Indirect Precursors of Perfluorooctane Sulfonate (PFOS): Human health tier II assessment
21 April 2016
- Chemicals in this assessment
- Grouping Rationale
- Import, Manufacture and Use
- Existing Worker Health and Safety Controls
- Health Hazard Information
- Risk Characterisation
- NICNAS Recommendation
Chemicals in this assessment
This assessment was carried out by staff of the National Industrial Chemicals Notification and Assessment Scheme (NICNAS) using the Inventory Multi-tiered Assessment and Prioritisation (IMAP) framework.
The IMAP framework addresses the human health and environmental impacts of previously unassessed industrial chemicals listed on the Australian Inventory of Chemical Substances (the Inventory).
The framework was developed with significant input from stakeholders and provides a more rapid, flexible and transparent approach for the assessment of chemicals listed on the Inventory.
Stage One of the implementation of this framework, which lasted four years from 1 July 2012, examined 3000 chemicals meeting characteristics identified by stakeholders as needing priority assessment. This included chemicals for which NICNAS already held exposure information, chemicals identified as a concern or for which regulatory action had been taken overseas, and chemicals detected in international studies analysing chemicals present in babies’ umbilical cord blood.
Stage Two of IMAP began in July 2016. We are continuing to assess chemicals on the Inventory, including chemicals identified as a concern for which action has been taken overseas and chemicals that can be rapidly identified and assessed by using Stage One information. We are also continuing to publish information for chemicals on the Inventory that pose a low risk to human health or the environment or both. This work provides efficiencies and enables us to identify higher risk chemicals requiring assessment.
The IMAP framework is a science and risk-based model designed to align the assessment effort with the human health and environmental impacts of chemicals. It has three tiers of assessment, with the assessment effort increasing with each tier. The Tier I assessment is a high throughput approach using tabulated electronic data. The Tier II assessment is an evaluation of risk on a substance-by-substance or chemical category-by-category basis. Tier III assessments are conducted to address specific concerns that could not be resolved during the Tier II assessment.
These assessments are carried out by staff employed by the Australian Government Department of Health and the Australian Government Department of the Environment and Energy. The human health and environment risk assessments are conducted and published separately, using information available at the time, and may be undertaken at different tiers.This chemical or group of chemicals are being assessed at Tier II because the Tier I assessment indicated that it needed further investigation.
For more detail on this program please visit:www.nicnas.gov.au
NICNAS has made every effort to assure the quality of information available in this report. However, before relying on it for a specific purpose, users should obtain advice relevant to their particular circumstances. This report has been prepared by NICNAS using a range of sources, including information from databases maintained by third parties, which include data supplied by industry. NICNAS has not verified and cannot guarantee the correctness of all information obtained from those databases. Reproduction or further distribution of this information may be subject to copyright protection. Use of this information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner. NICNAS does not take any responsibility whatsoever for any copyright or other infringements that may be caused by using this information.
The chemicals in this group are perfluoroalkyl sulfonates (PFSAs) and related compounds containing a chain of eight perfluorinated carbon atoms linked to a sulfonyl or sulfonamide group. Some members of this group include a range of perfluorinated chain lengths up to eight carbon atoms in length.
NICNAS has developed an action plan to assess and manage chemicals which may degrade to perfluorinated carboxylic acids (PFCAs), PFSAs and similar chemicals, which can be found in Appendix G of the Handbook for Notifiers on the NICNAS website (NICNASa). The primary assumption outlined in this action plan is that chemicals with a perfluorinated chain terminated by a sulfonyl group will degrade to the PFSAs.
On this basis, the chemicals in this group are considered to have the potential to degrade into the environmentally persistent perfluorooctane sulfonate (PFOS) anion and, therefore, are considered to be indirect PFOS precursors (Environment Canada, 2012). Some of the chemicals might also release shorter chain PFSAs, but the toxicity profile will be dominated by the most toxic degradant, PFOS.
