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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	115-29-7
Chemical Name	6,7,8,9,10,10-Hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepine 3-oxide; Endosulfan
Substance ID	R02-B-080-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	Not classified	- -	-	-	It was classified as "Not classified" from information that it is not combustible (ICSC (1998)).
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 (ICSC (1998)).
11	Self-heating substances and mixtures	Not classified	- -	-	-	It was classified as "Not classified" from information that it is not combustible (ICSC (1998)).
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	Classification not possible	- -	-	-	The substance is an organic compound containing chlorine and oxygen (but not fluorine), and the oxygen is chemically bonded to the element other than carbon or hydrogen (S). However, the classification is not possible due to no data.
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) - (7). [Evidence Data] (1) LD50 for rats: females: 10 mg/kg (JMPR (1999)) (2) LD50 for rats: females: 10-23 mg/kg, males: 40-120 mg/kg (ACGIH (7th, 2009)) (3) LD50 for rats: females: 10-240 mg/kg, males: 40-1,740 mg/kg (ATSDR (2015)) (4) LD50 for rats: females: 18 mg/kg, males: 43-121 mg/kg (EHC 40 (1984)) (5) LD50 for rats: females: 30 mg/kg, males: 82 mg/kg (EPA Pesticides RED (2002)) (6) LD50 for rats: 40-355 mg/kg (EHC 40 (1984)) (7) LD50 for rats: 80 mg/kg (IPCS PIM 576 (2000))
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) - (7). Besides, the classification result was changed from the previous classification due to the use of new information sources. [Evidence Data] (1) LD50 for rats: females: 74 mg/kg (EHC 40 (1984)) (2) LD50 for rats: females: 78 mg/kg, males: 130 mg/kg (ACGIH (7th, 2009)) (3) LD50 for rats: 130-681 mg/kg (EHC 40 (1984)) (4) LD50 for rats: females: 500 mg/kg (JMPR (1999)) (5) LD50 for rabbits: 147-359 mg/kg (EHC 40 (1984)) (6) LD50 for rabbits: 290 mg/kg (IPCS PIM 576 (2000)) (7) LD50 for rabbits: 2,000 mg/kg (EPA Pesticides RED (2002))
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) - (6). Besides, because exposure concentrations were higher than the saturated vapor pressure concentration (3.8E-006 mg/L), a reference value in the unit of mg/L was applied as dust. [Evidence Data] (1) LC50 for rats (nose exposure, 4 hours): females: 0.0126 mg/L, males: 0.0345 mg/L (ACGIH (7th, 2009), ATSDR (2015), IPCS PIM 576 (2000)) (2) LC50 for rats (4 hours): females: 0.013 mg/L (JMPR (1999)) (3) LC50 for rats (4 hours): 0.013-0.035 mg/L (GESTIS (Access on May 2020)) (4) LC50 for rats (4 hours): 0.08 mg/L (GESTIS (Access on May 2020), HSDB (Access on May 2020)) (5) LC50 for rats (4 hours): 0.16-0.5 mg/L (EPA Pesticides RED (2002)) (6) LC50 for rats (4 hours): 0.35 mg/L (EHC 40 (1984)) (7) Vapor pressure of this substance: 1.73E-007 mmHg (25 deg C) (HSDB (Access on May 2020)) (converted value for the saturated vapor pressure concentration: 3.8E-006 mg/L)
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1), (2). [Evidence Data] (1) This substance was not irritating in a skin irritation test with rabbits (JMPR (1999), GESTIS (Access on May 2020)). [Reference Data, etc.] (2) In a skin irritation test with rabbits on a formulation of this substance (effective concentration 50%) according to EPA OPPTS 870.2500, it was not irritating (EPA Pesticides RED (2002)). (3) Application of this substance to the rat skin for 6 hours/day, 5 days resulted in slight to moderate erythema, slight edema, dryness, and scaling at 62.5 mg/kg/day in females and 250 mg/kg/day in males, but application of up to 48 mg/kg/day in females and 192 mg/kg/day in males caused no irritation. And in an experiment in which this substance was applied to guinea pigs at 587 mg/kg/day for 6 hours/day, 3 days/week, 3 weeks, no erythema or edema was seen (ATSDR (2015)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1), (2). [Evidence Data] (1) This substance was not irritating in an eye irritation test with rabbits (JMPR (1999)). (2) Application of a 20% aqueous suspension of this substance did not cause irritation (ATSDR (2015)). [Reference Data, etc.] (3) In an eye irritation test with rabbits, this substance caused slight irritation (GESTIS (Access on May 2020)). (4) In an eye irritation test with rabbits on a formulation of this substance (effective concentration 50%) according to EPA OPPTS 870.2400, it was irritating, and corneal opacity was observed by day 13 after application (EPA Pesticides RED (2002)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) In a skin sensitization test with guinea pigs, this substance was not sensitizing (JMPR (1999), GESTIS (Access on May 2020)). (2) In a patch test on this substance in 14 farm workers with work-related dermatitis, no sensitization was observed (ATSDR (2015)). (3) In an experiment in which this substance was applied to guinea pigs at 587 mg/kg/day for 6 hours/day, 3 days/week, 3 weeks, no sensitization was observed (ATSDR (2015)). [Reference Data, etc.] (4) In a skin sensitization test with guinea pigs on a formulation of this substance (effective concentration 50%) according to EPA OPPTS 870.2600, it was not sensitizing (EPA Pesticides RED (2002)).
