NITE - Chemical Management Field

GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	95-48-7
Chemical Name	o-Cresol
Substance ID	H26-B-032, -
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	- -	-	-	Solid (GHS definition)
3	Aerosols	Not applicable	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not applicable	- -	-	-	Solid (GHS definition)
5	Gases under pressure	Not applicable	- -	-	-	Solid (GHS definition)
6	Flammable liquids	Not applicable	- -	-	-	Solid (GHS definition)
7	Flammable solids	Classification not possible	- -	-	-	No data available.
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 applicable	- -	-	-	Solid (GHS definition)
10	Pyrophoric solids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 555 deg C (ICSC (2008)).
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to solid (melting point <= 140 deg C) 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	- -	-	-	Solid (GHS definition)
14	Oxidizing solids	Not applicable	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.
15	Organic peroxides	Not applicable	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule.
16	Corrosive to metals	Classification not possible	- -	-	-	It is a solid with a melting point of 55 deg C or lower, but the classification is not possible due to no data.

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 two reports of LD50 values of 121mg/kg (ATSDR (2008), NTP TR550 (2008), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), SIDS (2001), EHC 168 (1995)), and 1350 mg/kg (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), ACGIH (7th, 2001)) for rats. Although each value corresponded to Category 3 or Category 4, respectively, it was classified in Category 3 to which the minimum LD50 value corresponded.
1	Acute toxicity (Dermal)	Category 3	Danger	H311	P302+P352 P280 P312 P321 P361 P364 P405 P501	There are reports of LD50 values of 620 mg/kg (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment) (2006), SIDS (2001), EHC 168 (1995)) and 620-1000 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO) (2007)) for rats, and 890 mg/kg (ATSDR (2008), NTP TR550 (2008), Initial Risk Assessment Report (NITE, CERI, NEDO) (2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment) (2006), EHC 168 (1995)), 890-1380 mg/kg (ATSDR (2008), NTP TR550 (2008)) and 890-=>2000 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO) (2007)) for rabbits. It was classified in Category 3 to which the larger number of values corresponded according to the GHS Classification Guidance for the Japanese Government.
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	Solid (GHS definition)
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, there is a report of LC 50 value (1 hour) of >1220 mg/m3 for rats (converted 4-hour equivalent value: 610 mg/m3 (=138 ppm)) (PATTY (6th, 2012), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment) (2006)). Since the LC50 value was lower than 90% of the saturated vapor concentration (325.8 ppm (=1.44 mg/L)), it was considered to contain no mist. From this LC50 value, it was not possible to specify as Category 2, Category 3, Category 4, or "Not classified." Therefore, it was classified as "Classification not possible."
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 are several reports that severe irritation or corrosivity was observed in tests in which this substance was applied to the skin of rabbits (EHC 168 (1995), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), PATTY (6th, 2012)). In addition, there is a description that this substance showed corrosivity to the skin (SIDS (2001), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)). From the above, it was classified in Category 1. Besides, this substance was classified in "C; R34" in EU DSD classification and in "H314 Skin Corr. 1B" in EU CLP classification.
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	There is a description that persistent corneal opacity and neovascularization were observed in a test in which a 33% solution of this substance was applied to rabbits (Initial Risk Assessment Report (NITE, CERI, NEDO) (2007)). In addition, there is a statement that this substance showed severe irritation or corrosivity to the eyes of rabbits (SIDS (2001), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment) (2006), DEFGOT vol. 14 (2000)). From the above, 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	- -	-	-	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 a dominant lethal test in mice, a micronucleus test with bone marrow cells of rats or mice, a bone marrow chromosomal aberration test in mice (Initial Risk Assessment Report (NITE, CERI, NEDO) (2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment) (2006), SIDS (2001), ATSDR (2008), DFGOT vol.14 (2000)). As for in vitro, it was negative in a bacterial reverse mutation test, a mouse lymphoma test in cultured mammalian cells, an unscheduled DNA synthesis test with cultured rat hepatocytes, positive in a chromosome aberration test and a sister chromatid exchange test with cultured mammalian cells, negative in a sister chromatid exchange test with human cells (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), SIDS (2001), DFGOT vol.14 (2000), ATSDR (2008)). From the above, though there were positive results in an in vitro chromosomal aberration test and a sister chromatid exchange test, this substance was negative in all of in vivo tests, therefore, it was judged to be not mutagenic in vivo.
