Latest GHS Classification Results by the Japanese Government (edited by NITE)
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 1319-77-3 |
| Chemical Name | Cresol |
| Substance ID | m-nite-1319-77-3_v1 |
| Download of Excel format | Excel file |
REFERENCE INFORMATION
| Item | Information |
|---|---|
| Guidance used for the classification (External link) | To Guidance List |
| UN GHS document (External link) | To UN GHS document |
| FAQ（GHS classification results by the Japanese Government） | To FAQ |
| List of Information Sources (Excel file) | List of Information Sources |
| List of Definitions/Abbreviations | Definitions/Abbreviations |
| Sample Label by MHLW (External link) | To Workplace Safety Site (MHLW) |
| Sample SDS by MHLW (External link) | To Workplace Safety Site (MHLW) |
| OECD/eChemPortal (External link) | To OECD/eChemPortal (External link) |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | Classification year (FY) | GHS Classification Guidance for the Japanese Government | |
|---|---|---|---|---|---|---|---|---|
| 1 | Explosives | Not classified (Not applicable) |
- |
- | - | There are no chemical groups associated with explosive properties present in the molecule. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 2 | Flammable gases | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 3 | Aerosols | Not classified (Not applicable) |
- |
- | - | Not aerosol products. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 4 | Oxidizing gases | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 5 | Gases under pressure | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 6 | Flammable liquids | Category 4 |
Warning |
H227 | P370+P378 P210 P280 P403 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. |
FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 7 | Flammable solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 8 | Self-reactive substances and mixtures | Not classified (Not applicable) |
- |
- | - | There are no chemical groups present in the molecule associated with explosive or self-reactive properties. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 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)). | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 10 | Pyrophoric solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 11 | Self-heating substances and mixtures | Classification not possible |
- |
- | - | Test methods applicable to liquid substances are not available. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 12 | Substances and mixtures which, in contact with water, emit flammable gases | Not classified (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). | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 13 | Oxidizing liquids | Not classified (Not applicable) |
- |
- | - | The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 14 | Oxidizing solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 15 | Organic peroxides | Not classified (Not applicable) |
- |
- | - | Organic compounds containing no bivalent -O-O- structure in the molecule | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 16 | Corrosive to metals | Classification not possible |
- |
- | - | No data available. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 17 | Desensitized explosives | - |
- |
- | - | - | - | - |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | Classification year (FY) | GHS Classification Guidance for the Japanese Government | |
|---|---|---|---|---|---|---|---|---|
| 1 | Acute toxicity (Oral) | Category 4 |
 Warning |
H302 | P301+P312 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. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 1 | Acute toxicity (Dermal) | Category 3 |
 Danger |
H311 | P302+P352 P361+P364 P280 P312 P321 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. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 1 | Acute toxicity (Inhalation: Gases) | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 1 | Acute toxicity (Inhalation: Vapours) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 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. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 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. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 4 | Respiratory sensitization | Classification not possible |
- |
- | - | Classification not possible due to lack of data. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 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. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 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. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 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. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 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." |
FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 8 | Specific target organ toxicity - Single exposure | Category 1 (central nervous system, respiratory organs, cardiovascular system, blood 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. |
FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 9 | Specific target organ toxicity - Repeated exposure | Category 1 (central nervous system, cardiovascular system, blood 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. |
FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 10 | Aspiration hazard | Classification not possible |
- |
- | - | Classification not possible due to lack of data. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | Classification year (FY) | GHS Classification Guidance for the Japanese Government | |
|---|---|---|---|---|---|---|---|---|
| 11 | Hazardous to the aquatic environment Short term (Acute) | Category 2 |
- |
H401 | P273 P501 |
It was classified into Category 2 from 48 hours EC50=7mg/L of the crustacea (Amphipod) (CERI/NITE Hazard Assessment Report (preliminary version), 2006). | FY2006 | GHS Classification Manual （10 Feb, 2006） |
| 11 | Hazardous to the aquatic environment Long term (Chronic) | Not classified |
- |
- | - | Since there was rapidly degrading (the decomposition (ortho, meta and para isomer): >60% (SIDS (1998, 2005)) and the bio-accumulation was low (log Kow=1.95 (PHYSPROP Database (2005))), it was classified into Not classified. | FY2006 | GHS Classification Manual （10 Feb, 2006） |
| 12 | Hazardous to the ozone layer | - |
- |
- | - | - | - | - |
NOTE:
|