GHS Classification Result
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 79-94-7 |
| Chemical Name | Tetrabromobisphenol A |
| Substance ID | H27-A-033/C-063A_P |
| Classification year (FY) | FY2015 |
| Ministry who conducted the classification | Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE) |
| New/Revised | New |
| Classification result in other fiscal year | |
| 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 | Not classified |
- |
- | - | It is non-flammable (GESTIS (Access on July 2015)). Besides, there is the information that a flash point is > 600 degrees C (NITE Chemical Risk Information Platform (Access on July 2015)). |
| 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 non-flammable (GESTIS (Access on July 2015)). Besides, there is the information that a flash point is > 600 degrees C (NITE Chemical Risk Information Platform (Access on July 2015)). |
| 11 | Self-heating substances and mixtures | Not classified |
- |
- | - | It is non-flammable (GESTIS (Access on July 2015)). Besides, there is the information that a flash point is > 600 degrees C (NITE Chemical Risk Information Platform (Access on July 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 fluorine or chlorine but contains oxygen, and the oxygen is 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 |
- |
- | - | No established test method suitable for solid substances. |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 1 | Acute toxicity (Oral) | Not classified |
- |
- | - | From reported LD50 values of > 2,000 mg/kg (Japan Existing Chemical Data Base, Ministry of Health, Labour and Welfare (Access on July 2015); NTP TR 587 (2014); EHC 172 (1995)), > 5,000 mg/kg (Result of the initial environmental risk assessment of chemicals, Vol. 1, Ministry of the Environment in Japan (2002); EHC 172 (1995)), and > 50,000 mg/kg (EU-RAR (2006)) for rats, it was classified as "Not classified." |
| 1 | Acute toxicity (Dermal) | Not classified |
- |
- | - | From reported LD50 values of > 1,000 mg/kg (NTP TR 587 (2014)), > 2,000 mg/kg (EHC 172 (1995)), and > 10,000 mg/kg (EU-RAR (2006)) for rabbits, it was classified as "Not classified." |
| 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) | Category 4 |
 Warning |
H332 | P304+P340 P261 P271 P312 |
From a reported LC50 value (2 hours) of 2.5 mg/L (converted to a 4-hour equivalent: 1.25 mg/L) for rats (NICNAS (2001)), it was classified in Category 4. Besides, a reference value of mists was applied because the LC50 value and the test concentration are higher than the saturated vapour pressure concentration (4.0x10-7 mg/L). |
| 2 | Skin corrosion/irritation | Not classified |
- |
- | - | It is reported that in a skin irritation test using rabbits, after application of 200 mg of this substance for 24 hours, marked erythema was observed but resolved within 48 hours (BUA 239 (2002)). Moreover, there are multiple reports of other skin irritation tests using rabbits, reporting that no irritation was observed after application of 500 mg of this substance resulted in (EHC 172 (1995), EU-RAR (2006), BUA 239 (2002)). It is reported that irritation was not found also in a test in which this substance was applied to rats (EHC 172 (1995)). It is concluded in EU-RAR (2006) that this substance is not irritating to skin (EU-RAR (2006)). The substance was classified as "Not classified" (Category 3 in UN GHS classification) from the above results. |
| 3 | Serious eye damage/eye irritation | Not classified |
- |
- | - | There are multiple reports of eye irritation tests using rabbits (EHC 172 (1995), EU-RAR (2006)), and it is reported that after application of this substance, irritation was not observed, or slight conjunctival redness, conjunctivitis, slight lacrimation, and so on were found, but recovery was shown. It was concluded that this substance is not irritating to eyes (EU-RAR (2006), EHC 172 (1995)). Besides, it is reported that in another eye irritation test using rabbits, moderate erythema and conjunctivitis were observed but resolved after 72 hours (BUA 239 (2002)). Furthermore, although it is not a detailed report, it is written that this substance is not irritating either to eyes (Result of the initial environmental risk assessment of chemicals, Vol. 1, Ministry of the Environment in Japan (2002)). As above, because it was concluded in multiple evaluation documents listed in List 1 that it is not irritating to eyes, the substance was classified as "Not classified." |
| 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 sensitization test using guinea pigs, sensitization by this substance was not observed (EHC 172 (1995), EU-RAR (2006)). Moreover, this substance was applied to the same place of 54 volunteers ten times, and it was applied to the different site for 48 hours after 10 to 14 days. After the challenge, one subject showed slight erythema, but the authors thought that this was a reaction caused by the tape (EU-RAR (2006)). It was judged that these reports on animals and humans are insufficient data to be used for the classification due to unknown test details. |
