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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	17804-35-2
Chemical Name	Methyl N-[1-(N-n-butylcarbamoyl)-1H-2-benzimidazolyl]carbamate; Benomyl
Substance ID	R02-B-039-MHLW
Classification year (FY)	FY2020
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)
New/Revised	Revised
Classification result in other fiscal year	FY2006 FY2019
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)	- -	-	-	Solid (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)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
7	Flammable solids	Classification not possible	- -	-	-	No data available. Besides, there is information that it is combustible (ICSC (2012)).
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	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
10	Pyrophoric solids	Not classified	- -	-	-	It was classified as "Not classified" because it is estimated that it does not ignite at normal temperatures from an autoignition temperature of 220 deg C (ICSC (2012)).
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). It was classified as "Not classified."
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
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. 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	- -	-	-	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. 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) - (3). [Evidence Data] (1) LD50 for rats: 9,590 mg/kg (ACGIH (7th, 2001)) (2) LD50 for rats: > 9,590 mg/kg (HSDB (Access on May 2020)) (3) LD50 for rats: > 10,000 mg/kg (EHC 148 (1993), JMPR (1995), GESTIS (Access on May 2020), HSDB (Access on May 2020), Patty (6th, 2012))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1), (2). [Evidence Data] (1) LD50 for rabbits: 10,000 mg/kg (ACGIH (7th, 2001)) (2) LD50 for rabbits: > 10,000 mg/kg (JMPR (1995), GESTIS (Access on May 2020), HSDB (Access on May 2020)) [Reference Data, etc.] (3) LD50 for rats: > 1 g/kg (> 1,000 mg/kg) (HSDB (Access on May 2020))
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] The category could not be determined from (1), (2), and it was classified as "Classification not possible." Besides, because exposure concentrations were higher than the saturated vapor pressure concentration (5.8E-008 mg/L), a reference value in the unit of mg/L was applied as dust. [Evidence Data] (1) LC50 for rats (4 hours): > 2 mg/L (ACGIH (7th, 2001), GESTIS (Access on May 2020), HSDB (Access on May 2020), Patty (6th, 2012)) (2) LC50 for rats (4 hours): > 4 mg/L (EHC 148 (1993)) (3) Vapor pressure of this substance: 3.7E-009 mmHg (25 deg C) (HSDB (Access on May 2020)) (converted value for the saturated vapor pressure concentration: 5.8E-008 mg/L)
2	Skin corrosion/irritation	Classification not possible	- -	-	-	[Rationale for the Classification] There are descriptions in (1) - (4), but it was classified as "Classification not possible" due to lack of data. The classification result was changed because the previous classification was conducted based on rat data, and newly obtained data were not sufficient to determine the category. [Reference Data, etc.] (1) In a skin irritation test in which a 40% paste was applied to the guinea pig skin, negligible irritation was seen (ACGIH (7th, 2014)). (2) In a skin irritation test in which this substance (5 mg/cm2, corresponding to 30 mg for the standard application area of about 6 cm2) was applied to the rabbit skin, it was reported to be a mild irritant (EHC 148 (1993), JMPR (1995)). (3) It was classified in Skin Irrit. 2 (H315) in EU-CLP classification (EU CLP classification (Access on July 2020)). (4) Application of aqueous suspensions of this substance to the skin of rabbits and guinea pigs did not produce significant irritation (Patty (6th, 2012)).
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	[Rationale for the Classification] There are descriptions in (1) - (4), but it was classified as "Classification not possible" due to lack of data. [Reference Data, etc.] (1) This substance caused eye irritation in humans (ACGIH (7th, 2014)). (2) In an eye irritation test in which this substance (5 mg) was applied to the rabbit eye, it was reported to be a mild irritant (EHC 148 (1993), JMPR (1995)). (3) Instillation of this substance into the rabbit eye produced temporary mild conjunctival irritation (Patty (6th, 2012)). (4) Eye irritation and contact dermatitis were reported in workers exposed to this substance (ACGIH (7th, 2014)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1A	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] It was classified in Category 1A from (1) - (5). Subcategorization was conducted due to new data obtained. [Evidence Data] (1) This substance was classified in occupational skin sensitizers Group 2 by the Japan Society for Occupational Health (JSOH) (OEL Documentations (Occupational Sensitizer classification) (Japan Society For Occupational Health (JSOH), 2018)). (2) This substance produced skin sensitization in guinea pigs and humans (ACGIH (7th, 2014)). (3) In a skin sensitization test with guinea pigs (maximization test), it was positive, and the positive rate was reported to be 100% (EHC 148 (1993), JMPR (1995), MAK (DFG) (2015)). (4) There are reports of sensitization in workers exposed to this substance (MAK (DFG) (2015)). (5) Eye irritation and contact dermatitis were reported in workers exposed to this substance (ACGIH (7th, 2014)). [Reference Data, etc.] (6) It was classified in Skin Sens. 1 (H317) in EU-CLP classification (EU CLP classification (Access on July 2020)).
