NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	81334-34-1
Chemical Name	(RS)-2-(4-Isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)nicotinic acid (synonym: imazapyr)
Substance ID	R03-A-025-METI, MOE
Classification year (FY)	FY2021
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	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	Not classified (Not applicable)	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is 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] Based on (1) to (4), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats (males): > 2,500 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), EFSA (2014)) (2) LD50 for rats (females): > 2,500 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), EFSA (2014)) (3) LD50 for rats (males): > 5,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), EFSA (2014), JMPR (2013)) (4) LD50 for rats (females): > 5,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), EFSA (2014), JMPR (2013))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (4), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats (males): > 2,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), EFSA (2014), JMPR (2013)) (2) LD50 for rats (females): > 2,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), EFSA (2014), JMPR (2013)) (3) LD50 for rabbits (males): > 2,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), EFSA (2014), JMPR (2013)) (4) LD50 for rabbits (females): > 2,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), EFSA (2014), JMPR (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)	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was not classified in Categories 1 to 3, but no category could be identified. Therefore, classification was not possible. [Reference Data, etc.] (1) LC50 for rats (males) (dust, 4 hours): > 1.3 mg/L (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), EFSA (2014), JMPR (2013)) (2) LC50 for rats (females) (dust, 4 hours): > 1.3 mg/L (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), EFSA (2014), JMPR (2013)) (3) LC50 for rats (mist, 4 hours): > 2.4 mg/L (OECD TG 403, GLP) (REACH registration dossier (Accessed May 2021))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in an acute dermal irritation/corrosion test (OECD TG 404, GLP, semiocclusive, 4-hour treatment, 72-hour observation) with rabbits (n=3), no skin irritation was observed (erythema score: 0/0/0, edema score: 0/0/0) (REACH registration dossier (Accessed May 2021)). (2) In a skin irritation test (72-hour observation) with rabbits (n=6), this substance was applied to a skin with damage and a skin without damage, and erythema was observed in the skin with damage after 24 hours, but it disappeared within 72 hours. It was reported that no skin irritation reactions were observed in the skin without damage after 24 and 72 hours (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), EFSA (2014), JMPR (2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)).
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 1. [Evidence Data] (1) It was reported that, in an eye irritation test (GLP, 21-day observation) with rabbits (n=6), corneal opacities persisted in 2 animals until 21 days later (cornea opacity score: 1/1/1/1.3/1/0.7, iris score: 0/0/0/0/0/0, conjunctival redness score: 1/1/2/2/2/2, chemosis score: 2/2/2.7/2.7/2.7/3) (REACH registration dossier (Accessed May 2021)). (2) It was reported that, in an eye irritation test with rabbits, a severe irritation was observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020)). (3) This substance was a severe eye irritant (EFSA (2014)). [Reference Data, etc.] (4) It was reported that, in an acute eye irritation/corrosion test (OECD TG 405, GLP, 7-day observation) with rabbits (n=3), observed eye irritant effects fully reversible within 7 days (cornea opacity score: 0/0/0, iris score: 0/0/0, conjunctival redness score: 1/0.7/0.7, chemosis score: 0.7/0.3/0.3) (REACH registration dossier (Accessed May 2021)).
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] Based on (1) to (4), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in a Buehler test (OECD TG 406, GLP, topical administration: 60% solution) with guinea pigs (n=20), the positive rate was 0% (0/20 animals) at both 24 and 48 hours after challenge (REACH registration dossier (Accessed May 2021)). (2) It was reported that, in a Buehler test (equivalent to OECD TG 406, GLP, topical administration: 100% solution) with guinea pigs (n=10), the positive rate was 0% (0/10 animals) at both 24 and 48 hours after challenge (REACH registration dossier (Accessed May 2021)). (3) It was reported that, in a Buehler test (equivalent to OECD TG 406, GLP, topical administration: 100% solution) with guinea pigs (n=12), the positive rate was 0% (0/12 animals) at both 24 and 48 hours after challenge (REACH registration dossier (Accessed May 2021)). (4) In a Buehler test (GLP) with guinea pigs, the result was negative (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (5), it was classified as "Not classified." [Evidence Data] (1) In a dominant lethal assay with rats (up to 1,000 mg/kg/day, dosed by gavage for 5 days), negative results were reported (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), JMPR (2013), EFSA (2014)). (2) In a micronucleus test (GLP) using the bone marrow cells of mice (up to 2,000 mg/kg, single oral dose), negative results were reported (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), JMPR (2013), EFSA (2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (3) In a bacterial reverse mutation test, negative results were reported (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), JMPR (2013), EFSA (2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (4) In a gene mutation assay using the cultured mammalian cells (CHO), negative results were obtained (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), JMPR (2013), EFSA (2014)). (5) In a chromosomal aberration test using the cultured mammalian cells (CHO), negative results were obtained (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), JMPR (2013), EFSA (2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) As for the carcinogenicity classification results by domestic and international organizations, the EPA classified this substance in Group E (Evidence of Non‐Carcinogenicity for Humans) (EPA OPP Annual Cancer Report 2020: classification in 1995). (2) In a 2-year combined chronic toxicity/carcinogenicity study with rats (dosed by feeding), a slightly increased incidence of brain astrocytomas was observed in males of a group treated at 10,000 ppm (503/639 mg/kg/day), but since it was not statistically significant, it was not judged to be the effect of the administration of the test substance. In addition, it was concluded that neither thyroid tumors (C-cell tumors) in males nor adrenal medullary tumors in females, for which tumor development was suspected, was not the effect of the administration of the test substance. No carcinogenicity was observed in this test (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), JMPR (2013), EFSA (2014)). (3) In an 18-month carcinogenicity study with mice (dosed by feeding), an increase in neoplastic lesions by the administration of the test substance was not observed at doses up to 10,000 ppm (1,560/2,000 mg/kg/day). No carcinogenicity was observed in this test (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), JMPR (2013), EFSA (2014)).