5	Germ cell mutagenicity	Category 2	Warning	H341	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] From (1), (2), it was classified in Category 2 based on expert judgment. There were conflicting results in the induction of chromosomal aberrations in germ cells, and they were not judged as clear evidence. The classification result was changed by the addition of new information. [Evidence Data] (1) As for in vivo, It is reported that it was negative in chromosomal aberration tests with spermatogonial cells and bone marrow cells after 5-day inhalation exposure of rats (ATSDR (2015), IPCS PIM 576 (2000), EHC 40 (1984), HSDB (Access on May 2020)), positive in a chromosomal aberration test with spermatogonial cells at 60 days after 5-day oral administration to mice (ATSDR (2015), ACGIH (7th, 2009)), positive in chromosomal aberration tests with bone marrow cells of mice or hamsters, negative in a micronucleus test with bone marrow cells after oral administration to mice, positive in a micronucleus test with bone marrow cells after oral administration to rats and a micronucleus test with bone marrow cells after intraperitoneal administration to mice (ATSDR (2015)). It was reported to be negative in a dominant lethal test in mice (IPCS PIM 576 (2000), EHC 40 (1984)). There were reports on significant changes in aberrant metaphases in bone marrow cells of rats or mice (ATSDR (2015)). (2) As for in vitro, it was positive and negative in bacterial reverse mutation tests (ATSDR (2015), HSDB (Access on May 2020), CEBS (Access on May 2020)), and it was reported in test systems in cultured mammalian cells, it was negative in a chromosomal aberration test (CEBS (Access on May 2020)), positive and negative in sister chromatid exchange tests (ATSDR (2015), ACGIH (7th, 2009), CEBS (Access on May 2020)), and positive in a micronucleus test (ATSDR (2015)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified in A4 by ACGIH (ACGIH (7th, 2009)), and NL (Not Likely to be Carcinogenic to Humans) by EPA (EPA Annual Cancer Report 2019 (Access on August 2020): classified in 2000).
7	Reproductive toxicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), since there was no effect that should be adopted as a rationale for the classification, it was classified as "Not classified." [Evidence Data] (1) In a two-generation reproduction toxicity study with rats dosed by feeding, reduced body weight gain was observed in parental animals, but no reproductive toxicity effects were observed (IRIS (1994), ACGIH (7th, 2009)). (2) In a developmental toxicity study with female rats dosed by gavage on days 6 to 17 of gestation, at a dose at which maternal toxicity (death, face rubbing, hyperactivity, rough coat, a decrease in body weight, etc.) was observed, a decrease in fetal weight, a decrease in crown-rump length, delayed ossification of the sternebrae, and extra ribs were observed in fetuses (IRIS (1994)). The ACGIH (7th, 2009) reported that maternal toxicity (death, etc.) was observed but no effect on development was observed. [Reference Data, etc.] (3) In a developmental toxicity study with female rabbits dosed by gavage on days 6 to 19 of gestation, even at a dose at which maternal toxicity (death, noisy breathing, rapid breathing, hyperactivity, etc.) was observed, no effect in fetuses was observed (IRIS (1994)). Beside, it was noted that the results of this study are difficult to interpret and data availability is limited due to the addition of animals during the study due to maternal deaths caused by dosing errors (IRIS (1994), ATSDR (2015)). In ACGIH (7th, 2009), it was reported that maternal toxicity (e.g., death) was observed, but no evidence of developmental effects was found. (4) It was reported that, in a 70-day oral toxicity test with male rats, reduced sperm count and altered testicular enzyme activityies, reduced intratesticular spermatid count and sperm production, and an increase in the incidence of abnormal sperm were observed (ACGIH (7th, 2009)). (5) The ATSDR (2015) states, "The data on the available reproductive studies indicates that this substance has no adverse effects on reproductive performance of animals. However, adverse effects on male reproduction end points (sperm parameters, histopathological changes of the testes, sex hormone levels) are seen in rats, mice, rabbits, and guinea pigs. The lack of effects in the studies that examined the male reproductive performance may be due to the fact that at least rats produce and ejaculate 10 times more sperms than are necessary for normal fertility and litter size."