5	Germ cell mutagenicity	Category 1B	Danger	H340	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] It was classified in Category 1B from (1), (2). [Evidence Data] (1) As for in vivo, there are multiple reports that it was negative in dominant lethal tests using rat germ cells, but it is reported that dose-dependent increases in the incidence of aneuploidy were observed in oocytes after oral administration of this substance to female rats. And it is reported that in chromosomal aberration tests in rats or mice, it was positive in embryo cells, negative in germ cells, and positive and negative in bone marrow cells. It is reported that it was positive in micronucleus tests using bone marrow cells of rats or mice (EHC 148 (1993), MAK (DFG) (2015), JMPR (1995)). (2) As for in vitro, there are reports on weakly positive and negative results and increased aneuploidy and polyploidy in chromosomal aberration tests using human lymphocytes. It is reported that it was weakly positive in a sister chromatid exchange test using human lymphocytes. And it is reported that it was positive and negative in bacterial reverse mutation tests, and it is reported in test systems using cultured mammalian cells that it was positive in a chromosomal aberration test and negative in a gene mutation test (same as the above). [Reference Data, etc.] (3) It was classified in Muta. 2 in EU CLP classification (EU CLP classification (Access on April 2020)). (4) It was classified in germ cell mutagenicity (2005) Category 3A in MAK in Germany (MAK (DFG) (2015)). (5) It is known that this substance has adverse effects on the male reproductive organs of various mammals, and not only Sertoli cells but also germ cells themselves were affected. The metabolite, carbendazim is responsible for the effects (MAK (DFG) (2015)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] There was no available report targeted at humans. It was classified in Category 2 from (1), (2). The classification result was changed based on the latest classification results by other organizations. [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified in A3 by ACGIH (ACGIH (7th, 2014)) and Group C (Possible Human Carcinogen) by EPA (EPA Annual Cancer Report 2019 (Access on September 2020): classification in 2000). (2) In carcinogenicity tests by 2-year diet administration of this substance to male and female rats and mice, no treatment-related tumor incidences were observed in rats. There were dose-dependent increases in the incidence of hepatocellular adenoma and carcinoma in female mice and significant increases in the incidence of hepatocellular adenoma and carcinoma in male mice in dosed groups except for the maximum dose group (ACGIH (7th, 2014)). [Reference Data, etc.] (3) In a test in which carbendazim, which was a major metabolite of this substance, was dosed to mice for 2 years by feeding, significant increases in the incidences of hepatocellular carcinoma tumor and combined (adenoma and/or carcinoma) hepatocellular tumor was observed (ACGIH (7th, 2014)).
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 1B. [Evidence Data] (1) In the OEL Documentations (Japan Society for Occupational Health (JSOH), 2018), although sufficient evidence based on epidemiology studies had not been shown, animal tests showed multiple evidences of reproductive toxicity. Therefore, it was classified in Group 2 of the reproductive toxicant classification. (2) In a developmental toxicity study with female rats dosed by gavage on days 7 to 21 of gestation, malformations in the cerebrum and whole body occurred, and when a protein-deficient diet was given, hydrocephalus (69.4%), meningocele (8.2%), cerebral hernia (14.3%), exencephaly (44.9%), anencephaly (14.3%), hypoplasia of the corpus callosum (26.5%), paraventricular necrosis (26.5%), and neoplasia of paraventricular cells (55.1%) were observed (OEL Documentations (Japan Society for Occupational Health (JSOH), 2018)). (3) In a developmental toxicity study with female rats dosed by gavage on days 7 to 21 of gestation, malformations of the eyes and cerebrum increased when a protein-deficient diet was given. The observed malformations of the eyes included retinal dysplasia (associated with formation of rosettes in the retinal cells or retinal invagination), cataract, microphthalmia, and anophthalmia (OEL Documentations (Japan Society for Occupational Health (JSOH), 2018)). [Reference Data, etc.] (4) In the EU CLP classification, it was classified as Repr.1B (Classification in EU CLP (Access on July 2020)). (5) In an acute oral toxicity test with rats and an inhalation exposure test with dogs, testicular degeneration associated with necrosis of the germinal epithelium and aspermatogenesis was observed (JMPR (1995)). (6) In a two-year oral toxicity study with dogs dosed by feeding, degeneration of the testes (a decrease in testicular weight, absence of sperms and spermatic giant cells) was observed (JMPR (1995), EHC 148 (1993)).
