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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	79-94-7
Chemical Name	Tetrabromobisphenol A
Substance ID	R01-B-002
Classification year (FY)	FY2019
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	FY2015
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	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified (Not applicable)."
2	Flammable gases	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
3	Aerosols	*	- -	-	-	Not aerosol products. It was classified as "Not classified (Not applicable)."
4	Oxidizing gases	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
5	Gases under pressure	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
6	Flammable liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
7	Flammable solids	*	- -	-	-	It was classified as "Not classified" from information that it is not combustible (GESTIS (Access on May 2019)).
8	Self-reactive substances and mixtures	*	- -	-	-	There are no chemical groups associated with explosive or self-reactive properties present in the molecule. It was classified as "Not classified (Not applicable)."
9	Pyrophoric liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
10	Pyrophoric solids	*	- -	-	-	It was classified as "Not classified" from information that it is not combustible (GESTIS (Access on May 2019)).
11	Self-heating substances and mixtures	*	- -	-	-	It was classified as "Not classified" from information that it is not combustible (GESTIS (Access on May 2019)).
12	Substances and mixtures which, in contact with water, emit flammable gases	*	- -	-	-	The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At). It was classified as "Not classified (Not applicable)."
13	Oxidizing liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
14	Oxidizing solids	*	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen. It was classified as "Not classified (Not applicable)."
15	Organic peroxides	*	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified (Not applicable)."
16	Corrosive to metals	*	- -	-	-	Classification is not possible because test methods applicable to solid substances are not available.
17	Desensitized explosives	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified."

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	*	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it corresponds to "Not classified" in accordance with the GHS Classification Guidance for the Japanese Government (Category 5 in UN GHS classification) or "Not classified." It was classified as "Not classified." [Evidence Data] (1) LD50 for rats: > 2,000 mg/kg (JECDB (Access on May 2015), NTP TR587 (2014), EHC 172 (1995)) (2) LD50 for rats: > 5,000 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.1, (Ministry of the Environment (2002)), EHC 172 (1995)). (3) LD50 for rats: > 50,000 mg/kg (EU-RAR (2006))
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) LD50 for rabbits: > 1,000 mg/kg (NTP TR587 (2014)) (2) LD50 for rabbits: > 2,000 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.1 (Ministry of the Environment (2002)), EHC 172 (1995)) (3) LD50 for rabbits: > 10,000 mg/kg (EU-RAR (2006))
1	Acute toxicity (Inhalation: Gases)	*	- -	-	-	[Rationale for the Classification] Solid (GHS definition). It was classified as "Not classified (Not applicable)."
1	Acute toxicity (Inhalation: Vapours)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	Category 4	Warning	H332	P304+P340 P261 P271 P312	[Rationale for the Classification] Based on (1), it was classified in Category 4. Besides, since exposure concentrations were higher than the saturated vapor concentration (0.000001 mg/L), the reference value in units of mg/L was applied as a dust. [Evidence Data] (1) LC50 for rats (2 hours): 2.5 mg/L (converted 4-hour equivalent value: 1.25 mg/L) (NICNAS PEC (2001)) [Reference Data, etc.] (2) After rats were exposed for 8 hours (converted 4-hour equivalent value: 1.0 mg/L) to a concentration of 0.5 mg aerosol/L air, no effects were observed (EU-RAR (2006), EHC 172 (1995)). (3) After rats were exposed for 1 hour (converted 4-hour equivalent value: 0.325 mg/L) to a concentration of 1.3 mg aerosol/L air, no effects were observed (EU-RAR (2006)).
2	Skin corrosion/irritation	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) In several skin irritation tests with rabbits, no irritation results were observed after 500 mg of this substance was applied (EHC 172 (1995), EU-RAR (2006), BUA 239 (2002)). (2) According to EU-RAR (2006), this substance was concluded as no skin irritant (EU-RAR (2006)).
3	Serious eye damage/eye irritation	*	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) There were several reports of eye irritation tests with rabbits, and no eye irritation was observed (EHC 172 (1995), EU-RAR (2006)). (2) There was a report that mild conjunctival redness, conjunctivitis and slight lacrimation were observed, however, all symptoms disappeared within 7 days (EU-RAR (2006), EHC 172 (1995)). (3) It is concluded in EU-RAR (2006) that this substance was not an eye irritant (EU-RAR (2006)). [Reference Data, etc.] (4) It is reported that in an eye irritation test with rabbits, slight or medium conjunctival redness was observed at 24 hours after the application, however, the symptoms disappeared by 72 hours (BUA 239 (2002)).
4	Respiratory sensitization	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	*	- -	-	-	[Rationale for the Classification] There were (1) and (2), however, since test details are unknown, these reports were considered as insufficient information to determine classifications. It was classified as "Classification not possible" due to lack of data. [Reference Data, etc.] (1) It was reported that in a sensitization test with guinea pigs, no sensitization by this substance was observed (EHC 172 (1995), EU-RAR (2006)). (2) In a closed patch sensitization test in which 3 to 5 mg of this substance was applied ten times to upper arm skin of 54 human volunteers for 10 to 14 days and subsequently test patches were reapplied on different sites for 72 hours, one case of slight redness after removing the patches was observed. However, this symptom was considered to have seen an effect of tape contacting. Therefore, this substance was identified as not sensitizing (EU-RAR (2006)).
