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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	51218-45-2
Chemical Name	2-chloro-2'-ethyl-N-(2-methoxy-1-methylethyl)-6'-methylacetanilide; Metolachlor
Substance ID	R02-B-100-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)	- -	-	-	Liquid (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)	- -	-	-	Liquid (GHS definition). It was classified as "Not classified."
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition). It was classified as "Not classified."
6	Flammable liquids	Not classified	- -	-	-	It was classified as "Not classified" from a flash point of 190 deg C (ICSC (2000)).
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition). It was classified as "Not classified."
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	Classification not possible	- -	-	-	No data available.
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition). It was classified as "Not classified."
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Classification is not possible because test methods applicable to liquid substances are not 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). It was classified as "Not classified."
13	Oxidizing liquids	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."
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition). 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	- -	-	-	No data 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)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (6). Besides, the classification result was changed from the previous classification by using new information sources. [Evidence Data] (1) LD50 for rats: females: 2,000 mg/kg, males: 3,300 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)) (2) LD50 for rats: females: 2,000 mg/kg, males: 3,302 mg/kg (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)) (3) LD50 for rats: females: 2,200 mg/kg, males: 3,100 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), Japanese Journal of Pesticide Science Vol. 14, No. 1 (Pesticide Science Society of Japan, 1989), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)) (4) LD50 for rats: 2,200 mg/kg (GESTIS (Access on June 2020)) (5) LD50 for rats: 2,200-2,877 mg/kg (HSDB (Access on June 2020)) (6) LD50 for rats: 2,780 mg/kg (EPA Pesticides RED (1995), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (5). [Evidence Data] (1) LD50 for rabbits: > 2,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009), HSDB (Access on June 2020)) (2) LD50 for rabbits: 10,000 mg/kg (EPA Pesticides RED (1995)) (3) LD50 for rabbits: > 10,000 mg/kg (GESTIS (Access on June 2020)) (4) LD50 for rats: 3,170 mg/kg (HSDB (Access on June 2020)) (5) LD50 for rats: > 4,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009))
1	Acute toxicity (Inhalation: Gases)	Not classified	- -	-	-	[Rationale for the Classification] Liquid (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)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1), (2). Besides, the classification result was changed from the previous classification by using new information sources. Because exposure concentrations were higher than the saturated vapor pressure concentration (4.8E-004 mg/L), a reference value in the unit of mg/L was applied as mist. [Evidence Data] (1) LC50 for rats (4 hours): > 1.75 mg/L (EPA Pesticides RED (1995), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009), GESTIS (Access on June 2020), HSDB (Access on June 2020)) (2) LC50 for rats (4 hours): > 4.33 mg/L (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009), HSDB (Access on June 2020)), no dead animals at 4.33 mg/L, the highest possible concentration (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)) (3) Vapor pressure of this substance: 3.14E-005 mmHg (25 deg C) (HSDB (Access on May 2020)) (converted value for the saturated vapor pressure concentration: 4.8E-004 mg/L)
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) This substance was reported to be not irritating in a skin irritation test with rabbits according to EPA OPP 81-5 (EPA Pesticides RED (1995)). (2) A skin irritation test with rabbits on this substance was conducted, and slight skin irritation was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), Japanese Journal of Pesticide Science Vol. 14, No. 1 (Pesticide Science Society of Japan, 1989), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)). (3) In a skin irritation test with rabbits on this substance, slight irritation were found (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), Japanese Journal of Pesticide Science Vol. 14, No. 1 (Pesticide Science Society of Japan, 1989), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)). [Reference Data, etc.] (4) A skin irritation test with rabbits on the S-isomer of this substance (CAS RN 87392-12-9) was conducted, and slight skin irritation was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) This substance was reported to be not irritating in an eye irritation test with rabbits according to EPA OPP 81-4 (EPA Pesticides RED (1995)). (2) An eye irritation test with rabbits on this substance was conducted, and slight irritation was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)). (3) In an eye irritation test with rabbits on this substance, no irritation was found (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), Japanese Journal of Pesticide Science Vol. 14, No. 1 (Pesticide Science Society of Japan, 1989)). [Reference Data, etc.] (4) An eye irritation