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 reproductive toxicity study (GLP) with rats dosed by feeding, no effect on fertility was observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), JMPR (2013), EFSA (2014)). (2) It was reported that in a developmental toxicity study (GLP, days 6-15 of gestation) with rats dosed by gavage, salivation (days 8-15 of gestation) was observed in parent animals at 1,000 mg/kg/day, but no effects of the administration of the test substance were observed in fetus (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), JMPR (2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). Besides, in the assessment by the EFSA, it was reported that an increase (not significant) in post-implantation embryo loss was observed at the highest dose, but no effects in fetuses were observed, and the reproduction/developmental toxicity classification was not proposed (EFSA (2014)). (3) It was reported that, in a developmental toxicity study (GLP, days 6-18 of gestation) with rabbits dosed by gavage, no teratogenicity was observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), JMPR (2013), EFSA (2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)).
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1) to (5), it was classified as "Not classified" in the oral route and dermal route. However, classification was not possible due to lack of data since there was not sufficient information for classification in the inhalation route. [Evidence Data] (1) It was reported that, in an acute oral toxicity test with rats, no effect was observed at 2,500 mg/kg (in the range corresponding to “Not classified”) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), EFSA (2014)). (2) It was reported that, in an acute oral toxicity test with rats, salivation (males) was observed at 5,000 mg/kg (in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), EFSA (2014), JMPR (2013)). (3) It was reported that, in an acute neurotoxicity test with rats dosed by gavage, no effect was observed at 2,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020)). (4) It was reported that, in an acute dermal toxicity test with rats, no effect was observed at 2,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), EFSA (2014), JMPR (2013)). (5) It was reported that, in an acute dermal toxicity test with rabbits, slight reddening was observed at 2,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), EFSA (2014), JMPR (2013)). [Reference Data, etc.] (6) It was reported that, in an acute inhalation (dust) exposure test (GLP, 4 hours) with rats, slight nasal discharge was observed at 1.3 mg/L (within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), EFSA (2014), JMPR (2013)). (7) It was reported that, in an acute inhalation toxicity study (mist) (OECD TG 403, GLP, 4 hours), salivation during exposure, tachypnea during and immediately after exposure, and ruffled fur from immediately after and one hour after exposure were observed at 2.4 mg/L (within the range for Category 2) (REACH registration dossier (Accessed May 2021)).
9	Specific target organ toxicity - Repeated exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1) to (4), it was classified as "Not classified" in the oral route. However, classification was not possible due to lack of data since there was not sufficient information available for classification in other routes. [Evidence Data] (1) It was reported that, in a 90-day oral toxicity test (GLP) with rats dosed by feeding, no effect was observed at 10,000 ppm (816 mg/kg/day (males), 940 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), JMPR (2013)). (2) It was reported that, in a 90-day oral toxicity study (GLP) with rats dosed by feeding, increases in absolute and relative kidney weight (females) were observed at 20,000 ppm (1,700 mg/kg/day (males), 1,780 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), JMPR (2013)). (3) It was reported that, in a 2-year combined chronic toxicity/carcinogenicity study (GLP) with rats dosed by feeding, no effect was observed at 10,000 ppm (503 mg/kg/day (males), 639 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), JMPR (2013)). (4) It was reported that, in an 18-month carcinogenicity study (GLP) with mice dosed by feeding, no effect was observed at 10,000 ppm (1,560 mg/kg/day (males), 2,000 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), JMPR (2013)). [Reference Data, etc.] (5) It was reported that, in a 21-day dermal toxicity test (GLP, 6 hours/day, 5 days/week) with rabbits, no effect was observed at 400 mg/kg/day (converted guidance value: 66.7 mg/kg/day, within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2020), EFSA (2014), JMPR (2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)).
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 14-day ErC50 = 0.052 mg/L for aquatic plants (Lemna gibba) (Recalculation result by expert, REACH registration dossier, 2021).
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 was not rapidly degradable (BIOWIN), and due to NOAEC = 43.1 mg/L for fish (Oncorhynchus mykiss) (REACH registration dossier, 2021). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained (algae), then it is classified in Category 1 because it was not rapidly degradable, and due to 14-day ErC50 = 0.052 mg/L for aquatic plants (Lemna gibba) (Recalculation result by expert, REACH registration dossier, 2021). 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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