GHS Classification Result

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GENERAL INFORMATION
Item Information
CAS RN 1163-19-5
Chemical Name Decabromo-1,1'-oxybis(benzene) (Decabromodiphenyl ether)
Substance ID H30-B-001-METI, MOE
Classification year (FY) FY2018
Ministry who conducted the classification Ministry of Economy, Trade and Industry (METI)/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
-
-
- - No data available. Besides, it is described that it is poorly flammable (GESTIS (Accessed Aug. 2018)).
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 Classification not possible
-
-
- - No data available.
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
-
-
- - [Rationale for the Classification]
Based on (1) and (2), it was classified as "Not classified" (corresponding to Category 5 in UN GHS classification or "Not classified").

[Evidence Data]
(1) LD50 for rats: > 2,000 mg/kg (PATTY 6th (2012))
(2) LD50 for rats: > 5,000 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), EHC 162 (1994))
1 Acute toxicity (Dermal) Not classified
-
-
- - [Rationale for the Classification]
Based on (1) and (2), it was classified as "Not classified" (corresponding to Category 5 in UN GHS classification or "Not classified").

[Evidence Data]
(1) LD50 for rats: > 3,000 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005))
(2) LD50 for rabbits: > 2,000 mg/kg (EHC 162 (1994))
1 Acute toxicity (Inhalation: Gases) Not applicable
-
-
- - [Rationale for the Classification]
Solid (GHS definition)
1 Acute toxicity (Inhalation: Vapours) Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
1 Acute toxicity (Inhalation: Dusts and mists) Not classified
-
-
- - [Rationale for the Classification]
Based on (1), it was classified as "Not classified." Besides, the reference value for the dust was applied because the test concentration was much higher than the saturated vapor concentration (9*10-8 ppm).

[Evidence Data]
(1) LC50 value (one hour) for rats: > 48,200 mg/m3 (converted 4-hour equivalent value: > 12.05 mg/L) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), EHC 162 (1994))
2 Skin corrosion/irritation Not classified
-
-
- - [Rationale for the Classification]
Based on (1)-(3), it was classified as "Not classified." The classification was changed by using new information sources.

[Evidence Data]
(1) In a test (n = 3) in which this substance was applied to the skin of rabbits for 24 hours, no irritation was observed (ATSDR (2017), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), EHC 162 (1994)).
(2) In a test in which this substance at purity of 77.4% was applied to the skin of rabbits, no irritation was observed (ATSDR (2017), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), EHC 162 (1994)).
(3) When solid or a 2% solution (solvent unknown) of this substance was applied to the skin of 200 volunteers for 24 hours, irritation was observed in some cases in which the solid was applied directly (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)).
3 Serious eye damage/eye irritation Category 2B
-
Warning
H320 P305+P351+P338
P337+P313
P264
[Rationale for the Classification]
Based on (1) and (2), it was considered that there was mild irritation which resolved within approximately 7 days, it was classified in Category 2B.

[Evidence Data]
(1) In an eye irritation test (GLP test) with rabbits (n = 6), there is a report that slight irritation was observed in the cornea at 1 hour after application, but no irritation was observed after 24 hours (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), EU-RAR (2002), REACH registration dossier (Accessed Sept. 2018), EHC 162 (1994)).
(2) In an eye irritation test with rabbits (n = 6), there is a report that, very slight conjunctival redness (4/6), very slight edema (2/6) and very slight eye discharge (1/6) were observed 24 hours after application, and that most changes resolved within 72 hours, but conjunctival edema was observed in 1 rabbit after 7 days (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), EU-RAR (2002), EHC 162 (1994)).
4 Respiratory sensitization Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
4 Skin sensitization Not classified
-
-
- - [Rationale for the Classification]
Based on (1) and (2), it was classified as "Not classified."

[Evidence Data]
(1) There is a report that induction treatment with 5% preparation (mixed with petrolatum) was performed on 50 volunteers for a total of 9 times (3 times per week, for 3 weeks), and the challenge test performed after 2 weeks showed no sensitization (EU-RAR (2002), PATTY 6th (2012), EHC 162 (1994)).
(2) There is a report that 24-hour dermal application of this substance to 200 volunteers was repeated 9 times, once every other days (induction), and the challenge test performed after 2 weeks showed no sensitization (EU-RAR (2002), EHC 162 (1994)).

