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 | 100-42-5 |
| Chemical Name | Styrene monomer |
| Substance ID | m-nite-100-42-5_v3 |
| 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) | MHLW Website (in Japanese Only) |
| Sample SDS by MHLW (External link) | MHLW Website (in Japanese Only) |
| 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. It was classified as "Not classified." | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 2 | Flammable gases | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition). It was classified as "Not classified." | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 3 | Aerosols | Not classified (Not applicable) |
- |
- | - | Not aerosol products. It was classified as "Not classified." | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 4 | Oxidizing gases | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition). It was classified as "Not classified." | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 5 | Gases under pressure | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition). It was classified as "Not classified." | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 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) (HSDB (Access on August 2020)). Besides, a stabilized one is classified in Class 3, PG III in UNRTDG (UN2055). | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 7 | Flammable solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition). It was classified as "Not classified." | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 8 | Self-reactive substances and mixtures | Type G |
- |
- | - | There is a chemical group associated with self-reactive properties, an unsaturated bond, present in the molecule, but because a stabilized one is classified in Class 3, PG III in UNRTDG (UN2055), this substance was considered to be not applicable to self-reactive substances and mixtures, hazards of the highest precedence, and it was classified in Type G. | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 9 | Pyrophoric liquids | Not classified |
- |
- | - | It was classified as "Not classified" because it is estimated that it does not ignite at normal temperatures from an autoignition temperature of 490 deg C (HSDB (Access on August 2020)). | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 10 | Pyrophoric solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition). It was classified as "Not classified." | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 11 | Self-heating substances and mixtures | Classification not possible |
- |
- | - | Classification is not possible because test methods applicable to liquid substances are not available. | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 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). It was classified as "Not classified." | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 13 | Oxidizing liquids | Not classified (Not applicable) |
- |
- | - | Organic compounds containing no oxygen, fluorine or chlorine. It was classified as "Not classified." | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 14 | Oxidizing solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition). It was classified as "Not classified." | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 15 | Organic peroxides | Not classified (Not applicable) |
- |
- | - | Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified." | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 16 | Corrosive to metals | Classification not possible |
- |
- | - | No data available. | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 17 | Desensitized explosives | Not classified (Not applicable) |
- |
- | - | There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified." | FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 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 | |
|---|---|---|---|---|---|---|---|---|
| 1 | Acute toxicity (Oral) | Not classified |
- |
- | - | [Rationale for the Classification] It was classified as "Not classified" from (1) - (4). [Evidence Data] (1) LD50 for rats: 2,650 mg/kg (Environmental Risk Assessment for Chemical Substances vol. 13 (Ministry of the Environment, 2015), GESTIS (Access on August 2020)) (2) LD50 for rats: 2,650-5,000 mg/kg (NTP CERHR (2006)) (3) LD50 for rats: 5,000 mg/kg (ACGIH (7th, 2020), JECFA FAS 19 (1984), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances vol. 13 (Ministry of the Environment, 2015), ATSDR (2010), EHC 26 (1983), IPCS PIM 509 (1996), US AEGL (2008), HSDB (Access on August 2020), Patty (6th, 2012)) (4) LD50 for rats: 5,500 mg/kg (JECFA FAS 19 (1984)) |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 1 | Acute toxicity (Dermal) | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 1 | Acute toxicity (Inhalation: Gases) | Not classified |