| 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, a micronucleus test in mouse peripheral erythrocytes in gavage administration was negative (NTP TR587 (2014)). As for in vitro, a bacterial reverse mutation test, a chromosomal aberration test, a sister chromatid exchange test, and an unscheduled DNA synthesis test in cultured mammalian cells were all negative (EHC 172 (1995); NTP TR587 (2014); EU-RAR (2006); Japan Existing Chemical Data Base, Ministry of Health, Labour and Welfare (Access on July 2015); EFSA (2011)). |
| 6 | Carcinogenicity | Category 2 |
 Warning |
H351 | P308+P313 P201 P202 P280 P405 P501 |
In a carcinogenicity test in 2-year gavage administration of this substance in rats and mice, increased incidences of the following were observed (NTP TR 587 (2014)): adenocarcinoma, adenoma, or malignant mixed Mullerian tumor (alone or combined) in the uterus, testicular interstitial cell adenoma at 500 mg/kg/day or higher in rats; and hepatoblastoma or hepatocellular carcinoma (alone or combined) at 250 mg/kg/day, and adenoma or carcinoma in cecum or colon, hemangiosarcoma (all organs) at 250 and 500 mg/kg/day in male mice. Among these, it was concluded that there is clear evidence of carcinogenicity for uterine epithelial tumors (mainly uterine adenocarcinoma) in female rats, and some evidence of carcinogenicity for hepatoblastoma in male mice, on the other hand, there is equivocal evidence of carcinogenicity for testicular interstitial cells in male rats and no evidence of carcinogenicity in female mice (NTP TR 587 (2014)). As above, although there is no classification result of carcinogenicity by other organizations, the substance was classified in Category 2 for this hazard class, judging from some or clear evidence of carcinogenicity obtained in the test using experimental animals of 2 species by US NTP. |
| 7 | Reproductive toxicity | Category 1B, Additional category: Effects on or via lactation |
Danger |
H360 H362 |
P308+P313 P201 P202 P280 P405 P501 |
There is no report on reproductive/developmental effects in exposure to this substance in humans. However, in a study in Germany and Norway, this substance was detected in lipid component of breast milk in analyses of breast milk samples (EU-RAR (2006)). As for experimental animals, in a two-generation reproductive toxicity test in gavage administration of this substance in rats, in parent animals, only lower serum T4 levels at 100 mg/kg/day or higher in F0, F1 generations (males only for F0), reduced weight gain at 1,000 mg/kg/day in F1 parent animals were observed, and toxic effects were not shown up to 1,000 mg/kg/day in either of the fertility in F0, F1 parent animals, effects on postnatal development of F1 and F2 offspring, and a neurobehavioral test (spontaneous motility, learning and memory ability, histopathological findings in brain and nervous system) conducted in F2 offspring on day 13 to 60 after birth (EU-RAR (2006)). Moreover, in a developmental toxicity test in gavage administration in pregnant rats, abnormalities were not observed either in maternal animals or in fetuses in biopsy on day 20 of gestation in either of a test administered maximum 1,000 mg/kg/day throughout a gestation period on day 0 to 19 of gestation or a test administered maximum 2,500 mg/kg/day similarly (EU-RAR (2006); Result of the initial environmental risk assessment of chemicals, Vol. 1, Ministry of the Environment in Japan (2002)). Furthermore, in a developmental neurotoxicity test (OECD TG 426) in gavage administration at doses of 50 or 250 mg/kg/day in pregnant rats from day 7 of gestation to day 17 after birth, there are no toxic effects at 250 mg/kg/day in maternal animals, and in F1 offspring, a decrease in (environment) "habituation capability" using motor activity as an indicator in F1 females on day 21 after birth, a decrease in learning and memory ability in a Morris water maze (significantly increased swim distances) at 9 to 13 weeks of age in F1 males were observed. However, it is written that it is not possible to draw conclusions on whether the effects were caused by administration of test substance because effects were small in size and not consistent over measure points (EU-RAR (2006)). After this report, various investigations were conducted and reported on developmental neurotoxicity effects in exposure to this substance during a fetal and neonatal period as shown below. In EU project on risk assessment of brominated flame retardants, in a one-generation reproductive toxicity test in administration of this substance in a dose range of 3 to 3,000 mg/kg/day before mating in male and female rats, decreased thyroid hormone levels (blood thyroxine (T4)) were shown in parent animals, but effects were not observed in a neurobehavioral test such as auditory responses and conditioned avoidance behavior in the offspring. However, it is reported that in an electrophysiological auditory response test by brain-stem auditory evoked potential done at 50 to 110 days of age, signs showing impaired hearing