The degradation of PFOS is very slow compared with its rate of formation from precursor degradation and PFOS will be the final degradant from all of these precursors. Therefore, the amount of the PFOS in the environment (general or local) is expected to be higher than that of any of the individual precursors. Whilst polymeric precursors generally do not present significant risks, direct exposure to their degradation products, such as PFOS, can pose health risks. However, the available information indicates that any use of these small molecule precursors is in small volume and/or low concentrations in Australia (see Australian import, manufacture and use). Consequently, the most important health risk is expected to arise from secondary exposure to PFOS through the environment. As such, the focus of this assessment is on the long-term effects of the chemicals due to the chemicals degrading to PFOS. Acute and local effects have not been considered.
Import, Manufacture and Use
Information collected by NICNAS indicate that chemicals in this group are not manufactured in Australia. Products containing chemicals based on PFSA, which may also include some of the chemicals in this group, have been used in Australia:
- as coatings in the photography and photolithographic industries;
- in aviation fluids;
- in surface treatments;
- in curatives;
- in fire fighting foams;
- in printing inks; and
- in industrial coatings as an oil and water repellent
In 2006 and 2007, approximately 7.4 tonnes and 13.6 tonnes, respectively, of chemicals based on PFSA were imported into Australia as technical grade chemicals and in products. However, most of the imports were chemicals based on perfluorobutane sulfonate (PFBS), a four-carbon PFAS. Based on the available information, only one of the chemicals in this group was reported as being introduced for use in the photography industry (surfactants—0.002 %) at very low volumes (less than 10 kg per annum).
In 2007, approximately 1600 kg fire fighting foams, containing 1–5 % chemicals based on PFSA (16–80 kg; chain length unspecified), were imported into Australia and over 60 tonnes (0.6–3 tonnes chemicals based on PFSA) were held in stock at sites around Australia (NICNAS, 2013).
It is noted that some of the chemicals in this group could be present in the environment due to historic use or due to release from articles.
The following international uses for chemicals of this group have been reported by the Organisation for Economic Co-operation and Development (OECD, 2011) or identified through Galleria Chemica and through internet searches for specific CAS numbers:
- as coatings and coating additives, in the photolithographic industry;
- as raw material to synthesise fluoropolymers;
- as surfactants;
- in fire fighting foams;
- as wetting agents;
- in industrial cleaning agents; and
- as oil and water repellent coatings.
According to an OECD survey published in 2011, no perfluorosulfonamides or sulfonamidoacrylates (included in the List of Substances) were reported as being manufactured or formulated into products (OECD, 2011).
A survey published in 2005 confirmed that PFOS, its salts and its precursors, are not being manufactured in, or being exported from, Canada. Only one substance was imported into Canada, representing a quantity of approximately three tonnes of PFOS. The imported substance was sold as a product that is used as a surfactant in the electroplating sector (Government of Canada, 2008).
No evidence of these chemicals in consumer products was found in the available North American databases (Household Products Database and Personal Care Council), indicating that the chemicals are not likely to be widely available for domestic or cosmetic uses.
No known mandatory restrictions have been identified for most of the chemicals assessed.
Measures taken to date to reduce the importation and use of PFOS compounds, their salts and precursors have largely been through NICNAS recommendations since 2002 and subsequent voluntary action by industry. NICNAS recommended that PFOS- and related PFSA-based chemicals be restricted to only essential uses for which no suitable or less hazardous alternatives were available (NICNAS, 2013).
Perfluorooctane sulfonates and perfluorooctane sulfonamides are listed on Annex III of the Rotterdam Convention on the Prior Informed Consent Procedure for Certain Hazardous Chemicals and Pesticides in International Trade, ratified by over 150 parties (Rotterdam Convention, 2013).
Canada introduced regulations to prohibit the production and use of PFOS and its salts and substances that contained one of the following groups: perfluorooctyl sulfonyl (C8F17SO2), sulfonate (C8F17SO3) or sulfonamide (C8F17SO2N). These regulations were established to prohibit the manufacture, use, sale, offer for sale and import of PFOS or products containing these substances with certain exemptions. Importers of PFOS-based fume suppressants were required to submit annual reports detailing types, quantities, sales and end uses for the substances that they imported (Government of Canada, 2008).
In the United States of America (USA) most of the chemicals in this group are subject to a Significant New Use Rule (SNUR). These SNURs allow the continuation of a few limited, highly technical uses of these chemicals for which no alternatives are available, and which are characterised by very low volume, low exposure, and low releases. Any other uses of these chemicals requires prior notice to and review by the United States Environmental Protection Agency (US EPA) (US EPA 2002; US EPA 2007).
