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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	1024-57-3
Chemical Name	1,4,5,6,7,8,8-Heptachloro-2,3-epoxy-3a,4,7,7a-tetrahydro-4,7-methano-1H-indene; heptachlor epoxide
Substance ID	R02-B-094-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	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	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)	- -	-	-	Solid (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)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
7	Flammable solids	Classification not possible	- -	-	-	No data available.
8	Self-reactive substances and mixtures	Classification not possible	- -	-	-	There is a chemical group associated with self-reactive properties, an epoxide, present in the molecule, but the classification is not possible due to no data.
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
10	Pyrophoric solids	Classification not possible	- -	-	-	No data available.
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	No data 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)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	The substance is an organic compound containing chlorine and oxygen (but not fluorine) which are chemically bonded only to carbon or hydrogen. 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	- -	-	-	Classification is not possible because test methods applicable to solid substances are not 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."

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Category 2	Danger	H300	P301+P310 P264 P270 P321 P330 P405 P501	[Rationale for the Classification] It was classified in Category 2 from (1) - (3). [Evidence Data] (1) LD50 for rats: 15 mg/kg (Environmental Risk Assessment for Chemical Substances vol. 7, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2009), GESTIS (Access on June 2020)) (2) LD50 for rats: males: 60 mg/kg (ATSDR (2007)) (3) LD50 for rats: 62 mg/kg (ACGIH (7th, 2001))
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Gases)	Not classified	- -	-	-	[Rationale for the Classification] Solid (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] Classification not possible due to lack of data.
2	Skin corrosion/irritation	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	[Rationale for the Classification] There was a description of (1), but the classification was not possible due to lack of data. [Evidence Data] (1) This substance was not known to be an eye irritant (HSDB (Access on June 2020)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
5	Germ cell mutagenicity	Classification not possible	- -	-	-	[Rationale for the Classification] It was classified as "Classification not possible" due to lack of data from (1), (2). [Evidence Data] (1) As for in vivo, it was reported to be negative in a dominant lethal test by intraperitoneal administration to mice (JMPR (1991), ATSDR (2005)). (2) As for in vitro, it was reported to be negative in a bacterial reverse mutation test and positive (with metabolic activation) in an unscheduled DNA synthesis test with cultured mammalian cells (JMPR (1991), IARC 79 (2001), ATSDR (2005)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] It was classified in Category 2 from (1) - (3). [Evidence Data] (1) As for classification results by domestic and international organizations, ACGIH classified heptachlor (CAS RN 76-44-8) and this substance in A3 (ACGIH (7th, 2001)), and this substance was classified in B2 by EPA (IRIS (1987)) and EU Carc.2 in CLP classification (EU CLP classification (Access on May 2020)). (2) In a carcinogenicity test by 108-week diet administration of this substance to male and female rats, formations of tumors in endocrine organs and liver tumors were observed in both males and females (ACGIH (7th, 2001)). (3) In a carcinogenicity test by 2-year diet administration of this substance to male and female mice, a significant increase in the incidence of hepatic carcinoma was found in males and females (ACGIH (7th, 2001)). [Reference Data, etc.] (4) IARC classified chlordane (CAS RN 57-74-9) and heptachlor (CAS RN 76-44-8) in Group 2B (IARC 79 (2001)).
7	Reproductive toxicity	Category 1B, Additional category for effects on or via lactation	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1B, and based on (1) and (3), "effects on or via lactation" were added. New information sources were used and the classification results were changed from the previous classification. [Evidence Data] (1) In Hawaii (Oahu Island), commercial milk was contaminated with this substance for 15 months during 1981 to 1982. It was reported that, in an examination of 120 infants born in 1982 who were potentially exposed to this substance in the uteri of their mothers or via breast milk, the mean concentration of this substance (in milk fat) from 69 mothers was 123 ng/g, and a significant association was found between the concentration of this substance in breast milk and low birth weight, gestational age and jaundice. A delay in learning behaviors at 4 and 8 months after birth was also observed, but it was not observed at 18 and 36 months after birth. No effect on physical growth was reported (Environmental Risk Assessment for Chemical Substances Vol. 7, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2009)). (2) In a two-generation reproduction toxicity test with dogs dosed by feeding, no death, no changes in body weight or behaviors, etc. were observed in parents (F0, F1), while there were increases in death rates in F1 pups in a 0.001% group and F2 pups in groups at or above 0.0003%, and F2 pups