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	Since it was classified as C by EPA (EPA (2002)), it was classified in Category 2. The category was changed according to the GHS Classification Guidance for the Japanese Government.
7	Reproductive toxicity	Classification not possible	- -	-	-	No effects on fertility were observed in a two-generation reproductive toxicity test by gavage in rats, a continuous mating test by dietary administration to mice, and a one-generation reproductive toxicity test using minks. No effects other than an effect on body weight were seen in pups of rats and mice (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment) (2006)). In a teratogenicity study by gavage with rats, dilatation of the lateral ventricles (1 fetus) and slight skeletal variations (5 fetuses) were observed in fetuses at the dose (450 mg/kg bw/day) where maternal toxicities including mortality (death in 4 out of 25 animals, decreased body weight gain, hypoactivity, ataxia, tremors, twitching, prone position, rale) were observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)). This study was not adopted because maternal mortality was more than 10%. In a teratogenicity study by gavage with rabbits, slight effects on fetuses (subepidermal hematoma (head), delayed sternal ossification) were observed at the dose at which maternal toxicities (abnormal breathing sound, eye discharge, hypoactivity) were observed (Initial Risk Assessment Report (NITE, CERI, NEDO) (2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment) (2006)). This study was not adopted because the effects on the fetuses were slight. In an epidemiological study in humans, there are reports that an abnormality in estrogen level and menstruation, increases in perinatal mortality and malformation incidence were noticed in women working in a factory where cresol and chlorobenzene or phosphoryl chloride were used (Initial Risk Assessment Report (NITE, CERI, NEDO) (2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment) (2006)). However, observed changes were not appropriate to be used for classification because their relevance to o-cresol exposure was not clear. As in the above, no effects on reproduction were observed in a two-generation study and a continuous mating study. As a result of examining the significance of the findings which were the basis for the previous classification, although there was no relevant information about abnormalities in the estrus cycle, there was a report that prolongation of both the estrous cycle and estrus stage, shortening of the diestrus stage, a decreased number of primary follicles and increased atresia in the ovaries were observed in a 4-month inhalation toxicity study with rats using cresol (a mixture of o-, m-, p-isomers) as the test substance (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment) (2006), EHC 168 (1995)). Since this information was a test on isomer mixtures and the details were unknown, using it for classification was judged to be inappropriate. Therefore, Category 2 of the previous classification was revised to "Classification not possible."
