NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	95-63-6
Chemical Name	1,2,4-Trimethylbenzene
Substance ID	R03-B-036-METI, MOE
Classification year (FY)	FY2021
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	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 (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	It was classified in Category 3 based on a flash point of 50 deg C (closed cup) (GESTIS (Accessed Aug. 2021)).
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 is estimated that it does not ignite at normal temperatures from an autoignition temperature of 485 deg C (GESTIS (Accessed Aug. 2021)).
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)	- -	-	-	Organic compounds containing no oxygen, fluorine or chlorine.
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)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (4), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: 5,000 mg/kg (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2009), SIAP (2012)) (2) LD50 for rats (males): 6,000 mg/kg (GLP) (REACH registration dossier (Accessed Aug. 2021)) (3) LD50 for rats (males): 3,550 mg/kg (REACH registration dossier (Accessed Aug. 2021), HSDB in PubChem (Accessed Aug. 2021)) (4) LD50 for rats (females): 3,280 mg/kg (REACH registration dossier (Accessed Aug. 2021), HSDB in PubChem (Accessed Aug. 2021))
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] Liquid (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)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." Also, the exposure concentration was higher than the saturated vapor pressure concentration 2,771.6 ppm (13.625 mg/L) and it was judged as mist. [Evidence Data] (1) LC50 (4 hours) for rats: 18,000 mg/m3 (18 mg/L) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2009), SIAP (2012), REACH registration dossier (Accessed Aug. 2021)) (2) The vapor pressure of this substance at 25 deg C was 2.10 mm Hg (HSDB in PubChem (Accessed Aug. 2021)).
2	Skin corrosion/irritation	Category 2	Warning	H315	P302+P352 P332+P313 P362+P364 P264 P280 P321	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 2. Also, based on the new findings, the classification result was changed. [Evidence Data] (1) This substance is irritating to the eyes, skin, and respiratory tract, and may have an effect on the central nervous system, and when the liquid is swallowed, it may be drawn in the lungs, causing chemical pneumonia. When it was inhaled or orally ingested, confusion, cough, vertigo, lethargy, headache, sore throat and vomiting occurred; when it contacted the skin, redness or dry skin was caused; and when it entered the eyes, redness or pain was caused (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2009)). (2) In the EU CLP, it was classified in Skin Irrit. 2.
3	Serious eye damage/eye irritation	Category 2	Warning	H319	P305+P351+P338 P337+P313 P264 P280	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 2. Also, based on the new findings, the classification result was changed. [Evidence Data] (1) This substance is irritating to the eyes, skin, and respiratory tract, and may have an effect on the central nervous system, and when the liquid is swallowed, it may be drawn in the lungs, causing chemical pneumonia. When it was inhaled or orally ingested, confusion, cough, vertigo, lethargy, headache, sore throat, and vomiting occurred; when it contacted the skin, redness or dry skin was caused; and when it entered the eyes, redness or pain was caused (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2009)). (2) Trimethylbenzene mixture containing this substance is an eye, nose, and respiratory irritant (ACGIH (2001)). (3) In the EU CLP, it was classified in Eye Irrit. 2.
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	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) As for in vivo, a micronucleus test using the bone marrow cells of mice (intraperitoneal administration) showed negative results, but a sister chromatid exchange test (intraperitoneal administration) showed positive results at high doses (>= 730 mg/kg) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2009), US AEGL (2012), EPA Tox. Review (2016), Patty (6th, 2012)). (2) As for in vitro, in a bacterial reverse mutation test, and a chromosome aberration test with cultured mammalian cells, negative results were obtained (Toxicity Testing Results for Existing Chemical Substances under the Chemical Substances Control Law (Accessed August 2021), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2009), EPA Tox. Review (2016)). (3) The EPA expressed their opinion that there was inadequate evidence to conclude that any isomer of trimethylbenzene was genotoxic (EPA Tox Review (2016)).
6	Carcinogenicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. There was no report on human carcinogenic potential, and in the study with experimental animals, only one dose was tested and no adequate analyses of the results were provided. [Reference Data, etc.] (1) As for the classification results by domestic and international organizations, the EPA reported that there is I (Inadequate information to assess carcinogenic potential) of this substance (EPA Tox. Review (2016)). (2) In a 2-year carcinogenicity study with rats dosed by gavage (only one dose of 800 mg/kg, 4 days/week), a slight increase in malignant tumors in males and females of the treated group and head tumors (including rare neuroesthesioepitheliomas in one male and two females) were observed, but no statistical analyses of the results were reported (EPA Tox. Review (2016), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2009)).
