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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	13684-63-4
Chemical Name	Methyl 3-(3-methylcarbaniloyloxy)carbanilate (synonym: phenmedipham)
Substance ID	R03-B-016-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	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	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	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures because it can be estimated that it does not decompose up to 240 deg C from the information that it decomposes at 240 deg C (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014)).
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	- -	-	-	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 (8), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats (males): > 5,000 mg/kg (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015)) (2) LD50 for rats (females): > 5,000 mg/kg (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015)) (3) LD50 for rats (males): > 12,800 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015)) (4) LD50 for rats (females): > 12,800 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015)) (5) LD50 for rats (males):> 2,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015)) (6) LD50 for rats (males):> 8,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015)) (7) LD50 for rats (females): > 8,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015)) (8) LD50 for other rats: > 8,000 mg/kg (EHC 64 (1986), EPA Pesticides RED (2005))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (6), 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, 2015)) (2) LD50 for rats (females): > 2,500 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015)) (3) LD50 for rats (males): > 2,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015)) (4) LD50 for rats (females): > 2,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015)) (5) LD50 for rats: > 4,000 mg/kg (EHC 64 (1986)) (6) LD50 for rabbits: > 4,000 mg/kg (EPA Pesticides RED (2005))
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)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." With the additional new information sources, classification results were changed. [Evidence Data] (1) LC50 (4 hours, aerosol) for rats:> 7 mg/L (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015))
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 a skin irritation test (GLP, 4-hour application, observation for 72 hours) with rabbits (n=3), no skin irritation reactions were observed in any animals (erythema and scab score: 0/0/0, edema score: 0/0/0) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014)). (2) This substance was not a skin irritant substance (EFSA (2018), EPA Pesticides (2005)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." Also, based on the new findings, classification results were changed. [Evidence Data] (1) It was reported that, in an eye irritation test (GLP, observation for 72 hours) with rabbits (n=3), mild conjunctival redness was observed in all animals after 1 hour, but it disappeared after 24 hours (cornea opacity score: 0/0/0, iritis score: 0/0/0, conjunctival redness score: 0/0/0, chemosis score: 0/0/0) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014)). (2) This substance was not an eye irritant substance (EFSA (2018), EPA Pesticides (2005)).
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 (3), it was classified as "Not classified." Also, based on the new findings, classification results were changed. [Evidence Data] (1) It was reported that, in a Maximization test (GLP, intradermal administration: 0.5% test substance) with guinea pigs (n=19), the positive rates in 24 and 48 hours after the first challenge were 0% (0/19 animals), and the positive rates in 24 and 48 hours after re-challenge were also 0% (0/19 animals) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014)). (2) It was reported that, in a Maximization test (GLP, intracutaneous administration: 5% test substance) with guinea pigs (n=20), the positive rates in 24 and 48 hours after induction were both 0% (0/20 cases) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014)). (3) This substance was not a skin sensitizing substance (EPA Pesticides (2005)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) As for in vivo, negative results were obtained in all of a chromosomal aberration test using the spermatogonia of mice (15,000 mg/kg dosed once by gavage) and two micronucleus tests using the bone marrow cells of mice (15,000 mg/kg dosed once by gavage, and up to 1,000 mg/kg dosed twice (24-hour interval) by gavage) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014), CLH Report (2017)). (2) As for in vitro, negative results were obtained in all of multiple bacterial reverse mutation tests, and negative results were obtained in a cultured mammalian cell (Chinese hamster lung cell V79) gene mutation assay (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014), CLH Report (2017)). In addition, in a human lymphocyte or cultured mammalian cell (Chinese hamster ovary cell: CHO) chromosomal aberration test, positive results were obtained at a high concentration at which cytotoxicity was observed, but negative results were obtained within a concentration range in which no cytotoxicity was observed, and therefore, it was concluded in Japan that results were negative (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014)). On the other hand, these chromosomal aberration test results were judged to be positive (CLH Report (2017)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (5), it was classified as "Not classified." [Evidence Data] (1) As for the classification results by domestic and international organizations, there is only Group D (Not Classifiable As To Human Carcinogenicity) of the EPA (EPA OPP Annual Cancer Report 2020 (Accessed July 2021): Classification in 1993). (2) In two carcinogenicity studies with rats (SD strain) dosed by feeding for two