The Evolution of Antimicrobial Quaternary Ammonium Compounds
The Evolution of Antimicrobial Quaternary
Ammonium Compounds
(QAC’s OR Quats)
Single Chain, Twin Chain, and Formulated Blends
Presentation Scope
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The focus of this presentation is to increase awareness of QAC and
QAC blends and their potential for application in the poultry industry.
No attempt has been made in this presentation to compare individual
poultry industry hygiene products.
Product names and brands have been avoided.
Why consider QACs?
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A wide rand of chemical-based, microbial control products and
strategies are currently available to the poultry industry..
In terms of human & animal toxicity and materials compatibility, QACbased products arguably represent on of the lower risk, more userfriendly options.
What is a Quaternary Ammonium Compound?
R2
I
R1---N+---R3
I
R4
In its generic form, a QAC is and organic compound that contains at least one
cationic (positively charged) nitrogen atom, often referred to as the
“quaternary nitrogen atom”.
Suggested QAC mode of Action – Bacteria/Fungi


Adsorption onto, and diffusion through the cell wall*.
Binding to, and disruption/ disorganisation of the cytoplasmic
membrane.
 Release of low molecular weight cytoplasm constituents.
 Degradation/ prescription of cell contents (eg proteins, nucleic acids).
 Wall lysis by autolytic enzymes leading to cell death.
*In the case of lipophilic viruses, QACs are presumed to be attracted to the
protein/ lipid envelope
General Susceptibility of Microbes to Antimicrobials
(Decreasing order of Resistance)
1. Spores (e.g. Clostridium botulinum)
2. Mycobacteria (e.g. Mycobacterium avium – Avian TB)
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The Evolution of Antimicrobial Quaternary Ammonium Compounds
3. Non-enveloped viruses (e.g. Infectious Bursal Disease Virus, Duck
Viral Hepatitis)
4. Fungi (e.g. Candida, Aspergillus sp)
5. Gram negative bacteria (e.g. Salmonella sp)
6. Gram positive bacteria (e.g. S. aureus)
7. Enveloped viruses (e.g. NCD, Avian Influenza Viruses)
Adapted from Block, 2001
Spectrum of Animicrobial Activity

Commercial antimicrobial QAC raw materials are active towards
vegetative bacteria, enveloped viruses (e.g. Avian Influenza, Newcastle
Disease, Herpes, HIV) and most yeast and moulds.
 On their own, these compounds show relatively poor activity against
spores, Mycobacteria, non enveloped viruses (e.g. Polio, Coxsackie),
certain moulds (e.g. Aspergillus sp) & certain gram negatives (eg
Pseudomonas sp).
-They need to be formulated with other ingredients to promote or boost
activity against these more intrinsically resistants groups of
microorganisms.
Antimicrobial QAC Origins
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Jacobs et al 1916- published 3 papers describing the antimicrobial
activity of a range of synthesized QACs.
Domagk 1935 – Reported on the improved antimicrobial activity of
QACs when a long chain alkyl-group was attached to the
quaternary nitrogen atom (ie increased lipophilic character).
First QAC based products appreaerd in the 13th ed. Of the US
Pharmacopeia (1949) and in the British Pharmacopoeia in 1951.
By 1952 over 500 articles on the QAC’s has been published.
Researched into the properties of these compounds has continued
through to today. Many different types of antimicrobial QACs and
blends have been developed and many QAC-based patents have
been granted.
First Generation (Single Chain)

Benzalkonium Compounds
e.g. Alkyldimethylbenzyl Ammonium Chloride (ADBAC), also known as
“Benzalkonium Chloride” (BAC)
CH3
CII
/\/\/\/\/\/\/\ N+ -CH2-C6h6
I
CH3
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The Evolution of Antimicrobial Quaternary Ammonium Compounds
Second Generation (Single Chain)

Substituted Benzalkonium Compounds
e.g. Alkyldimethylbenzyl Ammonium Chloride (ADEBAC)
CH3
CII
+
/\/\/\/\/\/\ N -CH2-C6h6
I
CH3
Third Generation
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“Dual Quats”
Blends of 1st and 2nd generation QACs of specific chain length
distributions
Also blends of single chain QACs with polymeric QACs (e.g.
Polyhexanide).
These sorts of combinations have been found to be synergistic such
that enhanced biocidal activity is obtained with relatively lower toxicity.
