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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	57-74-9
Chemical Name	1,2,4,5,6,7,8,8-Octachloro-2,3,3a,4,7,7a-hexahydro-4,7-methano-1H-indene; Chlordane
Substance ID	R02-B-033-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 FY2009
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	Not classified	- -	-	-	It was classified as "Not classified" from information that it is not combustible (GESTIS (Access on May 2020)). However, industrial products may be solutions in organic solvents, which may be combustible.
8	Self-reactive substances and mixtures	Not classified (Not applicable)	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties. It was classified as "Not classified."
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
10	Pyrophoric solids	Not classified	- -	-	-	It was classified as "Not classified" from information that it is not combustible (GESTIS (Access on May 2020)).
11	Self-heating substances and mixtures	Not classified	- -	-	-	It was classified as "Not classified" from information that it is not combustible (GESTIS (Access on May 2020)).
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 (but not fluorine or oxygen) which is 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 4	Warning	H302	P301+P312 P264 P270 P330 P501	[Rationale for the Classification] It was classified in Category 4 from (1) - (8). [Evidence Data] (1) LD50 for rats: 137 mg/kg (ATSDR (2018)) (2) LD50 for rats: 283 mg/kg (EHC 34 (1984), ATSDR (2018)) (3) LD50 for rats: males: 335 mg/kg, females: 430 mg/kg (IARC 79 (2001)) (4) LD50 for rats: 350 mg/kg (EHC 34 (1984)) (5) LD50 for rats: 371 mg/kg (JMPR (1970)) (6) LD50 for rats: 420 mg/kg (ATSDR (2018)) (7) LD50 for rats: 457 mg/kg (ATSDR (2018)) (8) LD50 for rats: 590 mg/kg (ACGIH (7th, 2019))
1	Acute toxicity (Dermal)	Category 3	Danger	H311	P302+P352 P361+P364 P280 P312 P321 P405 P501	[Rationale for the Classification] It was classified in Category 3 from (1) - (3). [Evidence Data] (1) LD50 for rats: males: 205 mg/kg, females: 530 mg/kg (EHC 34 (1984)) (2) LD50 for rats: 590-840 mg/kg (ACGIH (7th, 2019)) (3) LD50 for rats: males: 840 mg/kg, females: 530-690 mg/kg (ATSDR (2018)) [Reference Data, etc.] (4) LD50 for rabbits: 1,100-1,200 mg/kg (EHC 34 (1984), ATSDR (2018))
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	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), (2). [Evidence Data] (1) It was extremely irritating to rabbits' eyes but produced only mild irritant to their skin (IPCS PIM 574 (2000)). (2) This substance of technical grade was irritating to the skin and eye (HSDB (Access on May 2020)). [Reference Data, etc.] (3) Early use of this substance resulted in irritation of the eyes, mucous membranes, and skin of industrial and agricultural workers, but this did not appear to be a problem with the product manufactured since 1951 (HSDB (Access on May 2020)).
3	Serious eye damage/eye irritation	Category 2	Warning	H319	P305+P351+P338 P337+P313 P264 P280	[Rationale for the Classification] It was classified in Category 2 from (1), (2). [Evidence Data] (1) It was extremely irritating to rabbits' eyes but produced only mild irritant to their skin (IPCS PIM 574 (2000)). (2) This substance of technical grade was irritating to the skin and eye (HSDB (Access on May 2020)). [Reference Data, etc.] (3) Early use of this substance resulted in irritation of the eyes, mucous membranes, and skin of industrial and agricultural workers, but this did not appear to be a problem with the product manufactured since 1951 (HSDB (Access on May 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	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 is reported that it was negative in multiple dominant lethal tests by oral administration to mice (ATSDR (2018), EHC 34 (1984)), positive in a chromosomal aberration test with bone marrow cells after oral administration to mice, weakly positive in a micronucleus test with bone marrow cells after dermal administration to mice, positive in a DNA damage test with hepatocytes after oral administration to rats, and negative in a DNA adduct formation test with hepatocytes after oral administration to mice (ATSDR (2018), IARC 79 (2001)). (2) As for in vitro, it is reported that it was negative in a bacterial reverse mutation test and positive in a sister chromatid exchange test in human lymphocytes, and in test systems in cultured human or mammalian cells, gene mutation tests gave positive and negative results (ATSDR (2018), IARC 79 (2001)), and unscheduled DNA synthesis tests gave positive and negative results (ATSDR (2018)).