[Reference Data, etc.]
(3) It is described in the EU risk assessment report that application concentrations of (1) and (2) are very low (EU-RAR (2002)).
(4) There is a report that polybrominated diphenyl ether (PBDE) showed no sensitization in a skin sensitization test (OECD TG 406, according to GLP) with guinea pigs (EU-RAR (2002)).
(5) In the EU risk assessment report, it is concluded that this substance is not sensitizing based on animal test data from PBDE and human data of this substance (EU-RAR (2002)).
5 Germ cell mutagenicity Classification not possible
-
-
- - [Rationale for the Classification]
As for in vivo, although a positive result was obtained in (1), it was a finding of intraperitoneal administration at high doses exceeding the limit dose, the induction frequency is low (maximum of 0.43%). Moreover, results were negative in in-vitro tests including chromosomal aberration tests and a mouse lymphoma test. As a result, the biological significance of the test (1) is low, and it was classified as "Classification not possible" based on expert judgment. Accepting the expert judgment, the classification result was changed from the previous one.

[Evidence Data]
(1) As for in vivo, it was positive for males in a micronucleus test with rat bone marrow (NTP DB (Accessed Sept. 2018)).
(2) As for in vivo, regarding a product containing 77.4% of this substance, it was negative in a micronucleus test with rat bone marrow (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)).
(3) As for in vitro, reverse mutation tests were negative (partially positive result), chromosomal aberration tests and sister chromatid exchange tests with cultured mammalian cells, and mouse lymphoma test were negative (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), NTP TR309 (1986), ATSDR (2017), EU-RAR No.17 (2002)).
(4) As for In vitro, a comet assay was negative (ATSDR (2017)).
6 Carcinogenicity Category 2


Warning
H351 P308+P313
P201
P202
P280
P405
P501
[Rationale for the Classification]
As for carcinogenicity, there is no report available on humans.
Regarding classifications by other organizations, it is classified in Group 3 by IARC (IARC 71 (1999)), as S by EPA (IRIS (2008)).
By accepting the views and classification result of EPA (4) and the views of EFSA (5) which are more recent than IARC classification result (3) based on 2-year administration tests by feeding with rats and mice in (1) and (2), it was classified in Category 2.

[Evidence Data]
(1) In a carcinogenicity test of 2-year administration by feeding with rats, an increase in the incidence of neoplastic nodules in the liver was observed in both males and females (NTP TR309 (1986), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)).
(2) In a carcinogenicity test of 2-year administration by feeding with mice, an increase in a combined incidence of hepatocellular adenoma and carcinoma, and an increase in a combined incidence of follicular epithelium adenoma and carcinoma in the thyroid were observed in males (NTP TR309 (1986), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)).
(3) Based on (1) and (2), NTP concluded that there is some evidence of carcinogenicity in male and female rats, equivocal evidence in male mice and no evidence of carcinogenicity in female mice by administration of this substance (NTP TR309 (1986)). IARC concluded that there is limited evidence of carcinogenicity in experimental animals based on these results and classified the substance in Group 3 (IARC 71 (1999)).
(4) EPA classified it as S in 2008 based on a lack of data for humans and negative genotoxicity, although there is evidence of increased tumor development in mice, such as a slight increase in liver tumors (total frequency of benign/malignant tumors) at high doses in male mice, a small but not significant increase in thyroid tumors (total frequency of benign/malignant tumors) in male and female mice and a significant increase in hyperplasia of preneoplastic lesions in the thyroid in male and female mice (IRIS (2008)).
(5) The CONTAM panel of EFSA reanalyzed the result of the NTP carcinogenicity test and noted that an increase in hepatic adenomas with rats and an increase in hepatic adenomas and carcinomas with mice provided some evidence of carcinogenic potential of this substance and expressed the view that the mode of action of liver carcinogenicity was a secondary mechanism, not a genotoxic one (EFSA (2011)).
(6) As for classification results by domestic and international organizations, it was classified in Group 3 by IARC (IARC 71 (1999)), as S by EPA (IRIS (2008)). However, there are no classifications by other organizations.
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]
This substance is a congener of polybrominated diphenyl ethers (PBDEs). There are some reports, including PBDEs, suggesting neurodevelopmental toxicity on the experimental animals such as (1) to (3), and reproductive toxicity in the epidemiological report in humans such as (4) to (6). Therefore, it was classified in Category 1B. Moreover, this substance was detected in breast milk as in (7), so "an additional category for effects on or via lactation" was added to the classification. Besides, it was classified as "Not classified" based on (8) in the previous classification, however, the classification result was changed by addition of new information source.

