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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	116-29-0
Chemical Name	1,2,4-Trichloro-5-[(4-chlorophenyl)sulfonyl]benzene; Tetradifon
Substance ID	R02-A-038-METI, MOE
Classification year (FY)	FY2020
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)/Ministry of the Environment (MOE)
New/Revised	New
Classification result in other fiscal year
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)
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.
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
7	Flammable solids	Classification not possible	- -	-	-	No data available. Besides, there is information that it is combustible (Accessed Sep. (2020)).
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.
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
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).
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
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 an element (S) other than carbon or hydrogen. 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.
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.

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (4). [Evidence Data] (1) LD50 for rats (males): > 14,700 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)) (2) LD50 for rats: > 5,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)) (3) LD50 for rats: > 20,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)) (4) LD50 for rats: between 5,000-14,700 mg/kg (EHC (1986), IPCS HSG (1987), HSDB (Accessed Sep. 2020))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1), (2). [Evidence Data] (1) LD50 for rats: > 20,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)) (2) LD50 for rabbits: > 10,000 mg/kg (Japan Crop Protection Association (1992), HSDB (Accessed Sep. 2020))
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] The category could not be determined from (1), (2), and the classification is not possible. [Evidence Data] (1) LC50 for rats (4 hours): > 2.97 mg/L (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), Japan Crop Protection Association (1992)) (2) LC50 for rats (4 hours): > 3 mg/L (HSDB (Accessed Sep. 2020))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified." from (1). [Evidence Data] (1) It is reported that in a skin irritation test with rabbits (n = 3) (occlusive, 4-hour application, 72-hour observation), no anomalies in the skin were observed in any animal (EHC (1986), Agricultural Chemicals Times supplement "Agricultural chemicals technology information" No. 12 (Japan Crop Protection Association, 1992)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified." from (1). [Evidence Data] (1) It is reported that in an eye irritation test with rabbits (n = 3), slight conjunctival redness was seen after 1 hour but disappeared within 24 hours (EHC (1986), Agricultural Chemicals Times supplement "Agricultural chemicals technology information" No. 12 (Japan Crop Protection Association, 1992)).
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). [Evidence Data] (1) It is reported that in a maximization test with guinea pigs (intradermal administration: 30% diluted solution), no skin irritation changes were observed in any animal at 24, 48 hours after challenge (Agricultural Chemicals Times supplement "Agricultural chemicals technology information" No. 12 (Japan Crop Protection Association, 1992)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (6), it was classified as "Not classified." [Evidence Data] (1) In a micronucleus test using the bone marrow cells of rats (two oral doses), the substance was negative (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (2) In a micronucleus test using the bone marrow cells of mice (single oral dose), the substance was negative (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (3) In a bacterial reverse mutation test, negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (4) In a gene mutation test using CHL (V79) cells, negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (5) In a chromosomal aberration test using the human lymphocyte cultures, negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (6) It was weakly positive in a sister chromatid exchange (SCE) analysis using the human lymphocyte cultures (EHC 67 (1986), HSDB (Accessed Sep. 2020)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (4), it was classified as "Not classified." (1) shows an increase in the incidence of thyroid tumors, but since (3) shows that this was a mechanism via thyroid hormone catabolism acceleration associated with the induction of liver drug metabolic enzymes, and (4) shows that this was not considered to be a genotoxic mechanism, the possibility of its extrapolation to humans is low. In addition, thyroid tumors in rats were only benign ones. [Evidence Data] (1) In a 2-year combined chronic toxicity/carcinogenicity study with rats (dosed by feeding), the number of the incidence of thyroid follicular adenoma increased in the male and female groups at the maximum dosage of 3,000 ppm (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (2) In an 18-month carcinogenicity study with mice, the trend of an increase of hepatocellular carcinoma was observed in the male group at the maximum dosage of 640 ppm, but since there was no significant difference in the Fisher's test, and an increase of hepatocellular adenoma was not observed, it was not considered to be the effect of the administration of the test substance. The carcinogenicity was not observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (3) In a 90-day toxicity test with rats dosed by feeding, induction of liver microsomal enzymes was observed, and in a 90-day toxicity test, tissue changes were observed in the thyroid at 200 ppm. It was also reported that in a 2-year chronic toxicity study with rats dosed by feeding, induction of liver microsomal enzymes was observed at 1,200 ppm (EHC 67 (1986), IPCS HSG (1987)). (4) It was difficult to consider the mechanism of thyroid tumor formation to be a genotoxic one, and it was considered that the threshold could be set for evaluation (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)).
