Perfluoroalkyl sulfonates (PFSA) (C5-C7) and their direct precursors: Human health tier II assessment
29 June 2018
- 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 sulfonic acids, perfluoroalkyl sulfonic fluoride and salts of the perfluoroalkyl sulfonate (PFSA) anion, all of which contain 5–7 perfluorinated carbons terminated with a sulfonate group, and which have the potential to hydrolyse and/or dissociate into a range of environmentally persistent perfluorosulfonate anions.
NICNAS has developed an action plan to assess and manage chemicals which may degrade to perfluorinated carboxylic acids, perfluoroalkyl sulfonates and similar chemicals, which can be found in Appendix G of the Handbook for Notifiers on the NICNAS website (NICNASa). Under this action plan, perfluorooctane sulfonate (PFOS) hazard information is used to estimate the hazard of PFAS degradation products, apart from perfluorobutane sulfonate (PFBS). Data for the critical effects of bioaccumulation and hepatotoxicity, developmental toxicity and carcinogenicity would need to be provided to demonstrate that a lower toxicity profile applies.
This assessment will evaluate:
a) the relative hazard and risk of the chemicals in this group compared with PFOS; and
b) whether there are sufficient data to amend some or all of the default assumptions in the action plan.
Assessing these chemicals as a group also provides relevant information for the risk assessment of more complex derivatives of PFSA that contain 5–7 perfluorinated carbons that can degrade to the relevant perfluorinated anions in the environment (indirect precursors). These more complex derivatives of PFSA will be assessed separately under IMAP.
The focus of this assessment will be the chemicals' bioaccumulation potential and systemic long-term effects. Data for acute and local effects have been included where available. For certain endpoints such as irritation, sensitisation and genotoxicity, PFOS is considered a suitable analogue. For systemic end points, PFOS is considered to represent the worst case for toxicity of the chemicals in this group.
Import, Manufacture and Use
Information collected by NICNAS indicates that the chemicals in this group are not manufactured in Australia.
Whilst approximately 7.4 tonnes and 13.6 tonnes of PFSA (as technical grade and in products) were reported to be imported into Australia in 2006 and 2007, respectively, most were chemicals based on PFBS, a four-carbon PFSA. Various PFSA surfactants (chain length unspecified) were reported to be imported in fire fighting foams. In 2007, approximately 60 tonnes of fire fighting foams containing 1–5 % of PFSA substance were held in stock at sites around Australia (NICNAS).
It is noted that some of the chemicals in this group could be present in the environment due to historic use, due to release from articles or as breakdown products resulting from the use of indirect precursor chemicals not covered by this assessment.
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 (Galleria Chemica):
- as fluorinated anionic surfactants;
- as intermediates; and
- in anti-reflective coatings in photolithography.
The chemicals could potentially be used as paint additives and in fire fighting foams (OECD, 2013).
According to an OECD survey published in 2011, potassium perfluorohexane sulfonate (CAS No. 3871-99-6) and perfluorohexane sulfonyl fluoride (CAS No. 423-50-7) were reportedly produced in the United States (US) in 2008. They are mainly used as raw materials or precursors to produce PFSA-based products. Only one product containing the chemicals was reported. The concentration of the chemical in the product was <10% and its total residual quantity in the product was reported as approximately 0.5 tonnes (OECD, 2011).
No evidence of the presence of these chemicals in consumer products was found in 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.
All chemicals in this group are pre-registered under the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) legislation, but none have been registered under the REACH legislation at the time of assessment.
No known mandatory restrictions have been identified.
Measures taken to date to reduce the importation and use of PFSA compounds and their salts and precursors has largely been through NICNAS recommendations (published as alerts as part of NICNAS Factsheets) since 2002 and subsequent voluntary action by industry. NICNAS's first three alert Factsheets 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).
In the United States of America (USA), all 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 required prior notice to, and review by, the US Environmental Protection Agency (EPA) (US EPA, 2002; US EPA, 2007).
Whilst PFOS is restricted in several countries (NICNAS), the chemicals in this group are not covered by these restrictions.
