NITE - Chemical Management Field

GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	108-67-8
Chemical Name	1,3,5-Trimethylbenzene
Substance ID	H26-B-067, -
Classification year (FY)	FY2014
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)
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	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) (ICSC (2002)). Besides, it is classified in Class 3, PG III (UN2325) in UNRTDG.
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 estimated that it does not ignite at normal temperatures from an autoignition temperature of 550 deg C (ICSC (2002)).
10	Pyrophoric solids	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 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	- -	-	-	Organic compounds containing no oxygen, fluorine or chlorine
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)	Not classified	- -	-	-	There are 2 reports of LD50 values for rats of 4,300-8,642 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)) and 5,000 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013)). Based on one report that can identify the category, it was classified as "Not classified." New information sources (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)) were added, and the category was revised.
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)	Not classified	- -	-	-	Based on a report of an LC50 value (4 hours) for rats of 24 mg/L (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), DFGOT vol. 4 (1992)), it was classified as "Not classified." Besides, since the LC50 value is higher than the saturated vapor concentration (12.1 mg/L), a reference value for the mist was applied.
2	Skin corrosion/irritation	Category 2	Warning	H315	P302+P352 P332+P313 P362+P364 P264 P280 P321	In a skin irritation test with rabbits (according to OECD TG404), very slight redness was observed 1 hour after application, and this became moderate to severe after 144 hours (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). From the above result, it was classified in Category 2. Besides, there is a report that the edema was slight in observation after one hour and disappeared after 144 hours (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)).
3	Serious eye damage/eye irritation	Category 2B	- Warning	H320	P305+P351+P338 P337+P313 P264	Based on a description that slight irritation was observed as a result of application of 500 mg of this substance to rabbit eyes for 24 hours (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)), it was classified in Category 2B.
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, there is a report that in occupational exposure to mixed solvents containing isomers of this substance, when 37 paint shop employees were exposed to solvent vapor (composition: 30% of 1,3,5-trimethylbenzene, 50% of 1,2,4-trimethylbenzene, other substances possibly contained: 1,2,3-trimethylbenzene, 1-methyl-2-ethylbenzene and 1-methyl-4-ethylbenzene) for 7 years, 70% of humans exposed to the highest concentration developed asthmatic bronchitis (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). However, since this finding is based on mixed exposure and it is not possible to judge whether it is the effect of this substance, this data was judged insufficient to use for classification.
4	Skin sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.
5	Germ cell mutagenicity	Classification not possible	- -	-	-	This substance was classified as "Classification not possible" because it was not possible to classify a substance as "Not classified" according to the revised GHS classification guidance for the Japanese government. As for in vivo, it was negative in a micronucleus test with mouse bone marrow cells and positive only at a higher dose in a sister chromatid exchange test with mouse bone marrow cells (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013), PATTY (6th, 2012), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), HSDB (Access on August 2014)). As for in vitro, it was negative in bacterial reverse mutation tests (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013), PATTY (6th, 2012), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), DFGOT vol. 4 (1992)).
6	Carcinogenicity	Classification not possible	- -	-	-	Classification not possible due to lack of data.
7	Reproductive toxicity	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, in a teratogenicity test with rats by the inhalation route, at doses where maternal toxicity (decreased body weight gain, decreased food consumption) was observed, a slight effect on the fetuses (decreased fetal body weight) was observed but teratogenicity was not observed (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013)). Since there is no report on fertility, it was classified as "Classification not possible."
