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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	60-57-1
Chemical Name	1,2,3,4,10,10-Hexachloro-1,4,4a,5,6,7,8,8a-octahydro-6,7-epoxy-1,4:5,8-dimethanonaphthalene; dieldrin
Substance ID	R02-B-043-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)
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)).
8	Self-reactive substances and mixtures	Type G	- -	-	-	There is a chemical group associated with self-reactive properties, an epoxide, present in the molecule, but because it is classified in Division 6.1 in UNRTDG (UN2761), and it is considered to be not applicable to self-reactive substances and mixtures, hazards of the highest precedence, it was classified in Type G.
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 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. Besides, there is information that it attacks metals due to the slow formation of hydrogen chloride in storage (ICSC (1998)).
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) - (9). Besides, the previous classification was based on data in humans, but there was an LD50 estimate that was different from rationale data (LD50: 5 mg/kg) for the previous classification. Therefore, it was considered that there was a limitation in classification by using LD50 values in humans, and the substance was classified based on data experimental animals this time in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) LD50 for rats (preweaning): 25 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), ATSDR (2002), EHC 91 (1989)) (2) LD50 for rats: 24-167 mg/kg (IPCS PIM (1996)) (3) LD50 for rats (adults): 37 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), EHC 91 (1989)) (4) LD50 for rats: 37-46 mg/kg (ATSDR (2002)) (5) LD50 for rats: 37-87 mg/g (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), EHC 91 (1989), JMPR (1965), HSDB (Access on May 2020)) (6) LD50 for rats: 37-167 mg/g (ACGIH (7th, 2010)) (7) LD50 for rats: 46 mg/kg (Environmental Risk Assessment for Chemical Substances vol. 1 (Ministry of the Environment, 2002)) (8) LD50 for rats: 51-64 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), EHC 91 (1989)) (9) LD50 for rats (neonates): 168 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), ATSDR (2002), EHC 91 (1989)) [Reference Data, etc.] (10) Estimated LD50 for humans: 5 mg/kg (Patty (6th, 2012)) (11) Estimated LD50 for humans: 65 mg/kg (HSDB (Access on May 2020)) (12) Lethal dose for humans: about 5 g/kg (about 100 mg/kg: calculated supposing body weight as 50 kg) (ACGIH (7th, 2010))
1	Acute toxicity (Dermal)	Category 2	Danger	H310	P302+P352 P361+P364 P262 P264 P270 P280 P310 P321 P405 P501	[Rationale for the Classification] It was classified in Category 2 from (1) - (4). Besides, the classification result was changed from the previous classification by the use of new information sources. [Evidence Data] (1) LD50 for rats: females: 60 mg/kg (ATSDR (2002), HSDB (Access on May 2020)) (2) LD50 for rats: 60-90 mg/kg (ACGIH (7th, 2010), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), EHC 91 (1989), GESTIS (Access on May 2020)) (3) LD50 for rats: males: 90 mg/kg (ATSDR (2002), Environmental Risk Assessment for Chemical Substances vol. 1 (Ministry of the Environment, 2002), HSDB (Access on May 2020)) (4) LD50 for rabbits: < 150 mg/kg (HSDB (Access on May 2020)) [Reference Data, etc.] (5) LD50 for rabbits: 150 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), EHC 91 (1989)) (6) LD50 for rabbits: 250 mg/kg (GESTIS (Access on May 2020)) (7) LD50 for rabbits: 250-350 mg/kg (ACGIH (7th, 2010))
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)	Category 1	Danger	H330	P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501	[Rationale for the Classification] It was classified in Category 1 from (1). Besides, because an exposure concentration was higher than the saturated vapor pressure concentration (0.0001 mg/L), a reference value in the unit of mg/L was applied as dust. [Evidence Data] (1) LC50 for rats (4 hours): 0.013 mg/L (GESTIS (Access on May 2020)) (2) Vapor pressure of this substance: 5.89E-006 mmHg (25 deg C) (HSDB (Access on May 2020)) (converted value for the saturated vapor pressure concentration: 0.0001 mg/L)
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). The classification result was changed due to new data obtained. [Evidence Data] (1) In a skin irritation test with rabbits, no changes in the skin were seen for a powder, and by dissolving it in vegetable oil, slight irritation and scaly changes were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)). (2) This substance produced slight to severe irritation in the rabbit skin, which was attributable to the solvent (EHC 91 (1989)). (3) This substance (technical grade) applied as a powder to the rabbits' skin sometimes caused slight reddening but no distinct irritation, not even following application for several weeks (GESTIS (Access on May 2020)).
