NITE - Chemical Management Field

GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	106-44-5
Chemical Name	p-Cresol
Substance ID	H26-B-033, R-013
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 3 reports of LD50 values of 207 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), SIDS (2005), EHC 168 (1995)), 270 mg/kg (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)) and 1,800 mg/kg (ACGIH (7th, 2001)) for rats. According to the classification guidance for the Japanese Government, it was classified in Category 3 to which the most data (2 cases) corresponded.
1	Acute toxicity (Dermal)	Category 3	Danger	H311	P302+P352 P280 P312 P321 P361 P364 P405 P501	Based on reports of an LD50 value of 750 mg/kg for rats (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), EHC 168 (1995)) and of LD50 values of 300 mg/kg (NTP TR550 (2008), ATSDR (2008), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), SIDS (2005), EHC 168 (1995)) and 301 mg/kg (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)) for rabbits, it was classified in Category 3.
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	Solid (GHS definition)
1	Acute toxicity (Inhalation: Vapours)	Not applicable	- -	-	-	Solid (GHS definition)
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, there is a report of an LC50 value (1 hour) of >0.71 mg/L (=160 ppm) (converted 4-hour equivalent value: >0.355 mg/L) (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), SIDS (2005)) for rats. Since the LC50 value was higher than the saturated vapor concentration (1.49 mg/L=148 ppm), it was regarded as a mist. From this LC50 value, it was not possible to specify Category 2, Category 3, Category 4, or "Not classified." Therefore, it was classified as "Classification not possible."
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 after occlusive application of 0.5 mL of the undiluted liquid of this substance for 4 hours to rabbits, corrosivity (2/6 animals) was observed (EHC 168 (1995), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2005)). In another study, there is a report that after application of the undiluted liquid of this substance to rabbits, severe erythema and edema occurred within 24 hours and did not disappear within 72 hours (SIDS (2001)). 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" in EU CLP classification.
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	There is a report that after 0.1mL of the undiluted liquid of this substance was applied to rabbits, highly irritating effects on the conjunctiva, cornea and iris were observed and these did not disappear up to 72 hours after application (SIDS (2005)). Therefore, 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. Besides, there are reports that no sensitization reactions were observed in a skin sensitization test (modified Draize test) with guinea pigs (SIDS (2005), DFGOT Vol. 14 (2000)), and that no sensitization reactions were observed after applying 4% p-cresol dissolved in petrolatum to 25 volunteers (SIDS (2005)). However, since the test conditions and other details were unknown, the data was judged to be insufficient for classification, and the classification was revised.
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 mouse dominant lethal test and a mouse bone marrow chromosomal aberration test (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), ATSDR (2008), DFGOT vol. 14 (2000), SIDS (2005)). As for in vitro, it was negative in a bacterial reverse mutation test, a mouse lymphoma test with cultured mammalian cells, and a sister chromatid exchange test with human cells, and weakly positive in a mammalian cell chromosome aberration test and an unscheduled DNA synthesis test with human peripheral blood lymphocytes (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), SIDS (2005), ATSDR (2008), DFGOT vol. 14 (2000), NTP DB (Access on July 2014)). From the above, although the in vitro chromosomal aberration test showed positive results, the in vivo test results were all negative. Therefore, this substance was judged not to be mutagenic in vivo.
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	Because it was classified as C by EPA (EPA (1991)), it was classified in Category 2.
7	Reproductive toxicity	Classification not possible	- -	-	-	Effects on fertility were not observed in a two-generation reproductive toxicity study by the oral route (gavage) in rats (ATSDR (2008), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)). Besides, as for this study, it is described in SIDS (2005) that although no clear dose-dependent correlation was observed, there was an increase in stillbirth, therefore the NOAEL for the developmental toxicity could not be determined. In teratogenicity studies with rats and rabbits by the oral route, only marginal effects on fetuses (skeletal variations) were observed even at doses where maternal toxicities including death were observed (ATSDR (2008), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)). From the above, in the two-generation reproductive toxicity study with rats, although there were no clear dose-dependent effects, there was an increase in stillbirth and there is a report that the NOAEL for the developmental toxicity could not be determined. Therefore, it was classified as "Classification not possible."
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system, respiratory organs, cardiovascular system, liver, kidney)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	In humans, this substance showed respiratory tract irritation and caused corrosivity by ingestion. Inhalation of the vapor or aerosol might cause pulmonary edema. By inhalation, burning sensation, sore throat, cough, headache, nausea, vomiting, closeness and shortness of breath were observed, and by ingestion, nausea, vomiting, abdominal pain, shock/prostration, burning sensation, and effects on the central nervous system, cardiovascular system, lung, liver and kidney were observed, and at high concentrations, decreased consciousness was observed, resulting in death sometimes (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), ACGIH (7th, 2001)). As for experimental animals, mucosal irritation, neuromuscular excitation and convulsions, and hematuria (at very high concentrations) were reported for inhalation exposure to rats (SIDS (2005)). In addition, hypoactivity, salivation, incoordination, muscle twitches, tremors, convulsions, dyspnea, weakness, lethargy, coma and mortality, and as necropsy findings, inflammation of the gastrointestinal tract, hyperemia or hemorrhage of the lung, liver and kidney were reported for oral administration to mice or rats (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)). These findings were observed within the range of guidance values corresponding to Category 1 or Category 2. From the above, it was classified in Category 1 (central nervous system, respiratory organs, cardiovascular system, liver, kidney).
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	In humans, there are descriptions that 7 workers who were exposed to a vapor of a cresol mixture containing this substance (concentration unknown) by inhalation for 1.5 to 3 months developed headaches with nausea and vomiting, and 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 feeding studies of this substance in rats and mice, at doses corresponding to Category 2 (mice: 50-60 mg/kg/day (15.5-18.7 mg/kg/day (converted guidance value)), rats: 242-256 mg/kg/day (75.3-79.6 mg/kg/day (converted guidance value))), histological changes in the nasal cavity (hyperplasia of the respiratory epithelium, squamous metaplasia) were observed in both species, and increased relative liver weight and hypoplasia of the bone marrow were observed in rats, and findings of anemia tendency (decreases in erythrocyte counts and hemoglobin concentration), liver dysfunction (increases in serum AST and ALT), symptoms of the central nervous system (Lethargy, immobility, tremor, convulsions) were observed at the high dose corresponding to "Not classified" (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), SIDS (2005), ATSDR (2008)). Therefore, increased relative liver weight and hypoplasia of the bone marrow observed within the dose range of Category 2 were considered to be toxicologically significant, and the "liver" and the "hemal system" were added to the target organ. From the above, based on the findings in humans (mixture) and experimental animals (this substance: p-isomer), it was classified in Category 1 (central nervous system, cardiovascular system, kidney), Category 2 (respiratory organs, hemal system, liver). Besides, although it was classified based on the knowledge on experimental animals only in the previous classification, the classification result was reviewed in consideration of the consistency with the classification for other isomers and cresol mixtures this time.
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 48-hour LC50 = 1.4 mg/L for crustacea (Daphnia magna) (Initial Risk Assessment (NITE, CERI, NEDO, 2007)).
11	Hazardous to the aquatic environment (Long-term)	Category 3	- -	H412	P273 P501	It was classified in Category 3 due to rapid degradability (a degradation rate by BOD = 80-95% (SIDS, 2003)), and 21-day NOEC = 0.52 mg/L for crustacea (Daphnia magna) (Results of Aquatic Toxicity Tests of Chemicals conducted by Environment Agency in Japan (Environment Agency, 1997), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), Initial Risk Assessment (NITE, CERI, NEDO, 2007)).
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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