to be low as
workers are expected to wear appropriate eye protection, gloves and overalls when handling PPD.
Hairdressers may also come into contact with liquid
containing PPD when mixing the liquid that contains
the PPD with an oxidising solution to produce a hair
dye. In such situations, it is considered that inhalation
exposure to PPD is likely to be negligible. Dermal
exposures are expected to be significant however
because hairdressers tend not to wear gloves to protect
against dermal exposure. Hairdressers have already
been identified by HSE as one of the top ten occupational groups at high risk of work-related skin disease.
PARA-PHENYLENEDIAMINE
Occupational exposure standard
8-hour TWA: 0.1 mg.m-3
NOTATION: SKIN
Subject to consultation
IDENTITY AND PROPERTIES
Chemical name:
p-phenylenediamine
CAS No:
106-50-3
EINECS No:
203-404-7
Formula:
C6H8N2
Synonyms:
1,4-diaminobenzene,
p-diaminobenzene,
4-aminoaniline,
1,4-benzenediamine
Boiling point:
267oC
Melting point:
147oC
Vapour pressure:
1.3 Pa at 20oC
Solubility:
Soluble in water i.e.
31.8g/l at 20oC
Conversion factor:
1 ppm = 4.52 mg/m3 at
20oC
MEASUREMENT
There are no suitable direct-reading instrumental or
short-term gas detector tube methods. PPD is subject
to oxidation in air, therefore sampling methods which
collect PPD as the free amine in solution, or on solid
sorbents, are not recommended. Collection as the
stable amine salt on acid-coated filters is preferred,
using the IOM head as described in MDHS 14/31.
Filters may be extracted with an aqueous solvent and
analysed by liquid chromatography with UV
spectrophotometric detection (OSHA 87)2 or dual
electrochemical and UV detection (MDHS 75)3.
OSHA 87 and MDHS 75 differ in the filter extraction
method. In OSHA 87 the recovery and stability of
phenylenediamine isomers has been specifically
assessed using dilute EDTA solution for filter
extraction. MDHS 75 uses alkaline aqueous methanol
and has been validated for a range of aromatic amines,
including diaminodiphenylmethane, aniline and
o-toluidine, though not specifically PPD. Therefore in
the absence of MDHS 75 stability data for PPD, the
“neutral” pH extraction method of OSHA 87 is
preferred. On the basis of laboratory trials, OSHA 87
achieves significantly better than ± 30% uncertainty
requirement of EN 4824 over the range 0.002 - 0.2
mg⋅m-3 PPD. Overall uncertainty, including sampling,
would comply with EN 482, provided that the air
sampling itself was carried out with the IOM head
according to MDHS 14/3 and EN 4815. Both 15
minute STEL and 8-hour TWA sampling would
comply in this assessment, with the proviso that, to
prevent breakthrough, the filter is changed at least
every 100 minutes.
Para-phenylenediamine (PPD) is solid at room
temperature and appears as colourless to slightly red
crystals.
PPD is classified under the Chemicals (Hazard
Information and Packaging for Supply) [CHIP]
Regulations for health effects as Toxic, Sensitising,
Irritant and Dangerous for the environment. It is
labelled with the following risk (R) phrases:
R23/24/25: Toxic by inhalation, in contact with skin
and if swallowed
R36: Irritating to eyes
R43: May cause sensitisation by skin contact
R50: Very toxic to acquatic organisms
R53: May cause long-term effects in the aquatic
environment
OCCURRENCE AND USE
There is no production of PPD in the UK. Currently,
about 20 Te/yr of PPD are imported for use by the UK
chemical process industry for the formulation of hair
dyes.
HSE REVIEW 2001
31
PROPOSAL TO RETAIN OES AND ADD SKIN NOTATION
HEALTH EFFECTS7
BIOLOGICAL MONITORING
PPD does not fit all of HSE’s framework for
proposing biological monitoring guidance values.
Although dermal absorption of PPD may contribute to
systemic toxicity there have
been no reported
occupational exposure studies using biological
monitoring and there is no data on which to base a
guidance value at the moment. If gloves or other
protective equipment were used to prevent skin
contact then there may be a role for biological
monitoring to assess their efficacy. Biological
monitoring, based on the analysis of PPD and its
hydrolysable conjugates in urine, has been used to
assess dermal absorption of PPD in people using it in
hair dyes6. Modern analytical techniques based on
HPLC with electrochemical detection or capillary
GCMS would have sufficient sensitivity and
specificity to detect much lower levels of exposure.
Animal studies
In the only available acute inhalation toxicity study8 in
which rats were exposed nose-only for 4 hours to PPD
at concentrations of 0, 70, 300, 540, 940 or 1800
mg⋅m-3, deaths were observed at all doses except for
the lowest one within 48 hours of exposure. Clinical
signs of toxicity consisting of red ocular discharge
were observed in all treated animals throughout the
observation period. Red nasal discharge was also
observed at 300 mg⋅m-3 and above. The toxicological
significance of these findings is uncertain as they
might have been a stress-related response or due to the
slightly red coloration of the test substance. Pallor,
diarrhoea, loss of righting reflex and tremors were
seen at the two highest concentrations and cyanosis
was also noted at the top dose. An LC50 value of 920
mg⋅m-3/4h (0.92 mg/l/4h) was identified from this
study. This indicates that PPD is toxic following
single inhalation exposure in animals.
PPD
is toxic by the oral route. Oral LD50 values of 316-500
mg/kg in mice and of 80 mg/kg to 180 mg/kg in rats
have been reported. No effects on the nervous system
were seen in rats following single oral doses of 20, 40
or 80 mg/kg9.
Following single dermal
application to rabbits, deaths were observed at 5000
mg/kg (the only exposure level used). Signs of toxicity
in both the oral and dermal studies were oedema of
the face and neck, dyspnoea, and, only in rats and
mice, necrosis of skeletal muscle. These are unusual
findings without a clear explanation of the underlying
mechanisms involved. Also, these findings have not
been observed in repeated toxicity studies in which the
degree of toxicity noted is much lower. However, this
is likely to be due to differences in the method of
administration (gavage in the acute toxicity studies
and dietary administration in the repeated dose
toxicity investigations).
As with other
aromatic amines, methaemoglobin formation might be
of concern for humans. Methaemoglobin has been
detected in vitro when incubating PPD with
haemoglobin, erythrocytes or whole blood of rats and
humans. Following intra-peritoneal administration, a
methaemoglobin level of 12.9% was measured in
Wistar rats injected with a single dose of 10.8 mg/kg
PPD. In apparent inconsistency with this, another
study reported a level of 3.8% in Sprague-Dawley rats
injected with a single dose of 35 mg/kg PPD. A lower
level of 1.1% was detected in dogs dosed
intra-venously with 50 mg/kg. No increased
methaemoglobin formation has been reported in dogs
after single oral doses up to 10 mg/kg.
