NITE - Chemical Management Field

GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	1319-77-3
Chemical Name	Cresol
Substance ID	H26-B-034, -
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 82 deg C (closed cup) (ACGIH (7th, 2001)). Besides, it is classified in Division 6.1, Subsidiary Risk 8, PG II (UN2076) in UNRTDG.
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 555 deg C (GESTIS (Access on July 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 4	Warning	H302	P301+P312 P362+P364 P264 P270 P330 P501	Based on a report of an LD50 value of 1454 mg/kg for rats (HSDB (Access on July 2014), IUCLID (2000)), it was classified in Category 4.
1	Acute toxicity (Dermal)	Category 3	Danger	H311	P302+P352 P280 P312 P321 P361 P364 P405 P501	There are 3 reports of LD50 values of 242 mg/kg and 825 mg/kg for rats (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)), and 2,000 mg/kg for rabbits (ATSDR (2008), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EHC 168 (1995)). According to the GHS Classification Guidance for the Japanese Government, it was classified in Category 3 to which the larger number of values corresponded. New information sources (ATSDR (2008), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)) were added, and the category was revised.
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.
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	In skin irritation tests with rabbits, there are descriptions that irreversible tissue destruction was observed (EHC 168 (1995)), and that severe irritation was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)). In addition, there is a description that this substance showed severe irritation or corrosivity (DFGOT vol.14 (2000), OEL Documentations (Japan Society For Occupational Health (JSOH)) (1986)). 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	It is reported that in a test in which 0.1 mL of this substance was applied to the eyes of rabbits, strong irritation was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)), and that strong irritation was observed in rabbits and mice (EHC 168 (1995)). In addition, there is a description that this substance showed strong irritation or corrosivity to the eyes (DFG vol.14 (2000), OEL Documentations (Japan Society For Occupational Health (JSOH), 1986)). 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. Besides, there is a report that no sensitization was observed after applying this substance (mixture of m-cresol and p-cresol) to guinea pigs (DFGOT vol. 14 (2000)). However, since the details of the test method, etc. were unknown, the data was judged to be insufficient for use in classification.
5	Germ cell mutagenicity	Classification not possible	- -	-	-	Classification not possible due to lack of data. As for in vivo, a mixture of m- and p-cresol (60:40) was negative in a micronucleus test with mouse peripheral blood (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), ATSDR (2008), EHC 168 (1995), NTP TR 550 (2008)). As for in vitro, negative results were shown in a bacterial reverse mutation test of a mixture of o-, m-, and p-cresol (1:1:1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EHC 168 (1995), ATSDR (2008)) and in a bacterial reverse mutation test of a mixture of m-, p-cresol (60:40) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EHC 168 (1995), NTP TR 550 (2008)) and positive results were shown in a mouse lymphoma test, a sister chromatid exchange test, and an unscheduled DNA synthesis test with cultured mammalian cells using a mixture of o-, m-, and p-cresol (1:1:1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EHC 168 (1995), ATSDR (2008)). From the above, although there were negative results for in vivo test data using m- and p-cresol mixtures, since there were no in vivo test data using a mixture of o-, m- and p-cresol, it was judged that there was not enough data for the isomer mixture.
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	Although there was no carcinogenicity classification by international organizations as cresol (CAS RN 1319-77-3), there is the same classification for each isomer of this substance (o-, m-, p-cresol) (EPA (1991) classified as Group C), therefore, the GHS classification was done using these classification results, and it was classified in Category 2.