Existing Worker Health and Safety Controls
The chemicals are not listed on the Hazardous Substances Information System (HSIS) (Safe Work Australia).
No specific exposure standards are available for the chemicals in this group.
No specific exposure standards are available for the chemicals in this group.
Health Hazard Information
The chemicals in this group have the potential to hydrolyse and/or dissociate into PFSA anions that contain 5–7 perfluorinated carbons.
Limited toxicological data are available for the majority of chemicals in this group. Hazard data for perfluorohexanesulfonate (PFHxS) can be used to estimate hazards for the members of this group that contain five and six perfluorinated carbons. In the absence of toxicological data, PFOS hazard information is used to estimate systemic hazards. Due to lack of available data for the chemicals in this assessment, the data for direct precursors of PFBS and PFOS have been used to estimate the direct irritation potential of the chemicals that is independent of toxicokinetics of distribution, metabolism and excretion of the chemical.
Based on the available information, the chemicals in this group are expected to be rapidly absorbed after ingestion and, to a lesser extent, through inhalation. They are slowly eliminated, mainly in the urine. Elimination is substantially slower in humans than primates or rodents.
PFOS is well absorbed by the digestive tract and is mainly accumulated in the liver, followed by plasma, kidneys and lungs. It is mainly eliminated in urine, followed by faeces (NICNASb). PFHxS was shown to be mainly eliminated via urine in rats, with urinary excretion in males being dose-dependent. Mean daily faecal excretion was <0.5% of the administered dose at all time points (Sundstrom et al., 2012). PFHxS was shown to be distributed to the blood, liver and kidneys (Butenhoff et al., 2009; Sundstrom et al., 2012).
Once absorbed, PFOS is eliminated from the human body very slowly. The mean elimination half-life of PFOS in humans was estimated to be 5.4 years (3.9–6.9 years) based on the serum PFOS levels determined in retirees who had been exposed to PFOS during their working life (NICNASb). Much shorter serum half-lives were reported for PFOS in male and female monkeys (131 and 110 days, respectively) and rats (43 and 60 days, respectively).
Similarly for PFHxS, a long serum elimination half-life of 7–8 years was estimated in humans (estimate for the two females in the was 4,458 and 4,866 days) compared with shorter half-lives in male and female monkeys (141 and 87 days, respectively) and rats (30 and 1.5 days, respectively) (Sundstrom et al., 2012). In comparison, PFBS is eliminated substantially faster in humans than perfluoroalkyls with longer carbon chain lengths (e.g. PFHxS and PFOS) with serum half-lives of 28, 4 and 0.2 days in humans, monkeys and rats, respectively (OECD, 2013).
A comparative pharmacokinetic pro?le study of PFHxS across the three species (rat, mouse and monkey) showed that rats and mice (serum half-life of one month) are more effective at eliminating PFHxS than monkeys (half-life of four months). The authors concluded that this could be due to differences in expression of organic anion transporters between species. The study also demonstrated sex-speci?c elimination differences in the rat (females demonstrating faster elimination rates as also seen in the above study) but not in mice or monkeys (Sundstrom et al., 2012).
Biomonitoring studies have shown that exposure in the general population is widespread and that PFHxS and PFOS are the PFSAs commonly present in human serum (Calafat et al., 2006; Fromme et al., 2007; Kato et al., 2011). In pooled human sera from the Australian population, PFOS was the highest PFSA detected in concentrations ranging from 5.3–19.2 ng/mL (2008/2009) to 4.4–17.4 ng/mL (2010/2011). PFHxS levels ranged from 1.2–5.7 ng/mL (08/09) and 1.4–5.4 ng/mL (10/11). Median levels of PFHxS have not significantly changed from 2002 (Toms et al., 2014).
World wide, PFHxS is found in umbilical cord blood, human milk and child serum (ATSDR, 2009).
Perfluoroalkyl compounds have been found in human breast milk, but there are no studies that looked at whether a baby's health was affected by drinking this milk. Levels of perfluoroalkyls in breast milk are much lower than in the mother’s blood, indicating that these substances are not concentrated during milk production (ATSDR, 2009).
