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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	108-57-6
Chemical Name	m-Divinylbenzene
Substance ID	R01-B-100
Classification year (FY)	FY2019
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
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	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified (Not applicable)."
2	Flammable gases	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
3	Aerosols	*	- -	-	-	Not aerosol products. It was classified as "Not classified (Not applicable)."
4	Oxidizing gases	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
5	Gases under pressure	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
6	Flammable liquids	*	- -	-	-	No data available. Besides, there is information on a flash point of 76 deg C (open cup) for a mixture of o-, p-, m-isomers (CAS RN 1321-74-0) (ICSC (1997)), and it is estimated to correspond to Category 4, but it was not adopted because a mixture ratio is unknown.
7	Flammable solids	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
8	Self-reactive substances and mixtures	*	- -	-	-	There are unsaturated bonds, a chemical group associated with self-reactive properties, present in the molecule, but the classification is not possible due to no data.
9	Pyrophoric liquids	*	- -	-	-	No data available. Besides, from information on an autoignition temperature of 500 deg C for a mixture of o-, p-, m-isomers (CAS RN 1321-74-0) (ICSC (1997)), it is estimated to correspond to "Not classified," but it was not adopted because a mixture ratio is unknown.
10	Pyrophoric solids	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
11	Self-heating substances and mixtures	*	- -	-	-	Classification is not possible because test methods applicable to liquid substances are not available.
12	Substances and mixtures which, in contact with water, emit flammable gases	*	- -	-	-	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 (Not applicable)."
13	Oxidizing liquids	*	- -	-	-	Organic compounds containing no oxygen, fluorine or chlorine. It was classified as "Not classified (Not applicable)."
14	Oxidizing solids	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
15	Organic peroxides	*	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified (Not applicable)."
16	Corrosive to metals	*	- -	-	-	No data available.
17	Desensitized explosives	*	- -	-	-	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)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Reference Data, etc.] (1) LD50 for rats (isomeric mixture): 5 mL/kg (4,570 mg/kg) (Environmental Risk Assessment for Chemical Substances Vol.14 (Ministry of the Environment, 2016)) (2) LD50 for rats (isomeric mixture): > 2,000 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.14 (Ministry of the Environment, 2016))
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Gases)	*	- -	-	-	[Rationale for the Classification] Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
1	Acute toxicity (Inhalation: Vapours)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
2	Skin corrosion/irritation	Category 2	Warning	H315	P302+P352 P332+P313 P362+P364 P264 P280 P321	[Rationale for the Classification] Based on (1), it was classified in Category 2. Besides, since no data for each isomer were available, this substance was classified in accordance with the data on the isomeric mixture. [Evidence Data] (1) The isomeric mixture of this substance is moderately irritating to the eyes and skin (PATTY (6th, 2012)). [Reference Data, etc.] (2) It was classified as "Skin Irrit. 2 (H315)" in the EU-CLP classification (EU CLP classification (Access on November 2019)).
3	Serious eye damage/eye irritation	Category 2	Warning	H319	P305+P351+P338 P337+P313 P264 P280	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 2. Besides, since no data for each isomer were available, it was classified in accordance with the data on the isomeric mixture. [Evidence Data] (1) The isomeric mixture of this substance is moderately irritating to the eyes and skin (PATTY (6th, 2012)). (2) Instillation of 0.1 mL of an isomeric mixture of this substance into the eyes of rabbits was associated with a moderate pain response and discomfort within 30 seconds, but these symptoms disappeared within an hour. The conjunctiva remained inflamed 8 days after instillation (ACGIH (7th, 2001) Divinyl Benzene (isomer mixture)). [Reference Data, etc.] (3) It was classified as "Eye Irrit. 2 (H319)" in the EU-CLP classification (EU CLP classification (Access on November 2019)).
4	Respiratory sensitization	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	*	- -	-	-	[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. Besides, since no data for each isomer were available, it was classified according to the data on the isomeric mixture. Therefore, the classification result was changed from the previous classification. [Evidence Data] (1) For divinyl benzene isomeric mixtures (CAS RN 1321-74-0), as for in vivo, there were reports on negative and positive results in micronucleus tests with mice and positive results in a chromosomal aberration test and a sister chromatid exchange test (NTP TR534 (2006), PATTY (6th, 2012), Environmental Risk Assessment for Chemical Substances Vol.14 (Ministry of the Environment, 2016)). (2) For divinyl benzene isomeric mixtures (CAS RN 1321-74-0), as for in vitro, there were reports on negative results in bacterial reverse mutation tests, and a chromosome aberration test and a mouse lymphoma test with cultured mammalian cells (ACGIH (7th, 2001), Environmental Risk Assessment for Chemical Substances Vol.14 (Ministry of the Environment, 2016)).
