GHS Classification Result
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 108-88-3 |
| Chemical Name | Toluene |
| Substance ID | 24B6503 |
| Classification year (FY) | FY2012 |
| 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) | Physical Hazards and Health Hazards: GHS Classification Guidance by the Japanese Government (July, 2010) Environmental Hazards: UN GHS Document (4th 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 |
| 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 2 |
 Danger |
H225 |
P303+P361+P353
P370+P378 P403+P235 P210 P233 P240 P241 P242 P243 P280 P501 |
It corresponds to Category 2 from a flash point of 4.4 deg C [closed-cup] (Merck (14th, 2006)) < 23 deg C, and an initial boiling point of 110.6 deg C (Merck (14th, 2006)) > 35 deg C. |
| 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 480 deg C (HSDB (2010)). |
| 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. |
| 16 | Corrosive to metals | Classification not possible |
- |
- | - | No data available. Besides, there is the information that aluminum, ferritic and austenitic steel were usable as suitable materials for containers (GESTIS (Access on Apr. 2012)). |
| Hazard class | Classification |
Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 1 | Acute toxicity (Oral) | Not classified |
- |
- | - | All of seven LD50 values for rats [5000 mg/kg (Environmental Risk Assessment for Chemical Substances vol. 1 (Ministry of the Environment, 2002)), 5,580 mg/kg (EU-RAR (2003)), 5,900 mg/kg, 6.4 g/kg, 7.53 g/kg (above three, EHC 52 (1985)), 7.0 g/kg (JECFA 518 (1981)), 7300 mg/kg (ATSDR (2000))] correspond to "Not classified." Besides, data in young animals were not adopted for classification. |
| 1 | Acute toxicity (Dermal) | Not classified |
- |
- | - | There are reports on an LD50 value for rats of 12,000 mg/kg (ACGIH (2007)), and LD50 values for rabbits of 14,100 mg/kg (ACGIH (2007)) and 12,400 mg/kg (EU-RAR (2003)), and all correspond to "Not classified." |
| 1 | Acute toxicity (Inhalation: Gases) | Not applicable |
- |
- | - | Liquid (GHS definition) |
| 1 | Acute toxicity (Inhalation: Vapours) | Category 4 |
 Warning |
H332 |
P304+P340
P261 P271 P312 |
All of six LC50 values by 4-hour exposure of rats [7,460 ppm, 3,319-7,646 ppm, 8,762 ppm (above three, EU-RAR (2003)), 4,000 ppm, 8,000 ppm, 8,800 ppm (above three, PATTY (5th, 2001))] correspond to Category 4. Besides, because the LC50 values were lower than 90% of the saturated vapour pressure concentration (37,368 ppm), a reference value of gas was applied as vapour with little mist. |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Classification not possible |
- |
- | - | No data available. |
| 2 | Skin corrosion/irritation | Category 2 |
Warning |
H315 |
P302+P352
P332+P313 P362+P364 P264 P280 P321 |
In a test by a 4-hour semi-occlusive application of 0.5 mL of the test substance to seven rabbits (Annex V, method B2), by 72 hours after the application, all the animals showed slight to severe erythema and slight edema, on day 7, well-defined to severe erythema in all the animals and very slight to slight edema in five animals were observed, and it was assessed as moderately irritating (EU-RAR (2003)). Therefore, it was classified in Category 2. Besides, it is reported that it was slightly irritating in another skin irritation test with six rabbits (OECD TG 404), although data details are unknown (EU-RAR (2003)), and it is reported that eschar formation was seen in a test with guinea pigs given a 24-hour occlusive application of 0.5 mL of undiluted this substance, and after five days, a thick layer of scales and slight superficial fissuring of the skin were found (EU-RAR (2003)). |
| 3 | Serious eye damage/eye irritation | Category 2B |
Warning |
H320 |
P305+P351+P338
P337+P313 P264 |