7	Reproductive toxicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. Also, no developmental toxicity effects were observed in (1), but there was no data on effects on fertility. [Evidence Data] (1) It was reported that, in a developmental toxicity study by inhalation exposure with rats (days 6 to 20 of gestation, 6 hours/day), decreased body weight gain and decreased food consumption in parental animals and decreased body weight in fetuses were observed at or above 600 ppm (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2009), US AEGL (2012), EPA Tox. Review (2016)). [Reference Data, etc.] (2) In a three-generation reproduction toxicity study with rats by inhalation exposure using C9 mixture (containing 40.5% this substance, containing 8.4%1,3,5-isomers) as a test substance, decreased fertility index (F1 parental male animals), decreased live birth index (F1), lower viability index survival on postnatal days 0 and 4 (F2), etc. were observed at a high dose (1,500 ppm) at which a high incidence of deaths was observed in F0 to F2 parental female animals. At a medium dose (500 ppm) at which no deaths occurred in parental animals and reduced body weight gain (F0 males and females) and ataxia and reduced motor activity (F1 females) were observed, only lower weaning weight was observed in F3 pups (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2009), US AEGL (2012), EPA Tox. Review (2016)). (3) In a developmental toxicity study with mice by inhalation exposure using the same C9 mixture as (2) as a test substance, at a high dose (1,500 ppm) at which deaths/moribundities frequently occurred in dams, an increase in post-implantation embryo loss, increases in the incidences of cleft palate, and delayed ossification in fetuses were observed. Even at a medium dose (500 ppm), deaths/moribundities occurred in 2 of 30 dams, but no developmental effects other than lower body weight were observed in fetuses (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2009), US AEGL (2012), EPA Tox. Review (2016)).
8	Specific target organ toxicity - Single exposure	Category 3 (respiratory tract irritation, narcotic effects)	Warning	H335 H336	P304+P340 P403+P233 P261 P271 P312 P405 P501	[Rationale for the Classification] Based on (1) to (5), a mixture of isomers containing this substance was classified in Category 3 (respiratory tract irritation, narcotic effects). [Evidence Data] (1) It was reported that exposure of mice to the vapor of this substance at 5,000 to 9,000 ppm (24.6 to 44.2 mg/L, in the range corresponding to "Not classified") caused central nervous system depression (ACGIH (2001)). (2) It was reported that, in an acute inhalation exposure test (4 hours) with rats, the concentrations for 50% reduction (EC50s) in performance in a rotarod test and in pain stimulation threshold in a hot-plate test were 954 ppm (4.68 mg/L, within the range for Category 2) and 1,155 ppm (5.67 mg/L, in the range corresponding to "Not classified"), respectively (US AEGL (2012), EPA Tox Review (2016)). (3) It was reported that, in an acute inhalation exposure test with mice (2 hours), lateral position was observed at 8,100 ppm (converted 4-hour equivalent value: 79.5 mg/L, in the range corresponding to "Not classified") and loss of (righting) reflexes was observed at 8,100 to 9,100 ppm (converted 4-hour equivalent value: 79.5 to 89.4 mg/L, in the range corresponding to "Not classified") (US AEGL (2012)). (4) This substance is irritating to the eyes, skin, and respiratory tract, and may have an effect on the central nervous system. When inhaled or orally ingested, confusion, cough, vertigo, lethargy, headache, sore throat, and vomiting occurred (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2009)). (5) It was reported that this substance was an eye, nose, and respiratory irritant (ACGIH (2001)). [Reference Data, etc.] (6) It was reported that, in an experiment in volunteers exposed by inhalation to this substance and isomers of this substance, no irritating effects or central nervous system symptoms were observed at up to 25 ppm in 2-hour or 4-hour exposure and at up to 30 ppm in 8-hour exposure (US AEGL (2012), Patty (2012)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (central nervous system, respiratory organs)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Since central nervous system effects in humans were suggested in (1) and (2) and effects on the central nervous system and respiratory organs were observed within the dose range for Category 1 in (3) to (6), it was classified in Category 1 (central nervous system, respiratory organs). [Evidence Data] (1) In a survey of 27 painters and 10 assistants exposed to paint thinner containing more than 50% of this substance and more than 30% of 1,3,5-isomers for several years, the concentrations of high-boiling hydrocarbon in the air sample collected during paint work and after work were in the range of 10 to 60 ppm. These workers complained frequently of headaches, tiredness, dizziness, and numbness, and asthmatiform bronchitis was commony observed, and also gastric symptoms were observed in many workers. In