GHS Classification Results by the Japanese Government
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 119-61-9 |
| Chemical Name | Benzophenone |
| Substance ID | R03-B-010-MHLW |
| Classification year (FY) | FY2021 |
| Ministry who conducted the classification | Ministry of Health, Labour and Welfare (MHLW) |
| New/Revised | Revised |
| Classification result in other fiscal year | FY2016 FY2008 |
| Download of Excel format | Excel file |
REFERENCE INFORMATION
| Item | Information |
|---|---|
| Guidance used for the classification (External link) | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 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 |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 1 | Explosives | Not classified (Not applicable) |
- |
- | - | There are no chemical groups associated with explosive properties present in the molecule. |
| 2 | Flammable gases | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) |
| 3 | Aerosols | Not classified (Not applicable) |
- |
- | - | Not aerosol products. |
| 4 | Oxidizing gases | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) |
| 5 | Gases under pressure | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) |
| 6 | Flammable liquids | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) |
| 7 | Flammable solids | Classification not possible |
- |
- | - | No data available. Besides, there is information that it is combustible (GESTIS (Accessed Oct 2021)). |
| 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. |
| 9 | Pyrophoric liquids | Not classified (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 560 deg C (GESTIS (Accessed Oct 2021)). |
| 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 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). |
| 13 | Oxidizing liquids | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition) |
| 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. |
| 15 | Organic peroxides | Not classified (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. |
| 17 | Desensitized explosives | Not classified (Not applicable) |
- |
- | - | There are no chemical groups associated with explosive properties present in the molecule. |
| 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 P264 P270 P330 P501 |
[Rationale for the Classification] Based on (1) to (4), it was classified in Category 4 by adopting the category with the higher hazard. [Evidence Data] (1) LD50 for rats: 1,900 mg/kg (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2019), NTP TR533 (2006)) (2) LD50 for rats: > 10,000 mg/kg (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2019), AICIS IMAP (2015), NTP TR533 (2006)) |
| 1 | Acute toxicity (Dermal) | Not classified |
- |
- | - | [Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) LD50 for rabbits: 3,535 mg/kg (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2019), NTP TR533 (2006)) (2) LD50 for rabbits: > 2,000 mg/kg (AICIS IMAP (2015)) |
| 1 | Acute toxicity (Inhalation: Gases) | Not classified |
- |
- | - | [Rationale for the Classification] Solid (GHS definition). It was classified as "Not classified." |
| 1 | Acute toxicity (Inhalation: Vapours) | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
| 2 | Skin corrosion/irritation | Not classified |
- |
- | - | [Rationale for the Classification] Based on (1), it was classified as "Not classified." Also, based on the new findings, the classification result was changed. [Evidence Data] (1) It was reported that, in an acute dermal irritation/corrosion test (OECD TG 404, GLP, 2 to 100% (undiluted solution), semiocclusive, 4-hour application, observation for 72 hours) with rabbits (n = 4), no signs of skin irritation were observed at concentrations up to 100 % (AICIS IMAP (2015), REACH registration dossier (Accessed Dec. 2021)). |
| 3 | Serious eye damage/eye irritation | Not classified |
- |
- | - | [Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." Also, based on the new findings, the classification result was changed. [Evidence Data] (1) In an eye irritation test with rabbits (n=3), slight-to-moderate erythema was observed in the conjunctiva and nictitating membrane at 1 hour after application, and persisted for 24 hours. It was reported that slight erythema was observed in only one animal by 48 hours, and all eyes were normal by 14 days (Patty (6th, 2012)). (2) It was reported that, in an eye irritation test with rabbits (n=6), only a slight reaction was caused (REACH registration dossier (Accessed Dec. 2021), AICIS IMAP (2015)). (3) It was reported that, in an eye irritation test with rabbits, no eye irritation was observed (REACH registration dossier (Accessed Dec. 2021)). |
| 4 | Respiratory sensitization | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
| 4 | Skin sensitization | Not classified |
- |
- | - | [Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) In a sensitization test with 25 volunteers using a 6% solution of this substance, no positive reactions were observed (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2019), REACH registration dossier (Accessed Dec. 2021)). (2) In a Maximization test with guinea pigs (n=20) (intradermal injection: 1% solution), all animals showed no positive reactions (AICIS IMAP (2015), REACH registration dossier (Accessed Dec. 2021)). [Reference Data, etc.] (3) It was reported that, in a skin sensitization test with guinea pigs (n = 10) by a modified Draize method (intradermal injection: a 1% solution was applied four times), no sensitizing response was observed (AICIS IMAP (2015), REACH registration dossier (Accessed Dec. 2021)). |
| 5 | Germ cell mutagenicity | Not classified |
- |