[Evidence Data]
(1) As a result of single oral administration of 1.34-20.1 mg/kg to newborn mice on postnatal day 3, a decrease in behavioral quantity and a decrease in habituation ability were observed in postgrowth behavioral tests with newborn mice with administration of 2.2 mg/kg or above. These effects on behavior in the neurodevelopmental period were observed in the subsequent tests (ATSDR (2017)).
(2) As reports suggesting neurobehavioral effects of this substance on newborns, there is a negative report from a study in which neurodevelopmental toxicity in the next generation was investigated after administering to pregnant mice. On the other hand, there are reports that spatial learning disorders were detected in offspring, and that changes in electrophysiology and the immune system were detected in the hippocampus of offspring. Based on these findings of experimental animals and humans, it is described in ATSDR that the developing nervous system is the target of PBDEs and this substance (ATSDR (2017)).
(3) It is reported that as a result of administration of 146 mg/kg/day to pregnant rats and 1,500 mg/kg/day to pregnant mice during the pregnancy and lactation period, a significant decrease in serum T3 was observed in pups. It is reported that as a result of administration to newborn mice on postnatal day 2-15, a dose-related decrease in serum T4 was observed in male mice. Although human findings are inconsistent, based on the results of the experimental animals, it is suggested that PBDEs may disrupt thyroid hormones in infants and children (ATSDR (2017)).
(4) A number of epidemiological studies have been reported suggesting neurodevelopmental effects of PBDEs in children. Correlations are pointed out between concentrations of PBDEs in umbilical cord blood, maternal and baby serum and breast milk and cranial nerve developmental disorders in children such as cognitive and adaptive behavior disorders in infants, mental and physical developmental disorders in infants, and a decrease in language and social developmental quotients in infants at 24 months (ATSDR (2017)).
(5) In the birth cohort, there was no correlation between maternal serum PBDEs and the behavior of infants at 5 weeks of age or the auditory behavior of 4-5 years of age. On the other hand, in children of the same cohort, it is reported that serum PBDEs levels in mothers were correlated with low IQ at the age of 5, high hyperactivity, and executive dysfunction at the age of 5-8 (ATSDR (2017)).
(6) It is reported that exposure to PBDEs during infant development was negatively correlated with serum or cord blood T4 levels (ATSDR (2017)).
(7) In the epidemical study in Taiwan, 46 women had significantly prolonged pre-pregnancy menstrual cycles and increased breast milk levels after pregnancy (ATSDR (2017)).

[Reference Data, etc.]
(8) In the reproductive toxicity test in which rats were dosed by feeding from 60 days prior to mating through mating/pregnancy/lactation, and in the developmental test in which pregnant rats were dosed by gavage during the organogenesis or pregnancy period, no definitive finding was detected to classify this substance as a reproductive toxicant (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), EU-RAR (2002)).
8 Specific target organ toxicity - Single exposure Category 3 (Respiratory tract irritation)


Warning
H335 P304+P340
P403+P233
P261
P271
P312
P405
P501
[Rationale for the Classification]
As for the data in (1), eyes are not adopted as the target organ because findings in the eyes are considered to be due to eye irritation. Since no death occurred, dyspnea is considered to be a transient symptom not serious. Therefore, it was classified in Category 3 (respiratory tract irritation).

[Evidence Data]
(1) In a single inhalation exposure test in which rats were exposed to this substance for 1 hour, dyspnea and ocular discharge were observed at 2 mg/L (converted 4-hour equivalent value: 1 mg/L) corresponding to the range of Category 1(EU-RAR (2002)).
9 Specific target organ toxicity - Repeated exposure Category 2 (thyroid)


Warning
H373 P260
P314
P501
[Rationale for the Classification]
Based on the data in (1) and (2), the thyroid was judged to be the target organ, and it was classified in Category 2 (thyroid). Besides, because the evidence in the previous classification "centrilobular hepatocytes hypertrophy or vacuolation in the liver and hyaline degeneration of the renal tubules in the kidney" were observed at doses exceeding the range of Category 2 as shown in (1), the liver and kidney were excluded from the target organ. Moreover, although the effects on the pancreas are pointed out in reference data (5) and (6), no morphological change in the pancreas was observed in a 2-year administration test by feeding with rats in (4). Therefore, the pancreas was not designated as the target organ.