The use of chemicals containing the PFOS moiety, including neutral and ionic organic chemicals, polymers, telomers and unknown or variable composition, complex reaction products or biological materials (UVCBs), is restricted under European Commission Regulation No 850/2004 on Persistent Organic Pollutants (European Commission, 2010). These chemicals may only be used in select applications in electroplating systems, photolithography processes, photographic coatings, chromium plating and aviation hydraulic fluids. Use is to be phased out as alternative substances or technologies become available.
Twenty-seven chemicals in this group have been pre-registered for use in the European Union (EU) under the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) legislation (ECHA, 2015). However, the chemicals in this group have not undergone the full registration process (ECHA, 2014).
Existing Worker Health and Safety Controls
The chemicals covered in this assessment are not listed on the Hazardous Chemicals Information System (HCIS) (Safe Work Australia).
No specific exposure standards are available.
No specific exposure standards are available.
Health Hazard Information
Limited data are available for chemicals in this group. The primary health risk for the chemicals in this group is expected to arise from secondary exposure to PFOS (see Grouping Rationale). Avendano and Liu (2015) demonstrated that the aerobic soil degradation of two technical grade perfluoro sulfonamide derivatives, (N-ethyl perfluorooctane sulfonamidoethanol, CAS No. 1691-99-2; and N-ethyl perfluorooctane sulfonamide, CAS No. 4151-50-2) caused increased concentrations of PFOS. Their degradation in soil followed the same pathway as found in activated sludge and marine sediments.
Repeated exposure to PFOS resulted in hepatotoxicity and mortality. Adverse signs of toxicity included hepatic vacuolisation and hepatocellular centrilobular hypertrophy, gastrointestinal effects, haematological abnormalities, convulsions and death (NICNASb). Limited available data on oral repeated dose toxicity of some of these chemicals (N-EtFOSE; CAS No. 1691-99-2 and N-MeFOSE; CAS No. 24448-09-7) indicate similar effects and dose response as for PFOS (Health Canada, 2006). The target organ for all three chemicals was the liver and the lowest observed adverse effect level (LOAEL) of the two PFSAs was 2 mg/kg bw/day compared with 0.5 mg/kg bw/day for PFOS.
In a two-year cancer study in rats with N-EtFOSE, increased incidence of hepatocellular adenoma in females and of thyroid follicular cell adenoma in males was observed (Health Canada, 2006). PFOS is classified as hazardous with the risk phrase Carc. Cat 3 - Limited evidence of a carcinogenic effect (Xn; R40). The chemicals induced benign tumours of the liver and the thyroid gland (Sibinski, 1987, Biegel et al., 2001). Tumours of mammary glands were also observed in these studies; however, it has been argued that since the morphologic appearance, overall incidence, and distribution of the tumours observed in treated groups were similar to historical control data for mammary-gland tumours in untreated animals (Giknis and Clifford, 2004), the incidence of mammary gland tumours is not a result of chronic dietary administration of APFO (Hardisty et al., 2010).
Postnatal deaths and other developmental effects were reported in rat offspring exposed to low doses of PFOS (NICNASb). In a developmental study with N-EtFOSE in rats (oral gavage; days 6–17 of gestation), reduced live foetal body weight and increased skeletal and ossification alterations were seen in the presence of maternal toxicty (reduced bodyweight gain). The lowest observed effect level (LOEL) for maternal and foetal toxicity was 10 mg/kg bw/day.
Corrosion / Irritation
Repeated Dose Toxicity
Reproductive and Developmental Toxicity
Other Health Effects
Critical Health Effects
The focus of this assessment is on the long-term effects of the chemicals due to their degradation to PFOS. Acute and local effects (irritation and sensitisation) have not been considered. Whilst polymeric precursors generally do not present significant risks while in polymeric form, direct exposure to small molecule precursors, such as those in this assessment, can pose health risks. However, the available information indicates that any use of these chemicals in Australia is in small volumes and/or low concentrations (see Australian import, manufacture and use). Consequently, the primary health risk is expected to arise from secondary exposure to PFOS.