6	Carcinogenicity	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. When using (1) and (2) of the carcinogenicity test results of an isomeric mixture containing this substance, it was classified as "Classification not possible." [Reference Data, etc.] (1) In a test in which rats were exposed by inhalation to an isomeric mixture, DVB-80 (m-divinylbenzene of 60.3%, p-divinylbenzene (this substance) of 21.6%) containing this substance for 2 years, renal tubule carcinomas, and malignant glial cell tumors (malignant astrocytoma in two animals and oligodendroglioma in one animal) in the brain were observed in males, and incidences of these exceeded the historical range. Therefore, it was concluded by NTP that there was equivocal evidence of carcinogenic activity in male rats (NTP TR534 (2006), Environmental Risk Assessment for Chemical Substances Vol.14 (Ministry of the Environment, 2016), PATTY (6th, 2012)). (2) In a test in which mice were exposed by inhalation to an isomeric mixture, DVB-80 (m-divinylbenzene (this substance) of 60.3%, p-divinylbenzene of 21.6%) containing this substance for 2 years, the incidence of pulmonary tumors exceeded the historical range in females. Therefore, it was concluded by NTP that there was equivocal evidence of carcinogenic activity in female mice (NTP TR534 (2006), Environmental Risk Assessment for Chemical Substances Vol.14 (Ministry of the Environment, 2016), PATTY (6th, 2012)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1), as for the isomeric mixture, divinylbenzene (CAS RN 1321-74-0), reproductive effects were observed at the dose where parental toxicity was observed. Therefore, it was classified in Category 2. Since no information for each isomer was available, and it was difficult to classify each one, it was classified using data on the isomeric mixture. Therefore, the classification result was changed from the previous classification. [Evidence Data] (1) In a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD TG 422) with rats using an isomeric mixture, divinylbenzene (CAS RN 1321-74-0), at 1,000 mg/kg/day, as general toxicity in parental animals, decreased body weight gain in males and females, increased ALT and GGT, etc. in males, and death or moribund (1 animal each), degeneration and necrosis of renal tubules at the corticomedullary junction of the kidney, etc. were observed in females. Then, poor mammary gland development and nesting, deaths of all newborns in 7/9 maternal animals, decreases in the number of corpora lutea, the number of implantation scars and implantation rate were observed. In addition, lower values of total litter size, the number of newborns on lactation Day 0, birth rate, number of surviving newborns on lactation Day 4, survival rate, the number of live pups and viability index on lactation Day 4, and lower trends in delivery index and birth index were observed (JECDB (Access on November 2019)).
8	Specific target organ toxicity - Single exposure	Category 3 (narcotic effects, respiratory tract irritation)	Warning	H336 H335	P304+P340 P403+P233 P261 P271 P312 P405 P501	[Rationale for the Classification] Based on the information in (1) and (2) regarding the isomeric mixture, divinylbenzene (CAS RN 1321-74-0), it was classified in Category 3 (narcotic effects, respiratory tract irritation). The findings of liver damage in the fatal cases observed in (3) were not adopted as evidence because there was no original source information and details could not be confirmed. Since no information for each isomer was available, and it was difficult to classify each isomer, it was classified using data on the isomeric mixture. Therefore, the classification result was changed from the previous classification. [Evidence Data] (1) Mild irritation of the respiratory organs, skin, and eyes was observed among workers acutely exposed by inhalation to an isomeric mixture, divinylbenzene (compositional ratio of each isomer was unknown) (ACGIH (7th, 2001), Environmental Risk Assessment for Chemical Substances Vol.14 (Ministry of the Environment, 2016)). (2) In a test in which rats were exposed by a single inhalation to divinylbenzene (compositional ratio of each isomer was unknown) at 3,312 ppm for 7 hours, nasal discharge, rhinitis, body weight reduction and lethargy were observed (ACGIH (7th, 2001)). [Reference Data, etc.] (3) When mice were exposed by a single inhalation to divinylbenzene containing approximately 21% of this substance and 60% m-divinylbenzene (CAS RN 108-57-6), respectively, at 400 ppm for 6 hours, all animals died. The autopsy revealed damage to the liver (degeneration, necrosis). No dead animals were observed with a single exposure at 200 ppm (GESTIS (Access on October 2019)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (respiratory organs)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on