GHS Classification Results by the Japanese Government
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 98-82-8 |
| Chemical Name | Cumene |
| Substance ID | R03-B-011-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 | FY2011 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 (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) |
- |
- | - | Liquid (GHS definition) |
| 3 | Aerosols | Not classified (Not applicable) |
- |
- | - | Not aerosol products. |
| 4 | Oxidizing gases | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) |
| 5 | Gases under pressure | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) |
| 6 | Flammable liquids | Category 3 |
 Warning |
H226 | P303+P361+P353 P370+P378 P403+P235 P210 P233 P240 P241 P242 P243 P280 P501 |
It was classified in Category 3 based on a flash point of 31 deg C (closed cup) (GESTIS (Accessed Oct 2021)). Besides, it is classified in Class 3, PG III in UNRTDG (UN1918). |
| 7 | Flammable solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) |
| 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 |
- |
- | - | It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 420 deg C (GESTIS (Accessed Oct 2021)). |
| 10 | Pyrophoric solids | Not classified (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 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) |
- |
- | - | Organic compounds containing no oxygen, fluorine or chlorine. |
| 14 | Oxidizing solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) |
| 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 |
- |
- | - | No data available. |
| 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) | Not classified |
- |
- | - | [Rationale for the Classification] Based on (1) to (5), it was classified as "Not classified." Besides, as for (6), details were unknown, and therefore, it was classified according to the data in (1) to (5). [Evidence Data] (1) LD50 for rats: 2,700 mg/kg (ACGIH (2001)) (2) LD50 for rats: 2,900 mg/kg (DFG MAK (1999), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015)) (3) LD50 for rats: 2,910 mg/kg (EU RAR (2001)) (4) LD50 for rats: 3,980 mg/kg (EU RAR (2001)) (5) LD50 for rats: 4,000 mg/kg (EU RAR (2001)) [Reference Data, etc.] (6) LD50 for rats: 1,400 mg/kg (DFG MAK (1999), DFG MAK (2013), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015), AICIS IMAP (2016), ACGIH (2001)) |
| 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: 10,600 mg/kg (DFG MAK (1999), DFG MAK (2013), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015)) (2) LD50 for rabbits: > 3,160 mg/kg (DFG MAK (2013), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), AICIS IMAP (2016), EU RAR (2001), ACGIH (2001)) |
| 1 | Acute toxicity (Inhalation: Gases) | Not classified |
- |
- | - | [Rationale for the Classification] Liquid (GHS definition). It was classified as "Not classified." |
| 1 | Acute toxicity (Inhalation: Vapours) | Category 4 |
 Warning |
H332 | P304+P340 P261 P271 P312 |
[Rationale for the Classification] Based on (1) and (2), it was classified in Category 4. Also, since the exposure concentration was lower than 90% (5,300 ppm) of the saturated vapor pressure concentration, it was judged to be a vapor and classified based on the reference value in units of ppmV. In accordance with the GHS Classification Guidance for the Japanese Government, the data for rats were used, but they were in the range corresponding to "Not classified," and therefore, the classification result was changed based on the classification using the data for mice. [Evidence Data] (1) LC50 (7 hours) for mice: 2,000 ppm (converted 4-hour equivalent value: 2,645 ppm) (DFG MAK (2013), EU RAR (2001), AICIS IMAP (2015), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), ACGIH (2001)) (2) LC50 (2 hours) for mice: 5,000 ppm (converted 4-hour equivalent value: 3,535 ppm) (OEL Documentations (Japan Society For Occupational Health (JSOH), 2019)) [Reference Data, etc.] (3) LC50 (6 hours) for rats: > 3,520 ppm (converted 4-hour equivalent value: 4,311 ppm) (OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), AICIS IMAP (2016), EU RAR (2001)) |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Not classified |
- |
- | - | [Rationale for the Classification] Based on (1), it was classified as "Not classified." Besides, since the exposure concentration was higher than the saturated vapor pressure concentration (295,900 mg/L), it was judged as mist. [Evidence Data] (1) LC50 (4 hours) for rats: 39.3 mg/L (DFG MAK (2013), OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015), ACGIH (2001)) |