years, no carcinogenicity due to the administration of this substance was observed at doses up to the highest dose of 1,000 ppm (males/females: 50.1 to 54.8/67.5 to 73.1 mg/kg/day) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014)). (3) In a carcinogenicity study with rats (Wistar strain) dosed by feeding for two years, an increase in adenoma of the anterior lobe of the pituitary gland was observed in males of a group at the highest dose of 2,500 ppm (males/females: 118/171 mg/kg/day). In Japan, as a result of comparative analysis with historical control data from the testing laboratory, the incidence of the same tumor in the control group was at the value near the lower limit, and therefore, it was concluded that an increase in adenoma of the anterior lobe of the pituitary gland was due to the low incidence in the control group and was not a net effect of the administration of the test substance (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014)). Also, the authorities in the EU country proposing the CLP considered this to be an effect of the administration of the test substance, and judged that the results suggested carcinogenicity of this substance (CLH Report (2017), RAC (Background Doc.) (2018)). (4) In a carcinogenicity study with rats (SD strain) dosed by feeding for two years, there were no neoplastic lesions for which the incidence increased due to the administration of the test substance at the highest doses up to 500 ppm (males/females: 28/31 mg/kg/day), and it was concluded that no carcinogenicity was observed. Also, the authorities in the CLP proposing countries in the EU judged that an increase in endometrial stromal sarcoma was observed in females of a group at the highest dose (500 ppm) (CLH Report (2017), RAC (Background Doc.) (2018)). (5) In two independent carcinogenicity studies with mice of the same strain (ICR) dosed by feeding for 78 weeks and dosed by feeding for two years, no carcinogenicity due to the administration of this substance was observed at doses up to 7,000 ppm (males/females: 1,070/1,390 mg/kg/day) for the former and up to 1,000 ppm (males/females: 110/117 mg/kg/day) for the latter (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014), CLH Report (2017)). [Reference Data, etc.] (6) As for tumors observed in males and females in a group at the highest dose in carcinogenicity studies with rats in (3) and (4), there was a concern about the incidence of tumors related to the action of endocrine disruption of this substance, and therefore, the carcinogenicity classification (Carc. 2) was proposed (CLH Report (2017)). Against this, according to the RAC of the ECHA, an increase in the incidence of endometrial stromal sarcoma could not be adopted as the basis for classification because it was not a statistically significant finding and was not observed in other tests. In addition, an increase in pituitary adenoma was an effect related to the administration, but the spontaneous incidence of this benign tumor was high, without preneoplastic changes, and the findings were observed in one species and one sex, and based on the above, the RAC expressed its opinion that there was guarantee for no classification of this substance as a carcinogen (Category 2) (ECHA RAC Opinion (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 two two-generation reproduction toxicity studies with rats dosed by feeding, at a high dose (72.2 to 90.1 mg/kg/day or 225 mg/kg/day) at which reduced body weight gain and reduced food consumption were observed in parent animals, no effects on fertility were observed, and effects observed in offspring were also only minor effects (lower body weight/reduced body weight gain). It was also reported that, also in a three-generation reproduction toxicity study with rats dosed by feeding, no reproduction or developmental effects on fertility and offspring were observed at doses up to 500 ppm (34.1 to 47.2 mg/kg/day) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014), CLH Report (2017)). (2) It was reported that, in two developmental toxicity studies with rats dosed by gavage (days 6-15 of gestation), only minor effects (lower body weight, delayed ossification/incomplete ossification) were observed in offspring at a high dose (1,350 mg/kg/day or 2,500 mg/kg/day) at which general toxic effects (reduced body weight gain and reduced food consumption) were observed in parent animals (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014)). (3) It was reported that, in two developmental toxicity studies with rabbits dosed by gavage (days 6-18 of gestation), no developmental effects, or only minor effects (lower body weight, delayed ossification) were observed in pup at a high dose (1,000 mg/kg/day) at which general toxic effects (reduced food consumption and/or reduced body weight gain) were observed in parent animals (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014), CLH Report (2017)). [Reference Data, etc.] (4) In one study (150 to 1,350 mg/kg/day) out of developmental toxicity studies with rats in (2), reduced body weight gain was observed in parent animals from a low dose (150 mg/kg/day), an increase in the incidence of dwarfs (higher than the background incidence) was observed in fetuses from a low dose, and NOAEL was judged to be 150 mg/kg/day or lower both in dams and fetuses (CLH Report (2017)). Also in a preliminary study (only at one dose of 1,000 mg/kg/day) which preceded this study, dwarfs were observed. The authorities in the CLP proposing country judged that an increase in dwarfs constituted a serious concern about developmental toxicity, and proposed the reproductive toxicity classification (Category 2), but taking into account the very low incidence of abnormally small fetuses, the shallow dose-response curve, and inconsistent results between studies, the RAC of the ECHA stated that classification for developmental toxicity was not required (CLH Report (2017), RAC (Background Doc) (2018), ECHA RAC Opinion (2019)).
