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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	1563-66-2
Chemical Name	2,3-Dihydro-2,2-dimethyl-7-benzo[b]furanyl N-methylcarbamate; Carbofuran
Substance ID	R02-B-095-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 (GESTIS (Access on June 2020)).
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	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). 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)	Category 1	Danger	H300	P301+P310 P264 P270 P321 P330 P405 P501	[Rationale for the Classification] It was classified in Category 1 from (1) - (6). [Evidence Data] (1) LD50 for rats: 4.4-21 mg/kg (Canada Pesticides (2009)) (2) LD50 for rats: males: 5 mg/kg, females: 18 mg/kg (ACGIH (7th, 2004)) (3) LD50 for rats: 5 mg/kg (GESTIS (Access on June 2020), HSDB (Access on June 2020)) (4) LD50 for rats: females: 5.3-9.5 mg/kg, males: 8.6-13.3 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)) (5) LD50 for rats: 6.0-7.8 mg/kg (EPA Pesticides RED (2007)) (6) LD50 for rats: 6-14 mg/kg (EHC 64 (1986))
1	Acute toxicity (Dermal)	Category 4	Warning	H312	P302+P352 P362+P364 P280 P312 P321 P501	[Rationale for the Classification] It was classified in Category 4 from (1) - (6). Besides, the classification result was changed from the previous classification by using new information sources. [Evidence Data] (1) LD50 for rabbits: 1,000-2,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)) (2) LD50 for rabbits: > 2,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)) (3) LD50 for rabbits: 3,400 mg/kg (ACGIH (7th, 2004), EHC 64 (1986)) (4) LD50 for rabbits: 4,403 mg/kg (EPA Pesticides RED (2007)) (5) LD50 for rats: > 500 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)) (6) LD50 for rats: females: 3,094 mg/kg, males: > 5,000 mg/kg (Canada Pesticides (2009))
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 1	Danger	H330	P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501	[Rationale for the Classification] It was classified in Category 1 from (1) - (3). Besides, because exposure concentrations were higher than the saturated vapor pressure concentration (6.4E-006 mg/L), a reference value in the unit of mg/L was applied as dust. [Evidence Data] (1) LC50 for rats (4 hours): females: 0.04 mg/L, males: 0.06 mg/L (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)) (2) LC50 for rats (4 hours): 0.047 mg/L (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)) (3) LC50 for rats (4 hours): 0.08 mg/L (EPA Pesticides RED (2007)) (4) Vapor pressure of this substance: 5.4E-007 mmHg (25 deg C) (HSDB (Access on May 2020)) (converted value for the saturated vapor pressure concentration: 6.4E-006 mg/L)
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1), (2). The classification result was changed due to new data (1), (2) obtained. [Evidence Data] (1) In a skin irritation test with rabbits on this substance according to EPA OPPTS 870.2500, the primary irritation score was reported to be 0.25 (EPA Pesticides RED (2007)). (2) Eye and skin irritation tests with rabbits were conducted, and no eye and skin irritation was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). The classification result was changed due to new data (1) - (3) obtained. [Evidence Data] (1) It is reported that in an eye irritation test with rabbits on this substance according to EPA OPPTS 870.2400, there was minimal irritation (EPA Pesticides RED (2007)). (2) Eye and skin irritation tests with rabbits were conducted, and no eye and skin irritation was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (3) It is reported that in an eye irritation test with rabbits, it caused minimal irritation (HSDB (Access on June 2020)). [Reference Data, etc.] (4) In an eye irritation test with rabbits on this substance (5 mg), it was reported to be minimally irritating (Canada Pesticides (2009)).