- | - | [Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." Also, the classification result was changed in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) As for in vivo, negative results were obtained in all of four micronucleus assays using the bone marrow cells of mice of three strains (single intraperitoneal injection (500 to 2,000 mg/kg or 100 to 600 mg/kg), a 3-day intraperitoneal injection test (200 to 500 mg/kg) and a 14-week feeding test (1,250 to 20,000 ppm (200 to 4,200 mg/kg/day)) (AICIS IMAP (2015), EFSA (2017), Government of Canada, Screening Assessment (2021)). (2) As for in vitro, negative results were obtained in a bacterial reverse mutation assay, and a gene mutation assay using the L5178Y mouse lymphoma cell line (AICIS IMAP (2015), EFSA (2017), Government of Canada, Screening Assessment (2021)). [Reference Data, etc.] (3) Based on the available test results, this substance is not considered to be genotoxic, and genotoxicity is not considered relevant to the mode of action of carcinogenicity of this substance (EFSA (2017), CLH Report (2019), ECHA RAC Opinion (2020)). |
| 6 | Carcinogenicity | Category 1B |
 Danger |
H350 | P308+P313 P201 P202 P280 P405 P501 |
[Rationale for the Classification] Based on (1) and (2), an increase in the incidence of tumors including malign ones was observed in two animal species, and there was considered to be sufficient evidence of carcinogenicity in animal studies, and therefore, this substance was classified in Category 1B. Besides, the classification result was changed according to the new assessment. [Evidence Data] (1) In a carcinogenicity study with rats dosed by feeding (312 to 1,250 ppm) for two years, increased incidences of renal tubule adenoma (high-dose group) and mononuclear cell leukemia (low- and middle-dose group) were observed in males, and increased incidence of mononuclear cell leukemia (middle-dose group) was observed in females (IARC 101 (2013)). In addition, in the assessment by the EU including the EFSA, an increase in histiocytic sarcoma (rare carcinoma) was also added in females (NTP TR533 (2006), EFSA (2017), CLH Report (2019), ECHA RAC Opinion (2020), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2019), Government of Canada, Screening Assessment (2021)). (2) In a carcinogenicity study with mice dosed by feeding (312 to 1,250 ppm) for two years, the total increase in incidence of hepatocellular adenoma alone, and hepatocellular adenoma and hepatocellular carcinoma were observed in males, and an increase in histiocytic sarcoma (rare carcinoma) was observed in females (IARC 101 (2013)). In addition, in the assessment by the EU including the EFSA, an increase in hepatoblastoma (rare carcinoma) was also added in males (NTP TR533 (2006), EFSA (2017), CLH Report (2019), ECHA RAC Opinion (2020), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2019), Government of Canada, Screening Assessment (2021)). (3) Based on (1) and (2), evidence of carcinogenicity was obtained in two animal species, including increased incidence of the rare tumor histiocytic sarcoma in female mice and female rats. The RAC of the ECHA concluded that, although the incidence was low, histiocytic sarcoma was associated with the exposure to this substance and was of biological significance, and the incidence of rare carcinoma hepatoblastoma was also observed in male mice, and therefore, it was appropriate to change the category from Category 2 to Category 1B (ECHA RAC Opinion (2020)). (4) As for the classification results by domestic and international organizations, the IARC classified this substance in Group 2B (IARC 101 (2013)), and the Japan Society For Occupational Health (JSOH) classified it in Group 2B (Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH), 2020)). [Reference Data, etc.] (5) In a carcinogenicity study by 120-week dermal administration to female mice (5 to 50%, twice a week), there was no increase in the incidence of tumor even in treated areas (IARC101 (2013), EFSA (2009), EU REACH CoRAP (2018), CLH Report (2019), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2019), Government of Canada (2021)). |
| 7 | Reproductive toxicity | Not classified |
- |
- | - | [Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." Besides, based on (1), at a general toxicity dose in dams, increased incidences of abortion/early delivery were observed, and findings suggesting early termination of pregnancy were observed, but these were considered to be attributed to maternal toxicity. [Reference Data, etc.] (1) In a developmental toxicity study with female rabbits dosed by gavage (days 6 to 29 of gestation, 5 to 45 mg/kg/day), an increase in the incidence of early termination of pregnancy (abortion or early delivery) was observed (0/24, 0/24, 3/22 (4.5%), and 7/19 (36.8%) in a control group, a low-dose group, a middle-dose group, and a high-dose group, respectively) at or above a middle dose (25 mg/kg/day) at which maternal toxicity (death (2/24), reduced body weight gain, reduced food consumption) was observed. It was reported that in fetuses, only lower body weight was observed in a high-dose group (EFSA (2009; 2017), AICIS IMAP (2015), Government of Canada, Screening Assessment (2021), NTP (2004)). (2) In a two-generation reproduction toxicity study (OECD TG 416, 100 to 2,000 ppm) with rats dosed by feeding, in F0 and F1 parent animals, effects on the liver (increased weight, hepatocellular hypertrophy: adaptive change) were observed at or above 100 ppm (6.5 mg/kg/day (males), 8.4 mg/kg/day (females)), and reduced body weight gain, reduced food consumption, and effects on the kidney (increased weight, proximal tubule