- |
- | - | [Rationale for the Classification] Liquid (GHS definition). It was classified as "Not classified." |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 1 | Acute toxicity (Inhalation: Vapours) | Category 4 |
 Warning |
H332 | P304+P340 P261 P271 P312 |
[Rationale for the Classification] It was classified in Category 4 from (1) - (8). Besides, because exposure concentrations were lower than 90% of the saturated vapor pressure concentration (8,422 ppm), a reference value in the unit of ppm was applied as a vapor with little mist. [Evidence Data] (1) LC50 for rats (4 hours): 2,700 ppm (US AEGL (2008)) (2) LC50 for rats (4 hours): 2,761 ppm (US AEGL (2008)) (3) LC50 for rats (4 hours): 2,770 ppm (ACGIH (7th, 2020), Environmental Risk Assessment for Chemical Substances vol. 13 (Ministry of the Environment, 2015), OEL Documentations (Japan Society For Occupational Health (JSOH), 1999), NTP CERHR (2006)) (4) LC50 for rats (4 hours): 2,800 ppm (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)) (5) LC50 for rats (4 hours): 12 mg/L (2,817 ppm) (GESTIS (Access on August 2020)) (6) LC50 for rats (4 hours): 6,000 ppm (Patty (6th, 2012)) (7) LC50 for rats (4 hours): females: 6,310 ppm, males: 6,480 ppm (US AEGL (2008)) (8) LC50 for rats (4 hours): 6,410 ppm (US AEGL (2008)) (9) Vapor pressure of this substance: 6.40 mmHg (25 deg C) (HSDB (Access on August 2020)) (converted value for the saturated vapor pressure concentration: 8,422 ppm) |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 2 | Skin corrosion/irritation | Category 2 |
Warning |
H315 | P302+P352 P332+P313 P362+P364 P264 P280 P321 |
[Rationale for the Classification] It was classified in Category 2 from (1) - (3). [Evidence Data] (1) Exposure to this substance resulted in irritation of the eyes and skin in humans (JECFA FAS 19 (1984)). (2) This substance irritated the eye, skin, and respiratory tract, and erythema and pain occurred after an entry into the eye or contact with the skin (Environmental Risk Assessment for Chemical Substances vol. 13 (Ministry of the Environment, 2015), HSDB (Access on August 2020)). (3) Marked irritation with denaturation of the skin was noted when this substance was applied to the skin of rabbits for 4 weeks (20,000 mg/kg) (ATSDR (2010)). |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 3 | Serious eye damage/eye irritation | Category 2A |
Warning |
H319 | P305+P351+P338 P337+P313 P264 P280 |
[Rationale for the Classification] It was classified in Category 2A from (1) - (6). [Evidence Data] (1) Due to exposure to this substance, 35 workers reported acute eye irritation, and tearing and blurred vision were also reported (CLH Report (2011)). (2) Exposure to this substance resulted in irritation of the eyes and skin in humans (JECFA FAS 19 (1984)). (3) This substance irritated the eye, throat, and nose, and as ocular effects, mucous membrane irritation and conjunctivitis were seen (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)). (4) This substance irritated the eye, skin, and respiratory tract, and erythema and pain occurred after an entry into the eye or contact with the skin (Environmental Risk Assessment for Chemical Substances vol. 13 (Ministry of the Environment, 2015)). (5) Moderate conjunctival irritation and transient corneal injury were observed in rabbits, and the signs persisted by 7 days after application (ATSDR (2010), HSDB (Access on August 2020)). (6) It was confirmed in many studies in human volunteers that the gas of this substance was irritating to the eye and respiratory tract (US AEGL (2008)). In an eye irritation test with 4 rabbits, there was no individual animal that had the mean score of 1 or above for the cornea or iris or the mean score of 2 or above for conjunctival redness or edema, but conjunctival redness persisted for 7 days in 1/4 animals (ECETOC TR48 (2) (1998)). |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 4 | Respiratory sensitization | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 4 | Skin sensitization | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 5 | Germ cell mutagenicity | Category 2 |