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] It was classified as "Not classified" from (1) - (3). The classification result was changed due to new data (1) - (3) obtained. [Evidence Data] (1) This substance was not sensitizing in a skin sensitization test with guinea pigs by intracutaneous induction (ACGIH (7th, 2004), Canada Pesticides (2009), HSDB (Access on June 2020)). (2) In a skin sensitization test with guinea pigs according to EPA OPPTS 870.2600, this substance was reported to be not a sensitizer (EPA Pesticides RED (2007)). (3) Skin sensitization tests with guinea pigs (Buehler test, Draize test, maximization test) were conducted and gave negative results (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). [Reference Data, etc.] (4) As a result of patch testing on various pesticides in 30 farmers with contact dermatitis (20 persons in the control group), carbamates, including this substance, caused sensitization in seven persons (Environmental Risk Assessment for Chemical Substances vol. 3, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2004)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] From (1) - (3), it was classified as "Not classified" based on the weight of evidence. New information was added, and the classification result was changed. [Evidence Data] (1) As for in vivo, it was reported to be positive and negative in micronucleus tests with mouse bone marrow cells and chromosomal aberration tests with bone marrow cells from mice or rats (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), ACGIH (7th, 2004)). (2) As for in vitro, there were multiple reports that it was positive (in TA1535 without metabolic activation) and negative in bacterial reverse mutation tests. As for test systems in cultured mammalian cells, it was reported to be positive in a mouse lymphoma test and a sister chromatid exchange test and negative in a gene mutation test and a chromosomal aberration test (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), ACGIH (7th, 2004)). (3) It is described in ACGIH (2004) that based on WoE assessment, it was considered to have, at best, weak genotoxic potential (ACGIH (2004)). And it is described in the Risk Assessment Report (Pesticides) (Food Safety Commission of Japan) that it was considered that it did not have genotoxicity that could pose a problem in vivo (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified in A4 by ACGIH (ACGIH (7th, 2004)) and NL (Not Likely to be Carcinogenic to Humans) by EPA (EPA Annual Cancer Report 2019 (Access on September 2020): classified in 1997). (2) In two combined chronic toxicity/carcinogenicity tests by 2-year diet administration of this substance to male and female rats, no neoplastic lesions with a treatment-related increase in incidences were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (3) In a combined chronic toxicity/carcinogenicity test and a carcinogenicity test by 2-year diet administration of this substance to male and female mice, no neoplastic lesions with a treatment-related increase in incidences were found (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)).
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) and (2), at doses at which parental toxicity was observed, a decrease in survival rate in pups, an increase in stillborn pups, and developmental delay were observed, and therefore, it was classified in Category 1B. New information sources were used and the classification results were changed from the previous classification. [Evidence Data] (1) In a two-generation reproduction toxicity test with rats dosed by feeding, at doses at which parental toxicity (reduced body weight gain and a decrease in food consumption) was observed, lower survival rate, etc. (reduced body weight gain (postnatal day 21) and lower survival rate (postnatal days 4, 7, 14 and 21)) of pups were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (2) In a developmental neurotoxicity test with female rats dosed by feeding during the period from day 6 of gestation to day 10 of lactation, at doses at which maternal toxicity (reduced body weight gain (days 10 to 20 of gestation), a decrease in food consumption (days 6 to 10 of gestation)) was observed, a decrease in survival rate in pups, an increase in stillborn pups, and developmental delay in pups (a decrease in survival rate on postnatal day 4, lower body weight/reduced body weight gain (after postnatal day 0), delayed sexual maturation (vaginal opening and preputial separation), delays in pinna unfolding, eruption of incisors of the lower jaw and palpebral opening, delayed development of swimming ability (keeping the cephalic angle) (males and females, after postnatal day 6), an increasing trend of stillborn pups, an increase in the number of Y-shaped waterway trials (males: postnatal days 24, 25 and 30, females: postnatal day 24)) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). [Reference Data, etc.] (3) In a developmental toxicity study with female rats dosed by gavage on days 6 to 15 of gestation, even at doses at which maternal toxicity (lethargy, death (1 animal), corneal opacity, salivation, lacrimation, tremor and cramps) was observed, no effect was observed in fetuses (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (4) In a developmental toxicity study with female rats dosed by gavage on days 6 to 15 of gestation, maternal toxicity (salivation, tremors of the lower jaw (for two hours after treatment), reduced body weight gain) was observed, and lower body weight and an increasing trend of unossified 5th/6th sternebrae were observed in fetuses, but no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (5) In a developmental toxicity study with female rabbits dosed by gavage on days 6 to 18 of gestation, at a dose at which maternal toxicity (death (1/20 cases), unkempt fur, stained fur and reduced body weight gain (in the early stage of treatment, details unknown)) was observed, skeletal variations (abnormal alignment of the sternebrae 23.1%) were observed in fetuses (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)).