PFOS and its salts and perfluorosulfonyl fluoride (PFOSF) (direct precursors) have been added to the list of Persistent Organic Pollutants (POPs) under the Stockholm Convention (Stockholm Convention, 2015). POPs are chemicals that are toxic, persist in the environment, accumulate in the food chain, and pose a risk of causing adverse effects to human health and the environment, even at low concentrations. The chemicals in this group are slowly eliminated from the body following absorption. The chemicals are expected to accumulate in the liver. The critical health effects for risk characterisation include systemic acute and long-term effects (hepatotoxicity and developmental toxicity and benign tumours of the liver and thyroid) from oral exposure.
Public Risk Characterisation
Use in consumer products
Given the uses identified for these chemicals, it is unlikely that the public will be exposed. Hence, the public risk from these chemicals is not considered to be unreasonable.
Secondary exposure to PFOS via the environment
Public exposure to PFOS could occur through secondary exposure via the environment. In Australia, PFOS has been found in drinking water at concentrations up to 0.02 micrograms per litre (NICNAS, 2015). While long-term studies in animals showed adverse effects from exposure to PFOS, epidemiological studies in workers exposed to PFOS did not provide clear evidence of effects in humans; and exposure of the general public to similar levels is not expected. Serum concentrations of PFOS in the Australian population have decreased from 2002 through to 2011, with the concentrations in serum ranging from 4.4-17.4 ng/mL (Toms et al., 2014). These levels are similar to median serum PFOS levels ranging between 1.93–44.7 µg/L reported in a recent study in subjects from different geographic locations (China) (Zeng et al., 2015). These serum levels are several orders of magnitude lower than the maternal serum levels in experimental studies (82 µg/mL) that showed developmental toxicity in the offspring (Luebker et al., 2005). In addition, PFOS was not detected in a survey of 65 foods and beverages packaged in glass, paper, plastic or cans, conducted by Food Standards Australia New Zealand (FSANZ, 2010). Nevertheless, since these chemicals will ultimately degrade to PFOS, which is extremely persistent in all media and can bioaccumulate, it is recommended that the chemicals in this group be restricted to only essential uses for which no suitable or less hazardous alternatives are available.
Occupational Risk Characterisation
Based on the available use information, the chemicals or their products are not manufactured in Australia. The chemicals are not likely to be used in significant quantities in Australia. Further assessment of the chemicals in this group may be necessary to inform the risk to workers if information becomes available indicating that these chemicals are introduced into Australia in significant quantities.
Long-term occupational exposure to very low concentrations of PFOS (as contaminants) could occur while using these polymers or formulated products. However, epidemiological studies in workers exposed to PFOS did not provide clear evidence of effects in humans. Therefore, the chemicals are not considered to pose an unreasonable risk to the health of workers.
The chemicals in this group have been assessed as having the potential to give rise to adverse outcomes for the environment and public health. These chemicals are currently listed on the Australian Inventory of Chemical Substances (AICS), and are available to be introduced into Australia without any further assessment by NICNAS. Other chemicals with reduced potential for adverse outcomes are becoming available but, given the properties of these chemicals, their assessment as new chemicals under the Industrial Chemicals (Notification and Assessment) Act 1989 (the ICNA Act) is still required to fully characterise the human health and the environmental risks associated with their use.
It is recommended that NICNAS consult with industry and other stakeholders to consider strategies, including regulatory mechanisms available under the ICNA Act, to encourage the use of safer chemistry.
Advice for industry
Control measures to minimise the risk from exposure to the chemicals should be implemented in accordance with the hierarchy of controls. Approaches to minimise risk include substitution, isolation and engineering controls. Measures required to eliminate, or minimise risk arising from storing, handling and using a hazardous chemical depend on the physical form and the manner in which the chemicals are used. Examples of control measures which could minimise the risk include, but are not limited to:
- using closed systems or isolating operations;
- health monitoring for any worker who is at risk of exposure to the chemicals, if valid techniques are available to monitor the effect on the worker’s health;
- minimising manual processes and work tasks through automating processes;
- work procedures that minimise splashes and spills;
- regularly cleaning equipment and work areas; and
- using protective equipment that is designed, constructed, and operated to ensure that the worker does not come into contact with the chemicals.
