NITE - Chemical Management Field

GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	108-39-4
Chemical Name	m-Cresol
Substance ID	H26-B-137, R-083
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 4	- Warning	H227	P370+P378 P403+P235 P210 P280 P501	It was classified in Category 4 based on a flash point of 86 deg C (closed cup) (HSDB (Access on December 2014)).
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 558 deg C (HSDB (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	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.
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)	Category 3	Danger	H301	P301+P310 P361+P364 P264 P270 P321 P330 P405 P501	There are reports of LD50 values of 242 mg/kg (as multiple data; PATTY (6th, 2012), ATSDR (2008), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), SIDS (2005), DFGOT vol.14 (2000), EHC 168 (1995), EPA Pesticide (1992)), 825 mg/kg (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)), and 2,241 mg/kg (male) and 2,007 mg/kg (female) (using olive oil as the vehicle) (single dose oral toxicity test (JECDB)) for rats. Since there were multiple reports of 242 mg/kg, it was classified in Category 3 to which the largest number of values corresponded.
1	Acute toxicity (Dermal)	Category 3	Danger	H311	P302+P352 P280 P312 P321 P361 P364 P405 P501	There are 3 reports of LD50 values for rats: 1,000 mg/kg (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)), 1,100 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), EHC 168 (1995), EPA Pesticide (1992)) and 1,100 mg/kg (DFGOT vol. 14 (2000)). There are 3 reports of LD50 values for rabbits: 620 mg/kg (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)), 2,050 mg/kg (SIDS (2005), EPA Pesticide (1992)), and 2,830 mg/kg (ATSDR (2008), SIDS (2005), EHC 168 (1995)). Since 2 data each corresponded to Category 3, Category 4 or "not classified," respectively, it was classified in Category 3 to which the smaller LD50 value corresponded. Information sources (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), ATSDR (2008), SIDS (2005), DFGOT vol. 14 (2000), EPA Pesticide (1992)) were added, and the category was changed.
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. Besides, although there is a report of a 1-hour LC50 value of >0.71 mg/L (converted 4-hour equivalent value: 80.23 ppm) for rats (SIDS (2005), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2003)), category could not be specified only by this value.
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
2	Skin corrosion/irritation	Category 1	Danger	H314	P301+P330+P331 P303+P361+P353 P305+P351+P338 P304+P340 P260 P264 P280 P310 P321 P363 P405 P501	There is a report that when 0.5 mL of the undiluted liquid of this substance was applied to the skin of rabbits, severe erythema and edema occurred within 24 hours and this did not disappear within 72 hours (SIDS (2005)). In other tests with rabbits, there is a report that irreversible tissue destruction was observed 4 hours after application of this substance (EHC 168 (1995)), and that severe irritation and corrosion were observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)). From the above results, it was classified in Category 1. Besides, this substance was classified in "C; R34" in EU DSD classification and in "Skin Corr. 1B H314" in EU CLP classification.
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	It was reported that when 0.1 ml of the undiluted liquid of this substance was applied to rabbits' eyes, severe irritation was observed in the conjunctiva, cornea and iris and this did not disappear within 72 hours (SIDS (2005)). In addition, this substance was classified in Category 1 in skin corrosion/irritation. From the above results, it was classified in Category 1.
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.
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 chromosomal aberration test and a sister chromatid exchange test with mouse bone marrow (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), SIDS (2005), DFGOT vol. 14 (2000), EHC 168 (1995), ATSDR (2008)). As for in vitro, there were negative results of bacterial reverse mutation tests, a mouse lymphoma test with cultured mammalian cells, and negative or positive results of a chromosomal aberration test with cultured mammalian cells (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), JECDB (Access on December 2014), SIDS (2005), DFGOT vol.14 (2000), EHC 168 (1995), PATTY (6th, 2012), ATSDR (2008)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	It was classified in "Category 2" because it was classified as C by EPA (EPA IRIS (1992)).
7	Reproductive toxicity	Classification not possible	- -	-	-	In a two-generation reproductive toxicity study by the oral route with rats, there is a report that the survival rate of pups decreased at a dose (450 mg/kg/day) at which parental toxicities (mortality (F0 parental animals: male: 7/25 animals, female: 7/25 animals, F1 parental animals: male: 3/25 animals, female: 7/25 animals), decreased body weight gain, hypoactivity, ataxia, twitching, tremors, prostration, labored respiration) were observed (SIDS (2005), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), EHC 168 (1995), DFGOT vol.14 (2000), ATSDR (1992)). In the previous classification, it was classified in Category 2 by using this data. However, it was excluded from evidence of the classification due to the severe toxicity in parental animals. In this study, no effects on fertility or genital organs were observed at a dose at which toxicities to parental animals were seen. Also, there was no effect on pups at doses where no maternal toxicity was noted (SIDS (2005), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), EHC 168 (1995), DFGOT vol.14 (2000), ATSDR (1992)). As for information on teratogenicity, fetal effects were not observed at doses where maternal toxicities were observed in teratogenicity study by the oral route with rats and rabbits (SIDS (2005), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), EHC 168 (1995), DFGOT vol.14 (2000), ATSDR (1992)). As in the above, no effects were observed on parental fertility and offspring development, but pups were affected at doses where parental toxicities were observed. Therefore, it was classified as "Classification not possible."
