GHS Classification Result
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 335-67-1 |
| Chemical Name | Perfluorooctanic acid |
| Substance ID | H27-B-028/C-049B_P |
| Classification year (FY) | FY2015 |
| Ministry who conducted the classification | Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE) |
| New/Revised | Revised |
| Classification result in other fiscal year | FY2012 |
| Download of Excel format | Excel file |
REFERENCE INFORMATION
| Item | Information |
|---|---|
| Guidance used for the classification (External link) | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| UN GHS document (External link) | UN GHS document |
| Definitions/Abbreviations (Excel file) | Definitions/Abbreviations |
| Model Label by MHLW (External link) | MHLW Website (in Japanese Only) |
| Model SDS by MHLW (External link) | MHLW Website (in Japanese Only) |
| OECD/eChemPortal (External link) | eChemPortal |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 1 | Explosives | Not applicable |
- |
- | - | There are no chemical groups present in the molecule associated with explosive properties. |
| 2 | Flammable gases (including chemically unstable gases) | Not applicable |
- |
- | - | "Solids" according to GHS definition. |
| 3 | Aerosols | Not applicable |
- |
- | - | Not an aerosol product. |
| 4 | Oxidizing gases | Not applicable |
- |
- | - | "Solids" according to GHS definition. |
| 5 | Gases under pressure | Not applicable |
- |
- | - | "Solids" according to GHS definition. |
| 6 | Flammable liquids | Not applicable |
- |
- | - | "Solids" according to GHS definition. |
| 7 | Flammable solids | Classification not possible |
- |
- | - | The classification is not possible due to no data. Besides, it is written that it is flammable (ICSC (1997)). |
| 8 | Self-reactive substances and mixtures | Not applicable |
- |
- | - | There are no chemical groups present in the molecule associated with explosive or self-reactive properties. |
| 9 | Pyrophoric liquids | Not applicable |
- |
- | - | "Solids" according to GHS definition. |
| 10 | Pyrophoric solids | Not classified |
- |
- | - | It is practically non-flammable (HSDB (Access on June 2015)). |
| 11 | Self-heating substances and mixtures | Not classified |
- |
- | - | It is non-flammable (NITE Chemical Risk Information Platform (Access on June 2015)). |
| 12 | Substances and mixtures which, in contact with water, emit flammable gases | Not applicable |
- |
- | - | Not containing metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At). |
| 13 | Oxidizing liquids | Not applicable |
- |
- | - | "Solids" according to GHS definition. |
| 14 | Oxidizing solids | Not applicable |
- |
- | - | It is an organic compound which does not contain chlorine but contains oxygen and fluorine, and these elements are not chemically bonded to the elements other than carbon or hydrogen. |
| 15 | Organic peroxides | Not applicable |
- |
- | - | It is an organic compound that does not contain bivalent -O-O- structure in the molecule. |
| 16 | Corrosive to metals | Classification not possible |
- |
- | - | The classification is not possible because a solid with a melting point of 55 degrees C or lower has no data. Besides, there is the information that it corrodes many metals (ICSC (2005)). |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 1 | Acute toxicity (Oral) | Category 4 |
 Warning |
H302 | P301+P312 P264 P270 P330 P501 |
As LD50 values for rats, there are two reports of 500-1,000 mg/kg (males) and 250-1,000 mg/kg (females) (OEL Documentations (Japan Society For Occupational Health, 2008)). Because one corresponds to Category 4, and the category cannot be determined from the other, it was classified in Category 4. The category was revised by adding information of OEL Documentations (Japan Society For Occupational Health, 2008), which was obtained in this investigation. |
| 1 | Acute toxicity (Dermal) | Classification not possible |
- |
- | - | Classification is not possible due to lack of data. Besides, as LD50 values of the ammonium salt of this substance (ammonium perfluorooctanoate CAS RN: 3825-26-1), 7,000 mg/kg (males) and > 7,500 mg/kg (females) (Environmental Risk Assessment for Chemical Substances Vol. 9 (Ministry of the Environment, 2011), SIDS (2009)) are reported for rats, and > 2,000 mg/kg (SIDS (2009)) and 4,300 mg/kg (Environmental Risk Assessment for Chemical Substances Vol. 9 (Ministry of the Environment, 2011), SIDS (2009)) are reported for rabbits. |
| 1 | Acute toxicity (Inhalation: Gases) | Not applicable |
- |
- | - | "Solids" according to GHS definition. |
| 1 | Acute toxicity (Inhalation: Vapours) | Not applicable |
- |
- | - | "Solids" according to GHS definition. |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Classification not possible |
- |
- | - | Classification is not possible due to lack of data. As an LC50 value (4 hours) for rats of the ammonium salt of this substance (ammonium perfluorooctanoate CAS RN: 3825-26-1), 980 mg/m3 is reported (Environmental Risk Assessment for Chemical Substances Vol. 9 (Ministry of the Environment, 2011), SIDS (2009)). Besides, because it is described that the test was conducted on dust, and the LC50 value is larger than the saturated vapour pressure concentration, 0.0014 mg/L, the test substance was regarded as dust/mist. |
| 2 | Skin corrosion/irritation | Category 2 |
