NITE - Chemical Management Field

GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	1330-20-7
Chemical Name	Xylene
Substance ID	H26-B-135, R-081
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	- -	-	-	This substance was classified as a isomer mixture containing ethylbenzene. 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 25 deg C (closed cup) (GESTIS (Access on December 2014)). Besides, it is classified in Class 3, PG II, III (UN1307) in UNRTDG. Flash points are 32 deg C (closed cup) for o-xylene, and 27 deg C (closed cup) for m- and p-xylene (ICSC (2002)).
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 465 deg C (GESTIS (Access on December 2014)).
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	- -	-	-	This substance was classified as an isomer mixture containing ethylbenzene. Based on multiple reports of LD50 values, which ranged from 3,500 to 8,800 mg/kg, for rats (Hazard Assessment Report (CERI, NITE, 2008), ATSDR (2007), EPA Pesticide (2005), Environmental Risk Assessment for Chemical Substances Vol. 1 (Ministry of the Environment, 2002), ACGIH (7th, 2001), CEPA (1993), DFGOT vol. 5 (1993) and ECETOC JACC (1986)), this substance was classified as "Not classified" (Category 5 in the UN GHS classification or "Not classified"). By adding the new information sources (Hazard Assessment Report (CERI, NITE, 2008), ATSDR (2007), EPA Pesticide (2005), ACGIH (7th, 2001), DFGOT vol. 5 (1993), ECETOC JACC (1986)), the category was revised.
1	Acute toxicity (Dermal)	Category 4	Warning	H312	P302+P352 P280 P312 P321 P362 P364 P501	Since there were 2 reports of LD50 values of 1,700 mg/kg (EPA Pesticide (2005)) and >4,300 mg/kg (ACGIH (7th, 2001)) for rabbits, which corresponded to Category 4 and "Not classified" (Category 5 in UN GHS classification), respectively, this substance was classified in "Category 4" to which the lower LD50 value corresponded. By adding the new information sources (EPA Pesticide (2005), ACGIH (7th, 2001)), the category was revised.
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	Liquid (GHS definition)
1	Acute toxicity (Inhalation: Vapours)	Category 4	Warning	H332	P304+P340 P261 P271 P312	Based on multiple reports of LC50 values (4 hours) which the range from 6,350 to 6,700 ppm (Hazard Assessment Report (CERI, NITE, 2008), ATSDR (2007), Environmental Risk Assessment for Chemical Substances Vol.1 (Ministry of the Environment, 2002), ACGIH (7th, 2001), OEL Documentations (Japan Society for Occupational Health (JSOH), 2001), ECETOC JACC (1986), NTP TR327 (1986), DFGOT vol. 5 (1993)) for rats, this substance was classified in Category 4. Besides, although the mixing ratios of each isomer were unknown, the saturated vapour concentration (7,897 ppm) was obtained using the vapour pressure of m-isomer which was considered the main component. The LC50 values were lower than 90% of the saturated vapour concentration, the reference value in units of ppm was applied as a vapour without a mist. New information sources such as Hazard Assessment Report (CERI, NITE, 2008), ATSDR (2007), ACGIH (7th, 2001), OEL Documentations (Japan Society for Occupational Health (JSOH), 2001), ECETOC JACC (1986), NTP TR327 (1986) and DFGOT vol. 5 (1993) were added. In addition, since the guidance range of 2,500-5,000 ppm for Category 4 was revised to the 2,500-20,000 ppm, the category was changed.
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
2	Skin corrosion/irritation	Category 2	Warning	H315	P302+P352 P332+P313 P362+P364 P264 P280 P321	There is a report that after application of this substance to the skin of rabbits (application time is unknown), erythema, edema and necrosis were observed (Hazard Assessment Report (CERI, NITE, 2008)). In addition, there was a report that after application of this substance to rabbits, mice and guinea pigs (application time is not known), slight to strong irritation was observed (ATSDR (2007)). However, there were no descriptions of recovery from either. From the above, this substance was classified in Category 2.
3	Serious eye damage/eye irritation	Category 2	Warning	H319	P305+P351+P338 P337+P313 P264 P280	There are reports that after application of 0.05 to 0.5 mL of the undiluted liquid of this substance to rabbit eyes, discomfort caused by slight conjunctival irritation and very slight corneal necrosis, and blepharoclonus were observed (Hazard Assessment Report (CERI, NITE, 2008), EHC 190 (1997)), and that after application of 0.1 mL (87 mg) of this substance, mild to moderate irritation was observed (Hazard Assessment Report (CERI, NITE, 2008), ATSDR (2007)). In addition, there are multiple reports of eye irritation tests with rabbits in which mild to moderate irritations were observed (Hazard Assessment Report (CERI, NITE, 2008), EHC 190 (1997)). From the above, this substance was classified in Category 2.
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.
