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GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	58-89-9
Chemical Name	1,2,3,4,5,6-Hexachlorocyclohexane [Lindane]
Substance ID	H28-B-030, C-041B
Classification year (FY)	FY2016
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 (FY2013 revised edition (Ver. 1.1))
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 applicable	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.
2	Flammable gases (including chemically unstable gases)	Not applicable	- -	-	-	Solid (GHS definition).
3	Aerosols	Not applicable	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not applicable	- -	-	-	Solid (GHS definition).
5	Gases under pressure	Not applicable	- -	-	-	Solid (GHS definition).
6	Flammable liquids	Not applicable	- -	-	-	Solid (GHS definition).
7	Flammable solids	Not classified	- -	-	-	It is not combustible (ICSC(J) (1994)).
8	Self-reactive substances and mixtures	Not applicable	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.
9	Pyrophoric liquids	Not applicable	- -	-	-	Solid (GHS definition).
10	Pyrophoric solids	Not classified	- -	-	-	It is not combustible (ICSC(J) (1994)).
11	Self-heating substances and mixtures	Not classified	- -	-	-	It is not combustible (ICSC(J) (1994)).
12	Substances and mixtures which, in contact with water, emit flammable gases	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).
13	Oxidizing liquids	Not applicable	- -	-	-	Solid (GHS definition).
14	Oxidizing solids	Not applicable	- -	-	-	The substance is an organic compound containing chlorine (but not fluorine or oxygen) which is chemically bonded only to carbon or hydrogen.
15	Organic peroxides	Not applicable	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to solid substances are not available. Besides, there is the information that it is corrosive to metals (HSDB (Access on June. 2016)).

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Category 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	There are two reports of LD50 values for rats of 140 mg/kg (male) and 190 mg/kg (female) (Risk Assessment Report (pesticides) (Food Safety Commission of Japan, 2013), JMPR (2002)). Based on these data, it was classified in Category 3. Besides, based on expert judgement, the LD50 values of JMPR and Food Safety Commission were adopted preferentially as information source for this substance.
1	Acute toxicity (Dermal)	Category 3	Danger	H311	P302+P352 P361+P364 P280 P312 P321 P405 P501	There is a reported LD50 value for rats of 1,000 mg/kg (Risk Assessment Report (pesticides) (Food Safety Commission of Japan, 2013), JMPR (2002)), corresponding to Category 3. There is a reported LD50 value for rabbit of 900 mg/kg (JMPR (1997)), corresponding to Category 3. Based on these data, it was classified in Category 3. On the basis of newly obtained data, the category was revised. Besides, based on expert judgment, the LD50 values of the JMPR and the Food Safety Commission of Japan were preferentially adopted as information sources for this substance.
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	Besides, based on expert judgement, the LD50 values of JMPR and Food Safety Commission were adopted preferentially as information source for this substance.
1	Acute toxicity (Inhalation: Vapours)	Not applicable	- -	-	-	Solid (GHS definition)
1	Acute toxicity (Inhalation: Dusts and mists)	Category 4	Warning	H332	P304+P340 P261 P271 P312	There are 3 reports of LC50 values (4 hours) for rats of 0.002 mg/L (male and female) (JMPR (2002)), 1,560 mg/m3 (ATSDR (2005)) and 1,600 mg/m3 (DFGOT vol.16 (2001), JMPR (1989, 1997)). One corresponds to Category 1, and the other two correspond to Category 4. It was classified in Category 4 which has greater number of data. On the basis of newly obtained data, the category was revised.
2	Skin corrosion/irritation	Not classified	- -	-	-	In primary skin irritation tests using rabbits, no irritation was observed (ATSDR (2005), DFGOT vol.16 (2001), EHC 124 (1991), EPA RED (2002), JMPR (2002)), therefore, it was classified as "Not Classified."
3	Serious eye damage/eye irritation	Category 2B	- Warning	H320	P305+P351+P338 P337+P313 P264	In primary eye irritation tests using rabbits, mild irritation was observed (ATSDR (2005), DFGOT vol.16 (2001), EHC 124 (1991)), therefore, it was classified in Category 2B.
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.
4	Skin sensitization	Not classified	- -	-	-	Skin sensitization studies by the maximization test using guinea pigs resulted in negative (DFGOT vol.16 (2001), EHC 124 (1991), JMPR (2002)). Also, patch tests in farmers, etc. were negative (DFGOT vol.16 (2001), EHC 124 (1991)), therefore, it was classified as "Not Classified."