In a test in which 0.1 mL of the test substance was applied to six rabbits (OECD TG 405, GLP), redness, chemosis, and discharge in the conjunctiva were observed in all the animals 1 hour after the application and persisted after 24 and 48 hours, but decreased later, there was only redness after 72 hours and no irritation on day 7, and it was concluded to be slight eye irritation (EU-RAR (2003)). Therefore, it was classified in Category 2B. Besides, it is reported that the total irritation score, MMAS (equivalent to AOI) was 9 (maximum 110) in another eye irritation test with rabbits (OECD TG 405)(ECETOC TR 48 (2) (1998)), and the score corresponds to "Not classified." And as for effects in humans, it is reported that workers who were accidentally splashed with this substance developed a transient epithelial injury to the eyes such as conjunctival irritation and corneal damage but completely recovered within 48 hours (EHC 52 (1985)). |
| 4 | Respiratory sensitization | Classification not possible |
- |
- | - | No data available. |
| 4 | Skin sensitization | Not classified |
- |
- | - | In a maximization test with guinea pigs (EU guideline B6, GLP), only one out of 20 animals showed a reaction after the challenge with a 50% solution, and a positive rate was 5% (1/20). And from the result, it was concluded that this substance was not a skin sensitizer (EU-RAR (2003)), and it is described that toluene is not a skin sensitizer in humans (PATTY (5th, 2001)). Therefore, it was classified as "Not classified." |
| 5 | Germ cell mutagenicity | Not classified |
- |
- | - | There are reports on two negative results in dominant lethal tests after oral or inhalation administration to mice (in vivo germ cell mutagenicity test) (Initial Risk Assessment Report 87 (NITE, CERI, NEDO, 2006)), five negative results in chromosomal aberration tests with bone marrow cells after oral, inhalation, or intraperitoneal administration to mice or rats (in vivo somatic cell mutagenicity test) (Initial Risk Assessment Report 87 (NITE, CERI, NEDO, 2006), EHC 52 (1985), EU-RAR (2003)), and two negative results in micronucleus tests with bone marrow cells after oral or intraperitoneal administration to mice (in vivo somatic cell mutagenicity test) (Initial Risk Assessment Report 87 (NITE, CERI, NEDO, 2006), NTP DB (Access on Apr. 2012)). From the above, it was classified as "Not classified." Besides, a positive result is reported in a chromosomal aberration test with bone marrow cells after subcutaneous administration to rats, but it was not adopted due to the description that it was hard to assess the result because the purity of toluene and the decision criteria are unknown (Initial Risk Assessment Report 87 (NITE, CERI, NEDO, 2006)). Furthermore, as for in vivo genotoxicity tests, there are negative (Initial Risk Assessment Report 87 (NITE, CERI, NEDO, 2006)) and positive (EHC 52 (1985)) results in sister chromatid exchange tests after intraperitoneal or inhalation administration to mice or rats. On the other hand, as for in vitro tests, it is reported that it was negative in an Ames test (Initial Risk Assessment Report 87 (NITE, CERI, NEDO, 2006), NTP DB (1979)), positive in a mouse lymphoma test (Initial Risk Assessment Report 87 (NITE, CERI, NEDO, 2006)), and negative or positive in chromosomal aberration tests and micronucleus tests (Initial Risk Assessment Report 87 (NITE, CERI, NEDO, 2006), NTP DB (Access on Apr. 2012)). |
| 6 | Carcinogenicity | Classification not possible |
- |
- | - | It was classified as "Classification not possible" because it was classified in Group 3 for carcinogenicity by IARC (IARC 71 (1999)), A4 by ACGIH (ACGIH (2007)), Group D by U.S. EPA (IRIS (2007)). Besides, it is reported that in carcinogenicity tests with rats and mice by 103-week inhalation exposure (6.5 hours/day, rats 0, 600, or 1,200 ppm, mice 0, 120, 600, or 1,200 ppm), there was no evidence of carcinogenicity for males and females in either animal species (NTP TR 371 (1990)). |
| 7 | Reproductive toxicity | Category 1A, Additional category: Effects on or via lactation |
 Danger |
H360
H362 |
P308+P313
P201 P202 P280 P405 P501 |
