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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	2698-41-1
Chemical Name	2-Chlorobenzylidenemalononitrile
Substance ID	R02-B-003-MHLW, MOE
Classification year (FY)	FY2020
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	FY2006 FY2013
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. It was classified as "Not classified."
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products. It was classified as "Not classified."
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
7	Flammable solids	Classification not possible	- -	-	-	No data available. Besides, there is information that it is combustible (ICSC (2002)).
8	Self-reactive substances and mixtures	Classification not possible	- -	-	-	There is a chemical group associated with self-reactive properties, an unsaturated bond, present in the molecule, but the classification is not possible due to no data.
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
10	Pyrophoric solids	Classification not possible	- -	-	-	No data available.
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Classification is not possible because test methods applicable to solid (melting point <= 140 deg C) 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). It was classified as "Not classified."
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
14	Oxidizing solids	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. It was classified as "Not classified."
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified."
16	Corrosive to metals	Classification not possible	- -	-	-	Classification is not possible because test methods applicable to solid substances are not available.
17	Desensitized explosives	Not classified (Not applicable)	- -	-	-	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)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	[Rationale for the Classification] It was classified in Category 4 from (1). [Evidence Data] (1) LD50 for rats: males: 1,366 mg/kg, females: 1,284 mg/kg (ACGIH (7th, 2019), NTP TR377 (1990), HSDB (Access on April 2020))
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Gases)	Not classified	- -	-	-	[Rationale for the Classification] Solid (GHS definition). It was classified as "Not classified."
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)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. Besides, the classification result was changed from the previous classification because the exposure time is unknown in (1), which was used in the previous classification. [Reference Data, etc.] (1) Median lethal dose for rats L (ct) 50 value (aerosol, exposure time: unknown): 88,480 mg-min/m3 (ACGIH (7th, 2001))
2	Skin corrosion/irritation	Category 1	Danger	H314	P301+P330+P331 P303+P361+P353 P305+P351+P338 P304+P340 P260 P264 P280 P310 P321 P363 P405 P501	[Rationale for the Classification] It was classified in Category 1 from (1) - (3). [Evidence Data] (1) This substance is a strong irritant, direct exposure causes irritation of the mucous membranes, and also in humans, irritation by this substance is reported (US AEGL (2014)). (2) This substance is used as an incapacitating agent for riot control and causes intense skin and eye irritation in humans, and direct exposure produces eye irritation, lacrimation, conjunctivitis, and skin burning (ACGIH (7th, 2019), HSDB (Access on April 2020)). (3) It is severely irritating to the skin and eye (GESTIS (Access on April 2020)). [Reference Data, etc.] (4) In a skin corrosion test by reconstructed epidermis model (Episkin) (OECD TG 431), this substance (5%) was shown to be not corrosive, and in a test similar to OECD TG 439, it was proven to be an irritant (REACH registration dossier (Access on May 2020)).
