GHS Classification Results by the Japanese Government
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 103-11-7 |
| Chemical Name | 2-ethylhexyl acrylate |
| Substance ID | R02-B-022-MHLW, MOE |
| Classification year (FY) | FY2020 |
| Ministry who conducted the classification | Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE) |
| New/Revised | Revised |
| Classification result in other fiscal year | 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. It was classified as "Not classified." |
| 2 | Flammable gases | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition). It was classified as "Not classified." |
| 3 | Aerosols | Not classified (Not applicable) |
- |
- | - | Not aerosol products. It was classified as "Not classified." |
| 4 | Oxidizing gases | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition). It was classified as "Not classified." |
| 5 | Gases under pressure | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition). It was classified as "Not classified." |
| 6 | Flammable liquids | Category 4 |
Warning |
H227 | P370+P378 P210 P280 P403 P501 |
It was classified in Category 4 based on a flash point of 86 deg C (closed cup) (HSDB (Access on April 2020)). |
| 7 | Flammable solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition). It was classified as "Not classified." |
| 8 | Self-reactive substances and mixtures | Classification not possible |
- |
- | - | There is a chemical group associated with self-reactive properties, an unsaturated bond, present in the molecule, but the classification is not possible due to no data. |
| 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 252 deg C (NFPA (14th, 2010)). |
| 10 | Pyrophoric solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition). It was classified as "Not classified." |
| 11 | Self-heating substances and mixtures | Classification not possible |
- |
- | - | Classification is not possible because 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). It was classified as "Not classified." |
| 13 | Oxidizing liquids | Not classified (Not applicable) |
- |
- | - | The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen. It was classified as "Not classified." |
| 14 | Oxidizing solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition). It was classified as "Not classified." |
| 15 | Organic peroxides | Not classified (Not applicable) |
- |
- | - | Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified." |
| 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. It was classified as "Not classified." |
| 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] It was classified as "Not classified" from (1) - (7). [Evidence Data] (1) LD50 for rats: > 2,000 mg/kg (AICIS IMAP (2014)) (2) LD50 for rats: 4,000-6,000 mg/kg (SIAP (2004)) (3) LD50 for rats: 5.0 mL/kg (4,430 mg/kg) (EURAR (2005)) (4) LD50 for rats: 4,435 mg/kg (AICIS IMAP (2014)) (5) LD50 for rats: 6.5 mL/kg (about 5,770 mg/kg) (EURAR (2005)) (6) LD50 for rats: 5,750 mg/kg (GESTIS (Access on April 2020)) (7) LD50 for rats: 6,500 microL/kg (5,739.5 mg/kg) (HSDB (Access on April 2020)) |
| 1 | Acute toxicity (Dermal) | Not classified |
- |
- | - | [Rationale for the Classification] It was classified as "Not classified" from (1) - (6). [Evidence Data] (1) LD50 for rats: > 2,000 mg/kg (AICIS IMAP (2014)) (2) LD50 for rabbits: > 2,000 mg/kg (AICIS IMAP (2014)) (3) LD50 for rabbits: > 10,000 mg/kg (SIAP (2004)) (4) LD50 for rabbits: 16 mL/kg (about 14,180 mg/kg) (EURAR (2005)) (5) LD50 for rabbits: 7,500 mg/kg (GESTIS (Access on April 2020)) (6) LD50 for rabbits: 8,480 mg/kg (HSDB (Access on April 2020)) |
| 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) | 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] Because the category could not be determined from (1), the classification is not possible. Besides, information sources used in the previous classification were not adopted as the rationale because they could not be confirmed now. Because an exposure concentration was the saturated vapor pressure concentration (1.765 mg/L), the reference value in the unit of mg/L was applied as a vapor with mist. [Evidence Data] (1) There were no dead animals at the saturated vapor pressure concentration in an inhalation test (8 hours) (EURAR (2005), AICIS IMAP (2014), SIAP (2004)). (2) Vapor pressure of this substance: 0.178 mmHg (25 deg C) (HSDB (Access on April 2020)) (converted value for the saturated vapor pressure concentration: 1.765 mg/L) [Reference Data, etc.] (3) LC50 for mice (0.5 hour): > 7.713 mg/L (HSDB (Access on April 2020)) |
| 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) - (5). [Evidence Data] (1) In a skin irritation test with rabbits (4-hour occlusive application) similar to OECD and EU test guidelines, all the animals exhibited severe erythema and edema, and the mean score at 24 and 72 hours after application for erythema and edema was 3.2/2.7, 2.7/1.2, respectively. And score 4 and superficial chemical burns were shown in 1/6 animals after 3 days after application (EURAR (2005), AICIS IMAP (2014), GESTIS (Access on April 2020)). (2) In a skin irritation test according to US Federal Register Guideline (1964) by 24-hour occlusive application of this substance to intact and abraded skin of rabbits, all the animals showed severe erythema and edema, and the mean score at 24 and 72 hours for erythema and edema for intact skin was 1.75/2 and 3.25/3.25, respectively. Besides, no necrotic effects were observed in intact or abraded skin (EURAR (2005)). (3) In an in vitro skin corrosion test using reconstituted human epidermis model (EpiDerm), viability after 3 minutes and 60 minutes of exposure was 99% and 104%, respectively, and it was judged as not corrosive (EURAR (2005), REACH registration dossier (Access on June 2020)). (4) This substance caused severe irritation near corrosion after application to the skin of animals, but eye irritation was less severe (SIAP (2004)). (5) This substance is a severe skin and eye irritant (HSDB (Access on April 2020)). |
