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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	101-90-6
Chemical Name	1,3-Bis[(2,3-epoxypropyl)oxy]benzene
Substance ID	R03-C-014-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	FY2019 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

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Explosives	-	- -	-	-	-
2	Flammable gases	-	- -	-	-	-
3	Aerosols	-	- -	-	-	-
4	Oxidizing gases	-	- -	-	-	-
5	Gases under pressure	-	- -	-	-	-
6	Flammable liquids	-	- -	-	-	-
7	Flammable solids	-	- -	-	-	-
8	Self-reactive substances and mixtures	-	- -	-	-	-
9	Pyrophoric liquids	-	- -	-	-	-
10	Pyrophoric solids	-	- -	-	-	-
11	Self-heating substances and mixtures	-	- -	-	-	-
12	Substances and mixtures which, in contact with water, emit flammable gases	-	- -	-	-	-
13	Oxidizing liquids	-	- -	-	-	-
14	Oxidizing solids	-	- -	-	-	-
15	Organic peroxides	-	- -	-	-	-
16	Corrosive to metals	-	- -	-	-	-
17	Desensitized explosives	-	- -	-	-	-

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	-	- -	-	-	-
1	Acute toxicity (Dermal)	-	- -	-	-	-
1	Acute toxicity (Inhalation: Gases)	-	- -	-	-	-
1	Acute toxicity (Inhalation: Vapours)	-	- -	-	-	-
1	Acute toxicity (Inhalation: Dusts and mists)	-	- -	-	-	-
2	Skin corrosion/irritation	-	- -	-	-	-
3	Serious eye damage/eye irritation	-	- -	-	-	-
4	Respiratory sensitization	-	- -	-	-	-
4	Skin sensitization	-	- -	-	-	-
5	Germ cell mutagenicity	-	- -	-	-	-
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).
7	Reproductive toxicity	-	- -	-	-	-
8	Specific target organ toxicity - Single exposure	-	- -	-	-	-
9	Specific target organ toxicity - Repeated exposure	-	- -	-	-	-
10	Aspiration hazard	-	- -	-	-	-

ENVIRONMENTAL HAZARDS

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:

GHS Classification Result by the Japanese Government is intended to provide a reference for preparing a GHS label or SDS for users. To include the same classification result in a label or SDS for Japan is NOT mandatory.
Users can cite or copy this classification result when preparing a GHS label or SDS. Please be aware, however, that the responsibility for a label or SDS prepared by citing or copying this classification result lies with users.
This GHS classification was conducted based on the information sources and the guidance for classification and judgement which are described in the GHS Classification Guidance for the Japanese Government etc. Using other literature, test results etc. as evidence and including different content from this classification result in a label or SDS are allowed.
Hazard statement and precautionary statement will show by hovering the mouse cursor over a code in the column of "Hazard statement" and "Precautionary statement," respectively. In the excel file, both the codes and statements are provided.
A blank or "-" in the column of "Classification" denotes that a classification for the hazard class was not conducted in the year.
An asterisk “*” in the column of “Classification” denotes that “Not classified (or No applicable)” and/or “Classification not possible” is applicable. Details are described in the column of “Rationale for the classification”. If no English translation is available for “Rationale for the classification,” please refer to the Japanese version of the results.

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