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	[Rationale for the Classification] It was classified in Category 1 from (1) - (4). [Evidence Data] (1) This substance is a strong irritant, direct exposure causes irritation of the mucous membranes, and also in humans, irritation by this substance is reported (US AEGL (2014)). (2) This substance is used as an incapacitating agent for riot control and causes intense skin and eye irritation in humans, and direct exposure produces eye irritation, lacrimation, conjunctivitis, and skin burning (ACGIH (7th, 2019), HSDB (Access on April 2020)). (3) It is severely irritating to the skin and eye (GESTIS (Access on April 2020)). (4) This substance was classified in Category 1 in skin corrosion/irritation. [Reference Data, etc.] (5) In an eye damage test using isolated bovine cornea (OECD TG 437), this substance (5%) was shown to be not corrosive, and in an eye irritation test by Reconstructed Human Cornea-like Epithelium model (SkinEthic) according to OECD TG 492, it was judged as an irritant (REACH registration dossier (Access on May 2020)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] It was classified in Category 1 from (1) - (3). The classification result was changed due to new data obtained. [Evidence Data] (1) In a skin sensitization test according to OECD TG 442D (Keratinosens), Imax exceeded 1.5, and it was judged as positive (REACH registration dossier (Access on May 2020)). (2) It has the potential to sensitize the skin (GESTIS (Access on April 2020), HSDB (Access on April 2020)). (3) In the industry where this substance is handled, sensitization was suspected from the development of dermatitis, mainly in necks and arms (HSDB (Access on April 2020)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Although it was negative in an in-vivo test and positive in part of in vitro tests from (1) and (2), it was classified as "Not classified" based on the expert judgment. [Evidence Data] (1) As for in vivo, it was reported to be negative in a micronucleus test with mouse bone marrow cells by both oral and intraperitoneal administration (ACGIH (7th, 2001)). (2) As for in vitro, it was mostly negative in bacterial reverse mutation tests (NTP TR377 (1990), ACGIH (7th, 2019), CEBS (Access on April 2020)), and there are reports that it was positive in a mouse lymphoma test, a sister chromatid exchange test, and a chromosomal aberration test in cultured mammalian cells (NTP TR377 (1990), ACGIH (7th, 2019), CEBS (Access on April 2020)). [Reference Data, etc.] (3) This substance affected mitotic spindle damage and induced aneuploidy of chromosomes in vitro, and it did not bind to DNA in the liver or kidney in vivo but did bind to nuclear proteins in these organs (US AEGL (2014)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from classification results by other organizations in (1) and results of carcinogenicity tests in experimental animals in (2), (3). Besides, in the previous GHS classification guidance for the Japanese government, A4 by ACGIH was regarded as "Classification not possible," but in the current GHS classification guidance, A4 by ACGIH was taken as "Not classified." Therefore, the classification result was changed. [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified in A4 in ACGIH (ACGIH (7th, 2019)). (2) In a carcinogenicity test by 2-year inhalation exposure in rats (0.075, 0.25, 0.75 mg/m3), there were no treatment-related incidences of tumors in either males or females. Therefore, it was concluded that there was no evidence of carcinogenicity for male and female rats (NTP TR377 (1990)). (3) In a carcinogenicity test by 2-year inhalation exposure in mice (0.75, 1.5 mg/m3), there were no treatment-related incidences of tumors in either males or females. Besides, there were dose-dependent decreases in incidences of pituitary adenoma and lymphoma in females, but it was concluded that there was no evidence of carcinogenicity for male and female mice (NTP TR377 (1990)).
7	Reproductive toxicity	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1), no developmental effects were observed, but there was no data on reproductive function and fertility. Therefore, classification was not possible due to lack of data. [Evidence Data] (1) In inhalation toxicity tests with female rats on days 6 to 15 of gestation and female rabbits on days 6 to 18 of gestation, no embryo or fetal death nor teratogenicity was observed, and there was no effect on the number of implantations and litters produced (ACGIH (7th, 2019)). [Reference Data, etc.] (2) In an intraperitoneal administration test with female rats on days 6, 8, 10, 12 and 14 of gestation, no embryo or fetal death nor teratogenicity was observed, and there was no effect on the number of implantations and litters produced (ACGIH (7th, 2019)).