A study of Chinese women (n = 19) detected PFHxS (100 ng/L) and PFOS (45–360 ng/L) in breast milk (So et al., 2006). These levels of PFOS and PFHxS were far less than those reported in human blood or serum samples (PFOS: 5400–26000 ng/L and PFHxS: 370 ng/L) in a separate study in the Chinese population (Yeung et al., 2006).
Little variation was found in PFOS and PFHxS in composite milk samples collected each year between 1996 and 2003–2004 from four different regions in Sweden, indicating that the levels have been constant during the span of this study. The chemicals, PFOS (0.201 ng/mL) and PFHxS (0.085 ng/mL) levels in human milk were about 1 % of the corresponding level in serum. Mean maternal serum concentrations were 20.7 ng/mL (8.2–48 ng/mL) for PFOS and 4.7 ng/mL (1.8–11.8 ng/mL) for PFHxS (Karrman et al., 2007). While no clear temporal trend was established by Karrman et al (2007), a recent comprehensive study by Sundstrom and co-workers (2011) demonstrated that the PFOS and PFHxS levels in human milk samples showed increasing trends from 1972 to 2000, with a plateau in the 1990s and a decreasing trend during 2001–2008 (Sundstrom et al (2011).
Sundstrom et al (2011). A temporal trend study (1972–2008) of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in pooled human milk samples from Stockholm, Sweden. Environ Int 37(1):178-183.
The chemical, PFHxS was detected in 88 % of samples of maternal sera (n = 20) and umbilical cord sera (n = 20) taken from the general population of Seoul, South Korea. Concentrations between paired maternal (0.55 ng/mL) and cord (0.34 ng/mL) sera were significantly correlated. Within the same study, PFHpS and PFOS were also detected in maternal (0.09 and 2.93 ng/mL, respectively) and umbilical cord (0.06 and 1.26 ng/mL, respectively) sera (Kim et al., 2011).
No data are available for the chemicals in this group.
Based on the data for PFOS (oral median lethal dose (LD50) of 252 mg/kg bw for rats) (NICNASb), the chemicals in this group are expected to have moderate acute toxicity following oral exposure. Classification is considered warranted (see Recommendation section). If data become available for the individual group members, they should be used to determine individual classifications.
No data are available for the chemicals in this group or PFOS.
No data are available for the chemicals in this group.
Based on the data for PFOS (median lethal concentration (LC50) of 5.2 mg/L for rats) (NICNASb), the chemicals in this group are expected to have low acute toxicity following inhalation exposure. If data become available for the individual group members, they should be used to determine individual classifications.
Corrosion / Irritation
No data are available for the chemicals in this group.
Based on data for the potassium salt of PFOS and PFBS, which are non-irritating (NICNASb; NICNASd), the majority of chemicals in this group could be, at most, slight skin irritants. However, skin irritant/corrosive effects cannot be ruled out for perfluorohexane sulfonyl fluoride (which is reactive and could possibly hydrolyse to PFHxS). If data become available for the individual group members, they should be used to determine individual classifications.
No data are available for the chemicals in this group.
Whilst the potassium salt of PFOS was a slight irritant in rabbits, with effects that were not sufficient for classification (NICNASb), potassium PFBS is classified as hazardous with the risk phrase 'Irritating to eyes' (Xn; R36) in the HSIS (Safe Work Australia).
Eye irritant or corrosive effects cannot be ruled out for perfluorohexanesulphonyl fluoride (which could possibly hydrolyse to PFHxS). In the absence of additional information, based on potassium PFBS, a classification is considered warranted for all the chemicals in the group. If data become available for the individual group members, they should be used to determine individual classifications.
No data are available for the chemicals in this group or PFOS. Direct precusors of PFBS are considered non-sensitisers (NICNASd).
Repeated Dose Toxicity
Based on the available data, toxicity for PFHxS, following repeated exposure, was dose dependent. Similar to PFOS, the liver was considered the target organ. Overall, the data support classification for all the chemicals in the group (see Recommendation section). If data become available for the individual group members, they should be used to determine individual classifications.