TOXICOKINETICS7
After ingestion in the rat and mouse, PPD is absorbed
almost completely within 24 hours. Depending on the
amount applied, up to 50% of PPD is absorbed across
the skin in guinea pigs over a period of 48 hours. In
humans, at least 13% of PPD penetrates the skin
within 5 days after dermal application to the forearm.
There are no data relating to inhalation, but the
relatively high water solubility and the low molecular
weight of the substance suggest PPD would be well
absorbed by the lungs.
Absorbed PPD is distributed widely and rapidly
around the body.
PPD is rapidly and extensively metabolised. Like
other aromatic amines, this is a substrate for oxidation
by cytochrome P450 and subsequent conjugation by
phase II enzymes such as N-acetylases. One of the
main metabolites identified in the urine of rats and
dogs is N,N’-diacetyl-1,4-diaminobenzene. Other
diacetyl derivatives are also likely to occur. There is
only one available human study investigating the
metabolism
of
PPD.
In
this
study,
N,N’-diacetyl-1,4-diaminobenzene was also detected
in the urine of women within 30 minutes to 2 days
after hair dyeing with a mixture containing PPD.
Irrespective of the route of administration, up to 85%
of absorbed PPD is excreted as acetylated metabolites
in the urine within 1 to 6 days after administration,
while a smaller proportion is eliminated unchanged
via the faeces.
There are no data available to indicate whether PPD
or its metabolites can cross the placenta or whether
transfer to offspring through breast milk can occur.
HSE REVIEW 2001
32
PROPOSAL TO RETAIN OES AND ADD SKIN NOTATION
Several non-conventional studies are available for skin
and eye irritation. Those using methods closest to
current standards suggest PPD is irritant to rabbit eyes
but not especially to the skin of rabbits and guinea
pigs. No information is available on respiratory tract
irritation, although the nasal and ocular discharge
observed in the rat acute inhalation study suggests the
possibility of irritant effects at the site of contact.
parameters evaluated in the study. Neuropathology
evaluations did not reveal any abnormalities within the
nervous system or skeletal muscle and no effects were
seen on ocular tissue. Only wet chin and wet perineum
(females only) were observed at the top dose.
However, these findings are deemed to be incidental
observations of no toxicological significance. In mice
administered in the feed doses of PPD from 150 up to
700 mg/kg/d for 7 weeks, PPD caused a reduction in
body weight gain at all exposure levels except for the
lowest dose. No other signs of toxicity were observed.
No signs of systemic or local toxicity at the site of
application were observed in a well-conducted study
in which mice were given dermal doses of 40 or 80
mg/kg twice per week for 130 weeks.
It is well-established that PPD is a strong skin
sensitiser. Cross-sensitisation with structurally similar
substances also occurs.
There are
no useful animal data relating to respiratory
sensitisation.
In relation to the effects of repeated exposure, there
are no inhalation studies. However, a number of oral
and dermal studies are available. In rats
(10/sex/group) given dietary doses of 37.5, 75, 150 or
300 mg/kg/d PPD for 12 weeks, a dramatic reduction
(58% and 52% in males and females, respectively) in
body weight and a significant increase in relative liver
(27%/38% males/females) and kidney weights
(45%/33% males/females) were observed at the top
dose. Body weight was also significantly reduced at
the lower doses of 150 mg/kg/d (20%/24%
males/females) and 75 mg/kg/d (11% in females only).
Fatty degeneration of the liver was reported, but only
at the highest dose. No other signs of toxicity were
detected. Overall, there were no treatment-related
effects at 37.5 mg/kg/d. In a standard 2-year dietary
carcinogenicity study in F344 rats (20/sex/control
group and 50/sex/test group) administered doses of 0,
47 or 94 mg/kg/d PPD, a reduction of 12% and 20%
in body weight gain relative to controls was observed
at the top dose in males and females, respectively. No
other clinical signs of toxicity and no
histopathological abnormalities were seen. An
apparent no observed adverse effect level (NOAEL)
of 47 mg/kg/d was identified from this study. Deaths
(2/25) and significant reductions in body weight gain
(28-57%) were noted in pregnant rats administered
oral gavage doses of 30 mg/kg/d PPD on days 6-15 of
gestation. Body weight gain was also significantly
reduced (14-17%) over the dosing period at the lower
dose of 20 mg/kg/d. No effects were seen at 15
mg/kg/d and down to 5 mg/kg/d. A NOAEL of 15
mg/kg/d for repeated oral exposure in pregnant rats
was identified from this developmental study. Other
dietary studies in rats used lower doses of PPD and
add no further useful information. In a 90 day-study10,
specifically designed to assess the potential for
neurotoxicity, rats (10/sex/group) were administered
gavage doses of 0, 4, 8 or 16 mg/kg/d PPD. There
were no treatment-related changes in body weight
gains
and
feed
consumptions.
Also,
no
treatment-related effects were observed in any of the
functional observational battery and motor activity
HSE REVIEW 2001
PPD is mutagenic in bacteria in the presence of
metabolic activation. In vitro studies in mammalian
cells have yielded positive results for chromosomal
aberrations in the absence of exogeneous metabolic
activation, and also for mammalian cell gene mutation
(mouse lymphoma) both in the presence and absence
of metabolic activation. However, there is a large
body of studies in rats and mice indicating that PPD is
not mutagenic when tested in vivo. In a
well-conducted, standard micronucleus test, there was
no evidence of micronuclei formation in the bone
marrow of mice exposed intra-peritoneally up to the
highest dose of 100 mg/kg. At this dose, there was a
reduction of 33% in the PCE/NCE ratio indicating that
the bone marrow was exposed adequately. Additional
micronucleus tests in both the mouse and the rat
confirm this negative result. Also, negative results
were reported in a dominant lethal test in rats
administered intra-peritoneally 20 mg/kg PPD (which
was ¼ LD50) 3x/week for 8 weeks. Overall, it can be
concluded that there is sufficient evidence PPD is not
an in vivo mutagen.
No significant tumour findings were reported in a
standard 2-year dietary carcinogenicity study in which
F344 rats were administered doses of 0, 47 or 94
mg/kg/d PPD. In a similar study with B6C3F1 mice
(20/sex/control group and 50/sex/test group) given
dietary doses of 0, 94 or 188 mg/kg/d PPD, a
reduction of 10% in body weight gain relative to
controls was seen at the top dose only in females. No
changes in body weight gain and no other signs of
toxicity were observed in males. No significant
tumour findings were reported and no other
histopathological abnormalities were found. Negative
results have also been reported in an 80 week-study in
F344 rats (10/sex/group) given dietary doses of 0,
37.5 or 75 mg/kg/d PPD. No tumour findings were
observed in mice given dermal doses of 40 or 80
mg/kg twice per week for 130 weeks. These studies
together with other oral and dermal studies which do
not follow standard protocols, including a dermal
33
PROPOSAL TO RETAIN OES AND ADD SKIN NOTATION
study in rabbits, consistently show that PPD is not
carcinogenic in animals.
on the actual exposure to the para-isomer limits the
value of this report.