dilatation, regeneration of proximal tubule epithelium) were observed at or above 450 ppm (29 mg/kg/day (males), 38 mg/kg/day (females)), but no effects on fertility were observed. It was reported that, in F1 and F2 offspring, only reduced body weight gain was observed at 2,000 ppm (130 mg/kg/day (males), 167 mg/kg/day (females)) (EFSA (2009; 2017), AICIS IMAP (2015), Government of Canada, Screening Assessment (2021)). (3) It was reported that, in a developmental toxicity study with female rats dosed by gavage (days 6 to 19 of gestation, 100 to 300 mg/kg/day), delayed ossification (unossified sternebrae) was observed at and above a low dose at which maternal toxicity (weight loss, clinical signs (lethargy, piloerection), increased liver and kidney weight) was observed; skeletal variations (extra ribs) were observed at and above a middle dose; and lower fetal body weight per litter was observed at a high dose (EFSA (2009; 2017), AICIS IMAP (2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2019), Government of Canada, Screening Assessment (2021)). |
| 8 | Specific target organ toxicity - Single exposure | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. Besides, (1) was not adopted as evidence data because those effects were observed near lethal doses. [Reference Data, etc.] (1) It was reported that, in an acute oral toxicity test with mice, sedation, progressive depression of motor activity, unstable gait, tremors, and respiratory impairment were observed in lethal doses. Also, the LD50 was 2,895 mg/kg (REACH registration dossier (Accessed Dec. 2021)). |
| 9 | Specific target organ toxicity - Repeated exposure | Category 2 (liver, kidney) |
Warning |
H373 | P260 P314 P501 |
[Rationale for the Classification] Based on (1) to (4), it was classified in Category 2 (liver, kidney). Besides, based on (1), effects on the blood system were observed, but in (3), they were not observed in the range corresponding to the category in a longer test with the same species of animals, and therefore, the blood system was not adopted as the target organ. The classification result was changed in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) It was reported that, in a repeated dose 28-day oral toxicity study with rats dosed by feeding, reduced body weight gain, higher serum albumin, increased absolute and relative liver weight, increased relative kidney weight, hepatocellular hypertrophy, higher urea nitrogen (males), a decrease in red blood cell count (females), lower hematocrit level (females), total bilirubin (females), and higher total protein (females) were observed at 100 mg/kg/day (converted guidance value: 31.1 mg/kg/day, within the range for Category 2) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2019), Government of Canada (2021)). (2) It was reported that, in a repeated dose 14-week oral toxicity study with rats dosed by feeding, , lower body weight (females), effects on the liver (increased weight, centrilobular hepatocellular hypertrophy, cytoplasmic vacuolization, induction of liver microsomal cytochrome P450 2B (females)), and effects on the kidney (increased weight, tubule epithelial regeneration) were observed at 75 mg/kg/day (within the range for Category 2) (AICIS IMAP (2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2019), EFSA (2009, 2017), EU REACH CoRAP (2018)). (3) It was reported that, in a 105-week oral toxicity test with rats dosed by feeding, centrilobular hepatocellular hypertrophy, renal tubule hyperplasia, thyroid C-cell hyperplasia, pelvic transitional epithelium hyperplasia (males), exacerbation of nephropathy (males), and chronic active hepatitis/bile duct hyperplasia (females) were observed at 312 ppm (15.6 mg/kg/day, within the range for Category 2); and chronic active hepatitis (males), cystic degeneration of the liver (males), hyperplasia of the parathyroid (males), mineralization in the glandular stomach (males), lower body weight (females), and exacerbation of nephropathy (females) were observed at 625 ppm (31.3 mg/kg/day, within the range for Category 2) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2019), AICIS IMAP (2019), EFSA (2009; 2017), EU REACH CoRAP (2018)). (4) It was reported that, in a 105-week oral toxicity test with mice dosed by feeding, centrilobular hepatocellular hypertrophy, multinucleated hepatocytes (males), chronic active inflammation of the liver (males), exacerbation of nephropathy (males), hyperplasia of lymphoid follicles in the spleen (males), reduced body weight gain (females), nephropathy (females), mineralization of the kidney (females), hyperplasia of lymphoid follicles in the spleen (females), and hematopoietic cell proliferation (females) were observed at 312 ppm (15.6 mg/kg/day, within the range for Category 2); necrosis of hepatocytes (males), cystic degeneration of the liver (males), and renal cortical cyst (males) were observed at 625 ppm (31.3 mg/kg/day, within the range for Category 2); and respiratory epithelial metaplasia in the olfactory epithelium, clear cell foci of altered hepatocytes (males), mineralization of the testis (males), and exacerbation of nephropathy (females) were observed at 1,250 ppm (62.5 mg/kg/day, within the range for Category 2) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2019), AICIS IMAP (2019), EFSA (2009; 2017), EU REACH CoRAP (2018)). |
| 10 | Aspiration hazard | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 11 | Hazardous to the aquatic environment Short term (Acute) | - |
- |
- | - | - |
| 11 | Hazardous to the aquatic environment Long term (Chronic) | - |
- |
- | - | - |
| 12 | Hazardous to the ozone layer | - |
- |
- | - | - |
NOTE:
|