4	Skin sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, although there is a report that no sensitization was observed in a test with 24 volunteers (Hazard Assessment Report (CERI, NITE, 2008)), the details were unknown, therefore, the data were not adopted as the evidence for classification.
5	Germ cell mutagenicity	Classification not possible	- -	-	-	The 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 dominant lethal tests with rats and mice, a mouse bone marrow micronucleus test, chromosomal aberration tests with bone marrow cells of rats and mice, a sister chromatid exchange test with peripheral blood of human volunteers (Hazard Assessment Report (CERI, NITE, 2008), ATSDR (2007), ECETOC JACC 006 (1986), EHC 190 (1997), IARC 71 (1989), ACGIH (7th, 2001), DFGOT vol.15 (2001)). As for in vitro, it was negative in bacterial reverse mutation tests and negative in mouse lymphoma tests with cultured mammalian cells except for one positive test and negative in chromosomal aberration tests with human peripheral blood and cultured mammalian cells (Hazard Assessment Report (CERI, NITE, 2008), ACGIH (7th, 2001), ATSDR (2007), EHC 190 (1997), IARC 71 (1989), ECETOC JACC 006 (1986), NTP TR327 (1986), CEPA (1993)).
6	Carcinogenicity	Classification not possible	- -	-	-	This substance was classified as "Classification not possible" because it was classified in Group 3 by IARC (IARC, 1999), A4 by ACGIH (ACGIH (7th, 2001)) and as I by EPA (EPA IRIS, 2003).
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	Information on xylene for industrial use (the isomer mixture containing ethylbenzene) was obtained. There is a report that in a teratogenicity test of the isomer mixture by the inhalation route with rats, slight effects on fetuses (decreased body weight of fetuses) were observed at doses where no maternal toxicities were observed (ATSDR, 2007). Besides, although no descriptions regarding maternal toxicities were available or there were criticisms against test conditions, there are reports that in a teratogenicity test of the isomer mixture by the inhalation route with rats, an increased fetal resorption was observed at a dose where no maternal toxicity was observed (ATSDR (2007)), and that in another teratogenicity test of the isomer mixture by the inhalation route with rats, an increased fetal resorption in fetuses, microphthalmia and hydrocephalus were observed where maternal toxicities were unknown (Hazard Assessment Report (CERI, NITE, 2008), EHC 190 (1997), ATSDR (2007)). Furthermore, industrial xylene normally contains ethylbenzene and as for reproductive toxicity studies of ethylbenzene, there are reports that in a teratogenicity test with mice by the inhalation route, an increased incidence of malformations in the urinary system (no concrete description of the malformations) at a dose where no maternal toxicities were observed, that in a teratogenicity test with rats by the inhalation route although maternal toxicities were unknown, an increased incidence of malformations in the urinary system (no concrete description of the malformations), and that in a teratogenicity test with rabbits by the inhalation route, absorption (3 out of 3 animals) was observed at a dose where weak maternal toxicity (decreased body weight gain) was observed (ATSDR, (2010), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), SIDS (2005), Environmental Risk Assessment for Chemical Substances Vol.1 (Ministry of the Environment, 2002)). From the above, this substance was classified in Category 1B.
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system, respiratory organs, liver, kidney), Category 3 (narcotic effects)	Danger Warning	H370 H336	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	In humans, there were multiple reports of accidental cases and occupational exposure cases by the inhalation and oral routes. As for inhalation exposure cases, there is a report that irritation to the respiratory tract, headache, nausea, vomiting, dizziness, coma, narcotic effects, coordination ataxia, disorders of the central nervous system, decreased reaction, fatigue, agitation, confusion and tremors were observed, and death cases showed dyspnea, clouding of consciousness, memory disorders, severe damage of the respiratory organs (pulmonary congestion, alveolar hemorrhage and pulmonary edema), liver damage (congestion associated with enlarged liver and vacuolation of centrilobular hepatocytes), renal impairment, damage of the neuronal cells in the brain, and survivors showed symptoms such as cyanosis of extremities, liver damage, severe renal impairment and amnesia. By oral exposure, there are reports on coma, acute pulmonary edema, liver damage, hematemesis, pulmonary congestion and edema and death from centrally mediated respiratory depression (Hazard Assessment Report (CERI, NITE, 2008), ATSDR (2007), Environmental Risk Assessment for Chemical Substances Vol.1 (Ministry of the Environment, 2002), ACGIH (7th, 2001), EHC 190 (1997), DFGOT vol.15 (2001) and ECETOC JACC (1986)). In experimental animals, there were reports of coordination ataxia by inhalation exposure with rats at 1,300 ppm, central neurotoxicities such as obtundation, anesthesia and coma at 6,000 mg/kg by the oral route with rats. Furthermore, although exposure conditions such as doses were unknown, there were findings of narcosis, prostration, decreased hindleg movement, hunched posture, hypersensitivity, tremors, weakness, labored breathing, slowed breathing, muscle spasms, disorder of the visual and auditory organs, lung edema, lung bleeding, lung inflammation, findings suggesting liver toxicity such as increased relative weight (Hazard Assessment Report (CERI, NITE, 2008), ATSDR (2007)). In addition, there are descriptions that acute effects on experimental animals were effects on the nervous system, lungs and liver (CEPA (1993)), and that acute toxicity symptoms by the oral, inhalation and dermal routes in rats and mice were depression of the central nervous system (SIAP (2003), ATSDR (2007)). From the above, this substance was classified in Category 1 (central nervous system, respiratory organs, liver, kidney) and Category 3 (narcotic effects) because this substance affected the central nervous system, respiratory organs, liver and kidneys in addition to having narcotic effects. (Note that this classification result was not based on the data on each xylene isomer but the isomer mixtures (Xylenes including those of unknown compositions). Refer to separate classifications for each single isomer).
