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 | 101-90-6 |
| Chemical Name | 1,3-Bis[(2,3-epoxypropyl)oxy]benzene |
| Substance ID | m-nite-101-90-6_v2 |
| 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 (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 2 | Flammable gases | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition). It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 3 | Aerosols | Not classified (Not applicable) |
- |
- | - | Not aerosol products. It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 4 | Oxidizing gases | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition). It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 5 | Gases under pressure | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition). It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 6 | Flammable liquids | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition). It was classified as "Not classified (Not applicable)." Besides, this substance has a melting point of 32-33 deg C (HSDB (Access on October 2019)). From information on a flash point of 113 deg C (closed cup) (ICSC (2005)), even if it becomes liquid at high temperatures, it would be classified as "Not classified." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 7 | Flammable solids | Classification not possible |
- |
- | - | There is information that it is combustible (GESTIS (Access on Sep. 2019)), but the classification is not possible due to no data. | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 8 | Self-reactive substances and mixtures | Classification not possible |
- |
- | - | There are chemical groups associated with self-reactive properties (epoxides) present in the molecule, but the classification is not possible due to no data. | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 9 | Pyrophoric liquids | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition). It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 10 | Pyrophoric solids | Classification not possible |
- |
- | - | No data available. | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 11 | Self-heating substances and mixtures | Classification not possible |
- |
- | - | Classification is not possible because test methods applicable to solid (melting point <= 140 deg C) substances are not available. | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 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 (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 13 | Oxidizing liquids | Not classified (Not applicable) |
- |
- | - | Solid (GHS definition). It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 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. It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 15 | Organic peroxides | Not classified (Not applicable) |
- |
- | - | Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified (Not applicable)." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 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. | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 17 | Desensitized explosives | Not classified |
- |
- | - | There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified." | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 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] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: 2,570 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.9 (Ministry of the Environment, 2011), DFGOT vol.7 (1996)), 2.57 g/kg (2,570 mg/kg) (PATTY (6th, 2012), HSDB (Access on October 2019)) (2) LD50 for rats: 2,200-3,000 mg/kg (NTP TR257 (1986)) |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 1 | Acute toxicity (Dermal) | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. Since the exposure time in (1) was unknown and the purity was low (purity 60%), it was used as reference data. [Reference Data, etc.] (1) LD50 for rabbits: 0.64 mL/kg (774.4 mg/kg) (PATTY (6th, 2012)) |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 1 | Acute toxicity (Inhalation: Gases) | Not classified (Not applicable) |
- |
- | - | [Rationale for the Classification] Solid (GHS definition). It was classified as "Not classified (Not applicable)." |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 1 | Acute toxicity (Inhalation: Vapours) | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 2 | Skin corrosion/irritation | Category 2 |
 Warning |
H315 | P302+P352 P332+P313 P362+P364 P264 P280 P321 |
[Rationale for the Classification] Based on (1)-(5), it was classified in Category 2. [Evidence Data] (1) In a skin irritation test (Draize method) with rabbits, the skin irritation score was 5 (maximum 8), indicating moderate irritation (PATTY (6th, 2012)). (2) This substance is irritating to the skin and mucous membranes (DFGOT vol.7 (1996)). (3) Contact with this substance causes severe skin irritation in humans (DFGOT vol.7 (1996)). (4) This substance is moderately to highly irritating to the skin (HSDB (Access on October 2019)). (5) This substance is highly irritating to the skin and mucous membranes (GESTIS (Access on October 2019)). [Reference Data, etc.] (6) It was classified in "Skin Irrit. 2 (H315)" in the EU-CLP classification (EU CLP classification (Access on October 2019)). |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 3 | Serious eye damage/eye irritation | Category 2 |