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system, respiratory organs, cardiovascular system, haemal system, liver, kidney, pancreas, spleen), 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, this substance showed irritation to the respiratory tract, and by inhalation of a vapour or an aerosol of this substance, nasal constriction and dryness, throat irritation and pulmonary edema developed. In addition, burning sensation, sore throat, cough, headache, nausea, vomiting, breathlessness, shortness of breath, respiratory insufficiency (cough, forced breathing/tachypnea) were reported. In oral ingestion, vomiting, abdominal pain, burning sensation, shock/collapse, hemorrhagic diarrhea, and whitish necrotic lesions of mouth, throat and stomach were observed, and by an unknown route, central nervous system depression, confusion, pallor, sweating, weakness, headache, dizziness, tinnitus, irregular pulse, hypotension, shallow breathing, hypothermia, shock with respiratory insufficiency, seizure, unconsciousness, coma, effect on the cardiovascular system, hemolytic anemia, pulmonary edema, damage of the lung/liver/pancreas/spleen/heart/kidney and metabolic acidosis were observed. Acute pulmonary edema was also caused by dermal exposure (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), ACGIH (7th, 2001), HSDB (Access on June 2014)). As for experimental animals, it was reported that by inhalation exposure to mice or rats, irritation of the mucosa, excitation, muscle twitches, clonic convulsion were observed in mice, and by oral administration, hypoactivity, salivation, incoordination, muscle twitches, tremors, convulsion, dyspnea, prostration, lethargy, coma and mortality were observed. As necropsy findings, it was reported that by inhalation exposure, pulmonary edema, hepatic fatty change and centrilobular necrosis, renal edema, glomerular enlargement and tubular epithelial degeneration were observed, and by oral administration, inflammation of the digestive tract, hyperemia and hemorrhage of the lungs liver and kidneys were observed (Initial Risk Assessment Report (NITE, CERI, NEDO) (2007)). From the above, it was classified in Category 1 (central nervous system, respiratory organs, cardiovascular system, blood system, liver, kidney, pancreas, spleen), and in Category 3 (narcotic effects).
9	Specific target organ toxicity - Repeated exposure	Category 1 (central nervous system, cardiovascular system, haemal system, respiratory organs, liver, kidney)	Danger	H372	P260 P264 P270 P314 P501	In humans, there are descriptions that 7 workers who were exposed to the vapor of a cresol mixture containing this substance (concentration unknown) for 1.5 to 3 months developed headaches with nausea and vomiting, 4 of them also developed elevated blood pressure, impaired kidney function, blood calcium imbalance and marked tremors (ACGIH (7th, 2001), DFGOT vol. 14 (2000), PATTY (6th, 2012)). As for experimental animals, in 28-day dietary administration studies with minks or ferrets, increases in relative liver weights were observed at doses corresponding to Category 2 (80 mg/kg/day for minks (24 mg/kg/day (converted guidance value)), about 140 mg/kg/day for ferrets (44 mg/kg/day (converted guidance value))). However, in a 13-week dietary study with rats or mice, there were no toxicological findings within or lower the range of Category 2, and increased relative liver weight, tendency for anemia (decreases in erythrocyte count and hemoglobin concentration) and neurological symptoms (lethargy, tremor, convulsion) were observed at a high dose corresponding to "Not classified" (above 175 mg/kg/day) (NITE Initial Risk Assessment Report (NITE, CERI, NEDO) (2007), SIDS (2001), ATSDR (2008)). On the other hand, although it is a test with only 1 dose, in a inhalation exposure test for 1 month with mice and for 4 months with rats, at exposure concentrations corresponding to Category 1 (mouse: 50 mg/m3 (0.0056 mg/L/6 hours (converted guidance value)), rat: 9 mg/m3 (0.006 mg/L/6 hours (converted guidance value))), the effects on the respiratory organs (inflammation of the upper respiratory tract, pulmonary edema, bleeding and perivascular sclerosis), the central nervous system (decreased locomotor activity, lethargy, degeneration of nerve cells and glial elements), the cardiovascular system (heart muscle degeneration) and the blood system (increased leucocyte count, decreased erythroid/myeloid ratio (E/M)), and degeneration of the cardiac muscle, liver and kidneys were observed (NITE Initial Risk Assessment Report (NITE, CERI, NEDO) (2007), SIDS (2001), ATSDR (2008)). From the above, based on the toxicity information by the inhalation route in humans (mixtures) and experimental animals (this substance: o-isomer), it was classified in Category 1(central nervous system, cardiovascular system, blood system, respiratory organs, liver, kidney). The previous classification was based on an information source in List 3, and this time, based on the information source of List 1, and considering the consistency with the classification for other isomers and cresol mixtures, the classification result was revised.
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)	-	- -	-	-	-
11	Hazardous to the aquatic environment (Long-term)	-	- -	-	-	-
12	Hazardous to the ozone layer	-	- -	-	-	-

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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