NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	41205-21-4
Chemical Name	2,3-Dichloro-N-(4-fluorophenyl)maleimide; Fluoroimide
Substance ID	R02-A-032-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.
8	Self-reactive substances and mixtures	Classification not possible	- -	-	-	There is a chemical group associated with self-reactive properties (ethylene group) present in the molecule, but the classification is not possible due to no data.
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	Not classified (Not applicable)	- -	-	-	The substance is an organic compound containing fluorine, chlorine, and oxygen, which are chemically bonded only to carbon or hydrogen.
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), (2). [Evidence Data] (1) LD50 for rats (males): > 5,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)) (2) LD50 for rats: > 15,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) LD50 for mice: > 5,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013))
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 3	Danger	H331	P304+P340 P403+P233 P261 P271 P311 P321 P405 P501	[Rationale for the Classification] It was classified in Category 3 from (1), (2). [Evidence Data] (1) LC50 for rats (males) (4 hours): 0.57 mg/L (GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)) (2) LC50 for rats (females) (4 hours): 0.72 mg/L (GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1), (2). [Evidence Data] (1) It is reported that in a skin irritation test with rabbits (n = 2/group) (24-hour application, 3-day observation), when 10, 100, 1,000 mg of this substance was wetted with 0.5 mL of sterilized distilled water and was applied, slight erythema was seen after 1 day but disappeared after 2 days (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) It is reported that in a skin irritation test with rabbits (n = 6) (GLP, 75% wettable powder, 4-hour application, 7-day observation), very slight erythema was observed 1 hour after the end of application but disappeared after 3-5 days (erythema/eschar score: 0/0/0/0.8/0/1, edema score: 0/0/0/0/0/0) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	[Rationale for the Classification] It was classified in Category 1 from (1), (2). [Evidence Data] (1) It is reported that in an eye irritation test with rabbits (n = 6), in the group treated with 100 mg of this substance, the cornea became opaque, blood vessels appeared inside and outside of the eyeball, and the animals showed blindness after 14 days (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) It is reported that in an eye irritation test with rabbits (n = 6) (GLP, application of 75% wettable powder to the eye, 21-day observation), after 24, 48 hours, focal corneal opacity with vague or unclear details of the iris, the conjunctiva colored focal dark red or beef-like red, and chemosis with the eyelid half or more closed were observed, the reactions were gradually reduced after 72 hours, but corneal opacity persisted for 21 days in all the animals but one (corneal opacity score: 2/2/2/3/2.7/2.3, iritis score: 0/0/0/-/-/-, conjunctival redness score: 1.7/2.7/2.3/3/2.3/2, chemosis score: 3.3/3.3/3.7/4/3.3/3) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
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). [Evidence Data] (1) It is reported that in a local lymph node assay with mice (n = 4/group) (GLP), stimulation index (SI values) was 15.55 (2.5%), 23.09 (5%), 27.33 (10%), and it was judged as positive in skin sensitization (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) In a micronucleus test with mouse bone marrow cells (intraperitoneal injection), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) In a bacterial reverse mutation test, weakly positive (Salmonella typhimurium (TA98, TA100 strains)) and negative results were reported. With all findings including the higher-dose treatment results considered, the results were considered to be negative. Also, with the negative result of the in vivo test of (1) considered together, fluoroimide was considered to be not genotoxic (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (3) In an in vitro mammalian cell chromosome aberration test, negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] There were no classification results 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 two-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, no treatment-related increase in the incidence of neoplastic lesions was observed at doses up to 3,200 ppm (males/females: 150/184 mg/kg/day). No carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) In a two-year carcinogenicity study with mice dosed by feeding, no treatment-related increase in the incidence of neoplastic lesions was observed at doses up to 6,000 ppm (males/females: 942/1,120 mg/kg/day). No carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (5), it was classified in Category 1B. In (1), at the dose at which general toxicity effects were observed in parental animals, significant effects such as a lower number of litter size and a lower survival rate were observed in pups. In (2), skeletal abnormalities were observed in all generations of rats after postnatal dosing. [Evidence Data] (1) In a three-generation reproduction test with rats dosed by feeding, at 2,000 ppm, general toxicity effects (such as cornification of the esophagus and stomach and hemosiderosis in the spleen) were observed in P, F1, and F2 parental animals, reduced body weight gain (females) was observed in F1 and F2 parental animals and a lower number of litter size, a lower survival rate on day 25 after birth, and cornification of the esophagus and stomach were observed in pups. It was also reported that effects on fertility (lower mating rate and conception rate) in F1 and F2 parental animals were observed at the highest dose at which reduced body weight gain and decreased food consumption were observed in parental animals (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) It was reported that in a three-generation reproduction test with rats dosed by feeding, which was conducted as an additional test of (1), symptoms suggesting the occurrence of abnormalities in the skeletal morphology in the growth process, such as shortened femurs, tibias or fibulas, shortened humeri and vertebral abnormalities (such as spinal curvature), were observed in F1 and F2 parental animals and F1, F2, and F3 offspring (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (3) 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, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (4) It was reported that in a developmental toxicity study with rats dosed by gavage, at 1,000 mg/kg/day, reduced body weight gain and decreased food consumption in parental animals and lower body weight in pups (males and females) were observed, but no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (5) It was reported that in a developmental toxicity study with rabbits dosed by gavage, no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