information in (1)-(4) on the isomeric mixture, divinylbenzene (CAS RN 1321-74-0), it was classified in Category 1 (respiratory organs). Since no information for each isomer was available, and it was difficult to classify each isomer, it was classified using the data on the isomeric mixture. Therefore, the classification result was changed from the previous classification. [Reference Data, etc.] (1) In a 14-week inhalation exposure test (6 hours/day, 5 days/week) with rats using divinylbenzene (CAS RN 1321-74-0) containing approximately 60% of this substance, basal cell hyperplasia of the olfactory epithelium at or above 100 ppm (converted guidance value: 0.4 mg/L, within the range of Category 2), and degeneration of the olfactory epithelium at 200 ppm (0.8 mg/L, within the range of Category 2) were observed (NTP TR534 (2006)). (2) In a 14-week inhalation exposure test (6 hours/day, 5 days/week) with mice using divinylbenzene containing approximately 60% of this substance, necrosis of the nasal cavity lateral walls, olfactory epithelium and gland was observed in males and females in all exposure groups at or above 25 ppm (converted guidance value: 0.1 mg/L, within Category 1), and this was accompanied by atrophy of the olfactory epithelium and glands in females. All males (10/10) and 9/10 females at 200 ppm (converted guidance value: 1.1 mg/L, exceeding the range of Category 2) died, and necrosis in the liver and kidney was found in fatal animals (NTP TR534 (2006)). (3) In a 105-week inhalation exposure test (6 hours/day, 5 days/week) with rats using divinylbenzene containing approximately 60% of this substance, degenerative and regenerative changes in the olfactory epithelium in the nose were observed in all exposure groups at or above 100 ppm (converted guidance value: 0.5 mg/L, within the range of Category 2), and increased focal chronic inflammation in the lung, and increased incidences of renal tubule hyperplasia and nephropathy were observed in males at 400 ppm (2.1 mg/L) (NTP TR534 (2006)). (4) In a 105-week inhalation exposure test (6 hours/day, 5 days/week) with mice using divinylbenzene containing approximately 60% of this substance, increased atypical bronchiole hyperplasia was observed in males and females at or above 10 ppm (converted guidance value: 0.05 mg/L, within the range of Category 1), and severity and an incidence of alveolar epithelial hyperplasia increased in females at or above 30 ppm (converted guidance value: 0.16 mg/L, within the range of Category 1) (NTP TR534 (2006)).
10	Aspiration hazard	Category 1	Danger	H304	P301+P310 P331 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1. [Evidence Data] (1) This substance is a hydrocarbon. (2) Since the kinematic viscosity is 1.17 mm2/s at 20 deg C (calculated from 1.09 mPa*s for the viscosity at 20 deg C (HSDB (Access on November 2019)) and 0.9294 g/cm3 for the density (HSDB (Access on November 2019))), the kinematic viscosity at 40 deg C is 20.5 mm2/s or less.

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)	Not classified	- -	-	-	Toxicity data for this substance alone were not obtained. If acute toxicity data for a mixture with p-isomer (purity 80.2%, unknown mixture ratio) are used, it is classified as "Not classified" due to 72-hour ErC50 = 1,830 mg/L for algae (Pseudokirchneriella subcapitata), 48-hour EC50 = 1,870 mg/L for crustacea (Daphnia magna), and 96-hour LC50 = 4,160 mg/L for fish (Oryzias latipes) (all, Environmental Risk Assessment for Chemical Substances Vol. 14 (Ministry of the Environment, 2016)).
11	Hazardous to the aquatic environment Long term (Chronic)	Not classified	- -	-	-	This substance was not rapidly degradable (a degradation rate by BOD: 0% (Official Bulletin of Ministry of International Trade and Industry, 1988)), and low bioaccumulation is estimated (log Kow = 3.8 (KOWWIN)), but toxicity data for this substance alone were not obtained. If chronic toxicity data for a mixture with p-isomer (purity 80.2%, unknown mixture ratio) are used, then it is classified as "Not classified" due to 21-day NOEC = 353 mg/L for crustacea (Daphnia magna) (Environmental Risk Assessment for Chemical Substances Vol. 14 (Ministry of the Environment, 2016)). If acute toxicity data for a mixture with p-isomer (purity 80.2%, unknown mixture ratio) are used for a trophic level for which chronic toxicity data are not obtained, then it is classified as "Not classified" due to 96-hour LC50 = 4,160 mg/L for fish (Oryzias latipes) (Environmental Risk Assessment for Chemical Substances Vol. 14 (Ministry of the Environment, 2016)). From the above results, it is classified as "Not classified."
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	Classification not possible due to lack of data.

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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