5	Germ cell mutagenicity	Classification not possible	- -	-	-	The substance was classified as "Classification not possible" because it was not possible to classify a substance as "Not classified" according to the revised GHS classification guidance for the Japanese government. As for in vivo, results reported are negative in dominant lethal tests using rats and mice, negative in a micronucleus test using bone marrow cells of mice, and in chromosome aberration tests, negative in using bone marrow cells of rats, positive in using bone marrow cells of mice, and negative in using bone marrow cells of Syrian hamsters, and positive and negative in sister chromatid exchange tests using bone marrow cells of mice (ATSDR (2005), DFGOT vol.16 (2001), EHC 124 (1991), ACGIH (7th, 2001), JMPR (2002)). As for in vitro, the most of bacterial reverse mutation tests were negative, and in mammalian cell tests, gene mutation tests were negative, chromosome aberration tests gave positive and negative result, and sister chromatid exchange tests were negative (ATSDR (2005), ACGIH (7th, 2001), EHC 124 (1991), JMPR (2002)). Positive results were obtained in a part of reverse mutation tests, chromosome aberration tests, and SCE tests, however, the many other tests resulted in negative, in addition, it is concluded in JMPR (2002) that genotoxicity is not observed for this substance. Based on the above, it is concluded in Risk Assessment Report (pesticides) (Food Safety Commission of Japan, 2013) that this substance is not genotoxic in bodies. From the above, it was judged this substance has no genotoxicity also in this classification.
6	Carcinogenicity	Category 1A	Danger	H350	P308+P313 P201 P202 P280 P405 P501	In the latest evaluation, on the basis that there is sufficient evidence that this substance causes non-Hodgkin lymphoma in humans, IARC raised the classification from the past Group 2B (IARC Suppl. 7 (1987)) to Group 1 (IARC 113 (in prep., Access on June 2016), IARC Press Release No. 236 (Access on June 2016)). As for experimental animals, it is reported that in studies using rats and mice orally dosed, in addition to increased liver tumors, there were increases in lymphoreticular neoplasms in mice and thyroid tumors in rats, etc. (IARC Suppl. 7 (1987)). From the above, it was classified in Category 1A for this hazard class. Besides, as for the classification results by other organizations, ACGIH classified it in A3 (confirmed animal carcinogen: corresponding to Category 2) (ACGIH (7th, 2001)), NTP classified it as R (corresponding to Category 1B or 2) (NTP RoC (13th, 2014)).
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	As for humans, it is described that in a epidemiologic study which checked the blood concentration of this substance between the populations of infertile men and general men in Israel, it was higher in infertile men than in the general men (JMPR (2002)), and that 30 pregnant women in India diagnosed with intra-uterine fetal growth retardation showed higher blood concentrations of this substance and isomers than 24 normal pregnant women (ATSDR (2005)). As for experimental animals, in a two-generation reproductive toxicity study using rats dosed by feeding, at the dose where reduced body weight gain, increase in liver and kidney weight, periacinar hepatocyte hypertrophy, hydronephrosis, etc. were observed in F0, F1 parent animals, the lower body weight until weaning, and delays in tooth eruption and hair growth were observed in F2 pups (JMPR (2002)). On the other hand, in development toxicity studies using pregnant rats, pregnant mice, and pregnant rabbits given this substance by gavage administration during the period of organogenesis, even at doses where reduced body weight gain, death (rats, mice), abortion (mice), tachypnea and lethargy (rabbits) were observed in maternal animals, only slight effects (skeletal variations, lower body weight) were observed (JMPR (2002), DFGOT vol. 16 (2001)). However, it is reported that in a study using pregnant dogs (13-14 animals/group) orally dosed (feeding) at 7.5 and 15 mg/kg/day on days 1 to 5 of gestation, although there was no abnormality in the maternal animals, a dose-independent increase in the number of stillborn was observed (DFGOT vol. 16 (2001), JMPR (2002)). From the above, it was judged appropriate to classify it in Category 1B for this hazard class based on the limited findings on reproductive effects in humans and the findings in experimental animals (developmental delays in F2 rat pups after birth and increased stillborn in pregnant dogs).
8	Specific target organ toxicity - Single exposure	Category 1 (nervous system)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	In humans, by an oral or inhalation exposure to this substance, symptoms such as vomiting, convulsions, ataxia, and tremors were observed, leading to death by respiratory failure in the serious case (ACGIH (7th, 2001), DFGOT vol. 16 (2001), IPCS, PIM 859 (2001)). Also, in experimental animals, similar symptoms were reported although detailed doses were not described (ACGIH (7th, 2001), DFGOT vol. 16 (2001)). From the above, it was classified in Category 1 (nervous system).
