Quats
What are they?
Quats, or quaternary ammonium compounds, are a large class of chemical compounds with similar chemical structures.[1]
Quats destroy microorganisms including bacteria, viruses and fungi. They are used as antimicrobial and detergent ingredients in a wide range of products such as cleaners, disinfectants, sanitisers and laundry across a range of applications spanning agricultural, industrial, institutional, commercial and domestic uses.
Common household products that may contain quats include body wash, shampoo, hand lotions and toothpaste. They are also used in medicinals such as throat lozenges, nasal sprays and eye drops.
Quats are common ingredients with a history of safe use exceeding 60 years. The specific quat and the amount present in a product depends on the product category and its use.
What’s the myth?
‘Myth’ may not be quite the right word in this case.
Rather, some very preliminary research results have been picked up in the media to suggest that some specific quats may be linked to potential health issues.
For example, research has claimed that exposure to two specific quats – benzalkonium chloride (BAC, or ADBAC) and dodecyl dimethyl ammonium chloride (DDAC) – reduces the fertility of rodents,[2] and causes neural tube defects in offspring.[3] And a recent in vitro study[4] reported that some quats – but not all those tested – inhibited mitochondria[5] in human and rat cells. Cetylpyridinium chloride (CPC) and BAC were amongst the six quats that showed the inhibitory effect, and were also inhibitory to estrogen activity. The authors proposed that it could be this effect that underpinned the fertility and developmental issues previously observed in rodents.
Some media chose to take these preliminary results and run with an alarming and currently unwarranted human health angle. For example, “Chemicals in common household products could be making us infertile, scientists say.”[6]
So, what are some facts about quats, mitochondria and fertility?
FACT: Quats are not one uniform group, with identical properties
“Quats” include a large number of individual compounds with individual properties.
They all share one key feature: a positively charged nitrogen atom connected (covalently bonded) to four carbon atoms. However, the chemical groups attached to the four carbon atoms differ depending on the specific quat. It is the combination of these attachments that give a specific quat its specific properties.
So, although they do share some structural similarity, it is not possible to make helpful or accurate statements about the effect of quats in a general manner based only on observed effects for specific individual quats. As noted earlier quats are a large class of chemical compounds.
FACT: Quats are evaluated individually for safety in Australia
In Australia, quats are regulated for public health and safety by the Australian Industrial Chemicals Introduction Scheme (AICIS) and the Federal Health Department.
There are many individual quats listed on the Australian Inventory of Industrial Chemicals. This is a database of chemicals available for industrial use in Australia and administered by AICIS.
In Australia, quats are also scheduled via the national Poisons Standard, which controls how medicines and poisons are made available to the public. Depending on the concentration of quats present, the product must be labelled with either “CAUTION” or “POISON” and specified first aid statements.
Both AICIS and the Federal Health Department monitor any new scientific studies, media reports or even activist group allegations regarding chemical ingredients and act when warranted.
FACT: Quats have recently been assessed by NICNAS for human safety
NICNAS (now AICIS) conducted a human health assessment of BAC, ADBAC, DDAC and 11 other structurally similar quats.[7] The assessment reviewed scientific studies covering all aspects of human health, including reproductive and developmental toxicity.
Their conclusion was that “the risk to public health is not considered to be unreasonable and further risk management is not considered necessary for public safety”. NICNAS recommended that consumers use “normal precautions”, and handle products containing chemicals in this group “according to the instruction on the label”.
FACT: No conclusive link to potential human health impacts is possible at this stage
Let’s start with the cell culture study.[4]
There is a big difference between exposing individual cells to a chemical substance in vitro and the effect of the same substance on a human from normal day-to-day exposure.
Firstly, let’s consider where mitochondria are located – inside cells. For a substance to get to mitochondria it must enter the cell by crossing the cell membrane. The cell membrane is a good barrier to substances with an electrical charge, and quats are positively charged. So can quats cross the cell membrane? Does this happen in live tissues? In human tissues?
Secondly, the mode of exposure needs to be considered. In this study, cells are incubated directly with the undiluted substance whereas in the real world, humans are most likely to encounter quats as part of a formulated products via skin contact, eyes, or inhalation.v What is the actual exposure of human cells to quats? And which cells?
Related to the above point, the relevance of the concentration of quats used in the study also needs to be ascertained. What is its relationship to actual human exposure?
What about the rodent results?
There are a number of question marks concerning the study, including an atypical and extremely complex experimental design and high oral doses that are not representative of normal human exposure. As well as no rationale being provided for the doses selected, there is no clear dose-response identified and no ‘no-observed adverse effect level’ (NOAEL) identified.
No link between the findings and actual human exposure is made, or indeed is possible at this stage.