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] Base on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) As for in vivo, negative results were reported in a micronucleus test with peripheral blood erythrocytes of mice dosed by gavage (NTP TR587 (2014)). (2) As for in vitro, a bacterial reverse mutation test, a chromosomal aberration test, a sister chromatid exchange test, and an unscheduled DNA synthesis test with cultured mammalian cells were conducted, and all test results were reported as negative (NTP TR587 (2014), IARC 115 (2018), EHC 172 (1995), EU-RAR (2006), JECDB (Access on May 2019), EFSA (2011)).
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on classification results by other organizations (1), it was classified in Category 1B in accordance with the GHS Classification Guidance for the Japanese Government. Besides, the category was changed from the previous classification by using new information sources. [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified in Group 2A by IARC (IARC 115 (2018)). [Reference Data, etc.] (2) In a carcinogenicity test with rats dosed by gavage (250, 500, 1,000 mg/kg) for 2 years, increased incidences of uterine adenocarcinoma, adenoma or malignant mixed Mullerian tumor (each or combined) and testicular adenoma were observed at or above 500 mg/kg. From these results, it was concluded that there was clear evidence of carcinogenic activity in female rats based on increased incidences of uterine epithelial tumors (predominantly uterine adenocarcinoma), however, there was equivocal evidence of carcinogenic activity in male rats based on the occurrence of testicular adenoma (NTP TR587 (2014)). (3) In a carcinogenicity test with rats dosed by gavage (250, 500, 1,000 mg/kg) for 2 years, increases in the incidence of hepatoblastoma and of hepatocellular carcinoma or hepatoblastoma (combined) in males at doses of 250 mg/kg, and increased incidences of carcinoma or adenoma in the cecum or colon and hemangiosarcoma (all organs) in males at doses of 250 and 500 mg/kg were observed. From these results, it was concluded that there was some evidence of carcinogenic activity in male mice based on increased incidences of hepatoblastoma, on the other hand, there was no evidence of carcinogenic activity in female mice (NTP TR587 (2014)). (4) Based on several studies on the mechanism of carcinogenicity of this substance, the IARC Working Group considered that there was strong evidence for characteristics of carcinogens (the modulation of nuclear receptor-mediated effects, endocrine-disrupting effects, the induction of oxidative stress, and the induction of immunosuppression) and that these could be operative in humans, so the Group classified the substance in Group 2A (IARC 115 (2018)).
7	Reproductive toxicity	Category 1B, Additional category: Effects on or via lactation	Danger	H360 H362	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) and (2), as toxicity effects on neurodevelopment of pups were suggested, it was classified in Category 1B. As shown in reference data, no reproductive or developmental toxicity was confirmed in many standard reproductive toxicity tests. However, as shown in (1) and (2), by focusing on neurodevelopment effects on the next generations which were detectable under only specific test conditions, the category was determined. Also, findings described in (1) and (2) were observations due to administration during pregnancy and lactation periods, and as shown in (3), this substance was detected in human breast milk. Based on the above information, the additional category for effects on or via lactation was added to the classification. [Evidence Data] (1) In a 1-generation reproductive toxicity test with rats, decreases in serum T4 levels were observed as parental effects. Findings suggestive of auditory disturbance were observed in an auditory evoked potential examination in 50- to 110-day-old pups (Lilienthal, H. et al., Toxicology, 246 (1) (2008); Van der Ven, L.T. et al., Toxicology, 245 (1-2) (2008)). (2) In a toxicity test with maternal rats by feeding from gestational Day 10 to postpartum Day 20, increases in apoptotic bodies in subgranular zones of the hippocampal dentate gyrus of 20-day-old newborn pups were observed. These findings suggested neurogenesis disorders (Saegusa, Y. et al., Arch. Toxicol., 86 (9) (2012)). (3) In epidemiological researches in Germany and Norway, breast milk samples were analyzed in which this substance was detected in breast milk lipid components (EU-RAR (2006)). [Reference Data] (4) In a 2-generation reproductive toxicity test with rats dosed by gavage, as effects on parental animals, decreases in serum T4 levels and reduced body weight gain were observed, however, no effects on fertility and pups were observed (EU-RAR (2006)). (5) In a 2-generation reproductive toxicity test with rats, decreases in serum T4 levels and no effect on fertility of parental animals were observed. As for effects on pups, slight decreases in the thickness of the parietal cortex of F2 pups without histopathological changes were observed by image analysis inspection. It was reported that the biological significance of these findings was unknown (Cope, R. B. et al., Toxicology, 329 (2015)). (6) In a developmental toxicity test with pregnant rats dosed on gestational Days 0-19 by gavage, no effects on parental animals or fetuses were observed (EU-RAR (2006), Environmental Risk Assessment for Chemical Substances Vol.1 (Ministry of the Environment, 2002)). (7) In a developmental neurotoxicity study (OECD TG 426) with pregnant rats by feeding from gestational Day 7 to postpartum day 19, no effects on maternal animals, and slight decreases in abilities of habituation and learning/memory of pups were observed. However, it is described that it was not possible to draw definitive conclusions from the study (EU-RAR (2006)).