There are no studies investigating the potential effects
of PPD on fertility. However, given that long-term
studies in rats and mice have not demonstrated any
pathological changes in the reproductive organs, there
are no specific grounds to consider that PPD would
affect fertility.
There are no human data in relation to genotoxicity.
However, the animal evidence suggests it is unlikely
that PPD would be mutagenic in humans.
There are no adequate epidemiology studies that have
investigated the carcinogenic potential of PPD.
However, the findings from well conducted oral
carcinogenicity studies in animals suggest PPD would
not be carcinogenic in humans.
No developmental effects have been observed in rats
treated orally during gestation with PPD up to
maternally toxic doses.
There are no human data available in relation to
reproductive toxicity. However, given that no
pathological changes in the reproductive organs were
seen in repeated dose studies, it is unlikely that there
would be any concern for reproductive effects in
humans.
Human data
There are no data concerning the effects of single
inhalation or dermal exposures. Several case reports
describing the effects of accidental or intentional
ingestion of PPD have been published. Oedema of the
face and the neck, dyspnoea, hemolysis, necrosis of
the skeletal muscle, and renal failure (tubular
degeneration)
have
been
recorded.
Also,
methaemoglobinaemia (3.5%) has been reported in a
woman who ingested 40 ml of a 4% PPD solution.
This occurred together with other severe signs of
toxicity as described above.
BASIS FOR SETTING THE LIMIT
The toxicology assessment for PPD reveals no clear
evidence for occupational asthma, or for mutagenicity
or carcinogenicity. This suggests that, in principle, an
OES could be derived for PPD. However, there was a
lack of relevant toxicological information from which
to derive an OES value directly, with no meaningful
human data and no animal data concerning the effects
of repeated inhalation exposure. Nevertheless, from
the evidence available, WATCH agreed that exposure
to the pre-existing OES value of 0.1 mg.m-3 (8-hour
TWA) would not pose a significant risk to health.
Hence, WATCH agreed that a concentration of 0.1
mg.m-3 was appropriate as an OES (8-hour TWA).
It is well-established that PPD is a potent skin
sensitizer in humans, and is used as part of a battery of
allergens in clinical tests. Contact dermatitis has been
reported several times following occupational
exposure to dyes containing PPD. Cross-sensitisation
to various phenylenediamine isomers and other
aromatic amines has also been observed.
The apparent potency of PPD as a skin sensitiser
might raise concern as to whether this substance could
have the potential to cause occupational asthma. Early
reports of asthma in fur dyers exposed to PPD are
available, but no meaningful conclusions can be
drawn from these reports given the mixed exposures
to animal danders and dyestuffs which would have
occurred. There are no published reports of asthma
linked to PPD in hairdressers or other groups
occupationally exposed to this substance. Overall
therefore, there is no evidence to indicate that PPD is
a cause of occupational asthma.
There were no toxicological reasons to support the
need for a short-term (STEL) OES.
In view of the evidence for dermal penetration, and
given the potential for systemic toxicity, a ‘Sk’
notation was considered appropriate. In view of the
absence of clear evidence for occupational asthma, a
‘Sen’ notation was considered to be inappropriate.
In relation to whether a BMGV should be
recommended for PPD, there are methods for
measuring PPD and its metabolites in the urine, but
there are currently no data upon which to base either a
health guidance value (HGV) or benchmark value
(BMV). Furthermore PPD does not meet one of the
key criteria for recommending a BMGV i.e. a BMGV
for PPD would not be of practical value in the
workplace. Therefore, the development of a BMGV
was not recommended.
There are no adequate human data in relation to the
effects of repeated exposure. However, damage to
various organs such as liver atrophy, kidney vasculitis
and sensory disturbance has been reported in
association with chronic exposure to hair dyes
containing
PPD.
No
evidence
of
methaemoglobinaemia was found among 27 workers
involved in the manufacture of phenylenediamines
(ortho- meta- and para-isomers) exposed to a
maximum of 0.1 mg⋅m-3 phenylenediamines over a
period of 20 years. However, the lack of information
HSE REVIEW 2001
REFERENCES
1. Health and Safety Executive, General method for
the gravimetric measurement of respirable and total
inhalable dust, MDHS 14/3, HSE Books 2000, ISBN
0 7176 1749 1.
34
PROPOSAL TO RETAIN OES AND ADD SKIN NOTATION
2. Occupational Health and Safety Administration, US
Dept of Labour, m-, o- and p-Phenylenediamine,
Method 87, February 1991.
3. Health and Safety Executive, Aromatic amines in
air and on surfaces, MDHS 75, HSE Books 1993,
ISBN 0 11 886370 3.
4. British Standards Institution
Workplace
atmospheres - General requirements for the
performance of procedures for the measurement of
chemical agents,
European Standard
BS EN
482:1994, ISBN 0 580 23644 7.
5. British Standards Institution
Workplace
atmospheres - Size fraction definitions for
measurement of airborne particles,
European
Standard BS EN 481:1993, ISBN 0 580 221407.
6. Goetz, N., Lasserre, P., Bore, P., and Kalopissis, G.
(1988)
Percutaneous
absorption
of
p-phenylenediamine during an actual hair dyeing
procedure. International Journal of Cosmetic Science,
10, 63-73.
7. German Chemical Society-Advisory Committee on
Existing Chemicals of Environmental Relevance
(BUA). Phenylenediamines (1,2-Diaminobenzene,
1,3-Diaminobenzene, 1,4-Diaminobenzene). BUA
report 97 (June 1992). S. Hirzel. Wissenschaftliche
Verlagsgesellschaft Stuttgart, Germany. ISBN
3-7776-0647-2.
8. Unpublished. Aurgess, B.A. (1982) Initial
submission: inhalation median lethal concentration
toxicity study with 1,4-benzenediamine in rats with
cover letter dated 06/15/92 and attachments. E.I.
Dupont de Numours & Company, Haskell Laboratory
for Toxicology and Industrial Medicine, Newark,
NTIS OTS 0540657, EPA Document No.
88-920004309.
9. Unpublished. Driscoll, C.D. (1990) Acute oral
neurotoxicity studies of para-, meta-, and
ortho-phenylenediamine in rats with cover letter dated
09/17/90. E.I. Dupont de Numours & Company,
Haskell Laboratory for Toxicology and Industrial
Medicine, Newark, NTIS OTS 0528739, EPA
Document No. 40-9036454.
