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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	109-70-6
Chemical Name	1-Bromo-3-chloropropane
Substance ID	R03-B-016-MHLW
Classification year (FY)	FY2021
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)
New/Revised	Revised
Classification result in other fiscal year	FY2009
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
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 classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
6	Flammable liquids	Category 3	Warning	H226	P303+P361+P353 P370+P378 P403+P235 P210 P233 P240 P241 P242 P243 P280 P501	Regarding a flash point, there are data of 57 deg C (ICSC), > 140 deg C (GESTIS), and nonflammability (Hommel), but the data of 57 deg C on the safety side was adopted, and it was classified in Category 3.
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
8	Self-reactive substances and mixtures	Not classified (Not applicable)	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.
9	Pyrophoric liquids	Not classified	- -	-	-	It was classified as "Not classified" from information that there is not any auto-ignition temperature (REACH registration dossier (Accessed Jan 2022)).
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to liquid substances are not available.
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified (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 classified (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 classified (Not applicable)	- -	-	-	Liquid (GHS definition)
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule.
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.
17	Desensitized explosives	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.

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	[Rationale for the Classification] Based on (1) to (6), it was classified in Category 4. [Evidence Data] (1) LD50 for rats (males): between 1,300 to 2,000 mg/kg (OECD TG 401, GLP) (Toxicity Testing Results for Existing Chemical Substances under the Chemical Substances Control Law (2000)) (2) LD50 for rats (females): between 800 to 1,300 mg/kg (OECD TG 401, GLP) (Toxicity Testing Results for Existing Chemical Substances under the Chemical Substances Control Law (2000)) (3) LD50 for rats: 1,100 mg/kg (GLP) (REACH registration dossier (Accessed Jan. 2022)) (4) LD50 for rats: 680 mg/kg (REACH registration dossier (Accessed Jan. 2022)) (5) LD50 for rats (males): 930 mg/kg (REACH registration dossier (Accessed Jan. 2022)) (6) LD50 for rats (females): 1,100 mg/kg (REACH registration dossier (Accessed Jan. 2022))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) LD50 for rabbits: 3,000 mg/kg (REACH registration dossier (Accessed Jan. 2022)) (2) LD50 for rats: > 2,000 mg/kg (GLP) (REACH registration dossier (Accessed Jan. 2022))
1	Acute toxicity (Inhalation: Gases)	Not classified	- -	-	-	[Rationale for the Classification] Liquid (GHS definition). It was classified as "Not classified."
1	Acute toxicity (Inhalation: Vapours)	Category 3	Danger	H331	P304+P340 P403+P233 P261 P271 P311 P321 P405 P501	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 3. Also, since the exposure concentration was lower than 90% (7,580 ppm) of the saturated vapor pressure concentration, it was judged to be a vapor and classified based on the reference value in units of ppmV. [Evidence Data] (1) LC50 (4 hours) for rats (males): 1,009 ppm (REACH registration dossier (Accessed Jan. 2022)) (2) LC50 (4 hours) for rats (females): 1,129 ppm (REACH registration dossier (Accessed Jan. 2022)) (3) LC50 (1 hour) for rats: > 2,162 ppm (converted 4-hour equivalent value: >1,081 ppm) (REACH registration dossier (Accessed Jan. 2022))
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified" (Category 3 in UN GHS classification). [Evidence Data] (1) In a skin irritation test with rabbits (n = 3) (GLP, semi-occlusive, 4-hour application, observation for 5 days), in all animals after 1, 2, and 3 days, the average scores of erythema were 0.67, 2, and 1, respectively, and the average scores of edema were 0.33, 1, and 1, respectively. It was reported that the observed effects disappeared completely within 5 days (REACH registration dossier (Accessed Jan. 2022)). [Reference Data, etc.] (2) It was reported that, in a skin irritation test with rabbits (n=6) (semi-occlusive, 24-hour application, observation for 3 days), the primary dermal irritation index (PDII) was 2.63 (REACH registration dossier (Accessed Jan. 2022)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in an eye irritation test with rabbits (n = 3) (GLP, observation for 7 days), corneal opacity with iritis in 1 animal and conjunctival redness and chemosis in all animals were observed, but all effects were reversible within 7 days (corneal opacity score: 0/0/2, iritis score: 0/0/0.3, conjunctival redness score: 0.7/1/1.7, chemosis score: 0.3/0.7/1) (REACH registration dossier (Accessed Jan. 2022)). (2) It was reported that, in an eye irritation test with rabbits (n = 6) (observation for 8 days), clear conjunctival irritation was observed in 5 out of 6 animals, and among them, corneal opacity was also observed in 3 animals, but all effects were reversible within 8 days (Draize score after 1 to 4 days and 8 days: 17 (full score: 110)) (REACH registration dossier (Accessed Jan. 2022)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