| 2 | Skin corrosion/irritation | Not classified |
- |
- | - | [Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) In an acute dermal irritation/corrosion test with rabbits (n=6) (equivalent to OECD TG 404, intact/abraded skin, observation for 72 hours), no edema was observed after 24 and 72 hours, but mild reversible erythema was observed in all animals. Average scores (maximum score: 8) for each of 6 animals were 2, 1.5, 2, 2, 2, and 1.5, respectively, and there was no difference between scores for intact and abraded skin (AICIS IMAP (2016), EU RAR (2001), ACGIH (7th, 2001), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), REACH registration dossier (Accessed Dec. 2021)). [Reference Data, etc.] (2) This substance was a skin irritant (AICIS IMAP (2016), NTP (2009)). (3) The Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015) stated that this substance was slightly irritating with skin irritation/corrosion. (4) In a skin irritation test with rabbits (undiluted solution 0.5 mL, 24-hour application), a slight defatting with flaking of the skin was observed, and the substance was rated slightly irritating to the skin (ACGIH (7th, 2001), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), OEL Documentations (Japan Society For Occupational Health (JSOH), 2019)). |
| 3 | Serious eye damage/eye irritation | Category 2B |
Warning |
H320 | P305+P351+P338 P337+P313 P264 |
[Rationale for the Classification] Based on (1) to (3), it was classified in Category 2B in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) This substance was an eye irritant (AICIS IMAP (2016), NTP (2009)). (2) In an eye irritation test with rabbits, irritation with moderate erythema and copious discharge was observed, but effects were reversible within 120 hours (OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), ACGIH (7th, 2001), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), AICIS IMAP (2016)). (3) The Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015) stated that the serious eye damage/eye irritation of this substance was slightly irritating as a result of the hazard assessment. |
| 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), it was classified as "Not classified." [Evidence Data] (1) In a Maximization test (OECD TG 406, GLP, intradermal induction: 10% solution) with guinea pigs (n=20), the positive rate was 0% (0/20 animals) 48 hours after challenge (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), AICIS IMAP (2016), REACH registration dossier (Accessed Dec. 2021)). |
| 5 | Germ cell mutagenicity | Not classified |
- |
- | - | [Rationale for the Classification] Based on (1) to (4), weak reactions were observed in some in vivo administration routes and organs, but all other findings including in vitro ones were negative, and therefore, it was classified as "Not classified." [Evidence Data] (1) As for in vivo, weakly positive results were obtained in a rat bone marrow micronucleus test by intraperitoneal injection, but negative results were obtained in all of multiple mouse peripheral blood/bone marrow micronucleus tests by gavage administration or inhalation exposure (CLH Report (2019), ECHA RAC Opinion (2020), OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015)). In comet assays with male rats and male and female mice dosed by gavage (target organs: blood, lung, liver, kidney), weakly positive results were obtained in the liver of male rats and in the lung of female mice (CLH Report (2019), OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015)). (2) As for in vitro, it was all negative in a bacterial reverse mutation test, and a gene mutation test (HPRT gene loci) and a chromosomal aberration test with cultured mammalian cells (Chinese hamster ovary cells (CHO)) (CLH Report (2019), OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015)). (3) Although a weak genotoxic potential of this substance could not be excluded, the RAC of the ECHA agreed with the conclusion of the CLP classification proposer that this substance did not fall under the germ cell mutagenicity Category 1B/2 (ECHA RAC Opinion (2020)). (4) Based on the available data, this substance itself is not considered to be genotoxic, but there is some evidence of genotoxicity for alpha-methylstyrene oxide, a metabolite of this substance (Canada CMP Screening Assessment (2019), AICIS IMAP (2016)). |
| 6 | Carcinogenicity | Category 1B |
 Danger |
H350 | P308+P313 P201 P202 P280 P405 P501 |