10. Unpublished. Lochry, E.A. (1992) Subchronic oral
neurotoxicity study of ortho-, meta-, and
para-phenylenediamine in rats with attachments and
cover letter dated 06/30/92. E.I. Dupont de Numours
& Company, Haskell Laboratory for Toxicology and
Industrial Medicine, Newark, NTIS OTS 0572976,
EPA Document No. 40-9236508.
HSE REVIEW 2001
35
PROPOSAL TO WITHDRAW OES
Liquid formulations of subtilisin for all uses tend to be
stabilised with an additive which decreases the vapour
pressure.
SUBTILISINS
Notation:
Work practices in the soap detergent industry include
a high degree of automation, containment, engineering
control and use of PPE to control residual risks. The
potential for inhalation and dermal exposure is likely
to arise during the handling and tipping of dry and
liquid concentrated enzyme formulations and the
packing of dry product. However, the liquid-handling
processes are unlikely to generate aerosol and the
volatility and dustiness of the materials will be low.
About 1400 people are potentially exposed to subtilisin in the soap detergent industry, with exposure
generally kept below 15 ng.m-3.
Sen
Subject to consultation
IDENTITY AND PROPERTIES
CAS No: 1395-21-7 (Bacillus subtilis BPN)
9014-01-1 (Bacillus subtilis Carlsberg)
In the preparation of animal feeds, the potential for
inhalation and dermal exposure to subtilisin will occur
during filling the liquid reservoir, weighing and
addition of the dry enzyme concentrate formulation,
plant operation, QA sampling and lorry loading.
However, the processes are unlikely to generate
aerosol and the dustiness of the materials will be low;
three-quarters of the final product will be in pelletised
form. It is estimated that up to 1,000 people may be
potentially exposed to the 0.5% subtilisin concentrate
during weighing and/or tipping, and up to 15,000
exposed to the “downstream” animal feed containing
subtilisin at about 0.0005%.
Enzyme Commission No: EC.3.4.21.62
Synonyms and Trade names: Subtilisin Carlsberg,
Subtilisin A, Subtilopeptidase A, Subtilisin BPN,
Subtilisin B, Subtilopeptidase B, Subtilopeptidase C,
Alcalase, Savinase, Maxatase, Esperase, Biozym,
Milezyme, Opticlean.
Molecular weight: Approx 28,000
Subtilisin (9014-01-1) is classified under the Chemicals (Hazard Information and Packaging for Supply)
Regulations 1994 (CHIP) as irritant and sensitising to
be labelled with the risk phrases:
R37/38: Irritating to the respiratory system and skin.
Subtilisin is used in food processing to hydrolyse soya
bean, gelatin and yeast. Up to 25 tonnes of the enzyme
is used annually for these applications with concentrations of up to 10% enzyme. The potential for inhalation and dermal exposure to subtilisin will occur at the
point of dispensing the enzyme and adding to the
broth. However, the processes are unlikely to generate
aerosol and the dustiness of the materials will be low.
It is estimated that less than 50 people may be potentially exposed to the enzyme during food processing.
R41: Risk of serious damage to eyes.
R42: May cause sensitisation by inhalation.
OCCURRENCE AND USE
Subtilisin is not manufactured in Great Britain but is
imported by a handful of major suppliers. It is
estimated that, annually, up to 100 tonnes of the
enzyme is imported contained in up to 5,000 tonnes of
granulated powder, wheat substrate or liquid formulation with a concentration of subtilisin up to 10%.
Subtilisin is used in the manufacture of detergents and
animal feeds; also for food and leather processing.
Within leather processing, the potential for exposure
to subtilisin will occur at the point of weighing the
enzyme concentrate formulation and addition to the
drum. However, the dustiness of the substances will
be low. It has been estimated that less than 40 workers
are exposed to subtilisin during leather processing.
EXPOSURE
Subtilisin for soap detergent use is imported as granulates, liquids or slurries. The dustiness of the dry
product is controlled by “encapsulating” the enzyme
in a coarse granule (>150µ) of phosphate base using a
tacky non-ionic detergent. The enzyme is made even
less dusty by forming “prills” which are beads
containing enzyme embedded in a non-dusty matrix.
The result is non-dusty solid beads containing up to 5
% enzyme.
HSE REVIEW 2001
MEASUREMENT
Workplace air monitoring
The standard analytical method for measurement of
airborne enzyme is that based on the reaction of the
enzyme with N,N-dimethylcasein (Fulwiler et al.,
1972; Dunn and Brotherton, 1971). Air samples are
collected via a static high volume sampler - the Galley
Sampler (Soap and Detergent Industry Association,
1971; Soap and Detergent Industry Association,
1991). The sampled dust is collected onto desiccated
and weighed 150 mm glass fibre filter papers (Type
36
PROPOSAL TO WITHDRAW OES
values of 130 or 229 mg.m-3 were obtained in the rat
for two other subtilisin preparations. Subtilisins are of
low oral toxicity on single exposures. The systemic
effects of single dermal exposures have not been
studied but given the predicted lack of dermal absorption, systemic toxicity would not be anticipated by this
route.
GF/C). Sampling times of at least 1 hour are required
to ensure the collection of enough sample for analysis.
Sampling can be undertaken using low volume
personal samplers such as described in MDHS 14/2
(Health and Safety Executive, 1997) but sampling
times of 6 to 8 hours are required and then sampling is
some 20 to 60 times less sensitive. The filters are
extracted with a volume of sodium sulphite solution
and reacted with N,N-dimethyl casein. The reaction is
allowed to proceed for a fixed time under controlled
conditions (in a continuous flow analyser). Amino
acids liberated by the action of the protease enzyme
react with 2,4,6-trinitrobenzenesulphonic acid
(TNBSA) to form coloured complexes. To allow for
colour produced by non-enzymatic materials present
in the dust a blank determination is required following
deactivation of the enzyme in the sample by heating to
95ºC.
Mild erythema and oedema was observed in skin
irritation tests with concentrated subtilisin preparations and there is clear evidence to show that subtilisin
enzyme preparations are irritant to the eye. There is no
evidence to suggest that subtilisins have sensory
irritant properties.
In relation to skin sensitisation, very little testing has
been conducted in animals; an apparently positive
result was obtained in a single study in guinea pigs.
However, there are doubts about whether the skin
reactions observed were irritant or allergic in nature
and this “positive” finding has not been confirmed in
other animal studies. There is no useful information
concerning the effects of repeated inhalation exposure
to subtilisins in animals. However, results from single
exposure studies suggest that on repeated inhalation
exposure, chronic inflammatory damage could occur,
caused by the localised proteolytic activity of these
enzymes. Oral dosing studies in rats suggest that with
repeated high doses, local gastro-intestinal disturbances can occur, but this has no obvious relevance to
occupational exposure conditions. The only predicted
effects of repeated dermal exposure would be for local
skin irritation.