Warning |
H315 | P302+P352 P332+P313 P362+P364 P264 P280 P321 |
There is no specific information, but because it is written that this substance is irritating to skin (Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan (2011)), it was classified in Category 2. |
| 3 | Serious eye damage/eye irritation | Category 1 |
 Danger |
H318 | P305+P351+P338 P280 P310 |
Because an aqueous solution of this substance is a strong acid (pH2.6, SIDS (2009)) and strongly irritating to eyes (GESTIS (Access on July)), it was classified in Category 1. Moreover, it is written that this substance is irritating to eyes (Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan (2011)). Besides, this substance is classified in "Eye Dam. 1 H318" in EU CLP classification (ECHA CL Inventory (Access on June 2015)). |
| 4 | Respiratory sensitization | Classification not possible |
- |
- | - | Due to lack of data, the classification is not possible. |
| 4 | Skin sensitization | Classification not possible |
- |
- | - | The classification is not possible due to lack of data. Besides, it is reported that in a Buehler test using guinea pigs, sensitization was not observed after application of salt of this substance (unknown details) (GESTIS (Access on July 2015)). |
| 5 | Germ cell mutagenicity | Classification not possible |
- |
- | - | The classification is not possible due to lack of data. As for in vivo, it is reported that a micronucleus test using mouse bone marrow cells was negative (SIDS (2009); Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan (2011)), and in a micronucleus test using rat peripheral blood erythrocytes, the results of negative in females but positive in males were shown (NTP DB (Access on August 2015)), however, the NTP's data was not written in the evaluation document. As for in vitro, a bacterial reverse mutation test, a gene mutation test in cultured mammalian cells and a chromosomal aberration test in human lymphocytes were negative, but there are positive results in a chromosomal aberration test in cultured mammalian cells and a micronucleus test and comet assay (a DNA damage test) in HepG2, human cultured hepatocytes (SIDS (2009); Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan (2011); Rationale for setting the Recommendation of Acceptable Concentration of the Japan Society for Occupational Health (2008); NTP DB (Access on August 2015)). From the above, due to no clear information on in vivo mutagenicity of this substance, it was classified as "Classification not possible." |
| 6 | Carcinogenicity | Category 2 |
 Warning |
H351 | P308+P313 P201 P202 P280 P405 P501 |
In a cohort study in workers who worked more than one year in 1947-1997 at US plants manufacturing this substance, significant cancer formation was not shown (Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan (2011)). On the other hand, investigation of cancer incidence situations in workers at US fluorine chemistry plants using this substance in 1959-2001 revealed that Standardized Incidence Ratio (SIR) was significantly high as 1.9 (95% CI: 1.15-3.07) for bladder cancer and 2.3 (95% CI: 1.36-3.65) for kidney and urinary organ cancer. Moreover, although not significant SIR, it is reported that increased SIR was also observed for myeloid leukemia (SIR 2.02), laryngeal cancer (SIR 1.77), multiple myeloma and immune cell proliferative disease (SIR 1.72), malignant melanoma (SIR 1.3), testicular cancer (SIR 1.46), and brain tumor (SIR 1.2), but it is written that the relationship with this substance was unknown because worker exposure information and usage conditions of other chemical substance and so on were not described (Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan (2011)). As for experimental animals, in a carcinogenicity test in male and female rats in 2-year diet administration with ammonium salt of this substance (APFO), in high-dose administration (300 ppm: 14.2-16.1 mg/kg/day), increased incidences in testicular Leydig cell adenoma in males and hepatocellular carcinoma and mammary fibroadenoma in females were observed, but it was judged that mammary tumor in females was not effect of exposure to this substance from natural incidence in the same strain (SIDS (2009); Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan (2011)). Moreover, it is reported that in a test in male rats of the strain (SD) in 2-year diet administration with APFO at 300 ppm (13.6 mg/kg/day), significantly increased incidences of hepatocellular adenoma, testicular Leydig cell adenoma, pancreas acinar cell adenoma or carcinoma were observed (SIDS (2009); Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan (2011)). From the above 2 test results, exposure to this substance provoked increased formation of liver tumors in males and females and testicular and pancreatic tumors in males in rats, and mode of action was investigated, and it is thought in SIDS that liver and testicular tumors besides pancreatic tumor was caused by peroxisome proliferation via peroxisome alfa receptor and mode of action for pancreatic tumor formation is unknown (SIDS (2009)). A conclusion has not been reached at this time on interspecific extrapolation, whether tumor formation by peroxisome proliferation in rodents occurs in humans (ECHA RAC Opinion (2014)), but IARC classified this substance in Group 2B in carcinogenicity (IARC vol. 110, in prep), and EU also classified in Carc. 2 in CLP classification (ECHA CL Inventory (Access on June 2015)). By taking the above into account, it was judged that classification in Category 2 is appropriate in this hazard class. |