test with rabbits on the S-isomer of this substance (CAS RN 87392-12-9) was conducted, and slight irritation was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] It was classified in Category 1 from (1), (2). [Evidence Data] (1) This substance was reported to be positive for sensitization in a skin sensitization test with guinea pigs according to EPA OPP 81-6 (EPA Pesticides RED (1995)). (2) In skin sensitization tests with guinea pigs (a Buehler test and an Optimization test) on this substance, it was reported to be positive in both (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), Japanese Journal of Pesticide Science Vol. 14, No. 1 (Pesticide Science Society of Japan, 1989), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)). [Reference Data, etc.] (3) In a skin sensitization test with guinea pigs (maximization test) on the S-isomer of this substance (CAS RN 87392-12-9), it was reported to be positive (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), Japanese Journal of Pesticide Science Vol. 14, No. 1 (Pesticide Science Society of Japan, 1989)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1), (2). [Evidence Data] (1) As for in vivo, it was reported to be negative in a dominant lethal test by oral administration to mice, an unscheduled DNA synthesis test with rat liver, and a micronucleus test with hamster bone marrow cells (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), EPA Pesticides RED (1995), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009), Food sanitation research Vol. 49, No. 2 (Japan Crop Protection Association, 1999), Japanese Journal of Pesticide Science Vol. 14, No. 1 (Pesticide Science Society of Japan, 1989)). (2) As for in vitro, it was reported to be negative in a bacterial reverse mutation test and a gene mutation test with cultured mammalian cells, and positive and negative in chromosomal aberration tests with cultured mammalian cells (same as the above).
6	Carcinogenicity	Classification not possible	- -	-	-	[Rationale for the Classification] From (1) - (4), because it was classified in NL at doses that do not induce cellular proliferation in the liver in EPA's assessment, and by taking (2) into account, it was classified as "Classification not possible." [Evidence Data] (1) As for classification results by domestic and international organizations, EPA classified it in NL (Not Likely to be Carcinogenic to Humans) (EPA Annual Cancer Report 2019 (Access on September 2020): classified in 2017). (2) In a combined chronic toxicity/carcinogenicity test by 2-year diet administration of this substance to male and female rats, significant increases in the incidences of hepatocellular adenoma and hepatocellular adenoma and carcinoma (combined) were observed in females (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)). (3) In a carcinogenicity test by 18-month diet administration of this substance to male and female mice, there were no treatment-related increases in the incidence of neoplastic lesions (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)). (4) In 1994, EPA classified this substance in Group C (possible human carcinogen) based on liver tumors seen in female rats. However, in 2017, EPA re-classified the cancer classification for this substance in order to take into account additional mechanistic studies on S-metolachlor. As a result, EPA found that the development of liver tumors in rats orally administered this substance was initiated by activation of constitutive androstane receptor (CAR) in hepatocytes followed by altered gene expression, transient increased cell proliferation, increased hepatocellular foci, and hepatocyte toxicity (increased liver weight and liver hypertrophy). Consequently, EPA classified this substance and S-metolachlor as NL (Not Likely to be Carcinogenic to Humans) at doses that do not induce cellular proliferation in the liver (Federal Register Vol.84, No.47 (2019)).
7	Reproductive toxicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) In a two-generation reproduction study with rats dosed by feeding, at a dose (1,000 ppm) at which parental toxicity (no abnormalities in the P generation, an increase in relative thyroid weight in F1 males, and a decrease in food consumption in F1 females) was observed, pups exhibited reduced body weight gain in F1 males and females and F2 females (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)). (2) In a developmental toxicity study with female rats dosed by gavage on days 6 to 15 of gestation, no effect in fetuses was observed even at a dose at which maternal toxicity (a decrease in food consumption) was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)). (3) In a developmental toxicity study with female rabbits dosed by gavage on days 6 to 18 of gestation, no effect in fetuses was observed even at a dose at which maternal toxicity (miosis, hemorrhage in the vagina, reduced body weight gain, and a decrease in food consumption) was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)). [Reference Data, etc.] (4) In a developmental toxicity study with female rats dosed by gavage on days 6 to 15 of gestation, at a dose (1,000 mg/kg/day) at which maternal toxicity (death (4/25 cases), an increase in salivation, lacrimation, tonic or clonic convulsions, reduced body weight gain, a decrease in food consumption) was observed, lower body weight, delayed ossification of the ischial bone, etc. were observed in fetuses (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)).