Biological Monitoring
There are no published methods available for the
biological monitoring of exposure to subtilisin.
TOXICOKINETICS
No toxicokinetics studies are available. However, the
following aspects of toxicokinetic behaviour can be
predicted. The subtilisins are high molecular weight
water soluble proteins that may be present in the
workplace either as a dry powder or in a liquid preparation. If inhaled, the large molecular size of these
enzymes would minimise the potential for absorption
directly across the respiratory tract epithelium.
However, their proteolytic activity may enable these
enzymes to damage the epithelial barrier in the lung
thus increasing their potential for direct absorption. If
deposition in the alveolar lung occurred then it is
likely that the subtilisins will be phagocytosed by
macrophages and broken into smaller peptides by
proteolytic enzymes within lysosomes. Orally administered subtilisins will be subject to the same digestive
processes as any other protein. In relation to dermal
exposure, it is considered that absorption across intact
skin would be precluded by the large molecular size of
the molecule.
Negative results were obtained in Ames tests with two
subtilisin preparations, and in vivo tests in somatic and
germ cells were negative for one preparation. The
results support the conclusion that subtilisins are not
genotoxic. No studies have been conducted to investigate carcinogenic potential but this would not be
predicted for this class of substance. No studies have
been conducted to investigate reproductive toxicity.
Reproductive effects would not be anticipated as
systemic distribution to the reproductive organs is not
likely to occur via occupational routes of exposure.
Studies in humans
There are no human data on the systemic effects of
single exposures to subtilisins.
HEALTH EFFECTS
In human volunteer studies aqueous solutions containing up to 20% of a concentrated subtilisin preparation
were not irritant to intact skin but were irritant to
damaged skin. Workers directly handling concentrated
enzyme preparations reported skin problems mainly
on the fingertips, wrist and neck but the role of
subtilisins in causing these problems has not been
adequately explored.
Studies in animals
Single exposure inhalation studies in animals indicate
that subtilisins are toxic via the inhalation route,
causing direct effects on the lungs, haemorrhage,
congestion and oedema, probably reflecting the proteolytic activity of these enzymes. Guinea pigs appeared
to be more sensitive than rats or rabbits, with mild
microscopic changes reported in the lungs at 0.1
mg.m-3 enzyme. However, no changes were observed
in rats or rabbits at this concentration. Four-hour LC50
HSE REVIEW 2001
37
PROPOSAL TO WITHDRAW OES
sufficient to control exposure, and no suitable
methods are available for biological monitoring of
exposure to subtilisins
Extensive patch testing in large-scale human volunteer
studies has shown no evidence for the ability of
subtilisins to induce skin sensitisation. Negative
results have also been obtained in patch tests in
subtilisin-exposed
workers.
Furthermore,
no
confirmed cases of skin sensitisation caused by
subtilisins have been identified in workers engaged in
the manufacture/use of these enzymes. Overall, human
evidence suggests that subtilisins should not be
regarded as skin sensitisers.
REFERENCES
Dunn, E. and Brotherton, R. (1971)
The use of NN-dimethylcasein in the determination of
proteolytic enzymes in washing products and airborne
dust samples
Evidence from bronchial and nasal challenge studies
in detergent workers shows that subtilisins can cause
occupational asthma and allergic rhinitis. When
subtilisins were first introduced into the detergents
manufacturing process there were a large number of
cases of occupational asthma attributed to these
enzymes each year (7-39 before 1975). It is likely that
all of these cases were due to subtilisins as these were
the only enzymes used in detergent manufacture over
that time period. Since then, hygiene conditions have
improved, and there has been a corresponding drop in
the number of cases of detergent enzyme-related
asthma per year (0-4 since 1980). No personal
exposure data are available and there is no
information concerning the exposure-response
relationships for subtilisin-induced asthma/allergic
rhinitis. Other than occupational asthma and allergic
rhinitis, a large body of health surveillance data in
detergent workers reveals no evidence for other
adverse health effects relating to the use of subtilisin
preparations.
Analyst 96, 159-163
Fulwiler, R.D., Abbott, J.C., and Darcy, F.J. (1972)
Evaluation of detergent enzymes in air
Am Ind Hyg Ass J 33, 231-236.
Health and Safety Executive (1997)
General methods for the gravimetric determination of
respirable and total inhalable dust
HMSO, UK MDHS 14/2
Soap and Detergent Industry Association (1991)
The Standing Committee on Enzyme Washing
Products. Revised Operating Guidelines.
Fifth report Soap and Detergent Industry Association,
UK
BASIS FOR SETTING THE LIMIT
The key health concerns for subtilisins are their
potential to cause occupational asthma and allergic
rhinitis. The available data do not allow a threshold
for the induction of these conditions by subtilisins to
be identified nor is it possible to determine what the
exposure-response relationship might be. On this basis
WATCH consider that subtilisins do not meet the
criteria for the establishment of an OES. Hence, the
current OESs for subtilisins are not scientifically
sustainable. In view of the potentially serious nature of
occupational asthma, subtilisins meet the criteria for
the establishment of MEL(s). Since both long-term
repeated exposures and short-term peak exposures
may be of relevance to the induction of occupational
asthma and allergic rhinitis, both 8-hour TWA and
STEL MELs should be established.
In relation to other risk management measures, given
that there is clear evidence that subtilisins are a cause
of occupational asthma, an OEL for subtilisins should
be accompanied by a “Sen” notation. As dermal
absorption is not an issue, a “Sk” notation is not
warranted. Subtilisins do not meet the criteria for
establishing a BMGV because the lack of dermal
absorption indicates that an airborne limit will be
HSE REVIEW 2001
38
ANNEX 2
EXPLANATORY NOTE - COST BENEFIT ASSESSMENT METHODOLOGY FOR
REGULATORY
IMPACT
ASSESSMENT
AND
APPLICATION
TO
OCCUPATIONAL EXPOSURE LIMITS: AN OVERVIEW
1.
It is Government policy that the costs of all new or revised regulation must be
assessed. Since 1982 the Health and Safety Commission (HSC) has required cost benefit
assessments (CBAs) to be undertaken for all major proposals for health and safety
regulations unless the costs resulting from their introduction are negligible. This approach has
also been extended to the consultation period for Occupational Exposure Limits (OELs).
Since October 1998, costs and benefits are discussed in the regulatory impact assessment
(RIA) framework.
2.
The complexities of applying CBA/RIA methodology to occupational ill-health issues
as opposed to accident prevention mean that the results need to be considered with particular
caution. The uncertainties resulting from imperfect information on the cost of controls, and
validation of exposure compliance data can be more pronounced in relation to health issues,
so that estimates of the costs often need to be viewed as rough estimates. The extent of
uncertainty will vary according to each substance and the availability of accurate information.