7	Reproductive toxicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) It was reported that in a two-generation reproduction toxicity study with rats dosed by feeding, no effects on fertility were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), Japan Crop Protection Association (1992), EHC 67 (1986), IPCS HSG (1987)). (2) It was reported that in a developmental toxicity study with rats dosed by gavage, no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (3) In a developmental toxicity study with rabbits dosed by gavage, at 270 mg/kg/day, weight gain inhibition, a decrease in food intake, and two cases of miscarriage were observed in parental animals, but no effects were observed in offspring. It was reported that at 810 mg/kg/day, dwarfs (4/97 cases) and a decrease in sex ratio (male/female) were observed in offspring, but no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)).
8	Specific target organ toxicity - Single exposure	Category 2 (respiratory organs)	Warning	H371	P308+P311 P260 P264 P270 P405 P501	[Rationale for the Classification] Based on (1), it was classified in Category 2 (respiratory organs). [Evidence Data] (1) It was reported that in an acute inhalation (dust) exposure test with rats (4 hours), at 2.97 mg/L (within the range for Category 2), closed eye, weight gain inhibition, a decrease in food intake, an increase in water intake, alveolar macrophage aggregation, and pneumonia were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). [Reference Data, etc.] (2) It was reported that in an acute oral toxicity test with rats (male), at or above 4,640 mg/kg (in the range corresponding to "Not classified"), grooming, salivation, an excessive mastication motion, an irregular effort respiration, wheezing, and nasal discharge were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), Japan Crop Protection Association (1992), HSDB (Accessed Sep. 2020)). (3) It was reported that in an acute dermal toxicity test with rats, no symptom and dead animals were observed and LD50 was > 2,0000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (lung, liver)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1) to (3), the target organs were considered to be the lung and liver, and effects were observed within the dosage range for Category 2, therefore, it was classified in Category 2 (lung, liver). [Evidence Data] (1) It was reported that in a 2-year combined chronic toxicity/carcinogenicity studies with rats dosed by feeding, at or above 300 ppm (14.1 mg/kg/day (male), 17.1 mg/kg/day (female), within the range for Category 2), effects on the liver (centrilobular hypertrophy of hepatocytes, liver cyst degeneration (male)) and effects on the lung (localized alveolar macrophage aggregation/lung cholesterin crystals/lung alveolar gland epithelial metaplasia) were observed; and at 3,000 ppm (144 mg/kg/day (male), 181 mg/kg/day (female), in the range corresponding to “Not classified”), increases in the absolute/relative weight of the liver, hyperplasia of hepatocytes, increases in the absolute/relative weight of the thyroid (male) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (2) It was reported that in an 18-month combined chronic toxicity/carcinogenicity study with mice dosed by feeding, at 640 ppm (92.2 mg/kg/day (male), 108 mg/kg/day (female), within the range for Category 2 (male), in the range corresponding to "Not classified" (female)), effects on the liver (centrilobular hypertrophy of hepatocytes, acidophilic foci of hepatocytes/clear cell foci of hepatocytes/centrilobular hepatocyte degeneration/necrosis (with cloudy swelling, vacuolating, nuclei densely stained, and single cell necrosis) (male)) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (3) It was reported that in a 90-day oral toxicity test with rats dosed by feeding, at 1,000 ppm (50 mg/kg/day, within the range for Category 2), an increase in liver weights and smooth endoplasmic reticular whorls were observed (EHC 67 (1986)). [Reference Data, etc.] (4) It was reported that in a 90-day oral toxicity test with rats dosed by feeding, at 3,000 ppm (180 mg/kg/day (male), 227 mg/kg/day (female), in the range corresponding to "Not classified"), effects on the liver (increases in absolute/relative weight, centrilobular hypertrophy of hepatocytes) and effects on the thyroid (increases in absolute/relative weight, an increase in small follicles (female)) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (5) It was reported that in a 90-day oral toxicity test with dogs dosed by capsules, at 200 mg/kg/day (in the range corresponding to "Not classified"), cardiac inflammation (male), effects on the liver (single cell necrosis of hepatocytes, acidophilic degeneration of hepatocytes (male), proliferation of the hepatic bile duct (male), increases in ALT, AST and ALP (male), hepatic sinusoid intracavity leukocytosis (female)), and effects on the gallbladder (gallbladder inflammation, congestion/bleeding (male)) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (6) It was reported that in a 1-year chronic toxicity study with dogs dosed by feeding, at 5,000 ppm (125 mg/kg/day, in the range corresponding to "Not classified"), an increase in serum ALP and enlargement of the liver were observed (EHC 67 (1986)).
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 = 0.110 mg/L for crustacea (Gammarus lacustris) (EHC 67, 1986).
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 21-day NOEC = 0.1 mg/L for crustacea (Daphnia magna) (ECOTOX, 2021). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 2 because it is not rapidly degradable (BIOWIN) and due to 96-hour LC50 = 1.2 mg/L for fish (Oncorhynchus mykiss) (EHC 67, 1986). By drawing a comparison between 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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