Guidance on managing risks from hazardous chemicals are provided in the Managing risks of hazardous chemicals in the workplace—Code of practice available on the Safe Work Australia website.
Personal protective equipment should not solely be relied upon to control risk and should only be used when all other reasonably practicable control measures do not eliminate or sufficiently minimise risk. Guidance in selecting personal protective equipment can be obtained from Australian, Australian/New Zealand or other approved standards.
Obligations under workplace health and safety legislation
Information in this report should be taken into account to help meet obligations under workplace health and safety legislation as adopted by the relevant state or territory. This includes, but is not limited to:
- ensuring that hazardous chemicals are correctly classified and labelled;
- ensuring that (material) safety data sheets ((M)SDS) containing accurate information about the hazards (relating to both health hazards and physicochemical (physical) hazards) of the chemicals are prepared; and
- managing risks arising from storing, handling and using a hazardous chemical.
Your work health and safety regulator should be contacted for information on the work health and safety laws in your jurisdiction.
Information on how to prepare an (M)SDS and how to label containers of hazardous chemicals are provided in relevant codes of practice such as the Preparation of safety data sheets for hazardous chemicals—Code of practice and Labelling of workplace hazardous chemicals—Code of practice, respectively. These codes of practice are available from the Safe Work Australia website.
A review of the physical hazards of these chemicals has not been undertaken as part of this assessment.
Avendano and Liu, 2015. Production of PFOS from aerobic soil biotransformation of two perfluoroalkyl sulfonamide derivatives. Chemosphere 119:1084-90.
Biegel LB, Hurtt ME, Frame SR, O’Connor JC, Cook JC, 2001. Mechanisms of extrahepatic tumor induction by peroxisome proliferators in male CD rats. Toxicol Sci, 60:44–55.
Environment Canada, 2012. Perfluorooctane Sulfonate (PFOS) Its Salts and its Precursors - Risk Management Strategy. Accessed March 2015 at http://www.ec.gc.ca/lcpe-cepa/default.asp?lang=En&n=2AD798EA-1&offset=1&toc=show.
European Chemicals Agency (ECHA), 2014. Registered Substances., Helsinki, Finland. Accessed May 2014 at http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances.
European Chemicals Agency (ECHA), 2015. Pre-registered substances, Helsinki, Finland. Accessed April 2015 at http://echa.europa.eu/web/guest/information-on-chemicals/pre-registered-substances.
European Commission, 2010. Commission Regulation (EU) No 757/2010 of 24 August 2010 amending Regulation (EC) No 850/2004 of the European Parliament and of the Council on persistent organic pollutants as regards Annexes I and III. Official Journal of the European Union, 223, pp 29-36.
Food Standards Australia New Zealand (FZANS), 2010. Survey of Chemical Migration from Food Contact Packaging Materials in Australian Food. http://www.foodstandards.gov.au/science/surveillance/pages/surveyofchemicalmigr5148.aspx
Galleria Chemica. Accessed February 2015 at http://jr.chemwatch.net/galleria/.
Giknis, MLA and Clifford, CB, 2004. Compilation of spontaneous neoplastic lesions and survival in Crl:CDR (SD) rats from control groups. Charles River Laboratories.
Government of Canada 2008. Canada Gazette Vol 142, No. 12. Perfluorooctane Sulfonate and its Salts and Certain Other Compounds Regulations Accessed Mar 2017 at http://publications.gc.ca/gazette/archives/p2/2008/2008-06-11/pdf/g2-14212.pdf
Hardisty JF, Willson GA, Brown WR, McConnell EE, Frame SR, Gaylor DW, Kennedy GL, and Butenhoff JL, 2010. Pathology Working Group review and evaluation of proliferative lesions of mammary gland tissues in female rats fed ammonium perfluorooctanoate (APFO) in the diet for 2 years. Drug and Chemical Toxicology, 33: 131–137.
Health Canada, 2006. State of the Science Report for a Screening Health Assessment on Perfluorooctane Sulfonate, Its Salts and Its Precursors that Contain the C8F17SO2 or C8F17SO3 Moiety. Accessed March 2015 at http://www.ec.gc.ca/lcpe-cepa/default.asp?lang=En&n=EE479482-1&wsdoc=09F567A7-B1EE-1FEE-73DB-8AE6C1EB7658.