3.
On the other side of the scale, quantifying the benefits of an OEL also poses some
particular problems. Quantification is normally based upon how far the OEL reduces the risk
to employees exposed using dose-effect information. However, for substances such as
carcinogens the dose-effect relationship is commonly not established, and alternative ways of
deriving a monetary value to represent the benefits of setting OELs have been developed.
4.
In addition, there are a number of underlying benefits that can accrue from the
introduction of an OEL and lead to more general improvements in worker protection but
cannot easily be quantified. Such benefits are often less tangible, longer term, or relate to the
general principles of introducing an OEL rather than to its specific level. They may also lead
to consequential improvements in productivity, reduction in product loss and improvements
in employee recruitment and retention, some of which are difficult to quantify. These
potential benefits include factors such as:
39
v Defining a level playing field for all users.
v Defining adequate control.
v Providing clearer guidance on the level considered to be reasonably practicable.
v Providing a standard for new users.
v Reducing/ limiting scope of 'discretion' by enforcing authority.
v Providing consistency with international developments.
v Reinforcing/ improving good practice.
v Encouraging/ stimulating proper reporting of ill-health.
v Promoting more effective health surveillance.
v Reducing ambient air contamination generally.
5.
The Health and Safety Commission's Advisory Committee on Toxic Substances
(ACTS) takes such uncertainties and potential benefits into consideration when discussing
and agreeing proposals for OELs. It fully recognises that CBA is an aid to decision-making.
During the process of deciding on the proposal for an OEL, ACTS will consider the
CBA/RIA and the existence of the potential benefits, and will make a recommendation in the
context of its responsibilities for employee health protection, and the provision of help to
industry in risk management. The CBA/RIA provides a tool which enables HSC to make
decisions based on a knowledge of available factors including the socio-economic impact of
the proposed OEL. It is not, however, the over-riding determining factor.
.
40
ANNEX 3
MEL PROPOSALS:
SUMMARY COMPARISON OF COSTS AND BENEFITS
Substance
Summary of RIA
Chloroethane
There is very limited use of chloroethane in the UK. Uses
include as a chemical intermediate and as a local anaesthetic
Up to 10,000 workers may be exposed, including: Health
Services and related users (around 7000 workers) and
chemical manufacturing (50 - 100 workers). Other uses
include dental practices, chiropodists, veterinary surgeries,
tatooists and body piercers. If chloroethane is carcinogenic in
humans reductions in exposure should be connected with a
reduced incidence of ill-health. However, the evidence is
not available to quantify the benefits of this proposed
reduction in the OEL.
The quantifiable total costs to industry and services if the
limit was set at 50 ppm 8-hour TWA would amount to
between approximately £61,000 and £78,000, largely as a
result of initial assessment review and sampling
requirements to determine compliance with MEL. Costs per
worker are estimated at £6 - 16 for a MEL at 50 ppm. This
is at the lower end of the range of costs per employee for
several other substances of genotoxic concern.
Hydroquinone
Up to 5000 people are estimated to be occupationally
exposed to hydroquinone, however only about 1060 of these
incur exposure by inhalation of hydroquinone (in powder
form). Business sectors potentially affected by implementing
a MEL include: photographic/imaging product manufacture
and product use; chemicals industry (including
polymerisation inhibitors, manufacture of fine chemicals,
rubber, thermoplastic polymer, resin, surface coatings, inks);
plate making in printing; use of printing ink; and paint
surface coating spraying. In the opinion of the Committee on
Mutagenicity, occupational exposure is associated with a risk
of mutagenicity, but it is not possible to quantify that risk.
Reducing exposure would be expected to reduce risk.
However, the evidence is not available to quantify the
benefits of this proposed reduction in the OEL.
Cost savings of around £0.6 - £0.8 million over 10 years, in
present value terms are envisaged in the industry sector from
installation of LEV, which will make RPE obsolete. The
quantifiable total net costs to industry and services if the
limit was set at 0.5 mg.m-3 (8-hour TWA) would be around
41
£2.6 million over 10 years, in present value terms and the
costs per worker would be about £2500. This is higher than
past MELs for other carcinogenic substances.
Manganese and its inorganic
compounds
Between 65,000 and 90,000 employees are occupationally
exposed to manganese. The highest exposures are found in
steel making (1000 - 1500 workers), casting and finishing
manganese steel (~30,000 workers), welding manganese
steel (estimated to be 30,000 - 40,000 workers), trace
element fertiliser manufacture and animal feed supplement
premix manufacture (~200 workers). Other exposures are to
farm workers; in cosmetics formulation; battery
manufacture; the manufacture of other potassium
compounds, including potassium permanganate, manganese
octoate and manganese acetate; potassium permanganate use
in metal cleaning and printed circuit board manufacture; and
manganese octoate and manganese acetate use in
manufacture of inks and paints and in catalysis. Health
benefits arising from a MEL would be a reduction in the risk
of neurological effects. Although cases of manganism (a
neurological syndrome characterised by lack of motor
co-ordination, gait disturbance and physcological features
such as mania) are rare nowadays, workers exposed to lower
levels of manganese may still experience a fine tremor when
undertaking controlled hand-arm movements and may
perform less well in cognitive tests. Neurological changes
can be irreversible. Benefits associated with a MEL of 0.5
mg.m-3 Mn are estimated to be £ 127 million.
Of the 13 business sectors considered 7 incurred costs for the
0.5 mg.m-3 MEL proposal. The costs to industry overall in
complying with a MEL of 0.5 mg.m-3 (8 hour TWA) are
estimated to be £8 - 30k. Because some quantification of
benefits has been made costs per worker have not been
calculated. Initial consultation indicates that a MEL of 0.5
mg.m-3 (8 hour TWA) would be achievable but would have
significant cost implications for steel making/casting and
metal finishing/welding/mineral supplement, premix and
trace element fertiliser manufacture/battery manufacture.
42
ANNEX 4
Metal Working Fluids (MWF) - Summary of ACTS/WATCH position
New information from a Technical Development Survey and its implications for occupational
exposure limits and other risk control indicators for metalworking fluids (MWFs) were
discussed by ACTS at its meetings in July 1999 and March 2000. A revised wording of the
definition of mineral oils and mists, effectively excluding metal working fluids, for inclusion
in EH40, was agreed by ACTS in July 2000.
The OES for mineral oil mists has been on the programme of reviews for consideration by
WATCH since 1994. An exposure limit at the OES values of 5 mg m-3 (8-hour
time-weighted average) and 10 mg m-3 (short-term limit) has been in place since the
American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit
Values (TLVs) were adopted as guidance values in the 1960s.
