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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	57018-04-9
Chemical Name	O-(2,6-dichloro-p-tolyl) O,O-dimethyl thiophosphate; Tolclofos-methyl
Substance ID	R02-A-076-METI
Classification year (FY)	FY2020
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)
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.
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	- -	-	-	Test methods applicable to solid (melting point <= 140 deg C) substances are not available.
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified	- -	-	-	It contains a metalloid (P), but it is estimated that it does not react vigorously with water from measured data: water solubility of 0.3ｰ1.1 mg/L (20 deg C) (GESTIS (Accessed Dec. 2020)).
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 the element other than carbon or hydrogen (P). 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	- -	-	-	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 3 test results in (1) - (3). [Evidence Data] (1) LD50 for rats: > 5,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018), IPCS PIM (Accessed Dec. 2020)) (2) LD50 for rats (females): > 5,000 mg/kg (GLP) (CLH Report (2018)) (3) LD50 for rats: > 5,000 mg/kg (CLH Report (2018))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) LD50 for rats: > 5,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018), IPCS PIM (Accessed Dec. 2020)) (2) LD50 for rats: > 2,000 mg/kg (OECD TG 402, GLP) (CLH Report (2018)) (3) LD50 for rabbits: > 2,000 mg/kg (CLH Report (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] The classification is not possible because toxicity information is unknown at the upper limit for Category 4 from (1), (2). [Reference Data, etc.] (1) LC50 for rats (4 hours): > 3.32 mg/L (GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018), IPCS PIM (Accessed Dec. 2020)) (2) LC50 for rats (4 hours): > 2.07 mg/L (GLP) (CLH Report (2018))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) It is reported that in a skin irritation test with rabbits (n = 3) (OECD TG 404, GLP, occlusive, 4-hour application, 72-hour observation), all the animals showed erythema and edema after 1 hour, but all effects were fully reversible within 72 hours (erythema/eschar score: 0.7/0.3/0.7, edema score: 0.3/0/0.3) (ECHA RAC Opinion (2019), CLH Report (2018)). (2) It is reported that in a skin irritation test with rabbits (n = 6) (occlusive, 4-hour application, 7-day observation), no skin irritation reactions were seen in any animal (erythema/eschar score: 0/0/0/0/0/0, edema score: 0/0/0/0/0/0) (ECHA RAC Opinion (2019), CLH Report (2018), JMPR (1994)). (3) It is reported that in a skin irritation test with rabbits (n = 6) (semi-occlusive, 4-hour application, 72-hour observation), no skin irritation reactions were found in any animal (erythema/eschar score: 0/0/0/0/0/0, edema score: 0/0/0/0/0/0) (ECHA RAC Opinion (2019), CLH Report (2018)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) It is reported that in an eye irritation test with rabbits (n = 3) (OECD TG 405, GLP, 96-hour observation), all the animals showed irritation reactions in the conjunctiva but fully recovered within 96 hours (corneal opacity score: 0/0/0, iritis score: 0/0/0, conjunctival redness score: 1/0.3/0.3, chemosis score: 1.3/0/0) (ECHA RAC Opinion (2019), CLH Report (2018)). (2) It is reported that in an eye irritation test with rabbits (n = 8), no irritation reactions were observed in 5 in the washed eye group or 3 in the unwashed eye group (ECHA RAC Opinion (2019), CLH Report (2018), JMPR (1994)). (3) It is reported that in an eye irritation test with rabbits (n = 6), all the animals showed irritation reactions in the conjunctiva after 1 hour but fully recovered within 48 hours (corneal opacity score: 0/0/0/0/0/0, iritis score: 0/0/0/0/0/0, conjunctival redness score: 0/0.3/0/0/0/0, chemosis score: 0/0/0/0/0/0) (ECHA RAC Opinion (2019), CLH Report (2018)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1B	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] It was classified in Category 1B from (1) - (3). [Evidence Data] (1) It is reported that in a maximization test with guinea pigs (n = 20) (OECD TG 406, GLP, intradermal administration: 5% solution), a sensitization rate was 35% (7/20) (ECHA RAC Opinion (2019), CLH Report (2018)). (2) Skin sensitization tests with guinea pigs (Landsteiner-Draize test, Buehler test, maximization test) were conducted, and it was negative in a Landsteiner-Draize test and a Buehler test but moderate positive in a maximization test (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019)). (3) This substance is a skin sensitizer (EFSA (2017)).