addition, hematological effects (decreases in red blood cell count and blood platelet count, lengthened clotting times) were observed, but it was pointed out that they might have been caused by contamination of the solvent with benzene (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2009), ACGIH (2001), US AEGL (2012)). (2) In an investigation of 175 factory workers (107 males, 68 females) in Poland who were chronically exposed to an organic solvent containing this substance (over 30% this substance, over 9.5% 1,3,5-isomers) against 175 controls who matched by sex, age, etc., many of the exposed workers complained of headache, vertigo, impairment in concentration, sleep disorder, daytime drowsiness, short temper, and emotional disturbance. In an objective neurological test, no apparent disorders in the central or peripheral nervous system organs were observed, but abnormalities mainly in reaction latency were observed in a measurement of visual evoked potential, and paroxysmal changes were most commonly observed in the abnormal electroencephalogram record. The concentration of the organic solvent at the factory was within the permissible concentration range or within 1.5 times that range, but it was suggested that subclinical health effects in the nervous system were caused (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2009)). (3) It was reported that, in a 4-week inhalation exposure study with rats (males) (6 hours/day, 5 days/week), effects on the central nervous system were examined 14 to 54 days after the last exposure, and as a result, an increase in grooming (open field test), shortened latency in a passive avoidance test, and delayed latency in a hot plate test were observed at or above 492 mg/m3 (converted guidance value: 0.11 mg/L, within the range for Category 1), and a delay in learning in an active avoidance test was observed at 1,230 mg/m3 (converted guidance value: 0.27 mg/L, within the range for Category 2) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2009), US AEGL (2012), Patty (2012)). (4) It was reported that, in a 13-week inhalation exposure study with rats (males) (6 hours/day, 5 days/week), delayed latency in a hot plate test and lower performance in a rotarod (rotating rod) test were observed at 492 and 1,230 mg/m3 (converted guidance value: 0.36 and 0.89 mg/L, within the range for Category 2) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2009), US AEGL (2012), Patty (2012)). (5) It was reported that, in a 13-week inhalation exposure study with rats (6 hours/day, 5 days/week), histopathological alterations in the lungs (peribronchial lymphoid tissue proliferation and an increase in interstitial lymphocytic infiltration) and shortened clotting time (females) were observed at or above 492 mg/m3 (converted guidance value: 0.36 mg/L, within the range for Category 2), and shortened clotting time (females), decreased red blood cell count and increased white blood cell count (males), and decreased reticulocyte count (females) were observed at 1,230 mg/m3 (converted guidance value: 0.89 mg/L, within the range for Category 2) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2009)). (6) It was reported that, in a 90-day inhalation exposure study with rats, lesions in the lungs, increased alveolar macrophages, increases in immune cells and inflammatory cells in bronchoalveolar lavage fluid (BAL), etc. were observed at 123 mg/m3 (0.123 mg/, within the range for Category 1) (EPA Tox Review (2016)).
10	Aspiration hazard	Category 1	Danger	H304	P301+P310 P331 P405 P501	[Rationale for the Classification] Based on (1) - (4), it was classified in Category 1. Besides, based on (2), the kinematic viscosity was estimated to be lower value than guidance values: 20.5 mm2/s because of the kinematic viscosity of isomer of this substance: 1,3,5-Trimethylbenzene, then it was adopted as rationale for the classification. [Evidence Data] (1) This substance is a hydrocarbon compound. (2) The kinematic viscosity of 1,3,5-Trimethylbenzene was 0.843 mm2/s and 0.630 mm2/s at 20 deg C and 50 deg C (GESTIS (2021)). (3) It was reported that pulmonary instillation of liquid trimethylbenzene caused chemical pneumonitis at the site of contact (ACGIH (2001)). (4) It was reported that if this liquid is swallowed, aspiration into the lungs may result in chemical pneumonitis. (SIAR in PubChem (Accessed Aug. 2021), ICSC (2002)).

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 2	- -	H401	P273 P501	It was classified in Category 2 from 96-hour LC50 = 7.72 mg/L for fish (Pimephales promelas) (Risk Assessment for Priority Assessment Chemical Substances, 2015, REACH registration dossier, 2021).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 2	-	H411	P273 P391 P501	Reliable chronic toxicity data were not obtained. It was classified in Category 2 because it is not rapidly degradable (a 28-day degradation rate by BOD: Average 8.7% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, METI, 1980)) and it was classified in Category 2 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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