Recent technological developments meant that other substances including water mix
formulations needed to be included in the definition of Metalworking Fluids (MWF). The
health hazards and other technical issues to be addressed in the review were agreed by
WATCH in January 1995, and these were incorporated into a Technical Development Survey
(TDS) of metalworking carried out by HSE staff.
MWFs are estimated to be used in over 50,000 workshops and are used as lubricants/coolants
for the machining of metal parts. They vary in composition and the main health concern is
from skin contamination by the fluids, though there are respiratory issues as well. Potential
health risks arise both from components of the fluids and from contaminants occurring during
use. Poor fluid management was found in many of the workshops visited and over half had
reported health issues. MWFs can cause dermatitis and have been linked to occupational
asthma. Historically there have been concerns over cancer from MWF exposure. Modern
formulations have changed and there is little data on previous MWF formulations.
At its meeting in July 1999 ACTS considered the findings of the TDS and agreed that the best
strategy was to produce guidance on how to improve control measures and maintenance of
43
fluids. Guidance would aim to be user friendly for small businesses and should be linked into
the control guidance sheets in COSHH Essentials.
The following points were made in discussion:
Ÿ the definition of MWFs did not include quenching fluids but could include fume and
smoke (produced when fluid flow is too low) and mists.
Ÿ guidance could include an indicative value of what was achievable by good practice;
ACTS could endorse such a value outside the OEL framework.
Ÿ a full toxicological review covering all components was impracticable, but the
occurrence of respiratory sensitisation would be followed up; HSE were aware of nine
reported cases during 1998 of respiratory effects from exposure to coolant and lubricant
fluids and mists, but this was likely to be an under-estimate.
Ÿ the mineral oil mist OES should be retained because it had applications not related to
MWFs, but proposals could be made for revising the definition of scope in EH40. The
current limit was however not really helpful in the context of MWFs as a concentration of
5 mg m3 was often achievable without a full use of the available control measures.
Ÿ ACTS noted that part of the difficulty was that under the current OEL framework the
criteria for an OES were not met but it would be hard to justify a MEL.
Ÿ in principle, an OEL could be set for complex mixtures, and MWF can be measured as
an entity, but the rationale for doing so is weak as the formulations varied and could
change frequently.
All members agreed the need for improved control of MWFs including the proposed
guidance. In addition, further work should examine whether separate OELs could be set for
some contaminants. Consideration should also be focused on the potential to set generic
limits for water-mix and oil-based fluids.
In March 2000 ACTS considered an extract from the proposed draft guidance and noted the
different health and safety issues for water-mix and mineral oil MWFs. The two types of limit
would be approached separately and the guidance would include sections giving information
on best practice limits for both types. The guidance would also give advice on sump fluid
management which was where it was felt the key problem lay. It was noted that the British
44
Lubricants Federation (BLF) would be setting up a product stewardship scheme and HSE’s
guidance could be distributed through the BLF.
Members agreed that where an OES was to be disapplied and replaced by guidance an
evaluation of the impact of this would be beneficial. One member suggested it would be
helpful if the proposed guidance included handling of contaminated swarf.
Overall, ACTS concluded that there was not sufficient justification for setting a MEL for
either type of MWF because there was insufficient evidence of a link to severe health effects;
no OEL could be set for water-mix MWFs; and mineral oil MWFs should be removed from
the mineral oil mists OES as this hindered proper enforcement in this sector.
One ACTS member asked to see a caveat that the OES for mineral oil mists should only
apply to highly refined and pure mineral oil mists to reflect that the OES should not cover
fluids containing additional agents including impurities introduced during use. The member
suggested revising the relevant paragraph in EH40. Members felt that this needed further
consideration and agreed to review and amend the text by correspondence. The revised
wording for inclusion in EH40 was subsequently agreed at the July 2000 meeting.
The proposed new guidance is scheduled to be published in August/September 2002.
Following publication HSE will undertake an evaluation of the impact of this new guidance
and report the findings back to ACTS.
45
NOVEMBER 2001
CHAN 25
ANNEX 5
CHEMICAL HAZARD ALERT NOTICE
SULPHURIC ACID MIST
This guidance provides information on the health effects associated with exposure to
sulphuric acid mist at work. It also gives advice on good practice, which employers,
users and suppliers may find helpful in considering what they need to do.
Why issue a chemical hazard alert notice (CHAN)?
Sulphuric acid currently has an Occupational Exposure Standard (OES) of 1 mg.m-3,
8-hour time weighted average (TWA). This limit was established some years ago.
The aim of this alert notice is to focus attention on situations where the acid mist is
generated.
Recently, the European Sulphuric Acid Association commissioned new research on
sulphuric acid, a report of which was referred to the Health and Safety Executive
(HSE) in December 2000. The results of the research suggest that the present OES
of 1 mg.m-3 may not protect against chronic inflammation in the larynx (vocal
chords). There is also a question over whether this chronic inflammation can
predispose an individual to developing cancer in the larynx and upper respiratory
tract. In the light of the evidence available, HSC’s Advisory Committee on Toxic
Substances (ACTS) considers that the present OES may not adequately protect
workers’ health. ACTS will therefore recommend to HSC that it consults on the
withdrawal of the current OES in the next Occupational Exposure Limit (OEL)
consultation exercise, with a view to withdrawing it from 2003. It will take time to
agree a new OEL and this guidance provides interim advice and information to
suppliers, employers and users.
This guidance is issued by the Health and Safety Executive.
Following the guidance is not compulsory and you are free to take
other action. But if you do follow the guidance you will normally be
doing enough to comply with the law.
46
NOVEMBER 2001
CHAN 25
For substances where no exposure limit is set, employers should determine their
own working practices and in-house standards for control so that repeated exposure
does not cause ill-health. In the case of sulphuric acid mist, the National Sulphuric
Acid Association has recommended to member companies that ‘in-house’
occupational exposure levels should be reduced to ‘below 0.3 mg.m-3’ (8-hour TWA)
in order to control against inflammation - see Further help below. Thus this CHAN
advises that the existing OES is too high.
HSE plans to take up with a European committee(1) the question of whether the
information on sulphuric acid mist would be sufficient to match the criteria for a
carcinogen in the Carcinogens Directive. A recommendation may emerge on which
to base a proposal for an occupational exposure limit across the European Union.
Thus by 2002 it should become clearer what type and level of exposure limit is
appropriate for sulphuric acid mist. This CHAN would then be revised and it may
also be possible for the revised CHAN to offer further control advice.
What is sulphuric acid? - The pure acid is a corrosive liquid. It is mainly used
diluted to a variable extent with water. It is a strong acid which, under many
conditions of use, will form a fine mist that can remain airborne.
Where is it used? - Sulphuric acid is used in a wide variety of industries including
the extraction, fabrication and finishing of metal, acid cleaning (pickling),
electroplating, fertiliser production, battery manufacture and various segments of the
petroleum, chemical and petrochemical industries.
