NITE - Chemical Management Field

GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	80-05-7
Chemical Name	Bisphenol A
Substance ID	H28-B-044, C-064B
Classification year (FY)	FY2016
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	FY2006
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

PHYSICAL HAZARDS

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 associated with explosive properties present in the molecule.
2	Flammable gases (including chemically unstable gases)	Not applicable	- -	-	-	Solid (GHS definition).
3	Aerosols	Not applicable	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not applicable	- -	-	-	Solid (GHS definition).
5	Gases under pressure	Not applicable	- -	-	-	Solid (GHS definition).
6	Flammable liquids	Not applicable	- -	-	-	Solid (GHS definition).
7	Flammable solids	Classification not possible	- -	-	-	It is combustible, but the classification is not possible due to no data.
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	- -	-	-	Solid (GHS definition).
10	Pyrophoric solids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 510-570 deg C (ICSC(J) (2011)).
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	No data available.
12	Substances and mixtures which, in contact with water, emit flammable gases	Not applicable	- -	-	-	The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At).
13	Oxidizing liquids	Not applicable	- -	-	-	Solid (GHS definition).
14	Oxidizing solids	Not applicable	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.
15	Organic peroxides	Not applicable	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to solid substances are not available.

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Not classified	- -	-	-	There are 3 reported LD50 values for rats of 3,300 mg/kg, 4,100 mg/kg (EU-RAR (2010), HSDB (Access on June 2016)), 5,000 mg/kg (EU-RAR (2010)). On the basis of them, it was classified as "Not classified" (Category 5 in UN GHS classification). The category was revised based on newly obtained information.
1	Acute toxicity (Dermal)	Not classified	- -	-	-	On the basis of the 3 reported LD50 values of >2,000 mg/kg (EU-RAR (2010)), 3,000 mg/kg, 3,600 mg/kg (HSDB (Access on June 2016)) for rabbits, it was classified as "Not classified" (Category 5 in UN GHS classification). The category was revised based on newly obtained information.
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	Solid (GHS definition)
1	Acute toxicity (Inhalation: Vapours)	Not applicable	- -	-	-	Solid (GHS definition)
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	Classification not possible due to lack of data. Though there is a reported LC50 value (6 hours) for rats of > 0.17 mg/L (4-hour equivalent value: > 0.11 mg/L) (EU-RAR (2010), DFGOT vol.13 (1999), BUA 203 (1995)), category could not be specified by only this value, therefore, the classification was not possible.
2	Skin corrosion/irritation	Not classified	- -	-	-	Because in the result of a skin irritation test using rabbits (4-hour application, OECD TG 404), skin irritation was not observed (DFGOT suppl (2011), EU-RAR (2010)), it was classified as "Not classified."
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	In an eye irritation test using rabbits (OECD TG 405), effects on the cornea and iris were observed continuously for 28 days after application (DFGOT suppl (2011), EU-RAR (2010)). In addition, because slight-moderate irritation was reported in rabbits (DFGOT vol. 13 (1999)), it was judged that it causes eye damage, therefore, it was classified in Category 1.
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	In a skin sensitization test in guinea pigs by Buehler test, positive reaction was observed in 12.5% (2 of the 16 animals) by challenge with a 50% solution (DFGOT suppl (2011)), but it was below 15% of the guidance value. In addition, a maximization test in guinea pigs was negative (DFGOT vol. 13 (1999)), and a skin sensitization tests using mice (modified LLNA test) was negative by challenge with a 30% solution (DFGOT suppl (2011), EU-RAR (2010)). On the other hand, as for humans, in patch tests for workers who handled epoxy compounds etc. in addition to this substance and developed dermatitis, cases showing positive response to this substance were observed (EU-RAR (2010)), but it is also reported that in epidemiology surveys on workers of plants manufacturing this substance, all of 110-500 workers were negative in skin sensitization (EU-RAR (2010), DFGOT vol. 13 (1999)). This substance is listed as a sensitizer in a contact allergen list (Frosch et al. Contact Dermatitis 5th Ed. (2011)). As above, though there are reports that many of animal tests and epidemiology surveys in humans were negative, it was classified in Category 1 because clear evidence is insufficient. This substance was classified as "Skin sens. 1 H317" in EU CLP classification (ECHA C&L Inventory (Access on December 2015)). In addition, the information on skin sensitization of the Japanese Society for Dermatoallergology and Contact Dermatitis adopted in the previous classification was not available in this investigation.