8	Specific target organ toxicity - Single exposure	Category 1 (reproductive organs (male))	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 1 (reproductive organs (males)). New information sources were used and the classification results were changed from the previous classification. [Evidence Data] (1) In an acute oral toxicity test with rats (100 mg/kg or above, within the range for Category 1) and an inhalation exposure test with dogs (1.65 mg/L, the exposure time was not described), testicular degeneration associated with necrosis of the germinal epithelium and aspermatogenesis was observed (JMPR (1995)). (2) As a result of a 4-hour inhalation exposure of male dogs to aerosol of this substance (1.65 mg/L) (within the range for Category 2), a decrease in spermatogenic ability was observed 14 days after exposure in a histopathological examination (EHC 148 (1993)). (3) As carbendazim, which is an active metabolite of this substance, combines with beta-tubulin, there are concerns especially about the effects on the spermatogenic process (OEL Documentations (Japan Society for Occupational Health (JSOH), 2018)). [Reference Data, etc.] (4) In an acute oral toxicity test with rats (dose unknown), changes occured in the sperm depending on the stage of the spermatogenic cycle when the compound was administered (Patty (6th, 2012)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (nasal cavity, liver, reproductive organs (male))	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1) and (2), when this substance was administered in the oral route at a dose within the range for Category 2, effects on the liver and reproductive organs (males) were observed. Based on (3), in the inhalation route at a dose within the range for Category 2, effects on the nasal cavity were observed. Therefore, it was classified in Category 2 (nasal cavity, liver, reproductive organs (males)). Based on the examination of new information, the classification results were changed from the previous classification. [Evidence Data] (1) In a three-month oral toxicity study with dogs dosed by feeding, at 2,500 ppm (converted guidance value: 62.5 mg/kg/day, within the range for Category 2), increases in ALP and ALT, a decrease in the A/G ratio, a decreased weight of the thymus and an increased weight of the thyroid were observed in males and females, a decreased weight of the prostate was observed in males (3/4 cases), and decreases in erythrocyte count, hemoglobin concentration, and hematocrit value, as well as swelling of the spleen, myeloid hyperplasia of the spleen and bone marrow, and erythroid hyperplasia were observed in one female (JMPR (1995), EHC 148 (1993)). (2) In a two-year oral toxicity study with dogs dosed by feeding, at 2,500 ppm (converted guidance value: 62.5 mg/kg/day, within the range for Category 2), a decrease in food consumption, reduced body weight gain, bile duct proliferation, and hepatocyte vacuolation were observed; and in males, increases in cholesterol, ALP, and ALT, decreases in total protein and A/G ratio, and degeneration of the testes (a decrease in testicular weight, absence of sperms, and spermatic giant cells) were observed (JMPR (1995), EHC 148 (1993)). (3) In a 90-day inhalation exposure test with rats, degeneration of the olfactory epithelium was observed in males at or above 50 mg/m3 (0.05 mg/L, within the range for Category 2) and in females at 200 mg/m3 (0.2 mg/L, within the range for Category 2), and a decrease in body weight and a decrease in food consumption were observed in males at 200 mg/m3 (0.2 mg/L, within the range for Category 2) (JMPR (1995), EHC 148 (1993)).
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)	-	- -	-	-	-
11	Hazardous to the aquatic environment Long term (Chronic)	-	- -	-	-	-
12	Hazardous to the ozone layer	-	- -	-	-	-

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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