[Rationale for the Classification] Based on (1), in an adequate test with one animal species (mice), an increase in tumors including multiple kinds of malignant tumors such as lung tumor was observed both in males and females, and therefore, it was judged that there was sufficient evidence of carcinogenicity in animal studies, and it was classified in Category 1B. [Evidence Data] (1) In a carcinogenicity study by two-year inhalation exposure with mice (males: 250 to 1,000 ppm, females: 125 to 500 ppm), an increase in the total incidence of tumors including malignant ones in the lung were observed both in males and females, hemangiosarcoma in the spleen was observed in males, hepatocellular adenoma and carcinoma were observed in females, and a trend towards a significant increase in follicular cell adenoma of the thyroid was also observed in males. Also, as a result of assessment of K-ras and p53 mutations in the lung of mice exposed to this substance, K-ras and p53 mutations were observed in 87% and 52% of lung tumors, respectively, while in a control group, they were observed in 14% and 0%, respectively (OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), CLH Report (2019), NTP TR542 (2009)). (2) As for the classification results by domestic and international organizations, the IARC classified this substance in Group 2B (IARC 101 (2013)), the Japan Society For Occupational Health (JSOH) classified it in Group 2B (OEL Documentations (Japan Society For Occupational Health (JSOH), 2019): Classification in 2015), the EPA classified it in Category D (not classifiable as to human carcinogenicity) (IRIS (1997)), the NTP classified it in R (NTP RoC 14th. (2016)), the DFG classified it in Category 3 (List of MAK and BAT values 2020 (Accessed November 2021)). Also, the EU is expected to classify this substance in Carc. 1B in the future (ECHA RAC Opinion (2020)). [Reference Data, etc.] (3) In a carcinogenicity study with rats by 2-year inhalation exposure (males and females: 250 to 1,000 ppm), an increase in adenoma of the respiratory epithelium of the nasal cavity, the total incidence of adenoma and carcinoma of the renal tubules, and interstitial cell adenoma of the testis were observed in males and adenoma of the respiratory epithelium of the nasal cavity was observed in females (IARC 101 (2013), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015), AICIS IMAP (2016), CLH Report (2019), OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), NTP TR542 (2009)). (4) It was considered that kidney tumors observed in a test with rats were not relevant to humans because there was a sufficient possibility of kidney tumor formation associated with alpha 2mu-globulin nephropathy, which was specific to male rats (OEL Documentations (Japan Society For Occupational Health (JSOH), 2019)). In contrast, the RAC of the ECHA judged that those associated with alpha 2mu-globulin nephropathy in male rats were not relevant to humans, but a trend towards an increase in nephropathy (without significant difference) was also observed in females, and all kidney tumors in males were not necessarily attributed to the mechanism that was not relevant to humans, and therefore, kidney tumors in males could also be considered as limited evidence of carcinogenicity of this substance (ECHA RAC Opinion (2020), NTP RoC 14 th. (2016)). (5) As for cumene-induced lung tumors which were observed in male and female mice, the background incidence was high in the used strain of mice, but the rate of increase was high, and a significant increase in the incidence was observed from a low dose, and therefore, they were considered to be effects associated with administration and findings that were of biological significance. As for this mode of action, the involvement of alpha-methylstyrene and its oxides due to metabolism associated with CYP2F2 (oxidation of benzene ring) in Clara cells of the lung was assumed. The finding of accumulation of metabolites of cumene in the lung of mice was also observed. Mice had more Clara cells including CYP2E1 and CYP2F (as for CYP2F subfamilies, only one type appeared for each species: CYP2F2 for mice, CYP2F4 for rats, and CYP2F1 for humans) in the lung than rats, and therefore, it was considered that the metabolite distribution condition in the lung and expiration was different between mice and rats. In contrast, there was almost no distribution of CYP2F1 in the lung of humans, and therefore, the human metabolic ability was considered to be quite lower than that of rodents (OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), NTP RoC 14 th. (2016)). (6) The RAC of