| 3 | Serious eye damage/eye irritation | Not classified |
- |
- | - | [Rationale for the Classification] It was classified as "Not classified" from (1) - (4). The classification result was changed due to new data (1) - (4) obtained. [Evidence Data] (1) In an eye irritation test with rabbits according to OECD TG 405, the substance caused mild irritation, the mean score at 24 to 72 hours after application for corneal opacity, iris, conjunctival redness, and chemosis was 0.1, 0.1, 0.2, 0.1, respectively, and all the signs were reversible within 3 days (EURAR (2005), AICIS IMAP (2014), GESTIS (Access on April 2020)). (2) In an eye irritation test with rabbits according to US Federal Register Guideline (1964), moderate conjunctival irritation was seen, but no lesions on the cornea or iris were found (EURAR (2005)). (3) In an eye irritation test in which this substance (0.1 mL) was applied to the rabbit eye, slight or well-defined injection of the vessels of the conjunctiva and slight swelling (part of animals) were observed (EURAR (2005)). (4) In an eye irritation test with rabbits according to OECD TG 405, the mean score at 24/48/72 hours was less than 2 for the cornea and iris and less than 1 for conjunctival redness and chemosis, and all the reactions disappeared after 72 hours (REACH registration dossier (Access on June 2020)). [Reference Data, etc.] (5) This substance is a severe skin and eye irritant (HSDB (Access on April 2020)). |
| 4 | Respiratory sensitization | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
| 4 | Skin sensitization | Category 1B |
Warning |
H317 | P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501 |
[Rationale for the Classification] It was classified in Category 1B from (1) - (4). Sub-categorization was conducted because data (1) and (2) that enabled sub-categorization were obtained. [Evidence Data] (1) In a skin sensitization test with guinea pigs (maximization test, intradermal administration 1%), it was reported to be positive (positive rate: 26-57%) (MAK (DFG) vol.16 (2001)). (2) In two mouse local lymph node assays (LLNA) according to TG 429, it was judged as positive, and EC3 was reported to be 9.7% and 18.96% (AICIS IMAP (2014), REACH registration dossier (Access on June 2020)). (3) Seven volunteers who developed dermatitis to an acrylic-based adhesive and other persons were positive to this substance in patch tests (EURAR (2005), MAK (DFG) vol.16 (2001), AICIS IMAP (2014), HSDB (Access on April 2020)). (4) In skin sensitization tests with guinea pigs (an FCA test and a Polak test), it was reported to be positive (EURAR (2005), MAK (DFG) vol.16 (2001), AICIS IMAP (2014)). [Reference Data, etc.] (5) The survey in about 900 workers potentially exposed to this substance did not show any cases of sensitization or allergic contact dermatitis (EURAR (2005)). |
| 5 | Germ cell mutagenicity | Not classified |
- |
- | - | [Rationale for the Classification] It was classified as "Not classified" from (1), (2). [Evidence Data] (1) As for in vivo, in a chromosomal aberration test with mouse bone marrow cells, there was an inconclusive result due to methodological problems (EURAR (2005)). (2) As for in vitro, it is reported that it was negative in a bacterial reverse mutation test, negative in micronucleus tests with human lymphocytes or cultured mammalian cells, negative in an unscheduled DNA synthesis test with cultured mammalian cells, weakly positive in a sister chromatid exchange test, weakly positive in a mouse lymphoma test, equivocal result in a chromosomal aberration test, and negative in an HPRT gene mutation test (IARC 122 (2019), EURAR (2005)). |
| 6 | Carcinogenicity | Category 2 |
 Warning |
H351 | P308+P313 P201 P202 P280 P405 P501 |
[Rationale for the Classification] There is no information on carcinogenicity in humans. Although there is the assessment that skin tumors were due to irritative properties of this substance in carcinogenicity tests in mice as described in (4), it was classified in Category 2 based on IARC's classification result, which was the most recent, from (1), (2). [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified in Group 2B by IARC (IARC 122 (2019)), 2B by the Japan Society for Occupational Health (JSOH) (Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH)) (proposed in 2019)). (2) In carcinogenicity tests in which this substance was dermally applied to male mice (C3H/HeJ) for their lifetime, significant increases in the incidences of squamous cell papilloma of the skin, squamous cell papilloma or carcinoma (combined) of the skin, papilloma, cornified squamous cell carcinoma, malignant melanoma of the skin, and fibrosarcoma of the skin