| 7 | Reproductive toxicity | Category 1A, Additional category: Effects on or via lactation |
Danger |
H360 H362 |
P308+P313 P201 P202 P280 P405 P501 |
As for humans, as a relationship between exposure to this substance and fetal toxicity, at the same time as multiple negative reports, there exist multiple reports suggesting the relationship mentioned below (Rationale for setting the Recommendation of Acceptable Concentration of the Japan Society for Occupational Health (2014)). It is reported that in a multicenter cross-sectional study by Departments of Obstetrics and Gynecology in city of Baltimore in the US, increased trend in risk of delivering babies with lower body weight was observed in pregnant women who had high level of this substance (PFOA) in umbilical blood, and in the Danish large-scale cohort study, significant negative association between serum PFOA levels in pregnant women and birth body weight was observed, and it is also reported in the UK follow-up study of mothers and children that serum PFOA levels in pregnant women were associated with a decrease in birth body weight (Rationale for setting the Recommendation of Acceptable Concentration of the Japan Society for Occupational Health (2014)). Furthermore, it is written that in a Chinese report, a relationship between this substance excreted into body milk and health effects in nursing infants was suggested (SIDS (2009)). As for experimental animals, there are test results using ammonium salt of this substance (APFO). In a two-generation reproductive gavage administration toxicity test in rats, F1 offspring showed a lower trend in body weight, increased mortality soon after weaning and delayed sexual maturation at the doses (1-10 mg/kg/day) where effects (increased liver weight, decreased body weight and body weight gain) were observed in F0 and F1 parent animals (SIDS (2009); Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan (2011)). On the other hand, in a developmental toxicity test using APFO in which pregnant rats were administered in an oral and inhalation route during an organogenetic period (day 6-15 of gestation), no or fetal toxicity was not observed or only slight lower fetal weight even at the doses (oral: 50-150 mg/kg/day, inhalation: 10-25 mg/m3) where marked maternal toxicity (deaths (3/25 (oral); 2/13 (inhalation)), lethargy, decreased body weight and food consumption and so on) occurred (SIDS (2009), Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan (2011)). However, in a developmental toxicity test in pregnant mice in gavage administration with APFO on day 1-17 of gestation, maternal animals showed increased liver weight at 1 mg/kg/day or higher, weight gain reduction, increased maternal animals with resorption of all embryos at 5 mg/kg/day or above, and all animals had complete loss of embryos/fetuses at 40 mg/kg/day. As genetic/developmental toxicity effects in newborns/fetuses, acceleration of preputial separation at 1 mg/kg/day or higher, delayed growth after weaning at 3 mg/kg/day or above, increased stillborn pups and deaths of newborns, increased fetuses with defects of extremities and tails, delays in eye-opening day at 5 mg/kg/day or higher, and delayed vaginal opening, delayed estrous cycle and delayed preputial separation at 20 mg/kg/day were observed. Both maternal and fetal toxicity occurred to a greater degree in mice than in rats, and a species difference was suggested for developmental toxicity (SIDS (2009); Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan (2011)). Furthermore, in a test administered during gestation and lactation periods in which pregnant rats were administered by gavage with AFPO (3-30 mg/kg/day) from day 4 of gestation, and maternal animals were kept dosing after parturition until weaning of newborns, PFOA was detected not only in serum but in milk in maternal animals, and a dose-dependent increase in PFOA concentration in milk was observed (SIDS (2009)). As the classifications by other organizations, Japan Society for Occupational Health classified in "reproductive toxicity Group 1" stating that fetal toxicity in an epidemiological study in humans, and fetal and developmental toxicity in experimental animals are apparent (Rationale for setting the Recommendation of Acceptable Concentration of the Japan Society for Occupational Health (2014)), and it is classified in "Repr1B & Lact." in EU CLP classification (ECHA CL Inventory (Access on June 2015)). From the above, based on the classification result by Japan Society for Occupational Health, the substance was classified in Category 1A in this hazard class, and category for effects on or via lactation was added. |
| 8 | Specific target organ toxicity - Single exposure | Category 3 (respiratory tract irritation, narcotic effects) |
Warning |
H335 H336 |
P304+P340 P403+P233 P261 P271 P312 P405 P501 |
