Item | Information |
---|---|
CAS RN | 95-63-6 |
Chemical Name | 1,2,4-Trimethylbenzene |
Substance ID | m-nite-95-63-6_v2 |
Download of Excel format | Excel file |
Item | Information |
---|---|
Guidance used for the classification (External link) | To Guidance List |
UN GHS document (External link) | To UN GHS document |
FAQ(GHS classification results by the Japanese Government) | To FAQ |
List of Information Sources (Excel file) | List of Information Sources |
List of Definitions/Abbreviations | Definitions/Abbreviations |
Sample Label by MHLW (External link) | MHLW Website (in Japanese Only) |
Sample SDS by MHLW (External link) | MHLW Website (in Japanese Only) |
OECD/eChemPortal (External link) | To OECD/eChemPortal (External link) |
Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | Classification year (FY) | GHS Classification Guidance for the Japanese Government | |
---|---|---|---|---|---|---|---|---|
1 | Explosives | Not classified (Not applicable) |
- |
- | - | There are no chemical groups associated with explosive properties present in the molecule. | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
2 | Flammable gases | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
3 | Aerosols | Not classified (Not applicable) |
- |
- | - | Not aerosol products. | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
4 | Oxidizing gases | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
5 | Gases under pressure | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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)). | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
7 | Flammable solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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. | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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)). | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
10 | Pyrophoric solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
11 | Self-heating substances and mixtures | Classification not possible |
- |
- | - | Test methods applicable to liquid substances are not available. | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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). | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
13 | Oxidizing liquids | Not classified (Not applicable) |
- |
- | - | Organic compounds containing no oxygen, fluorine or chlorine. | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
14 | Oxidizing solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
15 | Organic peroxides | Not classified (Not applicable) |
- |
- | - | Organic compounds containing no bivalent -O-O- structure in the molecule. | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
16 | Corrosive to metals | Classification not possible |
- |
- | - | No data available. | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
17 | Desensitized explosives | Not classified (Not applicable) |
- |
- | - | There are no chemical groups associated with explosive properties present in the molecule. | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | Classification year (FY) | GHS Classification Guidance for the Japanese Government | |
---|---|---|---|---|---|---|---|---|
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)) |
FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
1 | Acute toxicity (Dermal) | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
1 | Acute toxicity (Inhalation: Gases) | Not classified (Not applicable) |
- |
- | - | [Rationale for the Classification] Liquid (GHS definition). It was classified as "Not classified." |
FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
1 | Acute toxicity (Inhalation: Vapours) | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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)). |
FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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. |
FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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. |
FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
4 | Respiratory sensitization | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
4 | Skin sensitization | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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)). |
FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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)). |
FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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)). |
FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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)). |
FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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)). |
FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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)). |
FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | Classification year (FY) | GHS Classification Guidance for the Japanese Government | |
---|---|---|---|---|---|---|---|---|
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). | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
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. | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | This substance is not listed in the Annexes to the Montreal Protocol. | FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
|