 Warning |
H341 | P308+P313 P201 P202 P280 P405 P501 |
[Rationale for the Classification] It was classified in Category 2 from (1), (2). [Evidence Data] (1) As for in vivo, it was reported to be positive and negative in micronucleus tests with mouse bone marrow cells, negative in micronucleus tests with bone marrow cells and peripheral blood lymphocytes of rats, negative in a micronucleus test with bone marrow cells of Chinese hamsters, negative in a chromosomal aberration test with mouse bone marrow cells, positive and negative in chromosomal aberration tests with rat bone marrow cells, negative in a chromosomal aberration test with bone marrow cells of Chinese hamsters, positive in sister chromatid exchange tests with mouse bone marrow cells and rat peripheral blood lymphocytes, positive in comet assays in mice (peripheral blood lymphocytes, liver, kidney, bone marrow), negative in a comet assay in rats (peripheral blood lymphocytes), and negative in an unscheduled DNA synthesis test with mouse liver (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances vol. 13 (Ministry of the Environment, 2015), ATSDR (2010), IARC 121 (2019), IARC 60 (1994), IARC 82 (2002)). (2) As for in vitro, there are positive and negative reports in all tests of bacterial reverse mutation tests, gene mutation tests, micronucleus tests, chromosomal aberration tests and sister chromatid exchange tests using cultured mammalian cells (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances vol. 13 (Ministry of the Environment, 2015), IARC 121 (2019), IARC 60 (1994), IARC 82 (2002), ATSDR (2010)). |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 6 | Carcinogenicity | Category 1B |
Danger |
H350 | P308+P313 P201 P202 P280 P405 P501 |
[Rationale for the Classification] From (1) - (9), it was classified in Category 1B based on the latest classification by IARC. The classification result was changed by using new information sources. [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified in Group 2A by IARC (IARC 121 (2019)), Group 2B by the Japan Society for Occupational Health (JSOH) (Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH)) (proposed in 1999)), A3 by ACGIH (ACGIH (7th, 2020)), R by NTP (NTP RoC (14th, 2016)), and Category 5 in MAK (DFG) (MAK (DFG) (2003)). (2) There were many studies on carcinogenicity in humans, and increases in risks of leukemia and lymphoma due to styrene exposure were found, especially increases in risks of acute myeloid leukemia (AML) and T-cell lymphoma were seen. However, results that showed increased risks generally had a small excess, and some had low precision. Overall, the epidemiological studies provided some credible evidence that exposure to styrene caused lymphohematopoietic malignancies in humans, but confounding, bias, or chance could not be ruled out. Therefore, IARC concluded that there was limited evidence in humans for the carcinogenicity of exposure to styrene (IARC 121 (2019)). (3) In a carcinogenicity test by 78-week gavage administration of this substance to male and female mice, a significant increase in the incidence of bronchioalveolar adenoma or carcinoma (combined) of the lung in males and a significant positive trend in the incidence of hepatocellular adenoma in females were observed (IARC 121 (2019)). (4) In two carcinogenicity tests in which mice were given gavage administration of this substance from day 17 of gestation, and male and female pups were given gavage administration of this substance for 120 weeks from week 16 after weaning, in one test, a significant increase in the incidence of lung carcinoma in female pups and a significant increase in the incidence of lung adenoma or carcinoma (combined) in male and female pups were found. No carcinogenicity was seen in the other test (IARC 121 (2019)). (5) In a carcinogenicity test by inhalation exposure of male and female mice to this substance for 98-104 weeks, significant increases in the incidences of bronchioalveolar adenoma and bronchioalveolar adenoma or carcinoma (combined) in males and females and a significant increase in the incidence of bronchioalveolar carcinoma in females were observed (IARC 121 (2019)). Furthermore, in a carcinogenicity test by 104-week inhalation exposure of male mice to this substance, a significant increase in the incidence of bronchioalveolar carcinoma was found (IARC 121 (2019)). (6) No carcinogenicity was seen in three carcinogenicity tests by 104-week inhalation