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] In (1) and (2), effects on the nervous system and accompanying symptoms (gastrointestinal complaints, disturbance to the respiratory function and disturbance to the cardiovascular system) were observed in humans. In (3) and (4), effects on the nervous system were observed in experimental animals at doses within the range for Category 1 both in the oral and inhalation routes. Therefore, it was classified in Category 1 (nervous system). [Evidence Data] (1) In five cases of acute lethal poisoning caused by ingestion of this substance, initial clinical symptoms including nausea, vomiting, diarrhea, agitation, writhing, loss of consciousness, cyanosis, dyspnea, foaming at the mouth, and noisy breathing were reported. At the autopsy in three cases, edema of the brain and lungs, hemorrhage of the renal medulla, acute lung emphysema, and chromatolysis of the neurons were observed (ACGIH (7th, 2009)). (2) Disturbances to the nervous system were an important symptom complex (vertigo, confusion, irritability, blurred vision and muscular twitching through to tonic-clonic convulsions). Accompanying symptoms were gastrointestinal complaints (nausea, vomiting, abdominal pain and diarrhea), disturbance to the respiratory function (dyspnea, increased respiratory rate), and disturbance to the cardiovascular system (tachycardia or bradycardia). In cases of seizures and disturbance to consciousness, changes to the electroencephalogram, disorientation and excitation sometimes persisted for some days. In one case, emotional and cognitive deficiencies (partial amnesia, impaired coordination, and an inability to carry out complex activities) were still clinically diagnosed after 2 years (GESTIS (Access on May 2020)). (3) The oral LD50s in experimental animals were 8.4 mg/kg in male mice, 40 to 120 mg/kg in male rats, 10 to 23 mg/kg in female rats and 76.7 mg/kg in male dogs, all within the range for Category 1. The observed symptoms of acute lethal poisoning were hyperexcitability, dyspnea, reduced respiration rate, tremors and tonic-clonic convulsions (ACGIH (7th, 2009)). (4) In an acute inhalation toxicity test with rats, irregular respiration was observed in both male and female rats. Dyspnea, tremors, ataxia were observed in females at 3.6 mg/m3 group and in males at 12.3 mg/m3 group (both within the range for Category 1). Furthermore, at higher concentrations (the concentration not described), tremor, tonic-clonic convulsions, and reduced reflexes (corneal reflex, pupil reflex, stepping reflex, shock reflex, pain reflex and skin reflex) were observed (ACGIH (7th, 2009)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system, blood system, kidney, reproductive organs (male)), Category 2 (liver)	Danger Warning	H372 H373	P260 P264 P270 P314 P501	[Rationale for the Classification] There was no report on repeated exposure to this substance in humans. Based on (1) to (10), effects on the nervous system, blood system, kidney, and reproductive organs (male) within the range for Category 1, and the liver within the range for Category 2 were observed in experimental animals. Therefore, it was classified in Category 1 (nervous system, blood system, kidney, reproductive organs (male)), and Category 2 (liver). As a result of reviewing the information, the classification result was changed from the previous classification. [Evidence Data] (1) It was reported that, in a three-month feeding test with rats, at or above 60 ppm (males/females: equivalent to 3.8/4.6 mg/kg/day, both within the range for Category 1), pigmentation of the proximal tubular cells was observed, and in females, increased brain acetylcholine esterase activity was also observed; and at 360 ppm (males/females: equivalent to 23/27 mg/kg/day, both within the range for Category 2), increases in urine volume and urinary protein concentrations, and yellow protein aggregation with intracytoplasmic eosinophilic droplets in the tubules in males, and decreases in plasma and erythrocyte cholinesterase (ChE) activity in females were observed (JMPR (1998)). (2) It was reported that, in a 13-week oral toxicity test with rats, at or above 0.8 mg/kg/day (within the range for Category 1), a decrease in hemoglobin concentration was observed, and at or above 1.9 