So what does this all mean?
It is not yet time to panic!
More research is needed. For example, the results should be independently replicated, further investigation of the in vitro results in animal models is needed, and exposure scenarios that are replicable and can be related to normal human exposure are required.
FACT: Overseas regulators and experts continue to monitor and assess specific quats as needed
Various quats have been assessed for human health safety by groups such as the US Environmental Protection Agency, US Food and Drug Administration (FDA), and the EU Scientific Committee on Consumer Safety (SCCS).
The US EPA conducted a risk assessment of DDAC (and related quats) based on its use in disinfectant and deodorant products spanning agricultural, food handling, commercial/institutional/industrial, residential and public access, and medical settings applications.[8] This risk assessment looked at relevant research data and, specifically relating to developmental toxicity, concluded that studies on rats and rabbits did “not indicate increased susceptibility in rats or rabbits from in utero and postnatal exposures to DDAC”.
More recently, the FDA announced that CPC could no longer be used in consumer antibacterial wash products sold in the USA.[9] However this was not was based on new evidence of safety concerns, but because “antibacterial hand and body wash manufacturers did not provide the necessary data” and “did not demonstrate that the ingredients are both safe for long-term daily use and more effective than plain soap and water in preventing illness and the spread of certain infections". CPC can still be used in other categories of products, and the FDA has requested further information on BAC.
In Europe, cosmetic regulations list maximum allowable concentrations for some specific quats, depending on the product type and application, e.g. leave-on vs rinse-off; face vs hair.[10]
On CPC specifically, the SCCS reviewed evidence on its use as a preservative in cosmetic products (oral hygiene products, skin lotions & creams, and antiperspirants). In its 2015 Opinion,[11] the SCCS determined “that the use of cetylpyridinium chloride in a single cosmetic product for oral or dermal application is safe for the consumer”. When considering whether simultaneous exposure to all these products posed a risk, the SCCS determined that this scenario was unlikely to occur.
The bottom line? There is no scientific evidence warranting further regulatory action on ADBAC, BAC or CPC. Consumers can be confident in their continued use of products containing these ingredients and that regulatory agencies around the world monitor for new scientific evidence, and act if necessary.
Sources
[1] A positively charged nitrogen atom connected (covalently bonded) to four carbon atoms; the specific chemical structures are attached to the carbon atoms result in specific quats with specific properties.
[2] Melin, V.E. et al, 2014. “Exposure to common quaternary ammonium disinfectants decreases fertility in mice”, Reproductive Toxicology, Vol 50, pp163-70; Melin, V.E., 2016. “Quaternary ammonium disinfectants cause subfertility in mice by targeting both male and female reproductive processes”, Reproductive Toxicology, Vol 59, pp159-166
[3] Hrubec, T.C. et al, 2017. Ambient and Dosed Exposure to Quaternary Ammonium Disinfectants Causes Neural Tube Defects in Rodents”, Birth Defects Research, Vol 109 (14), pp1166-1178.
[4] Datta, S. et al, 2017. “In Vitro Evaluation of Mitochondrial Function and Estrogen Signaling in Cell Lines Exposed to the Antiseptic Cetylpyridinium Chloride”, Environmental Health Perspectives, Vol 125(8). Accessed at https://ehp.niehs.nih.gov/EHP1404/ (15/9/2017)
[5] Mitochondria are cell organelles responsible for cellular energy production
[6] Daily Mail, Allen, V., 22 August 2017, “Fertility warning over antiseptic chemicals in cleaning fluid, wipes and mouthwash: Exposure to common household products damages human cells”. Accessed at www.dailymail.co.uk/health/article-4811866/Fertility-warning-cleaning-chemicals.html#ixzz4shZfDHYx (15/9/2017)
[7] NICNAS 2014, “Human Health Tier II Assessment for Cationic surfactants”.
[8] U.S. Environmental Protection Agency, Office of Pesticide Programs, Antimicrobials Division, 2006. DRAFT Didecyl Dimethyl Ammonium Chloride (DDAC) Risk Assessment”. Accessed at http://pi.ace.orst.edu/search/getDocketDocument.s?document=EPA-HQ-OPP-2006-0338-0019 (14/9/2017)
[9] U.S. Food & Drug Administration, September 2, 2016, “FDA issues final rule on safety and effectiveness of antibacterial soaps”. Accessed at https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm517478.htm (15/9/2017)
[10] EU Cosmetics Regulation 1223/2009. Accessed at http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2009:342:0059:0209:en:PDF (15/9/2017)
[11] SCCS (Scientific Committee on Consumer Safety), Opinion on Cetylpyridinium chloride - submission II (P97), SCCS/1548/15, 25 March 2015, revision of 15 December 2015
What are they?
