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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	57966-95-7
Chemical Name	1-[(EZ)-2-cyano-2-methoxyiminoacetyl]-3-ethylurea (synonym: Cymoxyanil)
Substance ID	R03-C-047-MHLW, MOE
Classification year (FY)	FY2021
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	FY2008
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	-	- -	-	-	-
2	Flammable gases	-	- -	-	-	-
3	Aerosols	-	- -	-	-	-
4	Oxidizing gases	-	- -	-	-	-
5	Gases under pressure	-	- -	-	-	-
6	Flammable liquids	-	- -	-	-	-
7	Flammable solids	-	- -	-	-	-
8	Self-reactive substances and mixtures	-	- -	-	-	-
9	Pyrophoric liquids	-	- -	-	-	-
10	Pyrophoric solids	-	- -	-	-	-
11	Self-heating substances and mixtures	-	- -	-	-	-
12	Substances and mixtures which, in contact with water, emit flammable gases	-	- -	-	-	-
13	Oxidizing liquids	-	- -	-	-	-
14	Oxidizing solids	-	- -	-	-	-
15	Organic peroxides	-	- -	-	-	-
16	Corrosive to metals	-	- -	-	-	-
17	Desensitized explosives	-	- -	-	-	-

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	-	- -	-	-	-
1	Acute toxicity (Dermal)	-	- -	-	-	-
1	Acute toxicity (Inhalation: Gases)	-	- -	-	-	-
1	Acute toxicity (Inhalation: Vapours)	-	- -	-	-	-
1	Acute toxicity (Inhalation: Dusts and mists)	-	- -	-	-	-
2	Skin corrosion/irritation	-	- -	-	-	-
3	Serious eye damage/eye irritation	-	- -	-	-	-
4	Respiratory sensitization	-	- -	-	-	-
4	Skin sensitization	Category 1A	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1A. Also, based on the new evaluation, the classification result was changed. [Evidence Data] (1) According to the OECD TG 406, the concentration used for intradermal induction should be the highest to cause mild-to-moderate skin irritation and for the challenge exposure should be the highest non-irritant dose. The concentrations used for intradermal induction and challenge (25%) in the studies of (3) and (4) were too low because no signs of skin irritation were observed in any of the animals in a preliminary test. Therefore, the reliability of the negative results obtained is questionable. No signs of skin irritation were induced even by 40% concentration used in a preliminary test of the study of (2), but in the main test, following intradermal induction with 40% concentration and challenge with 20% concentration, 90% animals showed slight to moderate erythema and slight to well-defined edema and necrosis was additionally observed in 3 animals exposed to 40% concentration. From the above, the study of (2) was considered as the most reliable assay in assessing skin sensitization. Based on that, it was proposed in the CLH Report that this substance should be classified in Skin Sens. 1A (CLH Report (2021)). (2) It was reported that, in a Maximization test (OECD TG 406, GLP, intradermal injection: 1% solution) with guinea pigs (n=10), the positive rate at 24, 48, and 72 hours after the challenge was 100% (10/10 animals) at both of the challenge concentrations of 20% and 40% (ECHA RAC Opinion (2012), CLH Report (2011)). [Reference Data, etc.] (3) It was reported that, in a Maximization test (OECD TG 406, GLP, intradermal injection: 3% solution) with guinea pigs (n=20), the positive rate was 0% (both 24 and 48 hours after the challenge (ECHA RAC Opinion (2012), CLH Report (2011)). (4) It was reported that, in a Maximization test (OECD TG 406, GLP, intradermal injection: 1% solution) with guinea pigs (n=10), the positive rate was 0% (both 24 and 48 hours after the challenge (ECHA RAC Opinion (2012), CLH Report (2011)). (5) The results of the two studies of (3) and (4) indicated no skin sensitizing effects of this substance. However, in the study of (2), in all test animals, dermal reactions (slight to moderate erythema and slight to well defined edema) were observed after challenge. No differences between the studies could be identified that could explain the contradictory results. Based on these results, the possibility of skin sensitization cannot be excluded (ECHA RAC Opinion (2012)).
