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 | 95-48-7 |
| Chemical Name | o-Cresol |
| Substance ID | m-nite-95-48-7_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) |
- |
- | - | Solid (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) |
- |
- | - | Solid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 5 | Gases under pressure | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 6 | Flammable liquids | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 7 | Flammable solids | Classification not possible |
- |
- | - | No data available. | 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 (Not applicable) |
- |
- | - | Solid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 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)). | 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 solid (melting point <= 140 deg C) 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) |
- |
- | - | Solid (GHS definition) | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 14 | Oxidizing solids | 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)) |
| 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 |
- |
- | - | It is a solid with a melting point of 55 deg C or lower, but the classification is not possible due to no data. | 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 3 |
 Danger |
H301 | P301+P310 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. | 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 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. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 1 | Acute toxicity (Inhalation: Gases) | Not classified (Not applicable) |
- |
- | - | Solid (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. 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." | 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 |
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. | 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 |
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. | 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. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 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. | 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 |
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. | FY2014 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0)) |
| 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." |
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, 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). |
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 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. |
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 LC50=5mg/L of the crustacea (Daphnia magna) (EHC168 (1995) and others.). | FY2006 | GHS Classification Manual （10 Feb, 2006） |
| 11 | Hazardous to the aquatic environment Long term (Chronic) | Not classified |
- |
- | - | Since there was rapidly degrading (the 20 days decomposition rate: 86% (SIDS, 1998)) and the bio-accumulation was low (BCF=10.7 (SIDS, 1998)), it was claasified into Not classified. | FY2006 | GHS Classification Manual （10 Feb, 2006） |
| 12 | Hazardous to the ozone layer | - |
- |
- | - | - | - | - |
NOTE:
|