8	Specific target organ toxicity - Single exposure	Category 1 (nervous system), Category 3 (narcotic effects)	Danger Warning	H370 H336	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	[Rationale for the Classification] Based on (1) to (6), it was classified in Category 1 (nervous system), and Category 3 (narcotic effects). [Evidence Data] (1) In humans who worked for about four hours in the field two hours after spraying pesticide containing this substance, symptoms such as nausea, headache, dizziness, muscle weakness, watery eyes, vomiting, salivation, bradycardia, sweating, and miosis appeared (Environmental Risk Assessment for Chemical Substances Vol. 3, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2004)). (2) In volunteers who were given a single oral dose of this substance, headache and dizziness were observed at 0.10 mg/kg (2 people), and symptoms of cholinesterase inhibition, such as thirst, salivation, sweating, abdominal pain, drowsiness, dizziness, anxiety, vomiting, and miosis, were observed at 0.25 mg/kg (4 people) (Environmental Risk Assessment for Chemical Substances Vol. 3, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2004), ACGIH (7th, 2004)). (3) A 23-year-old man who intentionally ingested this substance (concentration unknown, 100 mL) showed sensorimotor neuropathy (ACGIH (7th, 2004)). (4) In an acute oral toxicity test with rats, piloerection, abnormal body posture, abnormal gait, lethargy, pallor of limbs, salivation, and tremor were observed at or above 5 mg/kg (within the range for Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (5) In an acute dermal application test with rabbits (no description of the minimum dose at which effects were observed, and it was assumed that effects were observed at least around the LD50 value (1,000 to 2,000 mg/kg, within the range for Category 2)), piloerection, tremor, bruxism, unsteady gait, lethargy, crouching posture, steppage gait, an increase in respiratory rate, and a decrease in body weight were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (6) In an acute inhalation exposure test with rats (no description of the minimum dose at which effects were observed, and it was assumed that effects were observed at least around the LD50 value (males: 0.06 mg/L, females: 0.04 mg/L, within the range for Category 1)), wet hair coat, hunched posture, piloerection, ataxia, fasciculation, labored respiration, an increase or a decrease in respiratory rate, reddish brown staining of hair coat and around the eyes, nose, and head, lethargy, ptosis, tremor, pallor of limbs, proptosis, tiptoeing, and swelling of the cheek were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] There was no report on repeated exposure to this substance in humans. Based on (1) to (4), effects on the nervous system at doses of Category 1 were observed in experimental animals. Therefore, it was classified in Category 1 (nervous system). In (5) and (6), effects on the blood system, liver, and reproductive organs (male) were also reported, but in (3), no effect on them was observed. Since there was inconsistency in the data, the organs were not adopted as target organs. As a result of reviewing the information, the classification result was changed from the previous classification. [Evidence Data] (1) It was reported that, in a 90-week test with rats dosed by feeding, at or above 120 ppm (males/females: equivalent to 16.2/6.8 mg/kg/day, within the range for Category 2/Category 1), inhibition of brain cholinesterase (ChE) activity was observed, and at 720 ppm (males/females: equivalent to 38.7/43.5 mg/kg/day, within the range for Category 2 in both sexes), inhibition of erythrocyte ChE activity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (2) It was reported that, in a 13-week test with dogs dosed by feeding, salivation and inhibition of erythrocyte ChE activity were observed at or above 10 ppm (males/females: Equivalent to 0.45/0.41 mg/kg/day, both within the range for Category 1); and in a group which was treated at 250 ppm after being treated at 500 ppm for 5 days (males/females: Equivalent to 10.9/10.4 mg/kg/day, both within the range for Category 2), vellication, ataxia, lower motility, tachypnea/deep respiration, and vomiting were observed, and one male died (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), ACGIH (7th, 2004), JMPR (2008)). (3) In a one-year oral toxicity test with dogs dosed by capsules, at or above 1 mg/kg (within the range for Category 1), soft feces, miosis, inhibition of erythrocyte ChE activity were observed; and at 10 mg/kg/day (within the range for Category 1), vomiting was observed, in addition, salivation and tremor were observed in males (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (4) It was reported that, in multiple 21-day dermal administration tests with rabbits, inhibition of brain ChE activity was observed at or above 100 mg/kg/day (converted guidance value: 23.3 mg/kg/day, within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), ACGIH (7th, 2004)). [Reference Data, etc.] (5) It was reported that, in a one-year test with dogs dosed by feeding, reduced body weight gain associated with vomiting, muscular spasms, salivation, decreases in hematocrit, hemoglobin concentration, and red blood cell count, and inhibition of plasma, erythrocyte, and brain ChE activity were observed at 12.5 mg/kg/day (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), Environmental Risk Assessment for Chemical Substances Vol. 3, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2004)). In addition, it was reported that degeneration of the seminiferous tubules of the testes and giant cell formation in the seminiferous tubules of the testes were also observed in males, but it was pointed out that they might be secondary effects of decreased body weight, etc. (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (6) It was reported that, in a one-year test with dogs dosed by feeding, at 20 ppm (males/females: 0.84/0.63 mg/kg/day, both within the range for Category 1), fatty degeneration of hepatocytes was observed; and at 500 ppm (males/females: 14.6/13.4 mg/kg/day, both within the range for Category 2), vomiting, soft feces, salivation, weakness, decreases in hematocrit and hemoglobin, and pulmonary inflammatory changes were observed, and tremor, lethargy, a decrease in red blood cell count, and inhibition of erythrocyte and brain ChE activity were furthermore observed in males (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), ACGIH (7th, 2004)).
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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