5	Germ cell mutagenicity	Classification not possible	- -	-	-	Because it was not possible to classify a substance as "Not classified" according to the revised GHS classification guidance for the Japanese government, it was classified as "Classification not possible." As for in vivo, micronucleus tests using bone marrow cells of rats and mice were negative, chromosome aberration tests using bone marrow cells of mice gave positive and negative results, a sister chromatid exchange test using bone marrow cells of mice was negative, and DNA adduct formation tests using liver cells of rats were positive (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), EU-RAR (2010), DFGOT suppl (2011), Environmental Risk Assessment for Chemical Substances vol. 3 (Ministry of the Environment, 2004), NTP DB (Access on June 2016)). As for in vitro, results were negative in bacterial reverse mutation tests, for cultured mammalian cells, negative in mouse lymphoma tests, positive and negative results in mutagenicity tests, positive in micronucleus tests, positive and negative in chromosome aberration tests and sister chromatid exchange tests (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), EU-RAR (2010), DFGOT suppl (2011), Environmental Risk Assessment for Chemical Substances vol. 3 (Ministry of the Environment, 2004)). Besides, it is concluded in EU-RAR (2010) that this substance does not have significant mutagenic potential in vivo.
6	Carcinogenicity	Classification not possible	- -	-	-	In 2-year carcinogenicity tests using rats or mice by oral route (diet administration), the evidence of carcinogenicity was not shown in either rats or mice (NTP TR 215 (1982), EU-RAR (2010)). After that, in investigating promoting activity of this substance using multiple initiators, a promoting effect on the carcinogenesis was not detected in multiple organs (EU-RAR (2010)). In addition, it is reported that preneoplastic and neoplastic lesions were observed in mammary glands of animals exposed to this substance in prenatal period. However, in addition to technical problems in evaluation methodology and suspected reliability, preneoplastic lesions in mammary gland were not observed consistently in several reproductive toxicity tests, therefore, it was concluded that there was insufficient evidence of carcinogenicity (EU-RAR (2010)). Even in additional studies in which this substance was administered in prenatal and neonatal period, the evidence indicating promoting effect was not obtained. This supports the initial conclusion that the substance does not have carcinogenic potential based on the results of the 2-year carcinogenicity tests, and taking into account the data in experimental animals, EU concluded that it was suggested this substance does not have carcinogenic potential (EU-RAR (2010)). As above, it can be considered as "Not classified" from the conclusion of EU. However, because the information on carcinogenicity in non-oral routes such as inhalation or dermal is insufficient, it was classified as "Classification Not Possible" for this hazard class.
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	Though in a 2-generation study using rats dosed at low doses (0.2 - 200 microg/kg/day), no effect on fertility was observed, in a 3-generation study using rats, each generation at 500 mg/kg/day showed reproductive toxicity (reduction in litter size) along with general toxicity (reduction in body weight (male, female) and renal tubular denaturation (female only)) (EU-RAR (2010)). In addition, in a 2-generation study in which mice were dosed from very low dose to high dose (0.003 - 600 mg/kg/day), no effect on fertility was observed, and in a continuous breeding study using mice, in F0 at 600 mg/kg/day or above, the numbers of litters decreased, and reductions in litter size and numbers of live pups per litter were continuously observed in each of the 4-5 litters. These reproductive effects were observed at the dose without general toxicity in parent animals (EU-RAR (2010)). Through the reproductive toxicity studies above, NOAEL of 50 mg/kg/day was set for reproductive toxicity from the 3-generation study in rats. On the other hand, in standard development toxicity studies using rats or mice, no evidence that bisphenol A is development toxicant was obtained. However, in the above 3-generation study in rats, lower tendency in body weights by weaning