the ECHA stated that,as for lung tumors in mice, it was suggested that the hypothesis of the mode of action, which was associated with the increased metabolism of Clara cells of the respiratory tract and specific to mice, was not relevant to this substance because some findings (such as lack of cytotoxicity, not many metabolites, lack of difference with regard to metabolites between rat and mouse) via this mechanism, which were observed in alkylbenzene compounds such as styrene, could not be confirmed. Based on this, the RAC of the ECHA stated that there is still a possibility of a mechanism associated with K-ras mutation as another mode of action, and lung tumors should be regarded applicable to humans (ECHA RAC Opinion (2020)). (7) The RAC of the ECHA also stated that tumors of the nasal cavity observed in male and female rats were also evidence of carcinogenicity, but all of them were benign tumors and considered to be limited evidence. It stated that, as for liver tumors in female mice, the spontaneous incidence in the relevant strain was high, and the the weight of evidence was low. Based on the above, it stated that Carc. 1B was considered to be appropriate because benign/malignant tumors, for which extrapolation to humans could not be denied, occurred in multiple sites in two rodent species (ECHA RAC Opinion (2020)). |
| 7 | Reproductive toxicity | Classification not possible |
- |
- | - | [Rationale for the Classification] Based on (2), signs of embryonic/fetal toxicity were observed in a high-dose group in which marked maternal toxicity (mortality: 13%) occurred, and they are considered to be secondary effects of maternal toxicity. Maternal toxicity (decreased food consumption) was observed at or below the middle dose, but no developmental effects associated with exposure were observed. Therefore, based on (1) and (2), concerns regarding developmental effects of this substance are considered low, but since there is no toxicity information on effects on fertility, classification was not possible due to lack of data. [Evidence Data] (1) In a developmental toxicity study by inhalation exposure with female rats (days 6 to 15 of gestation), neither reproductive effects on dams nor developmental effects on fetuses were observed at doses up to the highest dose (1,200 ppm) at which reduced body weight gain, decreased food consumption, and increased liver weight were observed in dams (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015), OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), DFG MAK (2013), AICIS IMAP (2016), Canada CMP Screening Assessment (2019)). (2) In a developmental toxicity study by inhalation exposure with female rabbits (days 6 to 18 of gestation), in dams, decreased food consumption was observed from a low-dose group, and deaths (2/15 animals), abortion (1/15 animals), reduced body weight gain, and smudge around the oral cavity and nasal cavity, etc. were observed in a high-dose (2,300 ppm) group. In fetuses, an increase in the rate of fetuses with mottled hemorrhage on the head was observed in a low-dose group, but it was within the spontaneous incidence. In a high-dose group, an increase in resorption/post-implantation dead embryos, and a trend towards a decrease in the rate of live fetuses were observed (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015), OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), DFG MAK (2013), AICIS IMAP (2016), Canada CMP Screening Assessment (2019)). [Reference Data, etc.] (3) In a 14-week inhalation exposure test with rats and mice, a decrease in sperm count in the epididymis was observed in a group of male mice exposed to the highest concentration, but no other adverse effects on fertility were observed in either males or females (OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), DFG MAK (2013), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), AICIS IMAP (2016), Canada CMP Screening Assessment (2019)). |
| 8 | Specific target organ toxicity - Single exposure | Category 1 (nervous system), Category 3 (narcotic effects, respiratory tract irritation) |
Danger Warning |
H370 H336 H335 |
P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312 |