Sprague Dawley (SD) rats (15 rats/sex/group) were administered potassium PFHxS at 0, 0.3, 1, 3 or 10 mg/kg bw/day via oral gavage in a combined repeated dose study with a reproduction/developmental toxicity screening test (modified OECD Test Guideline (TG) 422). The male rats were treated for a total of 42 days; females were treated prior to mating through to postnatal day (PND) 22. The F1 generation pups were exposed in utero and potentially during lactation via milk, and were euthanised on PND 22. The effects in parental males included:
1) reduced serum cholesterol (all doses);
2) decreased prothrombin time (doses of 0.3, 3 and 10 mg/kg bw/day);
3) increased liver-to-body and liver-to-brain weight ratio, centrilobular hypertrophy, hyperplasia of thyroid follicular cells, decreased haematocrit (at 3 and 10 mg/kg bw/day); and
4) decreased triglycerides and increased albumin, urea nitrogen, alkaline phosphatase, Ca2+ and albumin/globulin ratio (at 10 mg/kg bw/day), but there were no significant gross or microscopic alterations in the kidneys (Butenhoff et al., 2009).
There were no treatment-related changes in dams or offspring. No significant gross or microscopic alterations were reported for the spleen, thymus, or mesenteric lymph nodes. Although no comprehensive neurological testing was conducted, tests for motor activity (autonomic functions; reactivity and sensitivity; excitability; and gait and sensorimotor coordination etc.) provided no indication of adverse neurological effects. No significant effects were noted in parental females (Butenhoff et al., 2009).
The chemicals, PFHxS and PFOS, administered (6 and 3 mg/kg bw/day, respectively, daily for 4–6 weeks) to male mice (APOE*3-Leiden.CETP) caused significant reductions in triglycerides, total cholesterol, non-high density lipoprotein, high density lipoprotein, plasma ApoA1, low density lipoprotein, apoB production, free fatty acids and glycerol, and significantly increased liver weights, lipase activity and clearance of triolein. These effects were dependent on the alkyl chain length as PFBS had no significant effects in this study (Bijland et al., 2011).
PFOS had adverse health effects following repeated oral exposure. In general, oral exposure to PFOS and its salts resulted in hepatotoxicity and mortality; the dose-response curve for mortality was found to be very steep for rats and primates (NICNASb).
In comparison, direct precursors of PFBS are not considered to cause serious systemic effects from repeated oral exposure (NICNASd).
No data are available for the chemicals in this group.
No data are available for the chemicals in this group.
No data are available for the chemicals in this group. Based on results from negative in vitro and in vivo genotoxicity and mutagenicity studies for direct precursors of PFOS and PFBS (NICNASb; NICNASd), the chemicals in this group are not expected to be genotoxic.
No data are available for the chemicals in this group.
PFOS is classified as hazardous—Category 3 carcinogenic substance—with the risk phrase ‘Limited evidence of carcinogenic effect’ (Xn; R40 in the HSIS, Safe Work Australia). 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).
Histopathological changes in the liver and thyroid were observed in a repeated dose oral toxicity study with PFHxS.
In the absence of information, the chemicals in this group are recommended for classification (see Recommendation section). If data become available for the individual group members, they should be used to determine individual classifications.
Reproductive and Developmental Toxicity
In the only available animal study, PFHxS did not have an adverse effect on reproductive or developmental parameters in rats.
Some effects were seen in epidemiological studies in humans, but the significance of the observations is not clear. In these studies, levels of PFOS were typically an order of magnitude higher than those seen in human populations for PFHxS. Based on the weight of evidence from the available information, the chemicals in this group with <6 perfluorinated carbon chains are not considered to be reproductive/developmental toxins at low dose levels. However, in the absence of information for the chemicals with >6 perfluorinated carbons (CAS Nos. 60270-55-5, 68259-09-6 and 70225-15-9), developmental effects observed with PFOS cannot be ruled out and classification is warranted for these chemicals. If data become available for the individual group members, they should be used to determine individual classifications.