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, IARC classified this substance, including its technical grade, in Group 2B (IARC 79 (2001)), and this substance was classified in Group 2B by the Japan Society for Occupational Health (JSOH) (Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH), proposed in 2001)), A3 by ACGIH (ACGIH (7th, 2019)), Carc.2 in EU CLP (EU CLP classification (Access on April 2020)), and 3B in MAK (DFG) (DFG List of MAK and BAT Values 2019). (2) In carcinogenicity tests by 80-week diet administration of this substance (analytical-grade chlordane) to male and female rats and mice, a significant increase in the incidence of hepatocellular carcinoma was observed in male and female mice. In rats, slight increases in malignant fibrous histiocytoma in males and thyroid follicle cell neoplasms in females were seen (IARC 79 (2001)). (3) In many epidemiological reports in humans, no results showed a significant association between incidences of cancers, including lung cancer, and exposure (IARC79 (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), fatal effects on the next generation via milk were suggested. However, since the effects of prenatal exposure could not be denied, it was classified in Category 1B and an additional category (effects on or via lactation). The data was reviewed and the classification result was changed from the previous classification. [Evidence Data] (1) In a test with rats dosed by feeding from the time of weaning of parents to lactation, a decrease in the number of mated females that delivered litters and a decrease in the number of live pups (no offspring survived to weaning) were observed (ATSDR (2018)). (2) In a test with pregnant mice dosed by feeding, offspring died within the first week of the lactation period. It was possible that exposure to high levels of this substance and/or metabolites via the dam's milk may have been responsible for these deaths (ATSDR (2018)).
8	Specific target organ toxicity - Single exposure	Category 1 (nervous system)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] It was not clear whether the accident cases of humans in (1) and (2) were caused by this substance or industrial chlordane. However, it was considered that there was no difference in the nature of toxicity that caused neurological symptoms, and therefore, it was classified in Category 1 (nervous system). [Evidence Data] (1) The fatal dose of chlordane in humans was estimated to be around 6 g, and convulsive symptoms occurred with as little as 2.25 g. Topical skin application of about 30 g to an adult resulted in death in 40 minutes (ACGIH (7th, 2019)). (2) There were many reports of neurological symptoms such as convulsions, vomiting, ataxia, and confusion in humans after a single exposure (IARC 79 (2001), EHC 34 (1984), IPCS PIM 574 (2000)). [Reference Data, etc.] (3) Chlordane produced before 1950 contained a considerable amount of hexachlorocyclopentadiene (EHC 34 (1984)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system, blood system, liver)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) to (3), (6) and (7), effects on the nervous system were observed, based on (4), effects on the blood system were observed, and based on (5), effects on the liver were observed, and therefore, it was classified in Category 1 (nervous system, blood system, liver). It was not known whether the data of humans were based on this substance or industrial chlordane, but since it was considered that there was no significant difference in essential toxicity, they were used for the classification. [Evidence Data] (1) In an accident in which a municipal water system in Tennessee in the United States was contaminated with this substance, 71 out of 105 residents in affected houses reported contact with contaminated water, and 13 (18%) complained of mild gastrointestinal and neurological symptoms (IARC 79 (2001)). (2) It was reported that, in workers employed in the manufacturing of chlordane for 3 months or more in 1946 to 1985, 20 deaths from cerebrovascular disease were observed for 11.7 expected deaths (IARC 79 (2001)). (3) It was reported that the most significant changes observed in neurophysiological and neuropsychological tests for 216 occupants of an apartment complex, of which exterior had been sprayed with chlordane 7 years before, were slowing of reaction times, balance dysfunction, reductions in cognitive function, impaired memory, etc. (IRIS (1997)). (4) Case reports of blood dyscrasias in 25 persons associated with exposure to chlordane or heptachlor included aplastic anemia, thrombocytopenia purpura, leukemia, pernicious anemia, and megaloblastic anemia (IARC 79 (2001)). (5) In a 78-week test by administration of this substance (alpha- and gamma chlordane 1:1 mixture) to rats by feeding, at or above 35 ppm (1.75 mg/kg/day, within the range for Category 1), minimal to slight cytoplasmic homogeneity of the centrilobular hepatocytes and cytoplasmic margination in the liver were observed, and at 50 ppm (5 mg/kg/day, within the range for Category 1), death was observed (EHC 34 (1984)). (6) In an 80-week test by administration of this substance (for analysis) to rats by feeding, a decrease in survival rate (18% decrease) was observed in females at 11.08 mg/kg/day (within the range for Category 2), and tremors were observed at 22.15 mg/kg/day (within the range for Category 2) (ATSDR (2018)). (7) In an 80-week test by administration of this substance (for analysis) to mice by feeding, a decrease in survival rate (40% decrease) was observed in males at 5.13 mg/kg/day (within the range for Category 1), and tremors were observed in males at 9.64 mg/kg/day (within the range for Category 1) and in females at 11.02 mg/kg/day (within the range for Category 2) (ATSDR (2018)).
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 = 0.0004 mg/L for crustacea (Penaeus duorarum) (EHC 34, 1984).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	If chronic toxicity data are used, then it is classified in Category 1 because it is not rapidly degradable (BIOWIN) and due to 189-day NOEC = 0.0005 mg/L for fish (Cyprinodon variegatus) (TR91, 2003). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 1 because it is not rapidly degradable (BIOWIN) and due to 96-hour LC50 = 0.0004 mg/L for crustacea (Penaeus duorarum) (EHC 34, 1984). From the above results, it was classified in Category 1.
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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