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
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] There was a description in (1), but it was classified as "Classification not possible" due to lack of data. [Reference Data, etc.] (1) A sensitizing action to the skin was unlikely because there was no indication of any allergic skin reactions from occupational experience with very large groups of persons exposed (EHC 91 (1989), GESTIS (Access on May 2020)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) As for in vivo, it was reported to be negative in a dominant lethal test and a mutual translocation test using mice, a chromosomal aberration test with Chinese hamster bone marrow cells, and a micronucleus test with mouse bone marrow (EHC 91 (1989), JMPR (1977), ATSDR (2002), ACGIH (7th, 2001)). (2) As for in vitro, a positive result in a gene mutation test with mouse lymphoma cells, a positive result in a sister chromatid exchange test with cultured rat cells, positive or negative results in chromosomal aberration tests using human peripheral blood lymphocytes or cultured mammalian cells, and positive or negative results in unscheduled DNA synthesis tests with hepatocytes from mice or rats were obtained. And negative results were obtained in a bacterial reverse mutation test and a cell transformation test with cultured mammalian cells (EHC 91 (1989), JMPR (1977), ATSDR (2002), IRIS (1988), ACGIH (7th, 2001), CEBS (Access on May 2020)). (3) It is reported that no chromosomal aberrations were observed in the peripheral blood lymphocytes of workers exposed to this substance (EHC 91 (1989), ATSDR (2002)). (4) It is described in the Risk Assessment Report (Pesticides) (Food Safety Commission of Japan) that it was considered that it did not have genotoxicity that could pose a problem in vivo (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)).
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] It was classified in Category 1B based on the IARC's latest classification in (1) and information in (2) - (4), which was the basis for the classification. The classification result was changed based on the IARC's latest classification result. [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified in Group 2A by IARC (IARC 117 (2019)), A3 by ACGIH (ACGIH (7th, 2010)), B2 (probable human carcinogen) by EPA (IRIS (1988)), and Carc. 2 in EU CLP (EU CLP classification (Access on May 2020)). (2) There were reports of multiple epidemiological studies on cancer risks related to exposure to this substance, some reported that risks of breast cancer, non-Hodgkin lymphoma, lung cancer, and leukemia increased by exposure to this substance, while there were reports that there were no increases (IARC 117 (2019)). (3) Many carcinogenicity tests by 52-week to 2-year diet administration of this substance to male and female mice were conducted by using multiple strains. In most of these tests, significant increases in the incidence of liver tumors (hepatocellular adenoma and carcinoma) were observed in male and female mice (IARC 117 (2019)). And in a test in which this substance was administered by gavage to female transgenic mice from 2 weeks before mating, throughout gestation and lactation periods until weaning, significant increases in the incidences of thoracic mammary gland tumors (mainly mammary gland adenocarcinoma) were observed (IARC 117 (2019)). (4) In carcinogenicity tests by 2-year diet administration of this substance to male and female rats and hamsters, no significant increases by treatment were found in tumor incidences (IARC 117 (2019)). (5) In liver tumor induction tests by intraperitoneal administration of diethylnitrosoamine, a hepatocarcinogen, to male rats and mice followed by 30-day or 60-day diet administration of this substance, significant effects were observed in the number of focal lesions in the liver, their size, and DNA labeling index in mice. No effects in those parameters were seen in rats (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)).
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] In the reproduction studies in (1) to (5), an increase in mortality of pups during the lactation period was observed. As possible causes, inadequate lactation due to maternal toxicity (hyperesthesia, hyperkinesia) in (3) and (4) and toxicity in pups via placental transfer and breast milk in (3), (5), (6), and (7) were reported. In developmental toxicity studies in (8) to (10), no clear evidence of teratogenicity was obtained, however, based on (11), a similarity to aldrin was considered. In addition, mammary transfer was observed in (5). Therefore, it was classified in Category 1B, Additional category: Effects on or via lactation. Because of the addition of effects on or via lactation, the classification results were changed from the previous classification. [Evidence Data] (1) In a three-generation reproduction study with rats dosed by feeding, an increase in mortality in F1b pups was observed in the highest dose group (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), EHC 91 (1989)). (2) In a three-generation reproduction study with rats dosed by feeding, an increase in mortality in pups during the lactation period was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)). (3) In a reproduction study with rats dosed by feeding, a decrease in the number of live pups in the weaning period was observed and pups died in convulsions (43%) or starvation (57%). It was considered that the starvation was caused by inadequate lactation due to hyperesthesia in dams and pups (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), EHC 91 (1989)). In this study, neural lesions (such as cerebral edema and hydrocephalus) were observed in pups in the lowest dose group for which no maternal toxicity was stated, but they were not observed at higher doses. Therefore, these changes were not considered as effects of this substance. (4) Similarly, in a reproduction study with mice dosed by feeding, an increase in pre-weaning mortality in pups was observed, and it was considered that pups died due to hyperactivity in dams (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), EHC 91 (1989)). (5) In a reproduction study with rats dosed by feeding, a decrease in survival rate in pups was observed, and it was shown that the concentration of dieldrin in breast milk in this study was 17 times higher than the concentration in feed, and the maximum amount secreted into the milk was 1 to 4 mg in the lactation period (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)). (6) In a reproduction study with mice dosed by feeding, pups prenatally exposed were nursed by unexposed foster dams, and as a result, all the pups died within 4 days (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), EHC 91 (1989)). (7) In tests using pregnant rats, mice, and rabbits, the results showed placental permeability (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)). (8) In developmental toxicity studies with female rats and rabbits dosed by gavage during the gestation period, no malformations were observed (EHC 91 (1989)). (9) In a developmental toxicity study with female mice dosed by gavage on days 7 to 16 of gestation, at a dose at which no maternal toxicity was observed, an increase in supernumerary ribs was observed in fetuses, and at a dose at which maternal toxicity (reduced body weight gain and an increase in relative liver weight) was observed, a decrease in the number of caudal ossification centers was additionally observed in fetuses (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), EHC 91 (1989)). (10) In a developmental toxicity study with female hamsters dosed by gavage on day 7, 8 or 9 of gestation, the number of live fetuses and fetal weight decreased and the incidence of abnormalities (cleft palate, open eyes, and webbed feet) increased. Since open eye and webbed foot were frequently associated with low fetal weight, it was suggested that the effects might simply be an expression of growth retardation (EHC 91 (1989)). In the EHC 91 (1989), it was indicated that the significance of these abnormalities in the presence of severe maternal toxicity was doubtful but the possibility of specific teratogenicity could not be ruled out completely. (11) In mammals, aldrin, which exhibits teratogenicity, is metabolized to this substance (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)).