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 dominant lethal test with rats (OECD TG478), negative results were reported (CLH Report (2018), IPCS INCHEM (Accessed Dec. 2020)). (2) In a chromosomal aberration test using the bone marrow cells from mice (by single-dose intraperitoneal administration), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018), IPCS INCHEM (Accessed Dec. 2020)). (3) In a micronucleus test (OECD TG474, GLP, single oral dose), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018)). (4) In a bacterial reverse mutation test, negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018), IPCS INCHEM (Accessed Dec. 2020)). (5) In an in vitro mammalian cell (Chinese hamster lung cells (V79)) gene mutation test, negative results were reported (CLH Report (2018), IPCS INCHEM (Accessed Dec. 2020)). (6) In an in vitro mammalian cell (CHO-K1) chromosome aberration test (OECD TG 473), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018), IPCS INCHEM (Accessed Dec. 2020)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] There was no classification result by domestic and international organizations. However, based on the test results of (1) and (2), it was classified as "Not classified." [Evidence Data] (1) In a 28/30-month combined chronic toxicity/carcinogenicity study with rats (dosed by feeding), at doses up to 1,000 ppm (male/female: 41.6/48.6 mg/kg/day), no neoplastic lesions increased in incidence frequency by the treatment, and no carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018), IPCS INCHEM (Accessed Dec. 2020)). (2) In a 2-year combined chronic toxicity/carcinogenicity study with mice (dosed by feeding), at doses up to 1,000 ppm (male/female: 134/137 mg/kg/day), no neoplastic lesions increased in incidence frequency by the treatment, and no carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018), IPCS INCHEM (Accessed Dec. 2020)).
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 three-generation reproduction toxicity study with rats dosed by feeding, no effect on fertility was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018), IPCS INCHEM (Accessed Oct. 2020)). (2) It was reported that in a developmental toxicity study with rats dosed by gavage (days 6 to 15 of gestation), no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018), IPCS INCHEM (Accessed Oct. 2020)). (3) It was reported that in a developmental toxicity study with rabbits dosed by gavage (days 6 to 18 of gestation), no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018), IPCS INCHEM (Accessed Oct. 2020)). [Reference Data, etc.] (4) In a one-generation reproduction toxicity study with rats dosed by feeding, reductions in body weight and body weight gain were observed in offspring at a low dose at which general toxic effects were not observed in parent animals, but it was considered that those symptoms were due to larger food consumption in offspring than in parent animals, and not the effects of higher susceptibility in offspring than in parent animals. In the Risk Assessment Report of the Food Safety Commission of Japan, those data were treated as reference data because the number of parent animals was as small as 10 animals in each male/female group (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018)).
8	Specific target organ toxicity - Single exposure	Category 2 (nervous system)	Warning	H371	P308+P311 P260 P264 P270 P405 P501	[Rationale for the Classification] Based on (1) and (2), limb or systemic ataxia, ataxic gait, and a decrease in locomotor activity were observed within the dose range for Category 2, and it was classified in Category 2 (nervous system). [Evidence Data] (1) It was reported that in an acute oral toxicity test with mice, a decrease in locomotor activity, limb or systemic ataxia, deep respiration and dyspnea, and ataxic gait were observed, and deaths were observed in males at 1,500 mg/kg and in females at 2,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019)). (2) It was reported that in an acute oral neurotoxicity study with rats (OECD TG 424, GLP), at or above 700 mg/kg (within the range for Category 2), a decrease in locomotor activity was observed on the day of the treatment (day 0), but rats recovered on day 4 and 7 (CLH Report (2018)). [Reference Data, etc.] (3) It was reported that in an acute dermal toxicity test with rats, neither death nor symptom was observed at 5,000 mg/kg (in the range corresponding to “Not classified”) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018)). (4) It was reported that in an acute inhalation (dust) toxicity test with rats (4 hours, GLP), at 3.32 mg/L (within the range for Category 2), eyelid closure, abnormal posture, and abnormal respiration were