[Evidence Data]
(1) As for the thyroid, there are reports that thyroid hyperplasia was observed at or above 80 mg/kg/day (converted guidance value: 26.7 mg/kg/day) within the range of Category 2 in the 30-day administration test with rats, and that centrilobular hepatocytes hypertrophy or vacuolation in the liver and hyaline degeneration of the renal tubules in the kidney were observed at a dose of 800 mg/kg/day (converted guidance value: 267 mg/kg/day) exceeding the range of Category 2 (ATSDR (2017), Environmental Risk Assessment for Chemical Substances Vol. 2 (Ministry of the Environment, 2003), Norris et al. (1975)).
(2) The CONTAM panel of EFSA expressed the view that the main targets of PBDEs including this substance are the liver, thyroid homeostasis, the genetic organs and the nervous system (EFSA (2011)).

[Reference Data, etc.]
(3) In a carcinogenicity test in which rats or mice were dosed by feeding for 2 years, non-neoplastic changes were observed in the forestomach, spleen, liver and lymph node of rats, and in the liver, thyroid and glandular stomach of mice. However, these were due to the effect of super-high doses such as 1,120 mg/kg/day or more in rats and 3,200 mg/kg/day or more in mice (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), EU-RAR (2002)).
(4) There are reports that hepatic enzyme induction was observed dose-dependently in a 28-day test in which rats were dosed by gavage of 1.87-60 mg/kg/day, and that centrilobular hypertrophy of hepatocytes was observed at 60 mg/kg/day (converted guidance value: 18.7 mg/kg/day) within the range of Category 2 (ATSDR (2017)).
(5) In an 8-week test in which 0.05-20 mg/kg/day of this substance was administered by gavage to male rats, an increased blood sugar level was observed at or above 0.05 mg/kg/day, and a significant decrease in a serum insulin level and morphological changes in the pancreas (blurred boundaries among pancreatic islet cells) were observed at or above 1 mg/kg/day (ATSDR (2017)).
(6) There is a report that slight or moderate insulitis (dose-unrelated changes) was observed in the majority of "samples of Langerhan's islet" in a test where rats were administered for 28 days via gavage. ATSDR indicates that the pancreas may be a target organ for PBDEs based on the experimental animal data (ATSDR (2017)).
10 Aspiration hazard Classification not possible
-
-
- - [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 (Acute) Not classified
-
-
- - It was classified as "Not classified" from 72-hour EC50 (growth rate) > 0.0052 mg/L for algae (Pseudokirchneriella subcapitata) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2018), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)), 48-hour EC50 (immobile) > 0.00479 mg/L for crustacea (Daphnia magna) (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)), and 96-hour LC50 > 0.00455 mg/L for fish (Oryzias latipes) (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)) above water solubility of 0.0001 mg/L (25 deg C, PHYSPROP Database: 2018).
11 Hazardous to the aquatic environment (Long-term) Not classified
-
-
- - If chronic toxicity data are used, 72-hour NOEC (growth rate) = 0.0052 mg/L for algae (Pseudokirchneriella subcapitata) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2018), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)), and 21-day NOEC (reproduction inhibition) > 0.00505 mg/L for crustacea (Daphnia magna) (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)) are above water solubility of 0.0001 mg/L (25 deg C, PHYSPROP Database: 2018). It is not rapidly degradable (not readily degradable, a degradation rate by BOD: 0% (J-CHECK, 1976)), but it does not have a high bioconcentration potential (J-CHECK, 1977). Therefore, it is classified as "Not classified."
If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, 96-hour LC50 > 0.00455 mg/L for fish (Oryzias latipes) (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)) is above water solubility of 0.0001 mg/L (25 deg C, PHYSPROP Database: 2018). It is not rapidly degradable (not readily degradable, a degradation rate by BOD: 0% (J-CHECK, 1976)), but it does not have a high bioconcentration potential (J-CHECK, 1977). Therefore, it is classified as "Not classified."
From the above results, it was classified as "Not classified."
12 Hazardous to the ozone layer Classification not possible
-
-
- - No data available.


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.
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  • 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.
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