In humans, there are reports on premature birth in pregnant women who inhaled toluene at high concentrations or for a long time, and craniofacial features resembling those in fetal alcohol syndrome such as microcephaly, low-set pinna, small nose, micrognathia, and palpebral fissure, developmental delay, hyperactivity, etc. in offspring (Initial Risk Assessment Report 87 (NITE, CERI, NEDO, 2006), IARC 71 (1999)). And it is reported that as a result of an epidemiological survey on 300 cases of malformations between 1982 and 1984 conducted in Canada, there was an increased risk of congenital malformations among women with a history of occupational exposure to aromatic solvents, especially toluene (ACGIH (2007)). Furthermore, spontaneous abortions in a cohort of women who had at some time been monitored for exposure to solvents were investigated (case-control study), the odds ratio for spontaneous abortion was increased among women who were exposed to toluene at least three days a week, and a risk of exposure to toluene was shown (IARC 71 (1999)). Based on the above knowledge in exposure in humans, it was classified in Category 1A. And it was classified in the Additional category: Effects on or via lactation because it is described that toluene passes the placenta with ease and is secreted into breast milk (SIDS (J) (Access on Apr. 2012)). Besides, as for animal tests, after inhalation exposure in rats from before mating and thorough a gestation period, or during a gestation period, there were increases in fetal mortality or embryonic and fetal mortality, and the number of live pups at birth was significantly decreased after natural birth (EU-RAR (2003), Initial Risk Assessment Report 87 (NITE, CERI, NEDO, 2006)), but there are no reports on teratogenicity. |
| 8 | Specific target organ toxicity - Single exposure | Category 1 (central nervous system), Category 3 (respiratory tract irritation, narcotic effects) |
Danger Warning |
H370
H335 H336 |
P308+P311
P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312 |
In humans, there were muscular weakness, confusion, impaired coordination, and enlarged pupils after 8-hour inhalation exposure to 750 mg/m3, and severe fatigue, pronounced nausea, mental confusion, etc., at 3,000 ppm, and heavy accidental exposure lead to coma (IARC 47 (1989)). And there is a report on 15 deaths by accidental ingestion of paint thinner containing this substance, and for a 51-year-old man who died 30 minutes after ingesting a large amount of toluene, the probable cause of death was reported to be severe central nervous system depression (IRIS tox. Review (2005)). In a case of a 46-year-old man who ingested approximately one quart of paint thinner containing this substance, he presented with severe central nervous system depression, severe abdominal pain, diarrhea, and gastric hemorrhage but recovered after 36 hours of supportive care (IRIS tox. Review (2005)). Other than the above, there are many reports on the effects of this substance on the central nervous system, and it was classified in Category 1 (central nervous system). On the other hand, in humans, narcosis is the likely result of acute exposure to this substance at high concentrations, and many workers who were rendered unconscious by the vapour of this substance have been published (EHC 52 (1985)). And in animal tests, narcotic effects are reported after inhalation exposure of mice or rats (IARC 47 (1989)). Therefore, it was classified in Category 3 (narcotic effects). Furthermore, because it is reported that volunteers exposed to a low concentration (200 ppm) showed transient slight irritation of the upper respiratory tract (PATTY (5th, 2001)), it was classified in Category 3 (respiratory tract irritation). |
| 9 | Specific target organ toxicity - Repeated exposure | Category 1 (central nervous system, kidney) |
Danger |
H372 |
P260
P264 P270 P314 P501 |