PFHxS was not a reproductive or developmental toxicant in rats (SD), exposed via gavage to up to 10 mg/kg bw/day as potassium PFHxS, for a period that included premating, gestation, and lactation (Butenhoff et al., 2009, see Repeated dose toxicity section). The offspring were potentially exposed via placental transfer in utero and through post-natal exposure via milk. There were no treatment-related reproductive (mating, fertility parameters in both males and females, birth outcome, gestation index, pregnancy rates and necroscopic examinations) or developmental effects in either the parents or offspring. The reproductive no observed adverse effect level (NOAEL) was 10 mg/kg bw/day, the highest dose tested.
Following a single treatment of potassium PFHxS (at 0, 0.61, 6.1 or 9.2 mg/kg bw) on PND 10 via gavage to NMRI mice, animals in the highest dose group exhibited changes in both spontaneous and nicotine-induced behaviour as adults (Viberg et al., 2013). This was similar to observations in similar experiments using PFOS, but the significance of these findings is not clear.
A recent study in 588 men from Greenland, Poland and Ukraine evaluated the possible association between PFC exposure and male semen quality. PFOS and PFHxS could be detected in >97 % of the samples. As for PFOS, a 35 % lower proportion of normal sperm was found at the highest tertile for PFHxS compared with the first, and a non-significant decrease in the proportion of normal sperm was also observed at the second tertile. However, PFHxS-induced effects could have been driven by effects of PFOS, which was measured at an ~20-fold higher concentration in the studied men (Toft et al., 2012).
A British study found that girls born to mothers with maternal serum concentrations of PFHxS in the upper tertile (>2.0 ng/mL) weighed significantly less at birth compared with girls born to mothers with serum concentrations in the lower tertile (<1.3 ng/mL). Birth length was also significantly lower. The models were adjusted for maternal smoking during pregnancy, maternal BMI, previous live births and gestational age. The babies weighed heavier at 20 months, but this was not statistically significant. Levels of PFOS were typically an order of magnitude higher than PFHxS. The magnitude of the differences in babies' birth weight, at 20 months and length by tertile was similar for PFOS (Maisonet et al., 2012). The study drew positive associations between maternal serum concentrations and markers of foetal and postnatal growth in girls.
Two other smaller Canadian studies did not find any significant associations between maternal PFHxS levels and foetal weight and length of gestation (Monroy et al., 2008; Hamm et al., 2010).
Taylor et al., (2014) observed a monotonic association between PFHxS exposure and menopause age using the National Health and Nutrition Examination Survey (NHANES) data, with women having higher concentrations after natural menopause. A positive association was also observed with the rate of hysterectomies. Levels of PFOS were typically an order of magnitude higher than PFHxS. Other studies have shown that association between perfluoroalkyl concentration and the menstrual cycle, whether delayed menarche or early onset menopause (including hysterectomies) are likely due to the underlying pharmacokinetics (clearance from the body) of perfluoroalkyls (Wu et al., 2015). Using PBPK models, Verner et al (2015) have shown that associations reported in epidemiological studies between perfluoroalkyl concentrations and birth weights are likely attributable to confounding by the maternal glomerular filtration rate.
PFOS did not have an adverse effect on the reproductive parameters in rats, but was toxic to development. Based on reduced birth weights, the NOAEL and the lowest observed adverse effect level (LOAEL) for the second generation of rodents (F2) were determined to be 0.1 mg/kg bw/day and 0.4 mg/kg bw/day, respectively (NICNASb). Based on animal data, PFBS was found not to be a reproductive or a developmental toxin (NICNASd).
Other Health Effects
Critical Health Effects
The chemicals in this group are slowly eliminated from the body following absorption. The critical health effects for risk characterisation include systemic long-term effects (hepatoxicity and developmental toxicity and benign tumours of the liver and the thyroid) from oral exposure. The chemicals can also cause eye irritation. The chemicals in this group with ≤6 perfluorinated carbon chains are not considered to be reproductive/developmental toxins at low dose levels. However, in the absence of information for the chemicals with >6 perfluorinated carbons (CAS Nos. 60270-55-5, 68259-09-6 and 70225-15-9), developmental effects similar to those observed for PFOS cannot be ruled out.