exposure to this substance in male mice (genetically modified mice in 2 of the tests) and a carcinogenicity test by intraperitoneal administration of this substance to female mice (IARC 121 (2019)). (7) In two carcinogenicity tests by 52-week or 104-week inhalation exposure to this substance in male and female rats, in a 52-week exposure test, significant increases in the incidences of malignant tumors and benign or malignant tumors (combined) of the mammary gland were observed in females. While, in a 104-week exposure test, a significant decrease in the incidence of mammary gland adenocarcinoma was found in females (IARC 121 (2019)). (8) There was no significant increase in the tumor incidence in multiple carcinogenicity tests by administration of this substance to male and female rats (three by gavage administration, one by drinking water administration, one by intraperitoneal administration, one by subcutaneous administration, one by gavage administration of this substance to pregnant rats and later, male and female pups) (IARC 121 (2019)). (9) IARC described that as mechanistic information that supported the classification of this substance in Group 2A, there was strong evidence that this substance had the following characteristics as shown in (A) - (D). (A) It is metabolically activated in animals and humans to an electrophile, styrene-7,8-oxide, (B) It is genotoxic, and this mechanism can also operate in humans, (C) It alters cell proliferation, (D) It modulates receptor-mediated effects, and these effects occur in humans (IARC 121 (2019)). |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 7 | Reproductive toxicity | Category 1B |
Danger |
H360 | P308+P313 P201 P202 P280 P405 P501 |
[Rationale for the Classification] Based on (1) to (6), it was classified in Category 1B because there was insufficient evidence of effects in humans, and although no effects on fertility were observed in experimental animals, neurobehavioral effects and effects such as malformations in pups were observed. [Evidence Data] (1) It was reported that the rate of spontaneous abortions increased in female workers who had worked at styrene and viscose rayon manufacturing factories, but there was also a report from a subsequent study that no increase in spontaneous abortions was observed (IARC 82 (2002), OEL Documentations (Reproductive toxicant classification) (Japan Society for Occupational Health (JSOH), 2015), ATSDR (2010)). (2) It was reported that, in a group of women occupationally exposed to styrene, menstrual disturbance, secondary amenorrhea, low birth weight of infants (4%, not statistically significant), etc. were observed, but it turned out that the women workers were exposed to not only styrene but also many solvents at the same time (IARC 82 (2002), OEL Documentations (Reproductive toxicant classification) (Japan Society for Occupational Health (JSOH), 2015), ATSDR (2010)). (3) In two-generation reproduction toxicity and developmental neurotoxicity tests by inhalation exposure in rats, it was concluded that no effect on fertility or no next-generation developmental neurotoxicity was observed (However, there were significant decreases in body weight and brain longitudinal diameter in F2 generation, as well as a significant shortening of the estrus cycle in F0 females) (OEL Documentations (Reproductive toxicant classification) (Japan Society for Occupational Health (JSOH), 2015)), Environmental Risk Assessment for Chemical Substances Vol. 13 (Ministry of the Environment, 2015)). (4) It was reported that, in a developmental toxicity study by inhalation exposure in female rats on days 7 to 21 of gestation, low birth weight was observed, and additionally, neurobehavioral effects in pups (growth retardation, such as delays in opening of the eyes, eruption of teeth, auditory reflex, startle reflex, and righting reflex, and a delay in development of the nervous function and balance function) were observed, and it was found that these behavioral toxicity effects were associated with the concentration difference of neurotransmitters, such as 5-hydroxytryptamine (5-HT) in the brain (OEL Documentations (Reproductive toxicant classification) (Japan Society for Occupational Health (JSOH), 2015)). (5) In a developmental toxicity study by inhalation exposure in female mice on days 6 to 16 of gestation, fetal resorption, malformation, and fetal death were observed at 250 ppm (OEL Documentations (Reproductive toxicant classification) (Japan