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system, haemal system)	Danger	H372	P260 P264 P270 P314 P501	As for humans, aplastic anemia and agranulocytosis from chronic inhalation of this substance are reported (ACGIH (7th, 2001)), and it is reported that as the result of a neurological study on 37 workers exposed to this substance over a period of 2 years (22 of the 37 had been exposed to Aldrin for 2 years previously), electroencephalogram abnormality was seen in 16 workers, the blood concentrations of this substance were 0.002 to 0.340 ppm, and the clinical symptoms and the frequency of EEG changes were higher at blood concentration of this substance of 0.02 ppm or higher (ACGIH (7th, 2001)). In addition, it is reported that in workers who were exposed to this substance, there were effects of paresthesia of the face and the extremities, headaches, giddiness, vomiting, apprehension, loss of sleep, and changes in some liver function parameters (gamma-GT, lactic dehydrogenase, ornithine carbamoyl transferase, etc.) (DFGOT vol.16 (2001)). As for experimental animals, it is reported that in a 2-week repeated dose toxicity study using rats dosed by feeding, at 800 ppm (converted guidance value: 12.4 mg/kg/day), which is equivalent to Category 2, effects on the testis (tubular atrophy, spermatogenic arrest, the interstitial edema) were observed (EHC 124 (1991)). It is reported that in a 90-day repeated dose toxicity study using rats dosed by feeding, at 20 ppm (1 mg/kg/day), which is equivalent to Category 1, recoverable effects on the liver (increased liver weight, liver cell hypertrophy) were observed, in addition, effects on the kidney in males (increased hyaline droplet, etc.) were observed (DFGOT vol.16 (2001), JMPR (2002), EHC 124 (1991), IRIS (2006), Risk Assessment Report (pesticides) (Food Safety Commission of Japan, 2013)). It is reported that in a 13-week repeated dose neurotoxicity study using rats dosed by feeding, at 500/400 ppm (male: 28.1 mg/kg/day, female: 30.2 mg/kg/day), which is equivalent to Category 2, effects on the nervous system (difficulty in handling, hypersensitivity reaction to the contact, etc.), and that in a 2-year repeated dose toxicity study using rats dosed by feeding, effects on the liver (increase in absolute and relative weight of the liver, centrilobular hepatocyte hypertrophy) at 100 ppm (male: 4.81 mg/kg/day, female: 6.00 mg/kg/day) corresponding to Category 1, and effects on the blood (decrease in a red blood cell count, hemoglobin amount and hematocrit value) at 400 ppm (male: 19.7 mg/kg/day, female: 24.3 mg/kg/day) corresponding to Category 2 were observed (Risk Assessment Report (pesticides) (Food Safety Commission of Japan, 2013). Of the above, followings were not adopted as the evidence of the classification: effects on testis because the report was only one 2-week study at one dose, and it was not observed in several longer-period studies; effects on the kidney because it was considered to be specific effect for male rats; effects on the liver because there were only changes in some liver function parameters, and no other report shows the effect on the liver in the case of humans, and there were only increase of weight and hepatocyte hypertrophy for experimental animals. Therefore, the substance was classified in Category 1 (nervous system, haemal system). In the previous classification, the kidney and testis were also adopted as target organs, but they were not taken due to the reasons mentioned above, and new information was added, therefore, the classification was changed
10	Aspiration hazard	Classification not possible	- -	-	-	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 (Acute)	Category 1	Warning	H400	P273 P391 P501	From 96-hour LC50 = 0.00017 mg/L for crustacea (Penaeus duorarum) (EHC 124, 1991), it was classified in Category 1.
11	Hazardous to the aquatic environment (Long-term)	Category 1	Warning	H410	P273 P391 P501	When chronic toxicity data are used, it is not rapidly degradable (BIOWIN), and its 28-day NOEC (lethal) = 0.0008 mg/L for crustacea (Gammarus pulex) (ECETOC TR91, 2003). Therefore, it was classified in Category 1.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	No data available.

NOTE:

* A blank or "-" in a cell of classification denotes that the classification of the hazard class was not conducted.
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Hazard_statement_and/or_Precautionary_statement are also provided in the Excel file.
* Classification was conducted by relevant Japanese Ministries in accordance with GHS Classification Guidance for the Japanese Government,
and is intended to provide a reference for preparing GHS labelling and SDS for users.
* This is a provisional English translation of classification results and is subject to revision without notice.
* The responsibility for any resulting GHS labelling and SDS referenced from this site is with users.
* Codes assigned to each of the hazard statements and codes for each of the precautionary statement are
based on the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) in United Nations.

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