were observed at higher doses (IARC 122 (2019), EURAR (2005)). (3) In a carcinogenicity test in which this substance was dermally applied to male mice (NMRI) for 2 years, a significant increase in the incidence of skin tumors was not found either with or without a subsequent application of a known promoter (12-O-tetradecanoylphorbol-13-acetate) (IARC 122 (2019), EURAR (2005)). [Reference Data, etc.] (4) It is described in the EU Risk Assessment Report that skin tumors found in dermal mouse carcinogenicity tests were associated with the highly irritative properties of this substance, no skin tumors were observed at a low concentration with transient irritation in a dermal carcinogenicity test, and there were no tumors seen for acrylic acid and 2-ethylhexanol, the hydrolysis products of this substance, therefore, the above tests did not give sufficient evidence that this substance should be considered as a carcinogenic substance (EURAR (2005)). And it is also written in GESTIS that increased incidences of skin tumors found in dermal carcinogenicity tests with mice were attributed to irritative effects but not to a genotoxic mechanism (GESTIS (Access on April 2020)). |
| 7 | Reproductive toxicity | Classification not possible |
- |
- | - | [Rationale for the Classification] There was only data on (1), and classification was not possible due to lack of data. [Evidence Data] (1) In a developmental toxicity study by inhalation exposure of female rats on days 6 to 20 of gestation, even at a dose at which maternal toxicity (reduced body weight gain, reduced food consumption) was observed, no effect was observed in embryos/fetuses (EURAR (2005), AICIS IMAP (2014), HSDB (Access on April 2020)). |
| 8 | Specific target organ toxicity - Single exposure | Category 3 (narcotic effects, respiratory tract irritation) |
Warning |
H336 H335 |
P304+P340 P403+P233 P261 P271 P312 P405 P501 |
[Rationale for the Classification] There was no report on single exposure to this substance in humans. Based on (1) to (3), it was classified in Category 3 (narcotic effects, respiratory tract irritation). [Evidence Data] (1) In an acute oral toxicity test with rats dosed with this substance, piloerection was observed at or above 1,810 mg/kg (within the range for Category 2); staggering and abdominal position were observed at or above 2,803 mg/kg (within the range exceeding Category 2); a symptom of diarrhea was observed at 4,444 mg/kg (within the range exceeding Category 2); and apathy and narcosis were also observed at or below lethal doses (EURAR (2005), AICIS IMAP (2014), REACH registration dossier (Access on June 2020)). (2) In an acute oral toxicity test with mice dosed with this substance, symptoms of reduced locomotor activity, ataxia, and abdominal breathing were observed at 5,000 mg/kg (within the range exceeding Category 2) (EURAR (2005), REACH registration dossier (Access on June 2020)). (3) It was reported that in an acute inhalation exposure test with rats dosed with this substance, nasal and ocular irritation was exhibited with saturated vapors (concentrations were unknown) (EURAR (2005), AICIS IMAP (2014), REACH registration dossier (Access on June 2020)). |
| 9 | Specific target organ toxicity - Repeated exposure | Category 2 (nasal cavity) |
Warning |
H373 | P260 P314 P501 |
[Rationale for the Classification] There was no report on repeated exposure to this substance in humans. Based on (1), there was information that effects on the nasal cavity were observed in experimental animals at doses within the range for Category 2. Therefore, it was classified in Category 2 (nasal cavity). [Evidence Data] (1) In a 90-day inhalation exposure test with rats dosed with this substance, at or above 30 ppm (0.225 mg/L, within the range for Category 2), lethargy, eyelid ptosis, and focal or diffuse degeneration of the olfactory epithelium were observed; and at 100 ppm (0.750 mg/L, within the range for Category 2), degeneration of the olfactory mucosa in the anterior part of the nasal cavity was observed (EURAR (2005), AICIS IMAP (2014)). |
| 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) | Category 2 |
- |
H401 | P273 P501 |
It was classified in Category 2 from 48-hour EC50 = 1.3 mg/L for crustacea (Daphnia magna) (SIAP, 2004, EURAR, 2005). |
| 11 | Hazardous to the aquatic environment Long term (Chronic) | Category 2 |
 - |
H411 | P273 P391 P501 |
If chronic toxicity data are used, then it is classified in Category 3 because it was rapidly degradable (a 28-day degradation rate by BOD: 75% (EURAR, 2005)) and due to 21-day NOEC = 0.136 mg/L for crustacea (Daphnia magna) (REACH registration dossier, 2020). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 2 due to high bioaccumulation (logKow = 4.6 (EURAR, 2005)) and 96-hour LC50 = 1.8 mg/L for fish (Oncorhynchus mykiss) (SIAP, 2004, EURAR, 2005), although it was rapidly degradable (a 28-day degradation rate by BOD: 75% (EURAR, 2005)). By drawing a comparison between the above results, it was classified in Category 2. The classification result was revised from the previous classification by changing how to classify it in chronic toxicity and using new information. |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | This substance is not listed in the Annexes to the Montreal Protocol. |
NOTE:
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