Warning |
H319 | P305+P351+P338 P337+P313 P264 P280 |
[Rationale for the Classification] Based on (1) and (2), it was classified in Category 2. [Evidence Data] (1) This substance is irritating to the skin and mucous membranes (DFGOT vol.7 (1996)). (2) In an eye irritation test (Draize method) with rabbits, the irritation score was 45 (maximum 110), indicating severe irritation (PATTY (6th, 2012), REACH registration dossier (Access on November 2019)). [Reference Data, etc.] (3) It was classified in "Eye Irrit. 2 (H319)" in the EU-CLP classification (EU CLP classification (Access on October 2019)). |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 4 | Respiratory sensitization | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 4 | Skin sensitization | Category 1A |
Warning |
H317 | P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501 |
[Rationale for the Classification] Based on (1)-(3), it was classified in Category 1A. [Evidence Data] (1) In a mouse local lymph node assay (LLNA) according to OECD TG 429, it was judged as positive, and the value of EC3 was estimated to be less than 2% (REACH registration dossier (Access on November 2019)). (2) In humans, contact with this substance causes severe skin irritation and some sensitization (DFGOT vol.7 (1996)). (3) This substance is sensitizing to the skin (GESTIS (Access on October 2019)). [Reference Data, etc.] (4) It was classified as "Skin Sens. 1B (H317)" in the EU-CLP classification (EU CLP classification (Access on October 2019)). |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 5 | Germ cell mutagenicity | Category 2 |
 Warning |
H341 | P308+P313 P201 P202 P280 P405 P501 |
[Rationale for the Classification] Based on (1) and (2), according to the weight of evidence, it was classified in Category 2. [Evidence Data] (1) As for in vivo, negative and positive results were reported in micronucleus tests with mice, but it was judged as positive overall based on the weight of evidence (DFGOT vol.7 (1996), IARC 71 (1999), PATTY (6th, 2012), NTP DB (Access on October 2019)). (2) As for in vitro, there were positive reports in bacterial reverse mutation tests, and a chromosome aberration test and a mouse lymphoma test with cultured mammalian cells, and a negative report in an unscheduled DNA synthesis test with cultured mammalian cells (DFGOT vol.7 (1996), IARC 71 (1999), PATTY (6th, 2012), NTP DB (Access on October 2019)). |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 6 | Carcinogenicity | Category 1B |
Danger |
H350 | P308+P313 P201 P202 P280 P405 P501 |
[Rationale for the Classification] Because of the emphasis on the latest CLP assessment in (1) and the fact that malignant tumors were observed in two species of animals in (2) to (6), it was classified in Category 1B. Also, based on the new findings, the classification result was changed. [Evidence Data] (1) As for the classification results by international organizations, the EU classified this substance in Carc.1B (EU-CLP Classification Results (Accessed Sep. 2021)). (2) In a carcinogenicity study with rats dosed by gavage (5 days/week) for two years (103 weeks) (including a supplemental study, 12.5 to 50 mg/kg/day), an increase in the incidence of benign and malignant neoplasms (squamous cell papilloma and squamous cell carcinoma) in the forestomach was observed in both males and females (CLH Report (2018), ECHA RAC Opinion (2018), IARC 71 (1999), AICIS (previous NICNAS) IMAP (2015), NTP RoC (14th, 2016), DFG MAK (1996), NTP TR257 (1986), Patty (6th, 2012), HSDB (Accessed Sep. 2021)). (3) In a carcinogenicity study with mice dosed by gavage (5 days/week) for two years (103 weeks) (50 and 100 mg/kg/day), increased incidences of benign and malignant tumors (squamous cell papilloma and squamous cell carcinoma) in the forestomach were observed in both males and females, and a significant increase in the incidence of liver tumors (hepatocellular carcinoma, hepatocellular carcinoma or adenoma (combined)) was also observed in females (CLH Report (2018), ECHA RAC Opinion (2018), IARC 71 (1999), AICIS (previous NICNAS) IMAP (2015), NTP RoC (14th, 2016), DFG MAK (1996), NTP TR257 (1986), Patty (6th, 2012), HSDB (Accessed Sep. 2021)). (4) As for the liver tumors observed in (3), considering the incidence of liver tumors in the historical control groups, the lack of a significant difference among different statistical methods, etc., it was judged that the tumor incidence was not related to the administration of this substance (CLH Report (2018), ECHA RAC Opinion (2018)). (5) The ECHA RAC analyzed the individual data of the carcinogenicity studies in the NTP and reported that, in the study with rats of (2), the first deaths in the low, middle, and high dose groups for malignant tumors (squamous cell carcinomas) in the forestomach occurred at weeks 76, 61 and 42, respectively (adjusted incidence: up to 100% (control group: 0% ), and metastatic tumors occurred at several distant sites (lymph nodes, pancreas, liver, spleen, lungs, brain) in at least 20 