[Rationale for the Classification] Based on (1) and (2), there were nervous system effects and respiratory tract effects in the human findings. Based on (3) to (8), there were effects on the central nervous system (ataxia, gait abnormalities, loss of consciousness) within the range for Category 1 in the findings in animals. Based on the above, it was classified in Category 1 (nervous system) and Category 3 (narcotic effects, respiratory tract irritation). [Evidence Data] (1) Dizziness, ataxia, lethargy, headache, and loss of consciousness were caused by inhalation or oral ingestion. It was reported that the TCLo for humans was 200 ppm (984 mg/m3. Drowsiness, reduced activity, irritability) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015)). (2) It was reported that a worker who was exposed to cumene at 300 to 400 ppm complained of pain in the eyes and upper respiratory tract (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015)). (3) It was reported that, in an acute inhalation exposure test with rats (vapor, 6 hours), a decrease in flexion reflex of limbs and an increase in horizontal movement (females) were observed at 0.461 mg/L (converted 4-hour equivalent value: 0.565 mg/L, within the range for Category 1), and lower rectal temperatures, increased horizontal movement, and gait disturbances (males) were observed at 1.03 mg/L (converted 4-hour equivalent value: 1.26 mg/L, within the range for Category 1) (DFG MAK (1999), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015)). (4) It was reported that, in an acute inhalation exposure test with rats (vapor, 4 hours), a loss of consciousness was observed at 1.98 mg/L (within the range for Category 1) (DFG MAK (1999), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015)). (5) It was reported that, in an acute inhalation exposure test with rats (vapor, 6 hours), increased activity and gait abnormalities were observed at 2.5 to 6 mg/L (converted 4-hour equivalent value: 3.06 to 7.35 mg/L, within the range for Category 1) (AICIS IMAP (2016)). (6) It was reported that, in an acute inhalation exposure test with mice (vapor, 4 hours), narcosis, ataxia, loss of reflexes, decreased respiratory frequency, fatty deposits in the liver and kidneys, and phagocytozed nuclear fragments in the reticular cells of the splenic follicles were observed at 1.72 mg/L (within the range for Category 1) (DFG MAK (1999), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015)). (7) It was reported that, in an acute inhalation exposure test with mice (vapor, 7 hours), respiratory failure due to central nervous system depression was observed at 10 mg/L (converted 4-hour equivalent value: 13.2 mg/L, within the range for Category 2) (AICIS IMAP (2016)). (8) It was reported that, in an acute oral toxicity test with rats, severe motor disturbances, narcosis, and reductions in the white blood cell count were observed at 1,350 mg/kg (within the range for Category 2), and all animals died within 24 hours at 2,000 mg/kg (within the range for Category 2) (DFG MAK (1999), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015)). |
| 9 | Specific target organ toxicity - Repeated exposure | Category 2 (respiratory organs) |
Warning |
H373 | P260 P314 P501 |
[Rationale for the Classification] Based on (1), in human findings, no severe effects were observed, but based on (5) and (6), effects on the respiratory organs were observed, and therefore, it was classified in Category 2 (respiratory organs). Besides, the classification result was changed in accordance with the GHS Classification Guidance for the Japanese Government. Also, based on (2) to (6), in animal findings, findings such as histopathological alterations in the kidney observed only in male rats were judged to be based on alpha 2mu-globulin nephropathy, and the kidney was not adopted as the target organ. [Evidence Data] (1) In workers who had used cumene as a solvent for one to two years, there was no incidence of disorders caused by daily exposures. It was reported that, for most workers, the concentration of 300 to 400 ppm caused pains in the eyes or upper respiratory tract, but some workers readily tolerated concentrations considerably in excess of 400 ppm (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015), AICIS IMAP (2016), OEL Documentations (Japan Society For Occupational Health (JSOH), 2019)). (2) It was reported that, in a 4-week repeated inhalation exposure test (vapor, 6 hours/days, 5 days/week), an increase in left and right movements of the head, and torticollis-like symptoms were observed at 0.517 mg/L (converted guidance value: 0.115 mg/L, within the range for Category 1); an increase in average absolute kidney weight (males) was observed at 1.476 mg/L (converted guidance value: 0.328 mg/L, within the range for Category 2); and increases in average absolute weight of the left and right kidneys (males), hunched posture (1/10 animals) (females), and an increase in average absolute kidney weight were observed at 2.947 mg/L (converted guidance value: 0.655 mg/L, within the range for Category 2) (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015), OEL Documentations (Japan Society For Occupational Health (JSOH), 2019)). (3) It was reported that, in a 14-week repeated inhalation exposure test with rats (GLP, vapor, 6 hours/day, 5 days/week), hyaline droplet accumulation in the renal cortex (males) was observed at 0.308 mg/L (0.22 mg/L, within the range for Category 2); an increase in the amount of alpha 2mu-globulin in the kidney and an increase in the incidence of renal medulla granular casts (males) were observed at 0.615 mg/L (0.439 mg/L, within the range for Category 2); and increases in kidney and liver weight (males) were observed at 1.23 mg/L (0.879 mg/L, within the range for Category 2) (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), AICIS IMAP (2016), NTP TR542 (2009)). (4) It was reported that, in a 14-week repeated inhalation exposure test with mice (vapor, 6 hours/day, 5 days/week), very slight focal chronic inflammation in the liver was observed at 0.308 mg/L (0.22 mg/L, within the range for Category 2); lower mean body weight and an increase in liver weight were observed at 0.615 mg/L (0.439 mg/L, within the range for Category 2); and decreases in cauda epididymis weight and sperm count (males), and individuals which died within 1 week after coma and ataxia (8/10 animals) were observed at 1.23 mg/L (0.879 mg/L, within the range for Category 2) (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), AICIS IMAP (2016), NTP TR542 (2009)). (5) It was reported that, in a 105-week repeated inhalation exposure test with rats (GLP, vapor, 6 hours/day, 5 days/week), basal cell hyperplasia of the olfactory epithelium, hyperplasia of the respiratory epithelium (males), and mineralization of the renal papilla (males) were observed at 1.23 mg/L (0.879 mg/L, within the range for Category 2); hyperplasia of the renal tubules, and hyperplasia of the transitional epithelium of the renal papilla (males) were observed at 2.46 mg/L (1.76 mg/L, in the range corresponding to "Not classified"); and hyperplasia of the respiratory epithelium (females) was observed at 4.92 mg/L (3.51 mg/L, in the range corresponding to "Not classified") (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015), AICIS IMAP (2016), OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), NTP TR542 (2009)). (6) It was reported that, in a 105-week repeated inhalation exposure test with mice (GLP, vapor, 6 hours/day, 5 days/week), an increase in the incidence of eosinophilic foci of altered hepatocytes (males), olfactory epithelium atrophy (males), hyperplasia of the olfactory epithelium glands (males), and basal cell hyperplasia of the olfactory epithelium (females) were observed at 1.23 mg/L (0.879 mg/L, within the range for Category 2), and suppurative inflammation, basal cell hyperplasia of the olfactory epithelium, atypical hyperplasia of the olfactory epithelium, epithelial hyperplasia of the forestomach, atypical hyperplasia of the olfactory epithelium (females), hyperplasia of the olfactory epithelium glands (females), and an increase in the incidence of squamous metaplasia of the respiratory epithelium (females) were observed at 2.46 mg/L (1.76 mg/L, in the range corresponding to "Not classified") (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015), AICIS IMAP (2016), OEL Documentations (Japan Society For Occupational Health (JSOH), 2019), NTP TR542 (2009)). |
| 10 | Aspiration hazard | Category 1 |
Danger |
H304 | P301+P310 P331 P405 P501 |
[Rationale for the Classification] Based on (1) - (4), it was classified in Category 1. [Evidence Data] (1) This substance is a hydrocarbon compound. (2) Aspiration of this substance (liquid) may cause chemical pneumonitis (Environmental Risk Assesment for Chemical Substance (Ministry of Environment, 2015)). (3) In EU and Australia, it was recommended that this substance was classified as hazardous with the risk phrase "Harmful: may cause lung damage if swallowed" based on the cumene's low kinematic viscosity as well as the post-mortem examination after acute oral toxicity assay which revealed pulmonary oedema and haemorrhage (AICIS IMAP (2016), EU RAR (2001)). (4) It was reported that the kinematic viscosity was 0.73* 10-6 mm2/s at 40 deg C (EU RAR (2001)). |
| 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:
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