mg/kg/day (within the range for Category 1), a decrease in mean corpuscular hemoglobin concentration was observed, and furthermore, a decrease in red blood cell count and an increase in mean corpuscular volume were observed in males (ATSDR (2015)). (3) It was reported that, in a 3-month test with mice dosed by feeding, convusions and salivation were observed at 54 ppm (males/females: 7.3/7.5 mg/kg/day, within the range for Category 1 in both cases) (JMPR (1998)). (4) It was reported that, in a 12-month feeding test with mice, giant-cell infiltration and large histiocytic cells filled with brown pigment in the liver, and giant-cell infiltration and reticuloendothelial cell proliferation in the lymph nodes were observed at 300 ppm (42 mg/kg/day, within the range for Category 2) (JMPR (1998)). (5) It was reported that, in a 30-day dermal exposure test with rats, tremors, tonic-clonic convulsions, hypersalivation, and decreases in serum, erythrocyte, and brain ChE activity were observed in males at the lethal dose of 190 mg/kg/day (converted guidance value: 44.3 mg/kg/day, within the range for Category 2), and a decrease in serum ChE activity was observed in females at or above 48 mg/kg/day (converted guidance value: 11.2 mg/kg/day, within the range for Category 1) (JMPR (1998)). (6) It was reported that, in a 30-day dermal exposure test with rats, enlargement of parenchymal cells in the periphery, loss of cytoplasmic basophilia in the liver, and decreases in serum and brain ChE activity were observed at or above 9 mg/kg/day (converted guidance value: 2.1 mg/kg/day, within the range for Category 1) which was the lethal dose in males (JMPR (1998)). (7) It was reported that, in a 70-day oral toxicity test with male rats, reduced sperm count and altered testicular enzyme activities were observed at or above 2.5 mg/kg/day (converted guidance value: 1.4 mg/kg/day, within the range for Category 1), and reduced intratesticular spermatid count and sperm production, and an increase in the incidence of abnormal sperm were observed at or above 5 mg/kg/day (converted guidance value: 2.8 mg/kg/day, within the range for Category 1) (ACGIH (7th, 2009)). (8) It was reported that, in a 78-week feeding test with rats, no effect was observed in females, but in males, at or above 220 ppm (converted guidance value: 11 mg/kg/day, within the range for Category 2), toxic nephropathy (degeneration of the proximal convoluted tubules with cloudy swelling, fatty degeneration and necrosis of the tubular epithelium, hyaline casts, regenerative tubular epithelium), calcium deposits in the stomach, kidney, testis, aorta, and mesenteric artery, and parathyroid hyperplasia were observed, and testicular atrophy characterized by degeneration and necrosis of the germinal cells in the seminiferous tubules and multinucleated cells with associated aspermatogenesis was observed (JMPR (1998), NTP TR62 (1978)) (9) It was reported that, in a 78-week oral toxicity study with male rats, testicular atrophy and degeneration and necrosis of the germinal cells lining the seminiferous tubules were observed at 20 mg/kg/day (within the range for Category 2) (JMPR (1998)). (10) It was reported that, in a three-week oral toxicity study with mice, decreases in sperm count and motility, and an increase in the frequency of sperm abnormalities were observed at 0.8 mg/kg/day (within the range for Category 1) (ATSDR (2015)). [Reference Data, etc.] (11) In the ATSDR (2015), it was indicated that adverse effects on male reproductive end points (sperm parameters, histopathological alterations in the testis, sex hormone levels) were observed in rats, mice, rabbits, and guinea pigs, and that mice were sensitive to these effects than other species and younger animals appeared to be more sensitive than the older ones.
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 = 0.00006 mg/L for fish (Mystus vittatus) (EHC 40, 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 28-day NOEC = 0.00027 mg/L for fish (Cyprinodon variegatus) (ECOTOX, 2020, EPA OPP Pesticide Ecotoxicity Database, 2020). 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 = 0.0002 mg/L for crustacea (Crangon septemspinosa) (EHC 40, 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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