8	Specific target organ toxicity - Single exposure	*	- -	-	-	[Rationale for the Classification] There was no acute toxic information on this substance. Based on oral and transdermal administration tests with experimental animals, it was classified as "Not classified." However, although no toxic effects were observed in inhalation tests by administration at the upper limit of the range of Category 1, the effects of administration at the upper limit of the range of Category 2 were unknown. Therefore, it was concluded in "Classification not possible." [Reference Data, etc.] (1) In three single oral dose toxicity tests with rats, no toxic symptoms were observed at 2,000 mg/kg (upper limit of the range of Category 2) or 5,000 mg/kg (exceeding the range of Category 2), and no administration-related lesions were also observed at necropsy (EU-RAR (2006), JECDB (Access on May 2019), EHC 172 (1995)). (2) In three single dose toxicity tests with rats by transdermal administration, no toxic symptoms were observed at 2,000 mg/kg (upper limit of the range for Category 2) or 3,160 mg/kg (exceeding the range of Category 2), and no administration-related lesions were also observed at necropsy (EU-RAR (2006), EHC 172 (1995)). (3) In single inhalation tests with rats, mice and guinea pigs exposed to 0.5 mg/L aerosol of this substance for 8 hours (converted 4-hour equivalent value: 1 mg/L, upper limit of the range of Category 2), no toxic symptoms were observed, and no administration-related lesions were also observed at necropsy (EU-RAR (2006), EHC 172 (1995)). Also, in a single inhalation test with rats exposed to 1.3 mg/L aerosol of this substance (converted 4-hour equivalent value: 0.325 mg/L, Category 1), no fatal cases and no toxic symptoms were observed (EU-RAR (2006)).
9	Specific target organ toxicity - Repeated exposure	*	- -	-	-	[Rationale for the Classification] Based on results of oral toxicity tests (1)-(5), it was classified as "Not classified." In the case of other administration routes, classification was not possible due to lack of data. [Evidence Data] (1) In a 14-week toxicity test with mice by gavage, renal tubular cytoplasmic alterations were observed at or above 500 mg/kg/day (converted guidance value: 389 mg/kg/day, exceeding the range of Category 2) (NTP TR587 (2014)). (2) In a 14-week toxicity test with rats by gavage, increases in liver weights and anemia were observed at or above 500 mg/kg/day (converted guidance value: 389 mg/kg/day, exceeding the range of Category 2) (NTP TR587 (2014)). (3) In a 3-month toxicity test with mice by feeding, decreases in reduced body weights, anemia, decreases in triglycerides and total protein, reduced weights and bleeding of the spleen were observed at or above 15,600 ppm (2,200 mg/kg/day, exceeding the range of Category 2) (Environmental Risk Assessment for Chemical Substances Vol.1 (Ministry of the Environment, 2002), EHC 172 (1995), NTP TR587 (2014)). (4) In a 2-year toxicity test with mice by gavage, renal tubular cytoplasmic alterations, ulcer/mononuclear cell cellular infiltration/inflammation/epithelial hyperplasia of the forestomach were observed at or above 250 mg/kg/day (exceeding the range of Category 2) (NTP TR587 (2014)). (5) In a 2-year toxicity test with rats by gavage, increased liver weights at a dosage of 1,000 mg/kg/day (exceeding the range of Category 2) at 3-month interim evaluation were observed (NTP TR587 (2014)).
10	Aspiration hazard	*	- -	-	-	[Rationale for the Classification] 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 Short term (Acute)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 96-hour LC50 = 0.4 mg/L for fish (Oncorhynchus mykiss) (EHC 172, 1995).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	As per the expert judgment, sufficient chronic toxicity data were not obtained. It was classified in Category 1 because it is not rapidly degradable (a degradation rate by BOD: 0% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1977)), and it was classified in Category 1 in acute toxicity.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	Classification not possible due to lack of data.

NOTE:

GHS Classification Result by the Japanese Government is intended to provide a reference for preparing a GHS label or SDS for users. To include the same classification result in a label or SDS for Japan is NOT mandatory.
Users can cite or copy this classification result when preparing a GHS label or SDS. Please be aware, however, that the responsibility for a label or SDS prepared by citing or copying this classification result lies with users.
This GHS classification was conducted based on the information sources and the guidance for classification and judgement which are described in the GHS Classification Guidance for the Japanese Government etc. Using other literature, test results etc. as evidence and including different content from this classification result in a label or SDS are allowed.
Hazard statement and precautionary statement will show by hovering the mouse cursor over a code in the column of "Hazard statement" and "Precautionary statement," respectively. In the excel file, both the codes and statements are provided.
A blank or "-" in the column of "Classification" denotes that a classification for the hazard class was not conducted in the year.
An asterisk “*” in the column of “Classification” denotes that “Not classified (or No applicable)” and/or “Classification not possible” is applicable. Details are described in the column of “Rationale for the classification”. If no English translation is available for “Rationale for the classification,” please refer to the Japanese version of the results.

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