Society for Occupational Health (JSOH), 2015)). (6) The OEL Documentations (2015) states, "In humans, with respect to the relationship between increased risk of infertility or abnormal gestation and delivery and exposure to this substance, no data corresponding to exposure concentration has been obtained. In addition, since there are many confounding factors for these reproductive effects, there is insufficient evidence for the effects in humans, but many animal experiments have shown effects of this substance on the next generation, and therefore, this substance is classified in Group 2 of reproductive toxicity" (OEL Documentations (Reproductive toxicant classification) (Japan Society for Occupational Health (JSOH), 2015)). [Reference Data, etc.] (7) In the EU CLP classification, it was classified as Repr.2 (Classification in EU CLP (Access on October 2020)). |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 8 | Specific target organ toxicity - Single exposure | Category 1 (central nervous system), Category 3 (respiratory tract irritation, narcotic effects) |
Danger Warning |
H370 H335 H336 |
P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312 |
[Rationale for the Classification] Based on (1) to (10), it was classified in Category 1 (central nervous system), and Category 3 (respiratory tract irritation, narcotic effects). Effects on the liver were reported only in one case with mice and not observed in other animal species including humans even in exposure to higher doses. In addition, the details were unknown and the data was considered to be less reliable. Therefore, it was not adopted. [Evidence Data] (1) In volunteers inhaling 350 ppm of this substance for 30 minutes, 380 ppm for one hour, 50 ppm for 1.5 hours, and 150 ppm for one hour, an increase in simple reaction time and a decrease in coordinated movements were observed (ACGIH (7th, 2020)). (2) In an acute exposure in humans, cerebral atrophy, cerebellar nerve abnormalities, neuritis, and abnormal reflexes were observed (ACGIH (7th, 2020)). (3) This substance irritates the eyes, skin, and respiratory tract. When its liquid is ingested, it may be drawn in the lungs, causing chemical pneumonia. It may affect the central nerve. When it is inhaled, dizziness, lethargy, headache, nausea, vomiting, lassitude, and unconsciousness occur. When it is orally ingested, nausea and vomiting occur (Environmental Risk Assessment for Chemical Substances Vol. 13 (Ministry of the Environment, 2015)). (4) In two male volunteers exposed to 800 ppm of this substance for 4 hours, irritation of the eyes and throat and increased nasal secretion were observed immediately after the exposure, and prominent and sustained metal taste, lower energy, drowsiness, and imbalance occurred. After the exposure, mild muscle weakness, uneasiness, lethargy, and depression were observed (Environmental Risk Assessment for Chemical Substances Vol. 13 (Ministry of the Environment, 2015), ATSDR (2010)). (5) This substance caused central nervous system disorders, such as dizziness, headache, insomnia, lassitude, confusion, impaired concentration, dysequilibrium, nystagmus, language learning disability, and logical memory disorder. Visual and hearing impairment, irritation of the eyes, throat, and nose, and nasal discharge were also observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)). (6) In 3 of 6 volunteers who were exposed to 100 mL/m3 of this substance by inhalation for 7 hours, irritation of the eyes and throat was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)). (7) In humans who were exposed to 376 ppm of this substance, irritation of the eyes and nose was observed (IPCS PIM 509 (1996)). (8) Subjective symptoms such as headache, dizziness, and vomiting, skin disorder, disorder of the anterior part of the eye, visual disturbance, and respiratory tract damage or peripheral neuropathy caused by this substance were specified as occupational diseases listed in Appended Table 1-2, Ordinance for Enforcement of the Labor Standards Act (Ministry of Labour Notification No. 33, 1996). (9) In an inhalation toxicity test (exposure concentration unknown) with rats and guinea pigs, the animals that inhaled 10,000 ppm became comatose within several minutes and died after 30 to 60 minutes of exposure (ACGIH (7th, 2020)). (10) In a 4-hour inhalation toxicity test with rats, at or above 2,983 ppm, irritation of the eyes and respiratory tract and such symptoms as closed