Quats, or quaternary ammonium compounds, are a large class of chemical compounds with similar chemical structures.[1]
Quats destroy microorganisms including bacteria, viruses and fungi. They are used as antimicrobial and detergent ingredients in a wide range of products such as cleaners, disinfectants, sanitisers and laundry across a range of applications spanning agricultural, industrial, institutional, commercial and domestic uses.
Common household products that may contain quats include body wash, shampoo, hand lotions and toothpaste. They are also used in medicinals such as throat lozenges, nasal sprays and eye drops.
Quats are common ingredients with a history of safe use exceeding 60 years. The specific quat and the amount present in a product depends on the product category and its use.
What’s the myth?
‘Myth’ may not be quite the right word in this case.
Rather, some very preliminary research results have been picked up in the media to suggest that some specific quats may be linked to potential health issues.
For example, research has claimed that exposure to two specific quats – benzalkonium chloride (BAC, or ADBAC) and dodecyl dimethyl ammonium chloride (DDAC) – reduces the fertility of rodents,[2] and causes neural tube defects in offspring.[3] And a recent in vitro study[4] reported that some quats – but not all those tested – inhibited mitochondria[5] in human and rat cells. Cetylpyridinium chloride (CPC) and BAC were amongst the six quats that showed the inhibitory effect, and were also inhibitory to estrogen activity. The authors proposed that it could be this effect that underpinned the fertility and developmental issues previously observed in rodents.
Some media chose to take these preliminary results and run with an alarming and currently unwarranted human health angle. For example, “Chemicals in common household products could be making us infertile, scientists say.”[6]
So, what are some facts about quats, mitochondria and fertility?
FACT: Quats are not one uniform group, with identical properties
“Quats” include a large number of individual compounds with individual properties.
They all share one key feature: a positively charged nitrogen atom connected (covalently bonded) to four carbon atoms. However, the chemical groups attached to the four carbon atoms differ depending on the specific quat. It is the combination of these attachments that give a specific quat its specific properties.
So, although they do share some structural similarity, it is not possible to make helpful or accurate statements about the effect of quats in a general manner based only on observed effects for specific individual quats. As noted earlier quats are a large class of chemical compounds.
FACT: Quats are evaluated individually for safety in Australia
In Australia, quats are regulated for public health and safety by the Australian Industrial Chemicals Introduction Scheme (AICIS) and the Federal Health Department.
There are many individual quats listed on the Australian Inventory of Industrial Chemicals. This is a database of chemicals available for industrial use in Australia and administered by AICIS.
In Australia, quats are also scheduled via the national Poisons Standard, which controls how medicines and poisons are made available to the public. Depending on the concentration of quats present, the product must be labelled with either “CAUTION” or “POISON” and specified first aid statements.
Both AICIS and the Federal Health Department monitor any new scientific studies, media reports or even activist group allegations regarding chemical ingredients and act when warranted.
FACT: Quats have recently been assessed by NICNAS for human safety
NICNAS (now AICIS) conducted a human health assessment of BAC, ADBAC, DDAC and 11 other structurally similar quats.[7] The assessment reviewed scientific studies covering all aspects of human health, including reproductive and developmental toxicity.
Their conclusion was that “the risk to public health is not considered to be unreasonable and further risk management is not considered necessary for public safety”. NICNAS recommended that consumers use “normal precautions”, and handle products containing chemicals in this group “according to the instruction on the label”.
FACT: No conclusive link to potential human health impacts is possible at this stage
Let’s start with the cell culture study.[4]
There is a big difference between exposing individual cells to a chemical substance in vitro and the effect of the same substance on a human from normal day-to-day exposure.
Firstly, let’s consider where mitochondria are located – inside cells. For a substance to get to mitochondria it must enter the cell by crossing the cell membrane. The cell membrane is a good barrier to substances with an electrical charge, and quats are positively charged. So can quats cross the cell membrane? Does this happen in live tissues? In human tissues?
Secondly, the mode of exposure needs to be considered. In this study, cells are incubated directly with the undiluted substance whereas in the real world, humans are most likely to encounter quats as part of a formulated products via skin contact, eyes, or inhalation.v What is the actual exposure of human cells to quats? And which cells?
Related to the above point, the relevance of the concentration of quats used in the study also needs to be ascertained. What is its relationship to actual human exposure?
What about the rodent results?
There are a number of question marks concerning the study, including an atypical and extremely complex experimental design and high oral doses that are not representative of normal human exposure. As well as no rationale being provided for the doses selected, there is no clear dose-response identified and no ‘no-observed adverse effect level’ (NOAEL) identified.
No link between the findings and actual human exposure is made, or indeed is possible at this stage.