8	Specific target organ toxicity - Single exposure	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (4), it was classified as "Not classified." With the additional new information sources, classification results were changed. [Evidence Data] (1) It was reported that, in four acute oral toxicity tests with rats, no effect was observed at 2,000 to 12,800 mg/kg (in the range corresponding to “Not classified”) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015)). (2) It was reported that, in two acute oral toxicity tests with mice, no effect was observed at 8,000 to 12,800 mg/kg (in the range corresponding to “Not classified”) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015)). (3) It was reported that, in two acute dermal toxicity tests with rats, no effect was observed at 2,000 to 2,500 mg/kg (in the range corresponding to “Not classified”) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015)). (4) It was reported that, in an acute inhalation exposure test with rats (4 hours, dust), hunched posture, tonic gait, and unkempt fur were observed at 7 mg/L (in the range corresponding to “Not classified”) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (blood system)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 2 (blood system). Also, it was judged that the finding observed in the liver was pigmentation and was not a serious effect that should be adopted for the classification. It was also judged that the findings observed in the spleen were extramedullary hematopoiesis and congestion which were secondary findings of the effects on the blood system. [Evidence Data] (1) It was reported that, in three 90-day oral toxicity studies (GLP) with rats dosed by feeding, at 150 to 1,000 ppm (13.0 to 71.0 mg/kg/day, within the range for Category 2), effects on the blood (decreases in RBC, Hb, and Ht, an increase in polychromatic erythrocytes and anisocytosis, increases in Ret and Heinz bodies, a decrease in A/G ratio, an increase in MetHb, a decrease in Alb) were mainly observed, and effects on the liver (mainly hemosiderin/brown pigment deposits to Kupffer cells), effects on the spleen (increased absolute and relative weight, increased extramedullary hematopoiesis), and effects on the kidney (hemosiderin deposit to the proximal tubules) were observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014)). (2) It was reported that, in two 1-year oral toxicity test (GLP) with rats dosed by feeding, effects on the blood (decreases in Ht, RBC, and Hb, increases in WBC and Lym), hemosiderin deposits to the liver and kidney, effects on the spleen (increased absolute and relative weight), and a decrease in urinary volume were observed at 250 to 1,000 ppm (14.6 to 87.1 mg/kg/day, within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014)). (3) It was reported that, in three 2-year carcinogenicity studies with rats dosed by feeding and a chronic toxicity/carcinogenicity studies (GLP), effects on the blood (decreases in RBC, Hb, and Ht, anisocytosis with increases in polychromatic erythrocytes and spherocytes, an increase in MeHb), effects on the spleen (increased spleen extramedullary hematopoiesis, congestion), effects on the liver (pigmentation of macrophages and Kupffer cells), effects on the kidney (renal tubular pigmentation/ urothelial hyperplasia, renal pelvis epithelial hyperplasia, macrophage pigmentation), endometrial sclerosis, etc. were observed at 500 to 1,000 ppm (23.6 to 73.1 mg/kg/day, within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014)). (4) It was reported that, in two 2-year carcinogenicity studies (GLP) with mice dosed by feeding, no effect was observed at 1,000 ppm (110 mg/kg/day, in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014)).
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 = 0.029 mg a.i./L for crustacea (Daphnia magna) (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, 2020) (a.i.: active ingredient).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	It was classified in Category 1 due to being not rapidly degradable (BIOWIN), and 21-day NOEC = 0.005 mg/L for crustacea (Daphnia magna) (EU CLP CLH, 2018).
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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