What is the key health hazard? - The key health hazard of exposure to sulphuric
acid is its corrosive effect, which will be seen following any contact with strong
solutions of the acid. Inhalation of the mist will cause severe irritation of the lungs
and throat and, in severe cases, may cause pulmonary oedema (fluid build up on
the lungs). Repeated exposure to lower concentrations of the mist may lead to
damage to the lining of the throat in the region of the larynx. It is possible that this
effect might lead to an increased risk of developing cancer of the larynx.
How does it get into the body? - The main route of exposure is by breathing in the
fine airborne mist.
What should suppliers do? - You should ensure that the information contained in
this notice is passed on to your customers as required by the Chemicals (Hazard
Information and Packaging for Supply) Regulations 1994, as amended. You should
take steps to review your safety data sheets to reflect the new findings.
What should employers do? w You should give priority to preventing your employees being exposed to
sulphuric acid by breathing in mist or aerosol particles.
1
The Scientific Committee on Occupational Exposure Limits (SCOEL)
47
NOVEMBER 2001
CHAN 25
w Where preventing exposure to sulphuric acid mist is not reasonably
practicable (e.g. by using a different substance), then you should
adequately control exposure by a combination of engineering and process
control measures. HSE recommends that, although the legal obligation
is to reduce exposure to the OES while it remains in force, it would be
prudent for you to control exposure to as low a level as is reasonably
practicable below the OES.
w Once the OES is withdrawn, your legal obligation under COSHH remains to
achieve adequate control. Since a safe level of exposure cannot be
determined it remains our recommendation that you should control mist
exposure to below 0.3 mg.m-3 (measured as sulphuric acid) to be
consistent with advice from the National Sulphuric Acid Association.
w In dealing with exposure, whether before or after the OES is withdrawn,
you should try to reduce the number of people exposed and the length of
time each is exposed as required by good hygiene practice.
w You must give all your employees who are, or who may be, exposed to
sulphuric acid mist sufficient information, instruction and training to
understand the potential problems and the precautions they need to take.
w You should make sure that employees, safety representatives or
representatives of employee safety are aware of this information and
consult on any action that you propose to take as a result.
What should employees do?
w You must co-operate with your employer in using the control measures
(such as ventilation and personal protective equipment) provided and
reporting any defects found in the control measures.
w You may wish to seek the advice of your safety representative or
representative of employee safety.
Further help: Contact HSE’s InfoLine Telephone: 08701 545500
Please note: The National Sulphuric Acid Association (tel. 01244 322200) has
issued a communication to UK manufacturers of sulphuric acid for cascading to their
customers. This offers helpful advice on measuring exposure to sulphuric acid mist.
48
ANNEX 6
THE HEALTH AND SAFETY COMMISSION'S POSITION ON
IMPLEMENTATION OF INDICATIVE OCCUPATIONAL EXPOSURE LIMIT
VALUES (IOELVs)
Where WATCH disagrees with SCOEL and recommends a substantially different
limit to the IOELV on scientific grounds, acceptance of this recommendation would
be vulnerable to challenge by the European Commission.
However a substantial divergence from the IOELV could be justified if it is based on:
w
Scientific evidence which postdates that used as the basis for the IOELV;
and/or
w
Significant scientific evidence that has been overlooked by SCOEL;
and/or
w
Evidence from SCOEL as to the effect of their preferred number system;
and/or
w
Grounds of reasonable practicability ie industry is unable to comply with
the IOELV that has been set; and/or
w
Clear evidence, sufficiently robust to be relied upon, that SCOEL had
failed to observe their own guidelines or had set a limit which did not
have any reasonable foundation.
Other factors may emerge over time. With respect to the last bullet point, it will be
very difficult to find any justification for a substantially different limit where SCOEL
have arrived at a recommendation which it was reasonable to reach on the basis of
the evidence before them.
49
ANNEX 7
RESPONSE FORM
Control of Substances Hazardous to Health 1999
Proposals for Maximum Exposure Limits,
and Occupational Exposure Standards
We would like you to tell us what you think about the proposals set out in this
consultative document. The proposals are summarised below in this reply form
which you may wish to copy or tear out and use. Please add extra sheets if you
wish.
Name of organisation or company:
Name of individual:
Address:
.......................................................................
.......................................................................
.......................................................................
.......................................................................
.......................................................................
Telephone number:
Question
1. Do agree with the 8 hour TWA MEL
Comment
proposal for chloroethane?
If you disagree, please explain why
If you think a limit higher than the IOELV
should be set, please explain which of
the criteria in Annex 6 are met and
provide any relevant evidence.
50
2. Do agree with the 8 hour TWA MEL
proposal for hydroquinone?
If you disagree, please explain why
3. Do agree with the 8 hour TWA MEL
proposal for manganese and its
inorganic compounds?
If you disagree, please explain why.
4. Do you agree with the proposal to
remove the current OES for subtilisins?
If you disagree, please explain why.
5. Do you agree with the proposal to
remove the current OES for sulphuric
acid?
If you disagree, please explain why.
6. Do you agree with the proposals to
remove the current OESs for
2,3-epoxypropyl ethers (glycidyl
ethers)?
If you disagree, please explain why.
51
7. Is there any residual significant use
of 2,3-epoxypropyl ether (glycidyl
ethers) in the UK?
If so, please give details.
8. Do you agree with the proposals to
retain the current OESs for
p-phenylenediamine and introduce a
‘Skin’ notation?
If you disagree, please explain why.
9. Do you agree with the proposal to
exclude metal working fluids from the
OES for mineral oil mists, and to include
the revised text for EH40 defining the
scope of the OES?
If you disagree, please explain why.
10. In your view how well does this
consultation document represent the
different policy issues involved in this
matter? [Tick one box]
11.
Is there anything you particularly
liked or disliked about this consultation?
(Please add extra sheets if you wish.)
52
q
q
q
q
Very Well
Well
Not Well
Poorly
Please return to:
Laura Whitford,
Health Directorate, Chemicals Policy Division,
Health and Safety Executive,
6th Floor, South Wing, Rose Court,
2 Southwark Bridge,
London SE1 9HS
email: [email protected]
Please note: All views will be placed in HSE Information Centres unless you
specifically state that this response, or a part of it, should be treated as confidential.
53
Printed and published by the Health and Safety Executive
C30 1/98
54
CONSULTATIVE
DOCUMENT
The full text of this and other Consultative Documents can be viewed
and downloaded from the Health and Safety Executive web site on the internet:
www.hse.gov.uk/condocs/
Consultative Documents are available from:
HSE Books, PO Box 1999
Sudbury, Suffolk CO10 2WA
Tel: 01787 881165
Fax: 01787 313995
Printed and published by the Health and Safety Executive
© Crown copyright 2002
CD182 C35 03/02