Fourth Generation (Twin Chain)
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Dialkyl Quats e.g. Didecyldimethyl Ammonium Chloride (DDAD or a
C10/C10)
CH3
CII
/\/\/\/\/\ N+ /\/\/\/\/\
I
CH3
Dialkyl Quats e.g. Didecyldimethyl Ammonium Chloride (DDAD or a
C10/C10)
Stronger antimicrobial ability compared to their single chain
predecessors
Improved tolerance to anionic surfactants, protein soil and water
hardness salts
Lower foam behaviour
Lower toxicity
Antibacterial Data for Single & Twin Chain QACs (Genn 1,2&4)
1000
800
ADBAC
600
ADEBAC
400
C8 / C10
200
C10 / C10
0
P.aeruginosa
S.aureus
Minimum Disinfection Concentration as ppm QAC (AOAC Use-Dilution
Method, Soil Absent)
Adapted from Ditoro, 1980
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The Evolution of Antimicrobial Quaternary Ammonium Compounds
Antifungal Data for Single & Twin Chain QACs (Genn 1&4)
1400
1200
1000
ADBAC
800
ADEBAC
600
C8 / C10
400
C10 / C10
200
0
Trichophyton Mantagrophytes
Minimum Fungicidal Concentration as ppm QAC (AOAC Fungicidal Test,
400ppm CaCO3 & 5% Serum)
Adapted from Counts et al, post-1992
Comparative Water Hardness Tolerance (Generation: 1,2&4)
Water Hardness Tolerance (ppm CaC03)
2000
1500
1000
500
0
ADBAC
ADEBAC
C8/C10
C10/C10
QAC Type
AOAC Germicidal & Detergent Sanitizer Method: 200ppm active QAC
solutions evaluated against E.coli.
Adapted from Ditoro, 1980
Comparative Performance Data (Generation: 3&4)
ppm Active QAC Required to Pass Test*
ADBAC+Synergists
DDAC Alone
S
P
.a
e
ru
.ty gin
ph os
im a
ur
i
Y
.e C um
.
nt j e
er j u
oc ni
o
L.
m S.a litic
on u a
oc re
yt nu
o s
C gen
.a e
lb s
ic
a
A ns
.n
ig
er
900
800
700
600
500
400
300
200
100
0
*EN1276 Suspension Test with 300 ppm CaCO3 & 0.03% protein load. Pass
Criteria: 5 min bacteriocidal and 15 minutes fungicidal.
Adapted from Akzo Nobel data, 2002
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The Evolution of Antimicrobial Quaternary Ammonium Compounds
Fifth Generation
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Mixtures of selected twin chain quats with ADBACs and/or other
synergists
Good performance in the presence of hard water, organic soiling and
anionic residues
Lower toxicity
Comparative Log Kill Data- Thermal Fog Formulae (Genn 3&5)
Challenge Organism
P.aeruginosa
Salmonella Salford
L. monocytogenes
Candida albicans
Aspergillus niger
ADBAC +
Synergists
>4
>4
>4
>4
0.4
DDAC + Synergists
>4
>4
>4
>4
>4
Prototype formulations tested to BS3286 guidelines in the absence of soil with
10 minute contract time.
Data from Biotest Laboratories
Viral Inactivation Data- 5th Generation mixed QACs.
Virus (All Enveloped)
Avian Influenza
Canine Distemper
Infectious Bronchitis
Mareks Disease (chicken Herpes Virus)
Newcastle Disease
Pseudorabies
Log Titer Reduction
>4
>4
>4
>4
>3
>4
AOAC methods (EPA Guidelines), 450 ppm QAC, 10 minutes contact 5% soil.
Adapted from Loza Inc. 2002
Viral Inactivation Data- 5th Generation mixed QACs+synergists
Virus
Adenovirus Type 4
Avian IBV
Canine Distemper
Feline Picornavirus
Influenza A
Rabies
Envelope
No
Yes
Yes
No
Yes
Yes
Log Tilter Reduction
5.5
6.0
3.5
5.0
8.0
4.5
AOAC methods (EPA Guidelines),660 ppm QAC, 10 min contact, 5% soil, 400
ppm CaCo3
Adapted from Lonza Inc, 1996
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The Evolution of Antimicrobial Quaternary Ammonium Compounds
Breakdown of APVMA Registered Surface Antimicrobial
Products for Poultry
QAC's
Phenolics & Coal Tar
Deriv's
Other Oxidants
Halogens
Aldehydes (incl
Glut/QAC blends)
Definitions
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Disinfectants: A non-selective chemical agent that is ordinarily applied
to inanimate surface to kill pathogenic microorganisms.
o In the U.S a disinfectant has a greater antimicrobial activity then
a sanitiser. Whilst in Europe, a disinfectant can have similar
level of activity to a U.S sanitiser.
o In Australia the term “Disinfectant” is normally reserved for
Therapeutic Goods whilst the “Sanitiser” term is normally used
for food processing applications.
Sanitiser: A chemical uses on inanimate surfaces to reduce the
microbial population to a “safe” level.