Luebker DJ, Case MT, York RG, Moore JA, Hansen KJ and Butenhoff JL, 2005. Two-generation reproduction and cross-foster studies of perfluorooctanesulfonate (PFOS) in rats. Toxicology, 215:126-148.
National Industrial Chemical Notification and Assessment Scheme (NICNASa). Data requirements for notification of new chemical substances containing a perfluorinated carbon chain. Available at https://www.nicnas.gov.au/notify-your-chemical/data-requirements-for-new-chemical-notifications/data-requirements-for-notification-of-new-chemicals-containing-a-perfluorinated-carbon-chain
National Industrial Chemical Notification and Assessment Scheme (NICNASb). Inventory Multi-tiered Assessment and Priorisation (IMAP): Human health Tier II assessment for perfluorooctane sulfonate (PFOS) and its direct precursors. Accessed March 2015 at http://www.nicnas.gov.au
National Industrial Chemicals Notification and Assessment Scheme (NICNAS), 2015. Environment Tier II Assessment for direct precursors to perfluorooctanesulfonate (PFOS). Accessed March 2015 at http://www.nicnas.gov.au
National Industrial Chemicals Notification and Assessment Scheme (NICNASc). Perfluorinated chemicals (PFCs) factsheet. Available at https://www.nicnas.gov.au/chemical-information/factsheets/chemical-name/perfluorinated-chemicals-pfcs
Organisation for Economic Co-operation and Development (OECD), 2007. Lists of PFOS, PFAS, PFOA, PFCA, Related Compounds and Chemicals that may degrade to PFCA. OECD Environment Health and Safety Publications, Series on Risk Management No. 21, 2007. Accessed March 2015 at http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?doclanguage=en&cote=env/jm/mono%282006%2915
Organisation for Economic Co-operation and Development (OECD), 2011. OECD series on Risk Management, No. 24. PFCs: Outcome of the 2009 survey on the production, use and release of PFOS, PFAS, PFOA, PFCA, their related substances and products/mixtures containing these substances.
Rotterdam Convention, 2013. Sixth meeting of the Conference of the Parties to the Rotterdam Convention, Geneva, Switzerland; 28 April – 10 May 2013. http://www.pic.int/TheConvention/ConferenceoftheParties/Meetings/COP6/tabid/2908/language/en-US/Default.aspx.
Safe Work Australia (SWA). Hazardous Chemicals Information System (HCIS). Accessed March 2017 at http://hcis.safeworkaustralia.gov.au/.
Sibinski LJ, 1987. Two-year oral (diet) toxicity/oncogenicity study of fluorochemical FC-143 in rats. Riker Experiment No. 0281CR0012, Riker Laboratories Inc/3M Company.
Stockholm Convention, 2015. The new POPs under the Stockholm Convention. http://chm.pops.int/Home/tabid/2121/mctl/ViewDetails/EventModID/870/EventID/543/xmid/6921/Default.aspx.
Toms L-ML, Thompson J, Rotander A, Hobson P, Calafat AM, Kato K, Ye X, Broomhall S, Harden F and Mueller JF, 2014. Decline in perfluorooctane sulfonate and perfluorooctanoate serum concentrations in an Australian population from 2002 to 2011. Environ. Intl. 71: 74-80.
United States Environmental Protection Agency (US EPA), 2002. Perfluoroalkyl Sulfonates; Significant New Use Rule [SNUR], Docket ID: EPA-HQ-OPPT-2002-0043 accessed March 2015 at http://www.epa.gov/oppt/pfoa/pubs/pfas.html
United States Environmental Protection Agency (US EPA), 2007. Federal Register/ Vol. 72, No. 194 / Tuesday, October 9, 2007 / Rules and Regulations accessed March 2015 at http://www.epa.gov/oppt/pfoa/pubs/pfas.html.
Zeng XW, Qian Z, Vaughn M, Xian H, Elder K, Rodemich E, Bao J, Jin YH and Dong GH, 2015. Human serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in Uyghurs from Sinkiang-Uighur Autonomous Region, China: background levels study. Environ Sci Pollut Res Int. 22:4736-4746.