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GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	124-48-1
Chemical Name	Dibromochloromethane
Substance ID	H29-B-103
Classification year (FY)	FY2017
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	FY2008
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	- -	-	-	Liquid (GHS definition)
3	Aerosols	Not applicable	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not applicable	- -	-	-	Liquid (GHS definition)
5	Gases under pressure	Not applicable	- -	-	-	Liquid (GHS definition)
6	Flammable liquids	Not classified	- -	-	-	It is not combustible (GESTIS (Access on September 2017)).
7	Flammable solids	Not applicable	- -	-	-	Liquid (GHS definition)
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 classified	- -	-	-	It is not combustible (GESTIS (Access on September 2017)).
10	Pyrophoric solids	Not applicable	- -	-	-	Liquid (GHS definition)
11	Self-heating substances and mixtures	Not classified	- -	-	-	It is not combustible (GESTIS (Access on September 2017)).
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	- -	-	-	The substance is an organic compound containing chlorine (but not fluorine or oxygen) which is chemically bonded only to carbon or hydrogen.
14	Oxidizing solids	Not applicable	- -	-	-	Liquid (GHS definition)
15	Organic peroxides	Not applicable	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.

HEALTH HAZARDS

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	Based on reports of LD50 values for rats of 370 mg/kg (male), 760 mg/kg (female) (Environmental Risk Assessment for Chemical Substances Vol.14 (Ministry of the Environment, 2016)), 1,186 mg/kg (male), and 848 mg/kg (female) (ATSDR (2005), Environmental Risk Assessment for Chemical Substances Vol.14 (Ministry of the Environment, 2016)), it was classified in Category 4.
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	Liquid (GHS definition)
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
2	Skin corrosion/irritation	Classification not possible	- -	-	-	Classification not possible due to lack of data.
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	Classification not possible due to lack of data.
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.
4	Skin sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.
5	Germ cell mutagenicity	Classification not possible	- -	-	-	As for in vivo, a micronucleus test with mouse bone marrow cells was negative, chromosomal aberration tests with bone marrow cells of rats and mice were positive, sister chromatid exchange tests with mouse bone marrow cells were positive and negative results, DNA damage tests with liver, kidney etc. of rats and an unscheduled DNA synthesis test were negative (Risk Assessment Report (Beverages) (Food Safety Commission of Japan, 2009), ATSDR (2005), IARC 71 (1999), Environmental Risk Assessment for Chemical Substances Vol.14 (Ministry of the Environment, 2016), IRIS (1990), NTP DB (Access on August 2017)). As for in vitro, a bacterial reverse mutation test was weakly positive, and a mouse lymphoma test, a chromosomal aberration test, and a sister chromatid exchange test with cultured mammalian cells were positive (Risk Assessment Report (Beverages) (Food Safety Commission of Japan, 2009), ATSDR (2005), IARC 71 (1999), IRIS (1990), Environmental Risk Assessment for Chemical Substances Vol.14 (Ministry of the Environment, 2016), NTP DB (Access on August 2017)). The positive result of the in vivo rat bone marrow chromosome aberration test was a finding of intraperitoneal administration at 20.8 mg/kg, and the test of 5-day oral administration to rats at 20.8 mg/kg/day by the same author was negative. In addition, micronucleus tests by intraperitoneal administration at up to 500 mg/kg were negative for both rats and mice. This substance is one kind of trihalomethane, the genotoxicity of trihalomethane depends on the reactivity with glutathione (GSH) (GSTT1-1 activity), and the activity of the GST pathway is markedly high in mice, very low in rats and hamsters, and even lower in humans (Risk Assessment Report (Beverages) (Food Safety Commission of Japan, 2009)). Based on the above findings, it was judged that the weight of positive results in rats was extremely low, and clear genotoxicity was not shown. From the above, it was classified as "Classification not possible" according to the GHS Classification Guidance for the Japanese Government.
6	Carcinogenicity	Classification not possible	- -	-	-	Among epidemiological studies which investigated the relationship between this substance in tap water and specific cancers, a significant correlation was found in a part of them, but many of them showed a result of no significant correlation between the two (Environmental Risk Assessment for Chemical Substances Vol. 14 (Ministry of the Environment, 2016)). As for experimental animals, in 2-year carcinogenicity studies with rats or mice dosed by gavage, in rats, no increase in the incidence of tumors was observed. However, in the mouse study, an increase in the incidence of hepatocellular carcinoma and a marginal increase in the combined incidences of hepatocellular adenomas and carcinomas in males of the high dose group, and an increase in the incidence of hepatocellular adenomas and an increase in the combined incidences of hepatocellular adenomas and carcinomas in females were observed (NTP TR282 (1985), IARC 52 (1991)). It was concluded in NTP that there was no evidence of carcinogenicity in either sex of rats, but that in mice, there was equivocal evidence of carcinogenicity in males and some evidence in females (NTP TR282 (1985)). Other than these, in a 2-year study with mice dosed by drinking water, an increase in the incidence of tumors was not observed in either sex (IARC 52 (1991)). As for classifications by other organizations, although the evidence of carcinogenicity is limited in experimental animals, because of its structural similarity to trihalomethane, which is a known carcinogen in experimental animals, EPA classified this substance as Category C (possible human carcinogen) (IRIS (1990)). On the other hand, IARC classified it in Group 3 based on the limited evidence for the carcinogenicity (IARC 52 (1991)) and did not change the classification result even in the re-evaluation in 1999 (IARC 71 (1999)). In addition, Ministry of the Environment gives the opinion that it is not possible to obtain sufficient findings on the carcinogenicity of this substance, and that it is not possible to judge the presence or absence of carcinogenicity in humans (Environmental Risk Assessment for Chemical Substances Vol. 14 (Ministry of the Environment, 2016)). From the above, based on the classification result by IARC, the evaluation year of which is new and the opinion on carcinogenicity in humans of Ministry of the Environment, it was classified as "Classification not possible."