eyes, eye and nasal secretion, salivation, and dyspnea were observed. Signs of central nervous system impairment were staggered or stalking gait, tremors, lying on the side and narcosis (US AEGL (2008)). [Reference Data, etc.] (11) In a 6-hour inhalation toxicity test with mice, severe centrilobular hepatic coagulative necrosis occurred at 500 ppm (converted 4-hour equivalent value: 612 ppm, within the range for Category 1) (ACGIH (7th, 2020)). |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 9 | Specific target organ toxicity - Repeated exposure | Category 1 (central nervous system, peripheral nervous system, auditory organ, visual organs, respiratory organs, liver) |
Danger |
H372 | P260 P264 P270 P314 P501 |
[Rationale for the Classification] Based on (1) to (3), it was reported that effects on the nervous system, hearing, color vision, and liver were observed in humans. Based on (4) to (8), it was reported that effects on the respiratory organs at doses within the range for Category 1, and on the hearing and liver at doses within the range for Category 2 were observed in experimental animals. Therefore, it was classified in Category 1 (central nervous system, peripheral nervous system, sensory organ (visual organs, auditory organ), respiratory organs, liver). The blood system, which had been identified as a target organ in the previous classification, was excluded from the target organs because the latest assessment report (ACGIH (7th, 2020)) did not contain any information that confirmed the rationale, and the classification result was changed from the previous classification. [Evidence Data] (1) A long-term exposure to styrene causes significant effects especially on the skin, mucosa, central and peripheral nervous systems, and liver. It was reported that major effects in humans who were occupationally exposed to styrene included color-vision impairment, peripheral and autonomic nervous systems disorders, neurobehavioral effects, abnormal brain wave, and short-term memory disorder (OEL Documentations (Japan Society for Occupational Health (JSOH), 2007). (2) It was suggested that there was a concern for potential liver damage in exposure to styrene. Exposure to 50 ppm or less of styrene was associated with a slow increase in transaminase concentration in the liver and a decrease in clearance of conjugated bilirubin in the liver. It was considered that these changes were also associated with mild cholestasis. These findings indicated that exposure to low-concentration styrene was associated with subclinical damages (OEL Documentations (Japan Society for Occupational Health (JSOH), 2007). (3) There were multiple reports of effects on the central nervous system, including color-vision deficiency and hearing impairment in the high-frequency, observed in humans (ACGIH (7th, 2020), Environmental Risk Assessment for Chemical Substances Vol. 13 (Ministry of the Environment, 2015)). (4) In a 4-week (12 hours/day, 5 days/week) inhalation toxicity test with rats, an increase in the threshold of hearing ability and a severe absence of outer hair cells in the organ of Corti of the inner ear were observed at 600 ppm (2.6 mg/L (converted guidance value: 0.6 mg/L, within the range for Category 2)) (Environmental Risk Assessment for Chemical Substances Vol. 13 (Ministry of the Environment, 2015)). (5) In an 8-week (4 hours/day, 7 days/week) inhalation toxicity test with rats, a slight increase in secretion and an increase in electron-dense matters in the nasal mucosa were observed at or above 30 ppm (0.13 mg/L (converted guidance value: 0.05 mg/L, within the range for Category 1)); and vacuolation, pyknosis, and desquamation of epithelial cells in the nasal cavity and trachea were observed at 800 ppm (3.4 mg/L (converted guidance value: 1.4 mg/L, exceeding Category 2)) (Environmental Risk Assessment for Chemical Substances Vol. 13 (Ministry of the Environment, 2015)). (6) In a 13-week (6 hours/day, 5 days/week) inhalation toxicity test with mice, at or above 50 ppm (0.2 mg/L (converted guidance value: 0.1 mg/L, within the range for Category 1)), decreased eosinophilia of bronchiolar epithelial cells, atrophy of olfactory epithelia, intraepithelial cyst, atrophy of olfactory nerve fibers, dilatation, hypertrophy or hyperplasia of Bowman's glands, and acidophilic inclusion of the respiratory and transitional epithelia were observed in males and females; at or above 100 ppm (0.4 mg/L (converted guidance value: 0.3 