8	Specific target organ toxicity - Single exposure	Category 1 (respiratory organs)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 1 (respiratory organs). The information in the information sources was reviewed and the classification result was changed from the previous classification. [Evidence Data] (1) This substance is a potent irritant that is used as tear gas, and symptoms of exposure to this substance include lacrimation, blepharospasm, erythema of the eyelids, chest tightness, and nasal discharge, salivation and coughing caused by irritation of the nose, mouth, and throat, nausea, vomiting (from swallowing excess saliva), and cutaneous irritation (US AEGL (2014)). (2) Humans in contact with this substance experienced intense eye and skin irritation, coughing, difficulty in breathing, chest tightness, running nose, dizziness, nausea, and vomiting. The symptoms appeared at concentrations ranging from 12 to 20 mg/m3 and at about 20 seconds after the exposure. The symptoms persisted for 5 to 104 minutes after the affected humans moved to a place with fresh air (ACGIH (7th, 2019)). (3) Four male volunteers were exposed to aerosol of this substance at 1.5 mg/m3 for 90 minutes. As a result, three subjects developed headache, and two subjects experienced headache for 24 hours following the exposure. One developed slight eye and nose irritation. When exposed to this substance at 4 to 5 mg/m3, the subjects had difficulty in solving mathematical calculation problems, although accuracy of the results was not impaired. Major effects of the exposure were eye irritation, conjunctivitis, lacrimation, and skin burning (ACGIH (7th, 2019)). (4) In a test with rats exposed by inhalation to aerosol of this substance at concentrations of 454 to 560 mg/m3 for 25 to 90 minutes followed by histopathologic examinations 14 days later, the rats became excitable and hyperactive immediately after the exposure began, and they exhibited lacrimation and salivation within 30 seconds and lethargy and dyspnea after 5 to 15 minutes. Dyspnea persisted for approximately an hour and other signs subsided about 5 min after the exposure ceased. The histopathologic examinations revealed an increase in the number of goblet cells in the respiratory tract and conjunctiva, necrosis in the respiratory and digestive tracts only if particles had impacted the surface, and pulmonary edema and hemorrhage in the adrenal glands were occasionally observed (US AEGL (2014)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (respiratory organs)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) and (2), in inhalation exposure tests with rats and mice, effects on the respiratory organs were observed at doses within the range for Category 1. Therefore, the substance was classified in Category 1 (respiratory organs). [Evidence Data] (1) In inhalation exposure studies with rats and mice exposed to aerosol of this substance (this substance: 94%, colloidal silica: 5%, hexamethyldisilazane: 1%) for 13 weeks (6 hours/day, 5 days/week), the rats exhibited lesions in the nasal passage (such as epithelial hyperplasia and squamous metaplasia in the nasal mucosa) at or above 0.4 mg/m3 (converted guidance value: 0.0003 mg/L, within the range for Category 1) and hyperplasia of the epithelium in the larynx, etc. at or above 3 mg/m3 (converted guidance value: 0.002 mg/L, within the range for Category 1),; and the mice exhibited lesions in the nasal passage (such as squamous metaplasia in the nasal turbinate) at or above 1.5 mg/m3 (converted guidance value: 0.001 mg/L, within the range for Category 1) (NTP TR377 (1990), ACGIH (7th, 2019)). (2) In inhalation exposure studies with rats and mice exposed to aerosol of this substance (this substance: 94%, colloidal silica: 5%, hexamethyldisilazane: 1%) for two years (6 hours/day, 5 days/week), lesions in the nasal passage were observed in rats at or above 0.25 mg/m3 and in mice at or above 0.75 mg/m3 (both within the range for Category 1) (NTP TR377 (1990), ACGIH (7th, 2019)). [Reference Data, etc.] (3) This substance is a potent irritant that is used as tear gas, and symptoms of exposure to this substance include lacrimation, blepharospasm, erythema of the eyelids, chest tightness, and nasal discharge, salivation and coughing caused by irritation of the nose, mouth and throat, nausea, vomiting (from swallowing excess saliva), and cutaneous irritation (US AEGL (2014)). (4) Seven men were exposed to this substance at concentrations ranging from 1 to 13 mg/m3 for 15 days. As a result, no effect was observed except for a rise in the thymol turbidity value (one of liver function test values) in one subject (ACGIH (7th, 2019)).
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)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 96-hour LC50 = 0.22 mg/L for fish (Oncorhynchus mykiss) (ECOTOX, 2020).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	Reliable chronic toxicity data were not obtained. It was classified in Category 1 because it is not rapidly degradable (BIOWIN), and it was classified in Category 1 in acute toxicity.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in the Annexes to the Montreal Protocol.

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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