7	Reproductive toxicity	Classification not possible	- -	-	-	As for experimental animals, information on reproductive toxicity study using cresol (a mixture of o-, m-, p-isomers) was not available. As for human epidemiology, there are reports that in women working in factories using cresol and chlorobenzene or phosphoryl chloride, changes in hormone levels, menstrual abnormalities, increases in perinatal mortality and an incidence rate of malformations (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)). However, the observed changes were not appropriate for classification because their relevance to cresol exposure was not clear. Besides, although it was not a reproductive toxicity test, it is reported that in a 4-month inhalation toxicity test with rats, 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 (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), EHC 168 (1995)). Details of this information were unknown. 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), Category 3 (narcotic effects)	Danger Warning	H370 H336	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	As for humans, in cases of persons who swallowed it by the oral route, dyspnea, coma and tachycardia with ventricular extrasystole were observed, and the people died of acute heart failure. Histopathological examination showed eosinophilic necrosis in the proximal tubules of the kidney, diffuse necrosis of the bronchial epithelium. By the dermal route, dizziness, vomiting, disturbance of consciousness, epilepsy with apnea, coma, reduced pulse rate, oliguria, severe nephropathy, acute renal failure, tubular necrosis, pulmonary edema, hemolysis, hemoglobinuria and death were reported, and pathological examination revealed hemorrhagic pulmonary edema, hepatic lobule necrosis, renal congestion and swelling, and congestion and swelling of the brain (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), ATSDR (2008), EHC 168 (1995)). there are reports of methemoglobinemia, Heinz body formation and hemolytic anemia in other information (Initial Risk Assessment Report (NITE, CERI, NEDO) (2007), EHC 168 (1995)). As for experimental animals, severe respiratory tract irritation, nervous excitation, convulsions, clonic convulsion and mortality were observed in an inhalation exposure study with rats. Respiratory tract irritation, corrosivity and hemorrhages by the oral route and respiratory tract irritation, hematuria, renal tubular damage, nodular pneumonia, liver congestion accompanied with pallor and hepatocyte necrosis by the unknown route were reported (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), ACGIH (7th, 2001), ATSDR (2008), DFGOT vol. 14 (2000)). As for the findings on experimental animal, the descriptions of exposure dose were lacking. From the above, the major target organs of cresol were considered to be the central nervous system, respiratory organs, cardiovascular system, blood system, liver, and kidney. In this classification, classification based on animal test results of the above isomer mixture, classification based on animal tests of the o-isomer (ID:32), m-isomer and p-isomer (ID: 33), and human findings on a mixture were combined and regarded as the classification result of "cresol." Toxicological information on "the m-isomer" for which classification results were not yet shown was described below. As for m-cresol, similar to the o-isomer and p-isomer, hypoactivity, salivation, incoordination, muscle twitches, tremors, convulsions, dyspnea, weakness, lethargy, coma and mortality were observed by oral administration to mice and rats (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), ATSDR (2008)). The findings indicating the effects of the m-isomer alone on the central nervous system were observed within the guidance value range corresponding to Category 1. From the above, based on the knowledge on humans (isomer mixture) and experimental animals (isomer mixture and individual isomers), it was classified in Category 1 (central nervous system, respiratory organs, cardiovascular system, blood system, liver, kidney), Category 3 (narcotic effects). Besides, classification results were revised this time based on the information sources of List 1 and considering the consistency with the classification of other isomers.
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 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, as information on mixtures other than the o-, m-, and p-isomers, tests in which a cresol mixture (m-, p-: 60%:40%) was administered by diet to rats or mice for 4 and 13 weeks, were judged to be the only available data. Among these, at doses corresponding to Category 2 (90-95 mg/kg/day (28-30 mg/kg/day (converted guidance value))) increased relative liver weight and hyperplasia of the respiratory epithelium in the nasal cavity were observed in a 4-week dietary administration study with rats. In the other three studies, in addition to histological changes in the nasal cavity and increased liver weight, central nervous system symptoms (lethargy, immobility, tremors), hypoplasia of the bone marrow and increased kidney weight were noted at high doses equivalent to "Not classified" (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), ATSDR (2008)). Classification based on animal test results for this isomer mixture, classification based on animal test results for the o-isomer (ID: 32), m-isomer and p-isomer (ID: 33), and human epidemiological knowledge on the mixtures were combined and regarded as the classification result for "cresol," and the toxicological information on the "m-isomer" which was not yet classified is described below. As for m-cresol, the effects on the central nervous system and respiratory system were observed at high doses corresponding to "Not classified" in multiple studies with rats or mice for 28 days or 13 weeks. However, there were no specific target organs within or lower than the dose range of Category 2. There was no toxicity information by other routes (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), ATSDR (2008)). Therefore, as for a classification result for the m-isomer alone, it was judged to be appropriate to classify it as "Classification not possible" due to lack of data because the findings in experimental animals (m-isomer) could not support the findings in humans (mixtures). From the above, based on the findings on humans (mixture) and experimental animals (mixture, and o-/p-isomer), it was classified in Category 1 (central nervous system, cardiovascular system, blood system, respiratory organs, liver, kidney). Besides, the previous classification was the classification result from the information source of List 3, and this time, based on the information sources of List 1, considering the consistency with the classification for other isomers, 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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