observed, but no death was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018)). (5) It was reported that in an acute inhalation (dust) toxicity test with rats (4 hours, GLP), at 2.07 mg/L (within the range for Category 2), abnormal respiration was observed, but rats recovered by day 3, and no macroscopic abnormality was observed in necropsy (CLH Report (2018)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (blood system, nervous system)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1) and (3), effects on the blood system were observed within the dose range for Category 2, and based on (2) and (4), effects on the nervous system by ChE activity inhibition were suggested, and since the effects were observed within the dose range for Category 2 in both cases, it was classified in Category 2 (blood system, nervous system). [Evidence Data] (1) It was reported that in a 6-month repeated oral toxicity test with dogs dosed by feeding, at 2,000 ppm (69.9 mg/kg/day (male), 62.9 mg/kg/day (female), within the range for Category 2), decreases in RBC and Hb, an increase in ALP, a decrease in Alb, and increases in absolute and relative weight of the liver were observed; and in males, increases in absolute and relative weight of the thyroid were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018), IPCS PIM (Accessed Dec. 2020)). (2) It was reported that in a 9-month repeated oral toxicity test with mice dosed by feeding, at 100 ppm (12.2 mg/kg/day (male), 13.8 mg/kg/day (female), within the range for Category 2), inhibition of erythrocyte ChE activity (male) was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018), IPCS PIM (Accessed Dec. 2020)). (3) It was reported that in a 1-year chronic toxicity study with dogs dosed by feeding, at 2,000 ppm (58.7 mg/kg/day (male), 61.9 mg/kg/day (female), within the range for Category 2), effects on the blood (decreases in RBC, Ht, and Hb, an increase in PLT), and effects on the liver (increases in absolute and relative weight of the liver, hypertrophy of the hepatocytes (diffuse and centrilobular), an increase in homogeneous material in the hepatocytes, hepatocellular pigment deposit, an increase in ALT in males) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018), IPCS PIM (Accessed Dec. 2020)). (4) It was reported that in a 2-year combined chronic toxicity/carcinogenicity study with mice dosed by feeding, at 250 ppm (32.2 mg/kg/day (male), 34.1 mg/kg/day (female), within the range for Category 2), inhibition of erythrocyte ChE activity (20% or above) was observed, and inhibition of brain ChE activity (20% or above) in females was observed; and at 1,000 ppm (134 mg/kg/day (male), 137 mg/kg/day (female), in the range corresponding to "Not classified"), inhibition of brain ChE activity (20% or above), an increase in Glu, and abscess of the preputial gland in males, and increases in absolute and relative weight of the pituitary, decreases in absolute and relative weight of the thymus and ovary (right), fibrosis of the tongue, and atrophy of the vagina in females were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018), IPCS PIM (Accessed Dec. 2020)). [Reference Data, etc.] (5) It was reported that in a 13-week repeated oral toxicity test with rats dosed by feeding, at 10,000 ppm (653 mg/kg/day (male), 696 mg/kg/day (female), in the range corresponding to "Not classified"), effects on the liver (increases in absolute and relative weight of the liver, hypertrophy of the hepatocytes) were observed; and in females, inhibition of erythrocyte ChE activity (20% or above), effects on the blood (decreases in Hb and MCH, increases in leukocyte (WBC) and lymphocyte counts), etc. were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018), IPCS PIM (Accessed Dec. 2020)). (6) It was reported that in a 13-week neurotoxicity test with rats dosed by feeding, at 10,000 ppm (736 mg/kg/day (male), 763 mg/kg/day (female), in the range corresponding to "Not classified"), no neurotoxicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018)). (7) It was reported that in a 6-month repeated oral toxicity test with rats dosed by feeding, at 3,000 ppm (166 mg/kg/day (male), 186 mg/kg/day (female), in the range corresponding to "Not classified"), effects on the liver (increases in absolute and relative weight of the liver, oval-cell proliferation of the liver (female)) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2018), IPCS PIM (Accessed Dec. 2020)).
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)	-	- -	-	-	-
11	Hazardous to the aquatic environment Long term (Chronic)	-	- -	-	-	-
12	Hazardous to the ozone layer	-	- -	-	-	-

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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