So what does this all mean?
It is not yet time to panic!
More research is needed. For example, the results should be independently replicated, further investigation of the in vitro results in animal models is needed, and exposure scenarios that are replicable and can be related to normal human exposure are required.
FACT: Overseas regulators and experts continue to monitor and assess specific quats as needed
Various quats have been assessed for human health safety by groups such as the US Environmental Protection Agency, US Food and Drug Administration (FDA), and the EU Scientific Committee on Consumer Safety (SCCS).
The US EPA conducted a risk assessment of DDAC (and related quats) based on its use in disinfectant and deodorant products spanning agricultural, food handling, commercial/institutional/industrial, residential and public access, and medical settings applications.[8] This risk assessment looked at relevant research data and, specifically relating to developmental toxicity, concluded that studies on rats and rabbits did “not indicate increased susceptibility in rats or rabbits from in utero and postnatal exposures to DDAC”.
More recently, the FDA announced that CPC could no longer be used in consumer antibacterial wash products sold in the USA.[9] However this was not was based on new evidence of safety concerns, but because “antibacterial hand and body wash manufacturers did not provide the necessary data” and “did not demonstrate that the ingredients are both safe for long-term daily use and more effective than plain soap and water in preventing illness and the spread of certain infections". CPC can still be used in other categories of products, and the FDA has requested further information on BAC.
In Europe, cosmetic regulations list maximum allowable concentrations for some specific quats, depending on the product type and application, e.g. leave-on vs rinse-off; face vs hair.[10]
On CPC specifically, the SCCS reviewed evidence on its use as a preservative in cosmetic products (oral hygiene products, skin lotions & creams, and antiperspirants). In its 2015 Opinion,[11] the SCCS determined “that the use of cetylpyridinium chloride in a single cosmetic product for oral or dermal application is safe for the consumer”. When considering whether simultaneous exposure to all these products posed a risk, the SCCS determined that this scenario was unlikely to occur.
The bottom line? There is no scientific evidence warranting further regulatory action on ADBAC, BAC or CPC. Consumers can be confident in their continued use of products containing these ingredients and that regulatory agencies around the world monitor for new scientific evidence, and act if necessary.
Sources
[1] A positively charged nitrogen atom connected (covalently bonded) to four carbon atoms; the specific chemical structures are attached to the carbon atoms result in specific quats with specific properties.
[2] Melin, V.E. et al, 2014. “Exposure to common quaternary ammonium disinfectants decreases fertility in mice”, Reproductive Toxicology, Vol 50, pp163-70; Melin, V.E., 2016. “Quaternary ammonium disinfectants cause subfertility in mice by targeting both male and female reproductive processes”, Reproductive Toxicology, Vol 59, pp159-166
[3] Hrubec, T.C. et al, 2017. Ambient and Dosed Exposure to Quaternary Ammonium Disinfectants Causes Neural Tube Defects in Rodents”, Birth Defects Research, Vol 109 (14), pp1166-1178.
[4] Datta, S. et al, 2017. “In Vitro Evaluation of Mitochondrial Function and Estrogen Signaling in Cell Lines Exposed to the Antiseptic Cetylpyridinium Chloride”, Environmental Health Perspectives, Vol 125(8). Accessed at https://ehp.niehs.nih.gov/EHP1404/ (15/9/2017)
[5] Mitochondria are cell organelles responsible for cellular energy production
[6] Daily Mail, Allen, V., 22 August 2017, “Fertility warning over antiseptic chemicals in cleaning fluid, wipes and mouthwash: Exposure to common household products damages human cells”. Accessed at www.dailymail.co.uk/health/article-4811866/Fertility-warning-cleaning-chemicals.html#ixzz4shZfDHYx (15/9/2017)
[7] NICNAS 2014, “Human Health Tier II Assessment for Cationic surfactants”.
[8] U.S. Environmental Protection Agency, Office of Pesticide Programs, Antimicrobials Division, 2006. DRAFT Didecyl Dimethyl Ammonium Chloride (DDAC) Risk Assessment”. Accessed at http://pi.ace.orst.edu/search/getDocketDocument.s?document=EPA-HQ-OPP-2006-0338-0019 (14/9/2017)
[9] U.S. Food & Drug Administration, September 2, 2016, “FDA issues final rule on safety and effectiveness of antibacterial soaps”. Accessed at https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm517478.htm (15/9/2017)
[10] EU Cosmetics Regulation 1223/2009. Accessed at http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2009:342:0059:0209:en:PDF (15/9/2017)
[11] SCCS (Scientific Committee on Consumer Safety), Opinion on Cetylpyridinium chloride - submission II (P97), SCCS/1548/15, 25 March 2015, revision of 15 December 2015