8	Specific target organ toxicity - Single exposure	Category 1 (respiratory organs)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] Based on (1), it was classified in Category 1 (respiratory organs). [Evidence Data] (1) In an acute inhalation exposure test with rats (GLP, for 4 hours), at and above 0.29mg/L (males, within the range for Category 1) and at and above 0.67mg/L (females, within the range for Category 1), deaths were observed and clinical symptoms, such as reduced spontaneous activity, irregular breathing, gasping, rale, and incontinence of urine, were observed. It was reported that at the necropsy in the rats that died, reddening of all lobes in the lungs, retention of pleural effusion, and retention of yellow matter in the trachea were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). [Reference Data, etc.] (2) It was reported that in an acute oral toxicity test with rats, no symptoms and deaths were observed at 2,000 to 4,000 mg/kg (from the range for Category 2 through the range corresponding to “Not classified”) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (3) It was reported that in an acute dermal toxicity test with mice, no symptoms and deaths were observed at 5,000 mg/kg (in the range corresponding to “Not classified”) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
9	Specific target organ toxicity - Repeated exposure	Classification not possible	- -	-	-	[Rationale for the Classification] (1) to (5) suggested the possibility that the target organ was the kidney, but since no clear effects were observed up to the range for Category 2, it was classified as "Not classified" in the oral route. However, there was not sufficient information available for classification in the other routes. Therefore, classification was not possible due to lack of data. [Evidence Data] (1) It was reported that in a repeated dose 90-day oral toxicity study with rats dosed by feeding, increases in absolute and relative kidney weight (females), increases in absolute and relative lung weight (females), and atrophy of small intestine crypts of Lieberkuhn (females) were observed at and above 1,000 ppm (57.7 mg/kg/day (males), 62.5 mg/kg/day (females), within the range for Category 2) and an increase in ALT (males), atrophy of lymph node lymphoid follicle (males), abnormal cell division of Paneth cells (males) and crypts of Lieberkuhn in the large intestine, desquamation of upper stomach epithelial cells (males), hepatocyte cloudy swelling (males), and edema of small intestine lamina propria mucosa (females) were observed at 10,000 ppm (577 mg/kg/day (males), 656 mg/kg/day (females), in the range corresponding to “Not classified”) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) It was reported that in a repeated dose 90-day oral toxicity study with rats dosed by feeding, pyknosis of renal tubular epithelial cells, crystal deposition in tubular epithelium, and splenic lymphoid follicular necrosis (females) were observed at and above 500 ppm (51.9 mg/kg/day (males), 57.8 mg/kg/day (females), within the range for Category 2), increased absolute and relative adrenal gland weights were observed at 1,000 ppm (111 mg/kg/day (males), 116 mg/kg/day (females), in the range corresponding to “Not classified”), and a decrease in Ht, Hb and RBC, an increase in MCV and WBC (males), a decrease in MCHC, increases in absolute and relative spleen weight, splenic red pulp hyperemia (males), and diarrhea were observed at 5,000 ppm (553 mg/kg/day (males), 582 mg/kg/day (females), in the range corresponding to “Not classified”) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (3) It was reported that in a repeated dose 90-day oral toxicity study with mice dosed by feeding, reduced body weight gain (males), decreased food consumption (males), and atrophy of small intestine crypts of Lieberkuhn (females) were observed at and above 1,000 ppm (123 mg/kg/day (males), 141 mg/kg/day (females), in the range corresponding to “Not classified”) and atrophy of large intestine crypts of Lieberkuhn, myelopoiesis hypofunction, kidney glomerulus rarefaction (males), renal tubular nephrosis (males), emergence of multinucleated hepatocytes (males), and degeneration of cerebral nerve cells (males) were observed at 10,000 ppm (1,210 mg/kg/day (males), 1,160 mg/kg/day (females), in the range corresponding to “Not classified”) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (4) It was reported that in a repeated dose 90-day oral toxicity study with mice dosed by feeding, crystal deposition in renal tubular epithelium was observed at 500 ppm (96.8 mg/kg/day (males), 74.1 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (5) It was reported that in a two-year combined chronic toxicity/carcinogenicity study with mice dosed by feeding, an increase in the incidence of keratitis (females) was observed at and above 2,000 ppm (279 mg/kg/day (males), 371 mg/kg/day (females), in the range corresponding to “Not classified”) and reduced body weight gain, decreases in absolute and relative kidney weight and kidney-to-brain weight ratio (males), an increase in corneal opacity, an increase in the incidence of keratitis (males), decreases in Hb and Ht (females), and decreases in absolute and relative spleen weight and spleen-to-brain weight ratio (females) were observed at 6,000 ppm (942 mg/kg/day (males), 1,120 mg/kg/day (females), in the range corresponding to “Not classified”) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). [Reference Data, etc.] (6) It was reported that in a two-year chronic toxicity study with dogs dosed by capsules, no effects were observed at 250 mg/kg/day (in the range corresponding to “Not classified”) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (7) It was reported that in a two-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, increases in AST and ALT (males) and a decrease in T.Chol (males) were observed at and above 800 ppm (37.2 mg/kg/day (males), 45.9 mg/kg/day (females), within the range for Category 2) and a decrease in RBC/Ht (males), a decrease in Hb, a decrease in ALP, a decrease in T.Chol (females), forestomach edema, edema, hyperkeratosis and erosion of forestomach mucosa, and hyperplasia of forestomach squamous epithelium (males) were observed at 3,200 ppm (150 mg/kg/day (males), 184 mg/kg/day (females), in the range corresponding to “Not classified”) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
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 48-hour EC50 = 0.883 mg/L for crustacea (Daphnia magna) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
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 as "Not classified" because it is not rapidly degradable (BIOWIN) and due to 72-hour NOErC = 36.43 mg/L for algae (Raphidocelis subcapitata) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). 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 48-hour EC50 = 0.883 mg/L for crustacea (Daphnia magna) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). 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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