5	Germ cell mutagenicity	Category 2	Warning	H341	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 2. It was classified based on new data. [Evidence Data] (1) As for in vivo, negative results were reported in all of a cell gene mutation test with transgenic mice targeting the liver, bone marrow, glandular stomach, and testis (continuous oral gavage for 28 days, 30 to 300 mg/kg/day), a micronucleus test using the peripheral blood reticulocytes of mice (single oral dose, 645 mg/kg), and a genetic damage test targeting the kidney of rats (alkaline elution: single intraperitoneal injection, 472 mg/kg), but positive results were reported in a chromosomal aberration test using the bone marrow cells of rats (chronic inhalation exposure, 45 mg/m3) (IARC 125 (2020), Toxicity Testing Results for Existing Chemical Substances under the Chemical Substances Control Law (2013, 2000)). (2) As for in vitro, positive results were reported in all of a bacterial reverse mutation test, three chromosomal aberration tests using the Chinese hamster lung fibroblasts (CHL), and a mouse lymphoma test using the L5178Y Tk+/- mouse lymphoma cells (IARC 125 (2020), Toxicity Testing Results for Existing Chemical Substances under the Chemical Substances Control Law (2010)).
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1), it was designated in the public announcement on guidelines in order to prevent the impairment of worker's health caused by the chemical substances decided by the Minister of Health, Labour and Welfare based on paragraph (3) of Article 28 of the Industrial Safety and Health Act, and based on (2) and (3), an increase in the incidence of malignant tumors was observed in two animal species, and there is sufficient evidence of carcinogenicity in animal studies, and therefore, it was classified in Category 1B. Also, based on the new information source, the classification result was changed. [Evidence Data] (1) This substance is a substance subject in the public announcement on guidelines in order to prevent the impairment of worker's health caused by the chemical substances decided by the Minister of Health, Labour and Welfare based on paragraph (3) of Article 28 of the Industrial Safety and Health Act (public announcement on guidelines to prevent the impairment of health, No. 23 on October 10, 2012). (2) In a carcinogenicity study by 2-year inhalation exposure with rats (OECD TG 451, GLP: vapor, 25 to 400 ppm), hepatocellular adenoma, hepatocellular carcinoma, hemangiosarcoma of the liver, bronchioloalveolar adenoma of the lung, and trichoepithelioma of the skin/appendage were observed both in males and females, and in addition, adenoma and adenocarcinoma in the large intestine were observed in males, and an increase in the incidence of adenoma in the large intestine was observed in females (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 2005), IARC 125 (2020)). (3) In a carcinogenicity study by 2-year inhalation exposure with mice (OECD TG 451, GLP: vapor, 25 to 400 ppm), an increase in the incidence of bronchioloalveolar adenoma, bronchioloalveolar carcinoma, and adenosquamous carcinoma and squamous cell carcinoma of the lung, squamous cell papilloma of the forestomach, and adenoma of the Harderian gland was observed in males, and an increase in the incidence of bronchioloalveolar adenoma, bronchioloalveolar carcinoma, squamous cell papilloma and squamous cell carcinoma of the forestomach, and adenoma of the Harderian gland was observed in females (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 2005), IARC 125 (2020)). (4) There is suggestive evidence that this substance induces inflammation and accelerates cell proliferation, and there is suggestive evidence that this substance is genotoxic (refer to the Reference Data), both of which are strong evidence in experimental systems that the substance has key characteristics of carcinogen (IARC 125 (2020)). [Reference Data, etc.] (5) As for the classification results by domestic and international organizations, the IARC classified this substance in Group 2B (IARC 125 (2020)), the Japan Society For Occupational Health (JSOH) classified it in Group 2B (Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH), 2021)).