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system, respiratory organs)	Danger	H372	P260 P264 P270 P314 P501	By inhalation exposure (geometric mean concentration: 14 ppm, average exposure period: 7 years) to a solvent (containing toluene and ethylbenzene but not a benzene other than xylene), more than 70% of which was from exposure to a xylene isomer mixture, a significantly increased prevalence of anxiety, forgetfulness, inability to concentrate, dizziness, nausea, anorexia, reduced grip strength, and weakened muscle strength was observed in comparison with the non-exposed group. However, no significant difference was observed in hematological test items and biochemical test items such as parameters of liver functions (Hazard Assessment Report (CERI, NITE, 2008), ATSDR (2007)). In addition, there are reports that by chronic occupational exposures, labored breath and dysfunction of the lungs were observed, and that among workers at a xylene manufacturing factory (15–40 ppm for 6 months to 5 years), headache, agitation, insomnia, dyspepsia and increased heartbeat rate in 33%, and nervous weakness and dysautonomia in 20% were observed. Furthermore, there are reports that in an epidemiological survey for paint workers who used xylene as a solvent, headache, memory loss, fatigue, encephalopathy caused by solvents, nervous weakness, dysfunction of the brain, disorder of electroencephalogram, development of organic psychiatric disorder and dementia, etc. were observed (Hazard Assessment Report (CERI, NITE, 2008), ATSDR (2007)). Therefore, although there were many reports from combined exposure cases containing substances other than xylenes, it seemed that adverse effects on the nervous system and respiratory system might be caused by chronic inhalation exposure to this substance alone even if the exposure conditions were considered. Other than the above, although effects on the hemal system (anemia and decreased number of leukocytes) were also concerned, they were possibly due to effects of benzene mixed in the solvent, and there is a report that no abnormality was observed in the hematological test of exposure cases in which the solvent was apparently free of benzene as described at the beginning of this column (ATSDR (2007)). On the other hand, in experimental animals, no effects were observed at up to the concentrations above the guidance value range, and no findings were available which could specify the target organs in multiple repeated exposure tests of this substance (assumed as the vapour) with rats (converted guidance value: 1.30–5.23 mg/L/6 hours (LOEC)) for 6 weeks to 2 years and in an 13-week inhalation test with dogs (converted guidance value: 3.51 mg/L/6 hours (NOEC)) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). From the above findings in humans, this substance was classified in Category 1 (nervous system, respiratory organs).
10	Aspiration hazard	Category 1	Danger	H304	P301+P310 P331 P405 P501	This substance is a hydrocarbon, but its kinematic viscosity could not be calculated because a basic value could not be obtained due to being a mixture. However, since each calculated kinematic viscosity of o-, m- and p- isomer (25 deg C) was 0.86, 0.67 and 0.70 mm2/s, respectively (calculated using each value of viscosity and density in HSDB (Access on December 2014)) and these values were similarly low, it seemed that the kinematic viscosity of a mixture should have a similar value. Therefore, this substance was classified in Category 1.

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)	Category 2	- -	H401	P273 P501	It was classified in Category 2 from 96-hour LC50 = 3.3 mg/L for fish (Oncorhynchus mykiss) (Initial Risk Assessment (NITE, CERI, NEDO, 2005)).
11	Hazardous to the aquatic environment (Long-term)	Category 2	-	H411	P273 P391 P501	If chronic toxicity data are used, then it is classified as "Not classified" from NOEC >= 1.3 mg/L for fish (Oncorhynchus mykiss) (SIAP (Conclusions Agreed in SIAM 16, 2003)), although it is not rapidly degradable (a degradation rate by BOD: 39% (Initial Risk Assessment (NITE, CERI, NEDO, 2005))). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 2 due to being not rapidly degradable (a degradation rate by BOD: 39% (Initial Risk Assessment (NITE, CERI, NEDO, 2005))), and 96-hour LC50 = 7.4 mg/L for crustacea (Palaemonetes pugio) (EHC 190, 1997, Initial Risk Assessment (NITE, CERI, NEDO, 2005)). By drawing a comparison between the above results, it was classified in Category 2.
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.

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