Public Risk Characterisation
Use in consumer products
Based on the available use information, the chemicals are not likely to be available for domestic or cosmetic uses. Hence, the public risk from direct use of these chemicals is not considered to be unreasonable.
Secondary exposure via the environment
Public exposure to the chemicals in this group could occur through secondary exposure via the environment. The chemicals in this group are not likely to be used in significant quantities in Australia. It is noted that the chemicals in this group could be present in the environment due to historic use, or due to release from articles or the use of chemicals not covered by this assessment. Median levels of PFHxS in Australian blood sera have not significantly changed from 2002 (Toms et al., 2014). In addition, PFHxS 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). Currently, 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. Further risk management will be determined as part of the IMAP Tier II Environment assessment report on these chemicals.
Occupational Risk Characterisation
Based on the available use information, the chemicals in this group are not likely to be used in significant quantities in Australia. Therefore, the chemicals are not considered to pose an unreasonable risk to the health of workers.
The data available support amendment to the hazard classification in the HSIS (Safe Work Australia) (refer to Recommendation section).
Currently, 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. Further risk management will be determined as part of the IMAP Tier II Environment assessment report for these chemicals.
It is recommended that this assessment be included in Appendix G (see NICNAS Handbook for Notifiers) as an additional source of toxicity data for chemicals that degrade to short-chain PFASs containing 5,6, and 7 perfluorinated carbons.
Any changes to the assessment outcomes under the action plan for chemicals that degrade to C5-C7 PFSA, will be considered as part of the IMAP assessment on the indirect precursors of these chemicals.
Work Health and Safety
The chemicals are recommended for classification and labelling under the current approved criteria and adopted GHS as below. This assessment does not consider classification of physical and environmental hazards.
Note 1: The developmental toxicity classification applies to only the chemicals with carbon chain lengths greater than >6 (CAS Nos. 60270-55-5, 68259-07-4 and 70225-15-9).
Note 2: If data become available for the individual group members, they should be used to determine individual classifications.
|Hazard||Approved Criteria (HSIS)a||GHS Classification (HCIS)b|
|Acute Toxicity||Harmful if swallowed (Xn; R22)||Toxic if swallowed - Cat. 3 (H301)|
|Irritation / Corrosivity||Irritating to eyes (Xi; R36)||Causes serious eye irritation - Cat. 2A (H319)|
|Repeat Dose Toxicity||Toxic: Danger of serious damage to health by prolonged exposure if swallowed (T; R48/25)||Causes damage to organs through prolonged or repeated exposure if swallowed - Cat. 1 (H372)|
|Carcinogenicity||Carc. Cat 3 - Limited evidence of a carcinogenic effect (Xn; R40)||Suspected of causing cancer - Cat. 2 (H351)|
|Reproductive and Developmental Toxicity||Repro. Cat 2 - May cause harm to the unborn child (T; R61) May cause harm to breastfed babies (Xn; R64)||May damage the unborn child - Cat. 1B (H360D) May cause harm to breast-fed children (H362)|
a Approved Criteria for Classifying Hazardous Substances [NOHSC:1008(2004)].
b Globally Harmonized System of Classification and Labelling of Chemicals (GHS) United Nations, 2009. Third Edition.
* Existing Hazard Classification. No change recommended to this classification
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;
- 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.
ATSDR (2009) Draft toxicological profile for perfluoroalkyls. Agency For Toxic Substances And Disease Registry. U.S. Department Of Health And Human Services Public Health Service, May 2009.
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.