Observation: There are inconsistencies in the use of these two terms
(outside of the Therapeutic Goods area) in Australia.
Description & Label Claims of some APVMA Registered
Poultry QAC Products. (Labels ex: infopest website)
Description
(Delared Actives)
- Disinfectant- Sanitiser
Deodorant (BAC)
-“for control of bacteria and mould in…”
- Hospital Grade
Disinfectant (BAC)
-“For use in disinfecting…”
- Detergent Sanitiser
Concentrate (BAC+synergist)
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Label Claim
-“Cleaner for..” / ”Sheds and stables etc
Sanitised with this product require
disinfection before restocking”
- Heavy Duty Disinectant
detergent (BAC+synergists)
-“For cleaning and sanitising surface in…”
- Sanitiser (BAC)
-“For sanitising…”
- Disinfectant (DDAC)
-“For disinfecting of…” / “Kills pathogenic
bacteria and some poultry viruses”
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The Evolution of Antimicrobial Quaternary Ammonium Compounds
APVMA Registered QAC product applications for Australian
Poultry
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General equipment cleaning and sanitising over a broad range of 160 –
2750 ppn QAC depending on the product
Poultry Drinking Water sanitising at 50 ppm QAC. (Qld only)
Egg Dipping at 2500 ppm QAC (Qld only)
Equipment disinfection with 1200 ppm DDAC (i.e. after cleaning with a
lower concentration
Recent applications research outside Australia
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The following examples of poultry field trails with QAC-based product
all involve the use of “continuous disinfection” programs
The aim is to provide a relative unbroken level of disinfection activity in
poultry quarters before and during use via application of chemical
agents with very low toxicity, in order to continuously minimise the
impact of microbial pathogens on peed conversation ratios, weight
gain, egg production and mortality rates.
Year long commercial hatchery trail. Humidifiers continuously fed with
12 ppm (BAC+synergists). Setters & hatchers fogged daily over a
specific time periods with 232 ppm (BAC+synergists)
o Aspergillus positives reduced to almost nil during the weeks of
treatment.
o No chick abnormalities observed.
o Seven day mortality rate reduced from 1% to 0.7%.
Temperley & Limper, 2003
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Poultry drinking water treated with 2.4 ppm DDAC (+synergists) and
exposed to three separate challenges with Newcastle Disease
Virus.
o No increase in chick NCD antibody titers and no visible
symptoms of the disease in the test group.
o Control (i.e. untreated group) showed increased titers, visible
disease symptoms and deaths.
Regular fogging/spraying of boiler chickens (i.e. 3-5 times/week)
with 1200 ppm DDAC +synergists
o 30% mortality reduction compared to the treated control group.
Regular fogging/ spraying of 18 week old chicken layers (i.e. 3-5
times/week) with 1200 ppm DDAC +synergists
o No negative effects on egg production or layers
Information from International Chemicals
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The Evolution of Antimicrobial Quaternary Ammonium Compounds
Bibliography
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4/04/2016
Akzo Nobel “TDS Guideline Formulations MCB and 210” 2002,
Biocides Product Information – Technical Data Sheets
APVMA PUBCRIS Database 2006, viewed 17-03-06
http://www.apvma.gov.au (links to the inforpest registered label
website)
Biotest Laboratories P/L, Report on Challenge tests conducted on
healf of Campnell Cleantec in 2006
Block S.S. “Disinfection, Sterilisation and Preservation” 2001, 5th
ed. Pp 288-293, 306-316, 550-511, 1099-1100. Lippincott Williams
& Wilkins.
Counts, M.W., Young-Bandal, L. & Hall, L.K. “Hard Surface
Disinfection using Optimised Quaternary Ammonium Compounds”
post-1992, paper supplied by Lonza Inc.
Ditoro R.D. “New Quat Meets EPA Organic Soil Challenge”
Soap/Cos./Chem Spec. May 1980, pp 34, 36
International Chemicals “Virukill – A Breakthrough in Poultry
Disease Control” 2002, viewed 15-02-06
http://www.icaonline.co.za/English/virukill.htm
Lonza Group Ltd. “FAQs” 2005, viewed 25-02-06
http://www.biocidl.com/biocidl/en/faqs
Lonza Inc “Research Bulletin for HWS Series” 1996
Russell A.D., Hugo, W.B &Ayliffe, G.A.J. “Principles and Practice of
Disinfection, Preservation & Sterilisation” 1994, 2nd ed. Pp 36, 192193 Blackwell Science Ltd.
Timperley, J.P and Limper, L “Novel Disinfectant for Aspergilus
Contol” 2003, International Hatchery Practice., Vol. 17 No. 6
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