NITE - Chemical Management Field

Latest GHS Classification Results by the Japanese Government (edited by NITE)

GENERAL INFORMATION

Item	Information
CAS RN	108-88-3
Chemical Name	Toluene
Substance ID	m-nite-108-88-3_v1
Download of Excel format	Excel file

REFERENCE INFORMATION

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)

PHYSICAL HAZARDS

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.	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
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.	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
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.	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
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)).	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to liquid substances are not available.	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
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).	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Organic compounds containing no oxygen, fluorine or chlorine.	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure.	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
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)).	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
17	Desensitized explosives	-	- -	-	-	-	-	-

HEALTH HAZARDS

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	- -	-	-	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.	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
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."	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
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.	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	No data available.	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
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)).	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
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)).	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
4	Respiratory sensitization	Classification not possible	- -	-	-	No data available.	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
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."	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
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)).	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
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)).	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
7	Reproductive toxicity	Category 1A,	Danger	H360 H362	P308+P313 P201 P202 P260 P263 P264 P270 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.	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
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).	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
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.	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
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)).	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）

ENVIRONMENTAL HAZARDS

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 48-hour EC50 = 3.78 mg/L for crustacea (Ceriodaphnia dubia) (Initial Risk Assessment (NITE, CERI, NEDO, 2006)).	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
11	Hazardous to the aquatic environment Long term (Chronic)	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.	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in the Annexes to the Montreal Protocol.	FY2012	GHS Classification Guidance by the Japanese Government （July, 2010）

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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