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] In the acute oral toxicity tests of (3) to (5), neurologic symptoms were observed, but the doses at which the symptoms appeared were unknown and effects were observed at the lowest dose. Therefore, no category could be identified. However, based on the information from the general pharmacological tests of (1) and (2), it was classified in Category 1 (central nervous system). As a result of a review of the data using a new information source, the classification was changed from the previous classification. [Evidence Data] (1) In a general pharmacological test with mice dosed by gavage (doses: 0, 200, 600, 1,000 mg/kg), at or above the lowest dose of 200 mg/kg (within the range for Category 1), effects on the central nervous system were observed. (The symptoms that appeared at 200 mg/kg were unknown. Findings in this test indicating effects on the central nervous system: convulsion, face rubbing movement, sensitivity reaction, Straub tail response and a subsequent tendency toward depression. A decrease in locomotor activity was found in an activity wheel test) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)). (2) In general pharmacological tests with mice and rats dosed by gavage (doses: 0, 30, 100, 300,1,000 mg/kg), effects on the central nervous system were observed in mice at or above 100 mg/kg (within the range for Category 1), (the symptoms that appeared at 100 mg/kg were unknown. Straub tail, spasm, convulsion, decreases in exploratory behavior/locomotor activity/touch stimulus response/pain response, mydriasis, etc. were found in this test), and an increase in touch stimulus response was observed in rats at 1,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)). The Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009) indicated that mice were more sensitive than rats. (3) In an acute oral toxicity test with rats (LD50 values: males: 3,300 mg/kg, females: 2,000 mg/kg), deaths were observed in males at or above 2,500 mg/kg (exceeding Category 2) and in females at or above 2,000 mg/kg (within the range for Category 2), and symptoms such as loose stool, miosis, lacrimation, salivation, collapse, dyspnea, hunched posture, tremor, ataxia, tonic convulsion, loss of righting reflex, and sensitivity reaction to contact were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)). The doses at which the symptoms appeared were unknown, but at least at the dose at which deaths occurred, the major symptoms were considered to have been observed. (4) In an acute dermal toxicity test with rabbits (LD50 values: > 2,000 mg/kg), no death was observed, and a decrease in locomotor activity and ataxic gait were observed at 2,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)). (5) In an inhalation exposure test with rats (LC50: > 4.33 mg/L), no death was observed, and a decrease in locomotor activity and piloerection were observed at 4.33 mg/L (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)).
9	Specific target organ toxicity - Repeated exposure	Classification not possible	- -	-	-	[Rationale for the Classification] There was no report on repeated exposure to this substance in humans. In a test with test animals by the oral route, based on (1) and (2), there were no toxicity findings by which target organs could be identified at doses within the range for Category 1 or Category 2, and therefore, it was considered to be "Not classified" in the oral route. However, since there was no information on toxicity in the other routes, it was determined that classification was not possible. [Evidence Data] (1) It was reported that, in a 90-day feeding test with rats, an increase in total protein, an increase in globulin, a decrease in A/G ratio, an increase in urinary leukocyte count, basophilic changes of the renal tubules, and atrophy of pancreatic acinar cells were observed in males at 3,000 ppm (males/females: equivalent to 210/259 mg/kg/day, both exceeding Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)). (2) It was reported that, in a two-year feeding test with rats, at 3,000 ppm (males/females: equivalent to 141/180 mg/kg/day, both exceeding Category 2), an increase in (total) altered hepatocellular foci was observed, and furthermore, an increase in relative liver weight in males and an increase in altered hepatocellular foci (eosinophilic cells) in females were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)).
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 72-hour ErC50 = 0.098 mg/L for algae (Raphidocelis subcapitata) (ECOTOX, 2020).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	It was classified in Category 1 because it is not rapidly degradable (BIOWIN) and due to 72-hour NOErC < 0.00070 mg/L for algae (Raphidocelis subcapitata) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)).
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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