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	This substance (purity 30% in human reports, purity 99% or more in experimental animals) is irritating to the respiratory organs in humans and experimental animals (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013), OEL Documentations (Japan Society For Occupational Health (JSOH), 1984)). In humans, headache, dizziness, drowsiness, incoordination and vomiting by inhalation exposure, and chemical pneumonitis due to aspiration into the lungs by ingestion have been reported (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013), OEL Documentations (Japan Society For Occupational Health (JSOH), 1984), ACGIH (7th, 2001), PATTY (6th, 2012), HSDB (Access on August 2014)). In experimental animals, there are reports that loss of righting reflex and central nervous system depression after an inhalation exposure of mice were observed, and by an inhalation exposure of rats, EC50 in a rotarod test was 963 ppm (4.73 mg/L), and EC50 for loss of pain sensitivity in a hot plate test was 1,212 ppm (5.96 mg/L) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), OEL Documentations (Japan Society For Occupational Health (JSOH), 1984), ACGIH (7th, 2001), PATTY (6th, 2012)). The effects on the central nervous system in humans and experimental animals were symptoms generally included in the narcotic effects, and the details of "confusion" in humans were unknown. In addition, findings of chemical pneumonitis in humans were considered in "10 Aspiration Hazard." From the above, it was classified in Category 3 (respiratory tract irritation, narcotic effects). "Respiratory tract irritation" was added to Category 3 (narcotic effects) in the previous classification.
9	Specific target organ toxicity - Repeated exposure	Category 1 (central nervous system, respiratory organs)	Danger	H372	P260 P264 P270 P314 P501	In humans, effects on the central nervous system (nervousness, tension, anxiety) and respiratory organs (asthmatic bronchitis) were observed in many of the 27 workers exposed to solvents containing 30% of this substance and 50% of 1,2,4-trimethylbenzene (10-60 ppm as hydrocarbon concentrations) for several years. In the hematological test, a trend of hypochromic anaemia and blood coagulation abnormalities (prolongation of coagulation time) was shown. It is also described that although the authors claimed that it was the effects due to trimethylbenzene exposure, another investigator pointed out that the hematologic toxicity was due to benzene contamination in the solvent (ACGIH (7th, 2001), Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013)). In experimental animals, in a study in which rats were exposed to this substance (estimated as a vapor) by inhalation for 4 weeks and behavioral tests to evaluate the effects on the central nervous system were conducted, shortening of latency in passive avoidance behavior, increased number of trials in conditioned active avoidance behavior and prolonged reaction time in a hot plate test were observed at concentrations corresponding to Category 1 (125-500 mg/m3: 0.038-0.15 mg/L/6 hours (converted guidance value)) (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)), and the effect on the central nervous system was suggested. However, in each study with rats exposed by inhalation at 3,000 mg/m3 (6 hours/day) for 5 weeks or 1,000 mg/m3 (4 hours/day) for 6 months, increased serum ALT activity (converted guidance value: 1.15 mg/L/6 hours ("Not classified")) in the former group, and inhibition of phagocytosis of leukocytes (converted guidance value: 0.67 mg/L/6 hours (equivalent to Category 2)) in the latter group were only observed, and no findings suspecting central nervous system effect and anaemia or blood coagulation disorder were obtained (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). On the other hand, a NOAEL of 200 mg/kg/day was determined in a 90-day gavage study with rats, and it is of no toxicity within and lower than the dose range of Category 2 (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). From the above, regarding the effects on the central nervous system, respiratory organs and hemal system that were concerns in the reports of findings in humans in repeated inhalation exposures to solvents containing 30% of this substance, in the studies with experimental animals, there were no effects by which the target organ can be confirmed by exposure to this substance. However, based on the findings in humans, it was classified in Category 1 (central nervous system, respiratory organs) similarly to trimethylbenzene (CAS RN 25551-13-7), isomer mixture.
10	Aspiration hazard	Category 1	Danger	H304	P301+P310 P331 P405 P501	This substance is a hydrocarbon and the kinematic viscosity is 8.9 mm2/s (calculated from the density of 0.8652 g/cm3 (20 deg C) (BUA 46 (1996))) and the viscosity of 7.66 Pa*s (15.6 deg C) (BUA 46 (1996)). Therefore, it was classified in Category 1. Besides, there is a description in ICSC in List 3 that the chemical pneumonitis may occur due to aspiration into the lungs in case of ingestion (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 (Acute)	-	- -	-	-	-
11	Hazardous to the aquatic environment (Long-term)	-	- -	-	-	-
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.

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