5	Germ cell mutagenicity	-	- -	-	-	-
6	Carcinogenicity	-	- -	-	-	-
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] In the reproduction toxicity studies in (1) to (3), at the doses at which general toxicity effects appeared in parental animals, effects on sexual function and fertility (such as reduced luteinization and reduced numbers of corpora lutea and implantations, increased post-implantation losses) in female parent animals and reduced viability in pups were observed. In the developmental toxicity studies with rats in (4) and (5), at the doses at which toxicity effects appeared in dams, skeletal variations and visceral variations were observed in fetuses but no apparent teratogenicity was observed. In the developmental toxicity studies with rabbits in (6) to (8), it was reported that, at the doses at which general toxicity effects appeared in dams, cleft palate in (6) and skeletal malformations in (8) occurred although with low frequency. From the above, since concerns about reproductive effects and teratogenesis were indicated at the doses at which slight general toxicity effects were observed in dams, it was classified in Category 1B. It was classified based on the new information source. [Evidence Data] (1) It was reported that, in a two-generation reproduction toxicity study with rats dosed by feeding (100 to 1,500 ppm), at the high dose (1,500 ppm) at which marked general toxicity effects in P and F1 parental animals (P and F1 males and females: reduced body weight gain, F1 males and females: such as decreased food consumption, necrotic tip or sore of tail, end of tail missing) were observed, a reduced number of live litters and reduced 0-4 day viability in F1 pups were observed, but only lower body weight was observed in F2 pups (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014), CLH Report (2011, 2021)). (2) It was reported that, in a two-generation reproduction toxicity study with rats dosed by feeding (150 to 1,350 ppm), at the high dose (1,350 ppm) at which reduced body weight gain and decreased food consumption (except P males) in P and F1 male and female parental animals were observed, reduced luteinization, a reduced number of implantations, an increased percentage of post-implantation loss of embryos, and a reduced percentage of live pups born were observed in F1 female parental animals, and decreased body weight was observed in F1 and F2 pups at or above the mid dose and decreased live pups were observed in F1 at the high dose (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2019), EFSA (2008), CLH Report (2011, 2021)). (3) It was reported that, in a one-generation reproduction toxicity study with rats dosed by feeding (750 to 3,000 ppm), reduced body weight gain and decreased food consumption in P female parental animals were observed at or above the mid dose (1,500 ppm),; reduced fertility index, reduced numbers of corpora lutea and implantations, increased pre-implantation and post-implantation loss of embryos, and reduced litter size in females and bilateral small and flaccid testes in males (5/15 animals) were observed at the high dose (3,000 ppm),; and only reduced body weight was observed in F1 pups at the low dose (CLH Report (2021)). (4) It was reported that, in a developmental toxicity study with female rats dosed by gavage (10 to 150 mg/kg/day, days 6 to 15 of gestation), reduced body weight gain and decreased food consumption were observed at or above 25 mg/kg/day; a reduction in the number of viable fetuses and an increase in resorptions were observed at the highest dose (150 mg/kg/day) in dams; delayed ossification (skull, vertebra) were observed at or above 25 mg/kg/day; and lower body weights and increased incidences of delayed ossification (sternebra, pelvis) and skeletal variations (wavy ribs) were additionally observed at the highest dose in fetuses (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014), EFSA (2008), CLH Report (2011, 2021)). (5) It was reported that, in a developmental toxicity study with female rats dosed by gavage (30 to 120 mg/kg/day, days 6 to 15 of gestation), increases in late resorptions, post-implantation loss rate, and the number of resorbed embryos were observed at the highest dose (120 mg/kg/day) at which reduced body weight gain and decreased food consumption were observed in dams, and fetuses showed delayed ossification (such as seventh cervical vertebra, phalanges, sternebra), skeletal variations (hypoplasia of sternebra, an increase in dumb-bell shaped thoracic vertebra, supernumerary ribs), and visceral variations (renal pelvis dilation) at low doses, and additionally showed lower body weight, delayed ossification (phalanges, caudal vertebra), an increase in split thoracic vertebrae at high doses but no apparent teratogenicity was observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2019), CLH Report (2011, 2021)). (6) It was reported that, in a developmental toxicity study with female rabbits dosed by gavage (1 to 32 mg/kg/day, days 6 to 18 of gestation), cleft palate was observed in two fetuses (1.7%) from two dams that lost weight (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014), EFSA (2008), CLH Report (2011, 2021)). (7) It was reported that, in a developmental toxicity study with female rabbits dosed by gavage (5 to 25 mg/kg/day, days 6 to 18 of gestation), increased incidences of visceral anomalies (dilation of heart ventricles and renal pelvis dilation), skeletal variations (accessory floating rib no. 13), and delayed ossification (middle phalange of the fore limb) were observed at the high doses at which reduced body weight gain and decreased food consumption were observed in dams (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2019), EFSA (2008), CLH Report (2011, 2021)). (8) It was reported that, in a developmental toxicity study with female rabbits dosed by gavage (8 to 32 mg/kg/day, days 6 to 18 of gestation), increased skeletal malformations (vertebral changes between upper cervical and mid-thoracic regions) were observed at the high doses at which reduced body weight gain and cold ears were observed in dams (CLH Report (2011, 2021)). [Reference Data, etc.] (9) In a developmental neurotoxicity test with female rats dosed by gavage during the period from day 6 of gestation to day 21 of lactation (5 to 100 mg/kg/day), no developmental neurotoxicity was observed in pups up to the high doses at which marked maternal toxicity effects (such as reduced body weight gain, increased females with all dead pups) were observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2019), CLH Report (2011, 2021)). (10) In the EU, it was classified in Repr. 2 (EU-CLP Classification Results (Accessed Nov. 2011)). (11) There were no additional significant findings based on which the classification should be changed to Repr. 1B from the previous proposal in 2011 in the review of the EU CLP Classification, and a proposal was made that the classification should remain unchanged at Repr. 2 (CLH Report (2021)). However, as of December 2021, no such opinion by the RAC has been published.
8	Specific target organ toxicity - Single exposure	-	- -	-	-	-
9	Specific target organ toxicity - Repeated exposure	-	- -	-	-	-
10	Aspiration hazard	-	- -	-	-	-

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 = 0.569 mg a.i./L for algae (Raphidocelis subcapitata) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014), Document for registration standards for agricultural chemicals set by the Minister of Environment to prevent harm to animals and plants in areas of public waters, 2014). The classification result was revised from the previous classification by using new information. (a.i.: active ingredient)
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	Reliable chronic toxicity data were not obtained. It was classified in Category 1 because it is not rapidly degradable (BIOWIN) and it was classified in Category 1 in acute toxicity. The classification result was revised from the previous classification by changing how to classify it in chronic toxicity and using new information.
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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