This substance is irritating to the respiratory tract (Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan (2011)). As for humans, a cough and pharyngalgia in inhalation exposure and abdominal pain, nausea, and vomiting in oral ingestion were described (Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan (2011)). As for experimental animals, nasal discharge and dry rales at 18,600 mg/m3 (18.6 mg/L) (corresponding to above Category 2), stomach irritation at doses of 380 mg/m3 (0.38 mg/L) (corresponding to Category 1) or higher were observed, and surviving rats at 100-2,150 mg/kg (corresponding to the dose higher than Category 1) showed eyelid ptosis, piloerection, hypoactivity, decreased tone in extremities, and incoordination (ATSDR (2009)). From the above, this substance was judged to have narcotic effects in addition to respiratory tract irritation, and it was classified in Category 3 (respiratory tract irritation, narcotic effects). By adding new information, the previous classification was revised. |
| 9 | Specific target organ toxicity - Repeated exposure | Category 1 (central nervous system, liver), Category 2 (bone marrow) |
Danger Warning |
H372 H373 |
P260 P264 P270 P314 P501 |
There is no human information. As for experimental animals, there are test results using ammonium salt of this substance. In a 13-week diet administration toxicity test using rats, increased liver weight and hepatocellular hypertrophy in the liver were observed at 5.64-7.7 mg/kg/day (Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan (2011); SIDS (2009)). In a 90-day gavage administration toxicity test using rhesus monkeys, at 30 mg/kg/day, deaths (1 males, 2 females), decreased activity, ataxia, swollen face, decreased body weight, a decreased number of bone marrow cells, atrophy of lymphoid follicles in the spleen and lymph nodes were found, and dead animals showed diffuse lipid depletion in the adrenals (Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan (2011); SIDS (2009)). Moreover, in a 26-week gavage administration toxicity test using cynomolgus monkeys, hindlimb paralysis, ataxia, and decreased reaction to pain stimulus were observed at 3 mg/kg/day (Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan (2011); Rationale for setting the Recommendation of Acceptable Concentration of the Japan Society for Occupational Health (2008); SIDS (2009)). In a 2-week inhalation toxicity test using rats, increased ALP, increased absolute/relative liver weight, swelling, hepatocellular hypertrophy/necrosis, and localized multifocal hepatocellular necrosis in the liver were observed at 7.6 mg/m3 (converted to a Guidance value equivalent: 0.0008 mg/L) (Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan (2011)). As above, liver, central nervous system, and bone marrow are thought to be target organs, and effects on the liver within a range of Category 1, effects on the central nervous system within a range of Category1 and 2, and effects on bone marrow within a range of Category 2 were found. Therefore, the substance was classified in Category 1 (central nervous system, liver), Category 2 (bone marrow). Besides, as for humans, in multiple epidemiological surveys, an apparent relationship between exposure to this substance and effects on liver function and serum lipid was not observed (Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan (2011); Rationale for setting the Recommendation of Acceptable Concentration of the Japan Society for Occupational Health (2008); SIDS (2009)). |
| 10 | Aspiration hazard | Classification not possible |
- |
- | - | Due to lack of data, the classification is not possible. |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 11 | Hazardous to the aquatic environment (Acute) | Category 3 |
- |
H402 | P273 P501 |
From 72-hour ErC50 = 90 mg/L for algae (Pseudokirchneriella subcapitata) (SIDS, 2009), it was classified in Category 3. |
| 11 | Hazardous to the aquatic environment (Long-term) | Not classified |
- |
- | - | Although being not rapidly degradable (hardly degradable, BOD: 5%, TOC : 3%, HPLC: 0% (Official Bulletin of Economy, Trade and Industry, 2002)), due to 96-hour NOEC = 10.9 mg/L for algae (Pseudokirchneriella subcapitata), 7-day NOEC (reproduction) = 3.125 mg/L for crustacea (Moinidae), and 85-day NOEC (growth and lethal) = 38.4 mg/L for fish (Oncorhynchus mykiss (embryos)) (all Result of the initial environmental risk assessment of chemicals, Vol. 9, Ministry of the Environment in Japan, 2011), it was classified as "Not classified." |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | No data. |
NOTE:
| * A blank or "-" in a cell of classification denotes that the classification of the hazard class was not conducted. * Hazard_statement_and/or_Precautionary_statement will show when hovering the mouse over a code of Hazard_statement_and/or_Precautionary_statement. Hazard_statement_and/or_Precautionary_statement are also provided in the Excel file. * Classification was conducted by relevant Japanese Ministries in accordance with GHS Classification Guidance for the Japanese Government, and is intended to provide a reference for preparing GHS labelling and SDS for users. * This is a provisional English translation of classification results and is subject to revision without notice. * The responsibility for any resulting GHS labelling and SDS referenced from this site is with users. * Codes assigned to each of the hazard statements and codes for each of the precautionary statement are based on the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) in United Nations. |