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] Based on (1) to (6), it was classified in Category 1 (nervous system). [Evidence Data] (1) Mild symptoms of intoxication of this substance are headache, dizziness, nausea, an increase in blood pressure, etc.; moderate symptoms are severe muscular spasms and temporary amnesia; and severe symptoms are loss of consciousness and tonic convulsive seizure, and in some cases, death may occur due to respiratory paralysis or ventricular fibrillation (Environmental Risk Assessment for Chemical Substances Vol. 1 (Ministry of the Environment, 2002)). (2) Symptoms of intoxication may be accompanied by (acute) hyperirritability, convulsions, coma, nausea, vomiting, and headache (ACGIH (7th, 2010)). (3) Symptoms of intoxication are general malaise, headache, sweating, dizziness, nausea and vomiting, cardiac arrhythmia, muscular weakness, motor hyperexcitability, hyperreflexia, myoclonic jerking, and convulsions in severe poisoning (IPCS PIM (1996)). (4) Typical symptoms appeared after 15 minutes through to 24 hours, dependent on the dose: headache, vertigo, nausea, weakness and muscular twitching; then tonicoclonic cramps (epileptiform activities in the electroencephalogram) in serious cases. In this phase, serious cardiovascular reactions (tachycardia, hypertension/hypotension), fever or hypothermia, an influence on the functions of the liver or kidneys and hematologic parameters (leukocytosis) also became apparent (GESTIS (Access on May 2020)). (5) The human LD50 was estimated to be 5 mg/kg, and signs of intoxication including headache, dizziness, malaise, hyperexcitability, muscle twitching, loss of consciousness, convulsions, and depression were observed (Patty (6th, 2012)). (6) Overdoses of this substance cause headache, vertigo, nausea, vomiting, and fatigue, followed by muscle twitching, myoclonic jerks, convulsions with sudden falls and loss of consciousness, etc., and some fatalities (Patty (6th, 2012)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system, liver, kidney)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1), effects on the nervous system were observed in humans. Based on (2) and (3), effects on the nervous system, liver, and kidney at doses within the range for Category 1 were observed in experimental animals. Therefore, it was classified in Category 1 (nervous system, liver, kidney). New information was used and the classification results were changed from the previous classification. [Evidence Data] (1) It was reported that, as a result of a review of occupational and accidental exposures in humans, this substance caused hypersensitivity and muscular fasciculations, followed by convulsive seizures and respective changes in electroencephalogram patterns (ACGIH (7th, 2010)). (2) In a combined chronic toxicity/carcinogenicity study with rats dosed by feeding, increases in absolute and relative liver weight were observed in females at or above 1 ppm (0.05 mg/kg/day, within the range for Category 1), and hypersensitivity, tremors and convulsions, and centrilobular hepatocyte hypertrophy (1 male and 6 females) were observed in males and females at 10 ppm (0.5 mg/kg/day, within the range for Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)). (3) In a two-year chronic toxicity study with rats dosed by feeding, an increase in relative liver weight and centrilobular hepatocyte hypertrophy were observed in females at or above 0.5 ppm (0.025 mg/kg/day, within the range for Category 1) and in males at or above 10 ppm (0.5 mg/kg/day, within the range for Category 1); a decrease in survival rate was observed at or above 50 ppm (2.5 mg/kg/day, within the range for Category 1); and hemorrhage and/or distension of the urinary bladder with nephritis were observed in males at or above 100 ppm (5 mg/kg/day, within the range for Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)).
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 (Cragon septemspinosa) (EHC 91, 1989).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	Sufficient chronic toxicity data were not obtained. It was classified in Category 1 because it is not rapidly degradable (BIOWIN), 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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