and delays in sexual maturation were observed at 500 mg/kg in F1-F3 offspring, and also in a 2-generation reproductive toxicity study using mice, at 600 mg/kg/day, along with lower body weights of F1 offspring, undescended testes and seminiferous tubule hypoplasia in F1 and F2 offspring at weaning were observed. Effects on generation/development in next generation were indicated (EU-RAR (2010)). As above, for this substance, there is sufficient evidence indicating reproductive/developmental toxicity in experimental animals, and especially in the continuous breeding study in mice, decreased fertility was found at doses without general toxicity in parent animals, therefore, it was classified in Category 1B for this hazard class. Besides, EU classified the reproductive toxicity of this substance as Repr. 1B (ECHA C&L Inventory (Access on December 2015)).
8	Specific target organ toxicity - Single exposure	Category 1 (respiratory organs), Category 3 (narcotic effects)	Danger Warning	H370 H336	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	There is no data on a single exposure to this substance in humans. As for experimental animals, it is described that in a single inhalation exposure study in rats, slight inflammation of the epithelium lining of the nose and slight ulceration of the oronasal mucosa were observed at a dose within the guidance value range of Category 1 (EU-RAR (2010)). In addition, it is described that in a single oral dose test in rats, lethargy and prostration were observed at 2,000 mg/kg/day though no animals died (EU-RAR (2010)). Moreover, it is reported that in a single oral administration to rats, mice and rabbits, excitation, followed by atonia, muscular spasms, ataxia, diarrhea, and diuresis were observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), DFGOT vol. 13 (1999)). From the above, it was classified in Category 1 (respiratory organs) and Category 3 (narcotic effects).
9	Specific target organ toxicity - Repeated exposure	Category 2 (gastrointestinal tract, respiratory organs)	Warning	H373	P260 P314 P501	There is no information in humans. In a 28-32-day repeated dose toxicity test using rats dosed by gavage, effects on the gastrointestinal tract (hyperplasia of colonic mucous membrane, central lacteal dilatation of the duodenum and jejunum) were reported at 200 mg/kg/day (28-day administration, converted guidance value: 62 mg/kg/day) corresponding to Category 2 (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). In addition, in an inhalation toxicity test using rats, effects on the respiratory organs (inflammation of the nasal cavity and respiratory mucosa, hyperplasia of squamous cells) were reported at 50 mg/m3 (6 hours/day, 65-day exposure: converted guidance value; 0.036 mg/L) corresponding to Category 2 (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), DFGOT suppl (2011), EU-RAR (2010)). Besides, in the previous classification, the liver and kidney were adopted as target organs in Category 2, but the liver was not adopted as a target organ because only hypertrophy of centrilobular hepatocytes was found at a dose corresponding to Category 2. As for the kidney, degeneration and necrosis of renal tubules were reported, but they were observed at a dose above the range of Category 2, thus, it was not adopted as a target organ. Therefore, it was classified in Category 2 (gastrointestinal tract, respiratory organs).
10	Aspiration hazard	Classification not possible	- -	-	-	Classification not possible due to lack of data.

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
11	Hazardous to the aquatic environment (Acute)	Category 2	- -	H401	P273 P501	From 96-hour LC50 = 1.1 mg/L for crustacea (Mysidopsis bahia) (ECETOC TR91, 2003; EU-RAR, 2010; Initial Risk Assessment (NITE, CERI, NEDO, 2005); Environmental Risk Assessment for Chemical Substances vol. 3 (Ministry of the Environment, 2004)), it was classified in Category 2.
11	Hazardous to the aquatic environment (Long-term)	Category 2	-	H411	P273 P391 P501	Due to being not rapidly degradable (a degradation rate by 2-week BOD: 0% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1977)), and 164-day NOEC = 0.16 mg/L for fish (Pimephales promelas) (Initial Risk Assessment (NITE, CERI, NEDO, 2005), Environmental Risk Assessment for Chemical Substances vol. 3 (Ministry of the Environment, 2004)), it was classified in Category 2.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	No data available.

NOTE:

* A blank or "-" in a cell of classification denotes that the classification of the hazard class was not conducted.
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* 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.

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