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	It was reported that in multiple epidemiological studies that examined the relationship of exposure to trihalomethane from drinking water with spontaneous abortion, semen quality, and congenital malformations in California, there was no relationship between them. However, there is a report that in a prospective study which examined the association between exposure to trihalomethane from tap water and the menstrual cycle in 18-39 year old married women living in northern California, the lengths of menstrual cycle and follicular phase were significantly shortened by the exposures to three kinds of trihalomethane including this substance and the total for bromides, but their degree were the largest by the exposure to this substance or the total for bromides (Environmental Risk Assessment for Chemical Substances Vol.14 (Ministry of the Environment, 2016), ATSDR (2005)). As for experimental animals, in a multigeneration study in which male and female mice were dosed by drinking water at up to 4 g/L, a decrease in litter size (F1c), a decrease in the lactation rate (F1b, F2b), and a decrease in the viability index on day 4 (F1b) were observed at or above 1 g/L (corresponding to 171-200 mg/kg/day) where decreased body weight gain (females only) was observed in F0 and F1b parental animals, furthermore, decreased conception rate (F2b), lower delivery index (F1a, F1b, F1c), a decrease in litter size (F1a, F1b, F2a, F2b), and a decrease in the viability index on day 4 (F1a, F1c, F2a) were observed at 4 g/L (corresponding to 685-800 mg/kg/day) where decreased body weight gain (males) and swelling of the liver were observed in F0 and F1b parental animals (Environmental Risk Assessment for Chemical Substances Vol.14 (Ministry of the Environment, 2016), Risk Assessment Report (Beverages) (Food Safety Commission of Japan, 2009), ATSDR (2005)). On the other hand, in a developmental toxicity study with pregnant rats dosed by gavage during the organogenesis period (gestational day 6-15), decreased body weight gain was observed at high dose in maternal animals. However, no developmental effect was observed in fetuses (Environmental Risk Assessment for Chemical Substances Vol.14 (Ministry of the Environment, 2016)). From the above, for one report in which effects on the menstrual cycle in humans were observed, the effects were due to the exposure to trihalomethane, and cannot be identified as to be due to exposure to this substance. However, based on the reproductive and developmental effects observed at the general toxic dose of the parental animals in the study with mice, it was judged to be reasonable to classify it in Category 2 for this hazard class. Besides, the classification result was changed due to the use of a new information source after the previous classification.
8	Specific target organ toxicity - Single exposure	Category 3 (Narcotic effects)	Warning	H336	P304+P340 P403+P233 P261 P271 P312 P405 P501	There is no single-exposure information on this substance in humans. As for experimental animals, there is a report that lethargy was observed at or above 310 mg/kg in a single oral dose test with rats (NTP TR282 (1985)), and that in a single oral dose test with mice, at 500 mg/kg, sedation and paralysis appeared within 30 minutes and persisted for about 4 hours (Environmental Risk Assessment for Chemical Substances Vol.14 (Ministry of the Environment, 2016)). In addition, there is a description that as acute oral toxicity of this substance in rats, piloerection, sedation, muscle relaxation, ataxia, and weakness were observed (Environmental Risk Assessment for Chemical Substances Vol.14 (Ministry of the Environment, 2016)), Risk Assessment Report (Beverages) (Food Safety Commission of Japan, 2009). Moreover, there is a description in ATSDR (2005) that this substance causes central nervous system depression such as lethargy, ataxia, and sedation in experimental animals. From the above, it was classified in Category 3 (narcotic effects).
9	Specific target organ toxicity - Repeated exposure	Category 2 (liver, kidney)	Warning	H373	P260 P314 P501	No information on humans is available. As for experimental animals, in a 90-day repeated oral dose toxicity test with rats, increased relative liver weight, centrilobular fatty change in the liver, and renal tubule degeneration at or above 50 mg/kg/day within the guidance value range for Category 2, and increased ALT, increased creatinine, increased relative kidney weight, and degeneration with tubular cell swelling at 100 mg/kg/day were observed (Environmental Risk Assessment for Chemical Substances Vol.14 (Ministry of the Environment, 2016)). In a 13-week repeated oral dose toxicity test with rats, vacuolar degeneration and necrosis of liver cells, and degeneration of renal tubule cells were observed at or above 60 mg/kg/day (converted guidance value: 43 mg/kg/day) within the guidance value range for Category 2. In a 2-year repeated oral dose toxicity test with rats, fatty degeneration and ground-glass cytoplasmic change in the liver, and an increase in the incidence of nephropathy were observed at or above 40 mg/kg/day within the guidance value range for Category 2 (Environmental Risk Assessment for Chemical Substances Vol.14 (Ministry of the Environment, 2016), NTP TR282(1985)). From the above, it was classified in Category 2 (liver, kidney).
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 72-hour EC50 (rate method) = 9.6 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, 2017)), it was classified in Category 2.
11	Hazardous to the aquatic environment (Long-term)	Category 1	Warning	H410	P273 P391 P501	Due to being not rapidly degradable (BioWin), and 21-day NOEC (reproduction inhibition) = 0.063 mg/L for crustacea (Daphnia magna) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2017)), it was classified in Category 1.
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.
* 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.

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