in groups at or above 0.0007% had pale or greasy liver (Environmental Risk Assessment for Chemical Substances Vol. 7, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2009), CICAD 70 (2006))). (3) In female rats, the amount of heptachlor and this substance found in milk, blood, fat, and tissues was proportional to the dose of heptachlor administered (CICAD 70 (2006)). [Reference Data, etc.] (4) In a developmental toxicity study by oral administration to female rabbits on days 6 to 11 of gestation, only a decrease in fetal body weight was observed (Environmental Risk Assessment for Chemical Substances Vol. 7, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2009), EHC 38 (1984)). (5) In a three-generation reproduction study with rats fed with heptachlor (CAS RN 76-44-8), there was a slight increase in the mortality rate of two- and three-week-old pups in F1 generation in a 10 ppm dosed group. No effect on fertility was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)). (6) Female rats were dosed with heptachlor by gavage on days 6 to 15 of gestation and developmental effects were studied. As a result, 5 of 13 maternal animals treated at 12.0 mg/kg/day died, and pups showed a slight growth retardation at or above 6.8 mg/kg/day, and a marked increase in postnatal death rate at 9.0 and 12.0 mg/kg/day (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), CICAD 70 (2006)). In the Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), this study was used as a reference material because it included insufficient observation items for a developmental toxicity test. (7) Heptachlor was subcutaneously administered to female rats at 5 or 20 mg/kg every other day before mating. As a result, in rats treated with 20 mg/kg, longer mean gestational lengths and lower proportion of pups still alive by weaning time were observed (CICAD 70 (2006)). (8) In a neurotoxicity test in which after heptachlor was administered to female rats by gavage for the period from day 12 of gestation to day 7 postpartum, heptachlor was directly administered to pups by gavage until day 21 or 42 after birth, the outcomes suggested developmental delays, alterations in GABAergic neurotransmission, and neurobehavioral changes including cognitive deficits at all dosages (CICAD 70 (2006)).
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	[Rationale for the Classification] There were data for (1) and (2), but the targets of exposure were unknown and there was no description of detailed information such as administration routes and dosages. Therefore, it was judged as classification not possible due to lack of data. [Reference Data, etc.] (1) Symptoms of acute poisoning by this substance in experimental animals included hyperexcitability, tremors, convulsions, paralysis and hypothermia, and liver damage might be observed with a delay (ACGIH (7th, 2001), CICAD 70 (2006)). (2) Irrespective of the exposure route, this substance might cause pronounced effects on the central nervous system up to the initiation of cramps and coma (GESTIS (Access on June 2020)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (liver)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1), it was classified in Category 1 (liver). [Evidence Data] (1) In a two-year test with dogs dosed with this substance by feeding, an increase in ALP and increases in the incidence of swelling and vacuolation of hepatocytes in the centrilobular zone were observed at or above 0.0003% (0.075 mg/kg/day, within the range for Category 1); serum albumin and total protein levels decreased at 0.0007% (0.175 mg/kg/day, within the range for Category 1); and an increase in GPT was observed at 0.001% (0.25 mg/kg/day, within the range for Category 1) (JMPR (1991), Environmental Risk Assessment for Chemical Substances Vol. 7, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2009)). [Reference Data, etc.] (2) This substance is the primary metabolite of heptachlor (CAS RN 76-44-8) (ATSDR (2007)). (3) Heptachlor was administered to mice by feeding for 10 weeks. As a result, a decrease in body weight, hepatitis, necrosis, granuloma, and congestion in the liver were observed at 9.3 mg/kg/day; difficulty in standing or walking, and stumbling were observed at 19 mg/kg/day; and granulomas in the kidneys were observed at 37 mg/kg/day (ATSDR (2007)). (4) Heptachlor was administered to mice by drinking water for 180 days. As a result, an increase in serum ALT activity and an increase in liver weight were observed at 6.9 mg/kg/day (no histopathologic examination was conducted) (ATSDR (2007)). (5) Heptachlor was orally administered to mice for 92 days. As a result, increases in ALT, ALP, and triglyceride in the serum, liver triglyceride, and liver weight were observed at 10 mg/kg/day (no histopathologic examination was conducted) (ATSDR (2007)).
10	Aspiration hazard	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.

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)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 96-hour LC50 = 0.00003 mg/L for crustacea (Penaeus duorarum) (CICAD 70, 2006).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	Reliable chronic toxicity data were not obtained. It was classified in Category 1 because it was not rapidly degradable (not readily degradable, a 28-day degradation rate by BOD, OECD TG301C: 0% (CICAD 70, 2006)), and it was classified in Category 1 in acute toxicity.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in the Annexes to the Montreal Protocol.

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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