7	Reproductive toxicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. Besides, (1) was not used for the classification because it lacked clear dose relationship, and there was no statistically significant difference. [Reference Data, etc.] (1) In a reproduction/developmental toxicity screening test with rats dosed by gavage (OECD TG421, GLP: 4 to 100 mg/kg/day, males: a total of 42 days including 14 days before mating to the mating period, females: 40 to 51 days from 14 days before mating to day 3 of lactation), no significant effects due to administration were observed in male or female parent animals except that an increase in liver weight and centrilobular hepatocellular hypertrophy were observed at the high dose (100 mg/kg/day). However, during the lactation period, insufficient nursing behavior was shown in 2 dams (2/12) at 20 mg/kg/day and in 1 dam (1/12) at 100 mg/kg/day, and all liveborn pups died. As a result, the viability indices on postnatal day 4 for liveborn pups were 96.8, 94.8, 75.5, and 72.0% in the control group, the 4 mg/kg/day dose group, the 20 mg/kg/day dose group, and the 100 mg/kg/day dose group, respectively, and a tendency of a decrease (without significant difference) in the viability index on postnatal day 4 was observed at or above 20 mg/kg/day. By individuals, in a mid-dose or higher group, even in some dams other than the above 3 cases, the viability index on postnatal day 4 in liveborn pups was considerably below the lower limit (83.3%) of the control group, and the group average was also below the range of the background data of the testing laboratory from 2005 to 2010 (81.8 to 100%). The authors stated that, although there is no dose relationship, it could not be denied that a decrease in nursing behavior in a 20 mg/kg/day or above dose group and a tendency of a decrease in the viability index on postnatal day 4 in liveborn pups were due to the administration of the test substance and reported that the NOAEL of reproductive and developmental toxicity was 4 mg/kg/day (Toxicity Testing Results for Existing Chemical Substances under the Chemical Substances Control Law (2010)).
8	Specific target organ toxicity - Single exposure	Category 3 (Narcotic effects)	Warning	H336	P304+P340 P403+P233 P261 P271 P312 P405 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 3 (narcotic effects). Also, based on the new findings, the classification result was changed. [Evidence Data] (1) It was reported that, in an acute oral toxicity test with rats (OECD TG 401, GLP), salivation was observed at 500 mg/kg (males, within the range for Category 2) and 800 mg/kg (females, within the range for Category 2), incomplete eyelid was observed at 1,300 mg/kg (within the range for Category 2), and a decrease in locomotor activity, prone position, incomplete eyelid, eyelid closure, ataxic gait, salivation, etc. were observed at 2,000 mg/kg (within the range for Category 2). Also, the LD50 was 1,300 to 2,000 mg/kg (males) and 800 to 1,300 mg/kg (females) (Toxicity Testing Results for Existing Chemical Substances under the Chemical Substances Control Law (2000)). (2) It was reported that, in an acute oral toxicity test with rats (GLP), gait abnormalities, lethargy, and a decrease in respiratory rate were observed; abnormal posture, paleness of the limbs, and ptosis were observed at 800 mg/kg (within the range for Category 2); and swelling of the membrane of the inner corner of the eye (4/5 animals (males), 1/5 animals (females)), and tremor (1/5 animals (females)) were observed at 1,000 mg/kg (within the range for Category 2) (REACH registration dossier (Accessed Nov. 2021)). (3) It was reported that, in an acute oral toxicity test with rats, depression, and hypoactivity were observed. Also, the LD50 was 930 mg/kg (males) and 1,100 mg/kg (females) (REACH registration dossier (Accessed November 2021)). (4) It was reported that, in an acute inhalation exposure test with rats (vapor, 4 hours), congestion and irritation of the trachea mucosa, and edema and swelling of the nerve tissues of the brain were observed; visceral congestion and hemorrhage in the lung were observed as necropsy