animals mainly in the middle dose group. Likewise, in the test with mice of (3), apart from primary tumors in the forestomach which were more frequent (adjusted incidence: up to 70%) in the low and high dose groups, metastatic tumors were observed at several distant sites (lungs, liver, lymph nodes, spleen, adrenal gland, kidney) in 24 animals (ECHA RAC Opinion (2018)). (6) Since malignant tumors of the forestomach were observed in two species, rat and mouse, and in both sexes, there is a possibility that this substance may exhibit site of contact carcinogenicity. Although humans do not have a forestomach, they do have comparable tissues to rodents in the sites such as the esophagus and the oral cavity. Due to lack of reliable data on carcinogenicity in the inhalation or dermal route, the possibility of the site-of-contact carcinogenicity in other routes cannot be ruled out (CLH Report (2018), ECHA RAC Opinion (2018)). (7) This substance belongs to the group of diglycidyl ether compounds and is an electrophilic compound carrying DNA-reactive epoxide groups. Read across to phenyl glycidyl ether (PDGE, CAS RN 122-60-1) in the same group was also considered. PDGE contains one of two glycidyl ether side chains of this substance and it was considered suitable for the read across. This substance was classified for carcinogenicity in Carc. 1B (EU CLP Classification Results (Accessed Sep. 2021)) in EU and Category 2 in Japan (GHS classification result in FY2017). (8) Also, the IARC classified it in 2B (IARC 71 (1999)), the NTP classified it in R (NTP RoC (16th, 2016)), and the Japan Society For Occupational Health (JSOH) classified it in Group 2B (Recommendation of Occupational Exposure Limits (2020): proposed in 1991). |
FY2021 | GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0)) |
| 7 | Reproductive toxicity | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 8 | Specific target organ toxicity - Single exposure | Category 3 (Respiratory tract irritation) |
Warning |
H335 | P304+P340 P403+P233 P261 P271 P312 P405 P501 |
[Rationale for the Classification] There are no reports on single exposure to this substance in humans. Based on (1) and (2), since in the case of inhalation exposure, it was considered to show respiratory tract irritation, it was classified in Category 3 (respiratory tract irritation). [Evidence Data] (1) It was described that the mist of this substance may be irritating to the eyes and respiratory tract (HSDB (Access on October 2019)). (2) There was a description that this substance showed strong irritation to the skin and eyes of rabbits (DFGOT vol.7 (1996)). [Reference Data, etc.] (3) In a single oral administration test with rats, dyspnea and central nervous system depression were observed. There is no description of the minimum dose where effects were observed. However, if they were observed at around 2,570 mg/kg, the LD50 value, this would correspond to exceeding the range of Category 2 (DFGOT vol.7 (1996)). |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 9 | Specific target organ toxicity - Repeated exposure | Classification not possible |
- |
- | - | [Rationale for the Classification] Based on (1) and (2), as a result of testing in the oral route in experimental animals, only lesions of the forestomach considered to be due to irritation were observed within the range for Category 1 and Category 2. Therefore, it was judged as "Not classified." As for other routes, classification was not possible due to lack of data. [Evidence Data] (1) In a 13-week repeated-dose toxicity test with rats dosed by gavage, lesions of the forestomach were observed. Also a reduced body weight gain was observed in males at or above 100 mg/kg/day (converted guidance value: 72 mg/kg/day, within the range of Category 2), and at 200 mg/kg/day (converted guidance value: 144 mg/kg/day, exceeding the range of Category 2), death (1/10 animals) and minimal to mild centrilobular fatty metamorphosis (only control and high-dose groups were tested) were observed in males, and a reduced body weight gain was observed in females (NTP TR257 (1986), DFGOT vol.7 (1996)). (2) In a 13-week repeated-dose toxicity test with mice dosed by gavage, lesions of the forestomach were observed. Deaths (male: 9/10, female: 7/10), focal necrosis and fatty metamorphosis in the liver (only control and high-dose groups were tested) were also observed in males and females at 400 mg/kg/day (converted guidance value: 289 mg/kg/day, exceeding the range of Category 2) (NTP TR257 (1986), DFGOT vol.7 (1996)). |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 10 | Aspiration hazard | Classification not possible |
- |
- | - | [Rationale for the Classification] Classification not possible due to lack of data. |
FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 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) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 11 | Hazardous to the aquatic environment Long term (Chronic) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | Classification not possible due to lack of data. | FY2019 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
NOTE:
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