Bijland S, Rensen PCN, Pieterman EJ, Maas ACE, van der Hoorn JW, van Erk MJ, Havekes LM, van Dijk KW, Chang SC, Ehresman DJ, Butenhoff JL and Princen HMG (2011). Perfluoroalkyl sulfonates cause alkyl chain length-dependent hepatic steatosis and hypolipidemia mainly by impairing lipoprotein production in APOE*3-leiden CETP mice. Toxicological Sciences 123(1), 290-303
Butenhoff JL, Chang S-M, Ehresman DJ and York RG (2009). Evaluation of potential reproductive and developmental toxicity of potassium perfluorohexanesulfonate in Sprague Dawley rats. Reproductive Toxicology 27:331-341
Calafat AM, Ye X, Silva MJ, Kuklenyik Z and Needham LL (2006). Human exposure assessment to environmental chemicals using biomonitoring. International Journal of Andrology 29(1):166-71
Food Standards Australia and New Zealand (2010). Survey of chemical migration from food contact packaging materials in Australian food. Accessed March 2015 at http://www.foodstandards.gov.au/consumer/chemicals/foodpackaging/Pages/default.aspx
Fromme H, Schlummer M, Möller A, Gruber L, Wolz G, Ungewiss J, Böhmer S, Dekant W, Mayer R, Liebl B and Twardella D (2007). Exposure of an adult population to perfluorinated substances using duplicate diet portions and biomonitoringdata. Environmental Science& Technology 41(22):7928-7933
Galleria Chemica. Accessed February 2015 at http://jr.chemwatch.net/galeria/ .
Giknis, M. L. A., Clifford, C. B. (2004). Compilation of spontaneous neoplastic lesions and survival in Crl:CDR (SD) rats from control groups. Charles River Laboratories.
Hamm MP, Cherry NM, Chan E, Martin JW, Burstyn I (2010). Maternal exposure to perfluorinated acids and fetal growth. J Expo Sci Environ Epidemiol 20, 589–597
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.
Karrman A, Ericson I, van Bavel B, Darnerud PO, Aune M, Glynn A, Lignell S and Lindstrom G (2007). Exposure of perfluorinated chemicals through lactation: levels of matched human milk and serum and a temporal trend, 1996-2004, in Sweden. Environmental Health Perspectives 115(2):226-30
Kato K, Wong LY, Jia LT, Kuklenyik Z and Calafat AM (2011). Trends in exposure to polyfluoroalkyl chemicals in the U.S. Population: 1999-2008. Environmental Science& Technology 45(19):8037-8045
Kim S, Choi K, Ji K, Seo J, Kho Y, Park J, Kim S, Park S, Hwang I, Jeon J, Yang H and Giesy JP (2011). Trans-Placental Transfer of Thirteen Perfluorinated Compounds and Relations with Fetal Thyroid Hormones. Environmental Science& Technology 45, 7465-7472
Maisonet M, Terrell ML, McGeehin MA, Christensen KY, Holmes A, Calafat AM and Marcus M (2012). Maternal concentrations of polyfluoroalkyl compounds during pregnancy and fetal and postnatal growth in British girls. Environmental Health Perspectives120(10):1432-1437
Monroy R, Morrison K, Teo K, Atkinson S, Kubwabo C, Stewart B and Foster WG (2008). Serum levels of perfluoroalkyl compounds in human maternal and umbilical cord blood samples. Environment Research 108, 56–62
National Industrial Chemicals Notification and Assessment Scheme (NICNAS). Perfluorinated chemicals (PFCs) factsheet. Available at https://www.nicnas.gov.au/chemical-information/factsheets/chemical-name/perfluorinated-chemicals-pfcs
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
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
NICNASc. Inventory Multi-tiered Assessment and Priorisation (IMAP): Human health Tier II assessment for Short chain PFCAs and its direct precursors. Accessed March 2015 at http://www.nicnas.gov.au
NICNASd. Tier II human health assessment for perfluorobutane sulfonate (PFBS) and its direct precursors. Australian Government Department of Health. Available at http://www.nicnas.gov.au
OECD (2011). Organisation for Economic Co-operation and Development (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.
OECD (2013), OECD/UNEP Global PFC Group, Synthesis paper on per- and polyfluorinated chemicals (PFCs), Environment, Health and Safety, Environment Directorate, OECD. Accessed January 2015 at http://www.oecd.org/env/ehs/risk-management/PFC_FINAL-Web.pdf
Olsen GW, Burris JM, Ehresman DJ, Froehlich JW, Seacat AM, Butenhoff JL and Zobel LR (2007). Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environmental Health Perspectives 115(9):1298-305
Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH). Accessed March 2015 at http://echa.europa.eu/information-on-chemicals/registered-substances
Safe Work Australia (SWA) Hazardous Substances Information System (HSIS). Accessed February 2015 at http://hsis.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.