In an epidemiological survey in 30 workers in printing exposed to toluene for an average of 29 years and 72 controls, there were significantly more reports on fatigue, memory problems, concentration difficulties, mood lability, and other neurasthenic symptoms in the printers than in the control group, and they performed significantly poorly in psychometric tests. And ataxia, incoordination, tremors in hands and legs, and diffuse atrophy in the cerebrum were observed in toluene addicts, and MRI examination revealed diffuse atrophy in the cerebrum, cerebellum, and brain stem, and differentiation between the gray and white matter became unclear throughout the central nervous system (Japanese Journal of Industrial Health Vol. 36 (1994)). It is reported that morphological changes such as atrophy in the brain and changes in white matter in the brain occur with functional disorders of the central nervous system especially in exposure to high concentrations (Japanese Journal of Industrial Health Vol. 36 (1994)). There are many other reports on the occurrence of central nervous system disorders by exposure to this substance, and it was classified in Category 1 (central nervous system). On the other hand, there are many case reports such as a case of a 19-year-old man who intentionally inhaled a solvent containing toluene, was hospitalized after persistent nausea and vomiting, and showed interstitial nephritis by kidney biopsy and renal disorders (Japanese Journal of Industrial Health Vol. 36 (1994)), a case of a 26-year-old man who ingested a solvent containing toluene developed acute renal failure, which was regarded as renal toxicity of toluene (Japanese Journal of Industrial Health Vol. 36 (1994)), and a case of a 17-year-old woman who was hospitalized due to paralysis of the extremities after intentional inhalation of toluene was diagnosed with renal tubular acidosis, and paralysis of the extremities was estimated to occur as a result of lesions in renal tubules by toluene intoxication (Japanese Journal of Industrial Health Vol. 36 (1994)). From the above, it was classified in Category 1 (kidney). Besides, as for animal tests, no adverse effects are reported at doses corresponding to the guidance value range in repeated dose test with rats and mice by the oral or inhalation route (Initial Risk Assessment Report 87 (NITE, CERI, NEDO, 2006), EU-RAR (2003), EHC 52 (1985)). And in humans, there is one report that an increase in a liver enzyme, the parameter for hepatic disorders, was observed after exposure to toluene, but there is also a report that there was no increase in enzymes, vice versa (EU-RAR (2003)). Therefore, the liver was not adopted for classification. |
| 10 | Aspiration hazard | Category 1 |
Danger |
H304 |
P301+P310
P331 P405 P501 |
It is a hydrocarbon, and the kinematic viscosity was 0.86 mm2/s (40 deg C) (a calculated value using viscosity of 0.727mPa*s (Renzo (1986)) and density of 0.8483 g/mL (CRC (91st, 2010))). Therefore, it was classified in Category 1. And in humans, it is described that direct contact of asperated liquid toluene with lung tissue causes severe irritation, "chemical pneumonitis" (DFGMAK-Doc.7 (1996)). |
| Hazard class | Classification |
Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 11 | Hazardous to the aquatic environment (Acute) | Category 2 |
- |
H401 |
P273
P501 |
It was classified in Category 2 from 48-hour EC50 = 3.78 mg/L for crustacea (Ceriodaphnia dubia) (Initial Risk Assessment (NITE, CERI, NEDO, 2006)). |
| 11 | Hazardous to the aquatic environment (Long-term) | Category 3 |
- |
H412 |
P273
P501 |
If chronic toxicity data are used, then it is classified in Category 3 due to being rapidly degradable (readily biodegradable (a 2-week degradation rate by BOD: 123%) (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1980)), and 7-day NOEC = 0.74 mg/L for crustacea (Ceriodaphnia dubia) (Initial Risk Assessment (NITE, CERI, NEDO, 2006)). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified as "Not classified" due to being rapidly degradable (readily biodegradable (a 2-week degradation rate by BOD: 123%) (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1980)), and a low bioaccumulation estimate (log Kow = 2.73 (PHYSPROP Database, 2008)). By drawing a comparison between the above results, it was classified in Category 3. |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | This substance is not listed in the Annexes to the Montreal Protocol. |
NOTE:
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