such as prolongation of wave IV latency were observed (Lilienthal, H. et al., Toxicology, 246(1) (2008); Van der Ven, L.T. et al., Toxicology, 245 (1-2) (2008)). On the other hand, in an experiment in diet administration of this substance at doses of 100 to 10,000 ppm in pregnant rats from day 10 of gestation to day 20 after parturition, immunohistochemical staining of the hippocampus of newborns on day 20 after birth, an increase in apoptotic bodies in the subgranular zone of hippocampal dentate gyrus was observed and regarded to be the finding suggesting developmental neurotoxicity. The finding was also observed in other brominated flame retardants (decabromodiphenyl ether (DBDE), hexabromocyclododecane (HBCD)), but while fluctuations suggestive of slightly decreased thyroid hormones were observed in a blood test on day 20 after birth for DBDE and HBCD, a group administered this substance did not show fluctuations in thyroid hormones. Therefore, the authors considered that this substance might exert a direct action on neuronal development in the brain from a fetal to postnatal period, not via thyroid hormones (Saegusa, Y. et al., Arch. Toxicol., 86(9) (2012)). However, in a two-generation reproductive toxicity test in rats conducted in the USA, although a decrease in serum T4 levels was observed in F0, F1 parent animals, effects were not observed in fertility in parent animals and reproduction/development in the offspring within a range of general neurobehavioral test items up to 1,000 mg/kg/day. However, at 1,000 mg/kg/day, a slight decrease in thickness of parietal cortices was observed in 11-day-old F2 offspring, but it is reported that its biological significance is unknown because it was not accompanied by histopathological changes (Cope, R. B. et al., Toxicology, 329 (2015)). As above, after the assessment by EU-RAR in 2006, as effects in an oral exposure to this substance, knowledge suggestive of toxic effects on neurogenesis/neurodevelopment in newborns in administration during a gestation/lactation period was reported. Especially, the morphological changes in hippocampal tissue are considered important knowledge that directly shows developmental disorder in the nervous system by this substance. Therefore, the substance was classified in Category 1B in this hazard class, and effects on or via lactation were added. |
| 8 | Specific target organ toxicity - Single exposure | Classification not possible |
- |
- | - | There are no human data on this substance. As for experimental animals, acute toxic signs were not reported in any of inhalation, oral, and dermal routes (EU-RAR (2006); Japan Existing Chemical Data Base, Ministry of Health, Labour and Welfare (Access on July 2015); EHC 172 (1995); BUA 239 (2002)). From the above, it was classified as "Classification not possible." |
| 9 | Specific target organ toxicity - Repeated exposure | Classification not possible |
- |
- | - | There are no human data. As for experimental animals, in a 14-week gavage administration toxicity test using mice, tubular cytoplasmic degeneration in the kidney was observed at 500 mg/kg/day or higher. In a 2-year gavage administration toxicity test using mice, tubular cytoplasmic degeneration in the kidney and ulcer, mononuclear cell infiltration, inflammation, and epithelial hyperplasia in forestomach were found at 250 mg/kg/day or above (NTP TR587 (2014)). Besides, increased liver weight and anemia at 500 mg/kg/day or higher in a 14-week gavage administration toxicity test using rats and increased liver weight in a 3-month examination at 1,000 mg/kg/day in a 2-year gavage administration toxicity test using rats were reported (NTP TR587 (2014)). Moreover, in a toxicity test using mice in 3-month diet administration, decreased body weight, anemia, decreased neutral fat, decreased total protein, increased weight and bleeding of spleen were reported at 15,600 mg/kg feed (2,200 mg/kg/day) or above (Result of the initial environmental risk assessment of chemicals, Vol. 1, Ministry of the Environment in Japan (2002); EHC 172 (1995); NTP TR587 (2014)). These were within a range that is above Category 2. Therefore, it corresponds to "Not classified" in an oral route, but there is no toxicity information in humans and other routes. The substance was classified as "Classification not possible" in this hazard class due to lack of data. |
| 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 1 |
 Warning |
H400 | P273 P391 P501 |
From 96-hour LC50 = 0.4 mg/L for fish (Oncorhynchus mykiss) (EHC 172, 1995; NICNAS, 2001), it was classified in Category 1. |
| 11 | Hazardous to the aquatic environment (Long-term) | Category 2 |
- |
H411 | P273 P391 P501 |
Due to being not rapidly degradable (a degradation rate by BOD in 14 days = 0%, a degradation rate by GC = 0.7% (Official Bulletin of Ministry of International Trade and Industry, 1997)), and 35-day NOEC (surviving fish) = 0.16 mg/L for fish (Pimephales promelas) (NICNAS, 2001), it was classified in Category 2. |
| 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. |