findings; and fatty degeneration of the liver and albumin-like degeneration of the kidney were observed as histopathological findings. Also, the LC50 was 6.5 mg/L (1,009 ppm (males)) and 7.27 mg/L (1,129 ppm (females)) (REACH registration dossier (Accessed Nov. 2021)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (respiratory organs), Category 2 (liver)	Danger Warning	H372 H373	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) to (4), effects on the respiratory organs and liver were observed, and therefore, it was classified in Category 1 (respiratory organs), and Category 2 (liver). In addition, the effects on the kidney observed in (3) were considered to be age-related symptoms, and therefore, the kidney was not adopted as the target organ. The classification results were changed based on the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) It was reported that, in a repeated dose 28-day oral toxicity study with rats dosed by gavage (OECD TG 407, GLP), salivation, increases in absolute and relative liver weight, centrilobular hepatocellular hypertrophy, a decrease in Ht (males), an increase in mean corpuscular hemoglobin concentration (males), increases in absolute and relative kidney weight (males), atrophy of the seminiferous tubules (males), hyperplasia of the forestomach mucosa (males), and an increase in serum chlorine concentration (females) were observed at 100 mg/kg/day (converted guidance value: 31.1 mg/kg/day, within the range for Category 2) (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 2000)). (2) It was reported that, in a repeated dose 13-week subchronic inhalation toxicity study with rats (OECD TG 413, GLP, vapor, 6 hours/day, 5 days/week), goblet cell proliferation of the nasopharynx (moderate to slight), an increase in liver weight (males), and goblet cell proliferation of the nasal cavity (slight) (males) were observed at 0.322 mg/L (converted guidance value: 0.23 mg/L, within the range for Category 2); an increase in liver weight (females) and goblet cell proliferation of the nasal cavity (slight) (females) were observed at 0.644 mg/L (0.46 mg/L, within the range for Category 2); and an increase in kidney weight, hyperplasia of the respiratory epithelium, and an increase in heart weight (females) were observed at 1.288 mg/L (0.92 mg/L, within the range for Category 2) (Results from preliminary Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 2002). (3) It was reported that, in a repeated dose 104-week inhalation toxicity study with rats (OECD TG 451, GLP, vapor, 6 hours/day, 5 days/week), inflammation of the respiratory epithelium (males) and an increase in the incidence of chronic nephropathy (females) were observed at 0.161 mg/L (converted guidance value: 0.115 mg/L, within the range for Category 1); and an increase in liver weight, an increase in kidney weight, a tendency of an increase in the number of severe cases of chronic nephropathy, an increase in urea nitrogen, bile duct proliferation, and respiratory epithelial metaplasia of the nasal gland (females) were observed at 0.644 mg/L (0.46 mg/L, within the range for Category 2) (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 2005)). (4) It was reported that, in a repeated dose 104-week inhalation toxicity study with mice (OECD TG 451, GLP, vapor, 6 hours/day, 5 days/week), an increase in bronchioloalveolar epithelium proliferation was observed at 0.161 mg/L (converted guidance value: 0.115 mg/L, within the range for Category 1), and an increase in the incidence of squamous hyperplasia of the forestomach (females), an increase in the incidence of eosinophilic alterations of the nasopharynx epithelium (females), and a decrease in platelet count (females) were observed at 0.644 mg/L (0.46 mg/L, within the range for Category 2) (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 2005)).
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 Short term (Acute)	-	- -	-	-	-
11	Hazardous to the aquatic environment Long term (Chronic)	-	- -	-	-	-
12	Hazardous to the ozone layer	-	- -	-	-	-

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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