So MK, Yamashita N, Taniyasu S, Jiang Q, Giesy JP, Chen K and Lam PKS (2006). Health risks in infants associated with exposure to perfluorinated compounds in human breast milk from Zhoushan, China. Environmental Science Technology 40:2924-2929
Sundstorm M, Chang S-C, Noker, P, Gorman G, Hart JA, Ehresman DJ, Bergman A and Butenhoff JL (2012). Comparitive pharmacokinetics of perfluorohexanesulfonate (PFHxS) in rats, mice, and monkeys. Reproductive Toxicology 33:441-451
Sundstrom M, Ehresman DJ, Bignert A, Butenhoff JL, Olsen GW, Chang SC, BergmanA (2011) A temporal trend study (1972-2008) of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in pooled human milk samples from Stockholm, Sweden. Environ Int 37:178-83.
Taylor KW, Hoffman K, Thayer KA and Daniels JL (2014). Polyfluoroalkyl chemicals and menopause among women 20-65 years of age (NHANES). Environmental Health Perspectives 122(2):145-150
Toft G,Jonsson BA, Lindh CH, Giwercman A, Spano M, Heederik D, Lenters V, Vermeulen R, Rylander L, Pedersen HS, Ludwicki JK, Zviezdai V and Bonde JP (2012). Exposure to perfluorinated compounds and human semen quality in Arctic and European populations. Human Reproduction 27(8):2532-40
Toms LM, Thompson J, Rotander A, Hobson P, Calafat AM, Kato K, Ye X, Broomhall S, Harden F, Mueller JF (2014). Decline in perfluorooctane sulfonate and perfluorooctanoate serum concentrations in an Australian population from 2002 to 2011. Environ Int. Oct;71:74-80.
United States (US) Personal Care Product Council International Nomenclature of Cosmetic Ingredients (INCI) dictionary. Accessed March 2015 at http://gov.personalcarecouncil.org/jsp/gov/GovHomePage.jsp
US Department of Health and Human Services, Household Products Database (HHPD), health and safety information on household products. Accessed March 2015 at http://householdproducts.nlm.nih.gov/
US EPA (2002). United States Environmental Protection Agency (US EPA): 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
US EPA (2007). United States Environmental Protection Agency (US EPA): Perfluoroalkyl Sulfonates; Significant New Use Rule [SNUR], Docket ID: EPA-HQ-OPPT-2005-0015 accessed March 2015 at http://www.epa.gov/oppt/pfoa/pubs/pfas.html
Verner M-A, Loccisano AE, Morken N-H, Yoon M, Wu H, Mcdougall R, Maisonet M, Marcus M, Kishi R, Miyashita C, Chen M-H, Hsieh W-S, Andersen ME, Clewell III HJ and Longnecker MP (2015) Associations of perfluoroalkyl substances (PFAS) with Lower birth weight: an evaluation of potential confounding by glomerular filtration rate using a physiologically based pharmacokinetic model (PBPK). Environmental Health Perspectives. Http://dx.doi.org/10.1289/ehp.1408837.
Viberg H, Lee I and Eriksson P(2013). Adult dose-dependent behavioral and cognitive disturbances after a single neonatal PFHxS dose.Toxicology 304:185-91
Wu H, Yoon M, Verner M-A, Xue J, Luo M, Anderson ME, Longnecker MP and Clewelll HJ (2015). Can the observed association between serum perfluoroalkyl substances and delayed menarche be explained on the basis of puberty-related changes in physiology and pharmacokinetics? Environment International. 82: 61–68.
Yeung LW, So MK, Jiang G, Taniyasu S, Yamashita N, Song M, Wu Y, Li J, Giesy JP, Guruge KS and Lam PK (2006). Perfluorooctanesulfonate and related fluorochemicals in human blood samples from China. Environmental Science& Technology 40(3):715-20