mg/L, within the range for Category 2)), focal dense-growing of non-ciliated cells in the bronchiole, metaplasia of the respiratory epithelium in the olfactory epithelium, infiltration of inflammatory cells of Bowman's gland lumen, etc. were observed in males and females, and localized hyperplasia of epithelium in the bronchiole was observed in females; at or above 150 ppm (0.6 mg/L (converted guidance value: 0.4 mg/L, within the range for Category 2)), centrilobular aggregation of iron phagocytes with inflammation and fibrosis in the liver was observed in females; and at 200 ppm (0.9 mg/L (converted guidance value: 0.7 mg/L, within the range for Category 2)), focal absence of hepatocytes with iron phagocytes was observed in males and females, centrilobular aggregation of iron phagocytes with inflammation and fibrosis in the liver was observed in males, and lower body temperature, lethargy and a decrease in respiration rate were observed in females in the first week, and two mice died. In the mice that died, centrilobular hepatocellular necrosis, and congestion of the sinusoidal capillary vessels were observed (Environmental Risk Assessment for Chemical Substances Vol. 13 (Ministry of the Environment, 2015)). (7) In a 104-week inhalation toxicity test with rats, at or above 50 ppm (0.2 mg/L, within the range for Category 1), atrophy or degenerative changes of the nasal mucosal epithelia and manifestation of Bowman's glands were observed in males and females, and atrophy or dilatation, hypertrophy and hyperplasia of Bowman's glands, etc. were observed in males; and at or above 200 ppm (0.9 mg/L, within the range for Category 2), atrophy or dilatation, hypertrophy and hyperplasia of Bowman's glands, etc. were observed in females (ACGIH (7th, 2020), Environmental Risk Assessment for Chemical Substances Vol. 13 (Ministry of the Environment, 2015)). (8) In a test by inhalation exposure of male mice for 104 weeks and female mice for 98 weeks, at or above 20 ppm (0.09 mg/L, within the range for Category 1), respiratory epithelial metaplasia, dilatation, epithelial hyperplasia, eosinophilic material and cholesterol crystals in the olfactory epithelium and Bowman's glands beneath it of the nasal cavity, bronchial epithelial hyperplasia in the lungs, decreased eosinophilia of Clara cells in the terminal bronchioles, bronchial epithelial hyperplasia extending into the alveolar ducts, and bronchiolar/alveolar hyperplasia were observed in males and females; and at or above 40 ppm (0.17 mg/L, within the range for Category 1), atrophy of olfactory nerve fibers was observed in males and females (ACGIH (7th, 2020), Environmental Risk Assessment for Chemical Substances Vol. 13 (Ministry of the Environment, 2015)). [Reference Data, etc.] (9) Subjective symptoms such as headache, dizziness, and vomiting, skin disorder, disorder of the anterior part of the eye, visual disturbance, respiratory tract damage or peripheral neuropathy caused by styrene were specified as occupational diseases listed in Appended Table 1-2, Ordinance for Enforcement of the Labor Standards Act (Ministry of Labour Notification No. 33, 1996). |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 10 | Aspiration hazard | Category 1 |
Danger |
H304 | P301+P310 P331 P405 P501 |
[Rationale for the Classification] It was classified in Category 1 from (1) - (3). [Evidence Data] (1) It is a hydrocarbon. (2) When this substance is ingested, it may be aspirated into the lung to cause chemical pneumonia (Environmental Risk Assessment for Chemical Substances vol. 13 (Ministry of the Environment, 2015)). (2) From the kinematic viscosity of 0.772 mm2/s at 25 deg C (calculated from viscosity at 25 deg C: 0.696 mPa*s (HSDB (Access on August 2020)) and density of 0.9016 g/cm3 (HSDB (Access on August 2020))), the kinematic viscosity at 40 deg C was 14 mm2/s or less. |
FY2020 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 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 |
In preparation. Check the Japanese version. | FY2023 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.1)) |
| 11 | Hazardous to the aquatic environment Long term (Chronic) | Category 3 |
- |
H412 | P273 P501 |
In preparation. Check the Japanese version. | FY2023 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.1)) |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | In preparation. Check the Japanese version. | FY2023 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.1)) |
NOTE:
|