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system, respiratory organs, cardiovascular system, haemal system, liver, kidney)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	This substance was irritating to the respiratory tract (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)). In humans, there was a description of cough, headache, breathlessness, nausea, vomiting, sore throat and loss of consciousness by inhalation, and of abdominal pain, headache, burning sensation, dizziness, sensation obtundation, shock/collapse, loss of consciousness and effects on the central nervous system by ingestion (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)). As for experimental animals, there were reports of neuromuscular excitation, convulsions and hematuria by inhalation exposure (aerosol) to rats at a concentration of 58 mg/m3 (0.058 mg/L), of hypoactivity, tremors, convulsions and weakness by oral gavage at or above a dose of 242 mg/kg to rats, and of inflammation of the gastrointestinal tract, and hyperemia of the lung, liver and kidney in the dead animals. In addition, though the animal species or dosages used were unknown, there was a report of salivation, incoordination, muscle twitches, muscle weakness, dyspnea, lethargy, coma, damage of the renal tubules, nodular pneumonia, congestion of the liver and necrosis of the hepatic cells (it was not described whether these were in the survived animals) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), ATSDR (2008), SIDS (2005), PATTY (6th, 2012), JECDB (Access on December 2014)). Both findings by inhalation and oral exposure in the experimental animals were within the guidance value range corresponding to Category 1. From the above, though respiratory tract irritation and the effects on the central nervous system are thought of as the findings for this substance, since effects on the central nervous system, respiratory organs, cardiovascular system, blood system, liver and kidney were observed as the common effects among the o- and p- isomers, and cresol (mixtures), it was considered reasonable to classify this substance, one isomer, alongside these substances. Therefore, it was classified in Category 1 (central nervous system, respiratory organs, cardiovascular system, blood system, liver, kidney). Besides, refer to the classification result of the other cresol isomers (o-, p-) and cresol (mixture).
9	Specific target organ toxicity - Repeated exposure	Category 1 (central nervous system, cardiovascular system, kidney), Category 2 (respiratory organs, haemal system, liver)	Danger Warning	H372 H373	P260 P264 P270 P314 P501	Although there are no findings on adverse effects on by human exposure to this substance alone, there are descriptions that 7 workers who were exposed to the vapor (concentration unknown) of a cresol mixture containing this substance for 1.5 to 3 months developed headaches with nausea and vomiting, 4 of whom, furthermore, developed elevated blood pressure, impaired kidney function, blood calcium imbalance and marked tremors (ACGIH (7th, 2001), DFGOT vol. 14 (2000), PATTY (6th, 2012)). This knowledge, the only finding on hazardous effects on humans, was used to classify related substances (the o-isomer (CAS RN: 95-48-7), p-isomer (CAS RN: 106-44-5) and cresols (CAS RN: 1319-77-3)) (refer to the classification result of ID: 32-34). As for experimental animals, in a 13-week oral gavage study of this substance with rats, hypoactivity, salivation, increased respiratory rate and labored respiration were observed at 50 mg/kg/day corresponding to Category 2 (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), ATSDR (2008)). In 28-day dietary studies with mice or rats, increased relative liver weight was observed in mice at doses corresponding to Category 2 (66-193 mg/kg/day: (converted guidance value: corresponding to 20.5-60.0 mg/kg/day)), in rats at high doses corresponding to "Not classified" (862-870 mg/kg/day (converted guidance value: corresponding to 268-271 mg/kg/day)), and at much higher doses, increased relative kidney weights were observed in both species (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), ATSDR (2008)). As for this substance, in addition to the knowledge of hazards by exposure to mixtures in humans and exposure to this substance alone in experimental animals, considering the consistency with the classification results of the related substances, the o-isomer (CAS RN: 95-48-7), p-isomer (CAS RN: 106-44-5) and cresol (CAS RN: 1319-77-3), it was classified in Category 1 (central nervous system, cardiovascular system, kidney), Category 2 (respiratory organs, blood system, liver).
10	Aspiration hazard	Classification not possible	- -	-	-	Classification not possible due to lack of data.

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 = 2.31 mg/L for fish (Poecilia reticulata) (SIDS, 2003).
11	Hazardous to the aquatic environment (Long-term)	Not classified	- -	-	-	Reliable chronic toxicity data were not obtained. It was classified as "Not classified" due to rapid degradability (a 28-day degradation rate by OECD 301D: 65-90%, a 40-day degradation rate by OECD 301C: 80-95% (both SIDS, 2003)), and low bioaccumulation (BCF = 20 for fish (Leuciscus idus melanotus) (SIDS, 2003)) although it was classified in Category 2 in acute toxicity.
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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