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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	40487-42-1
Chemical Name	N-(1-Ethylpropyl)-2,6-dinitro-3,4-xylidine; Pendimethalin
Substance ID	R02-B-087-MHLW, MOE
Classification year (FY)	FY2020
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	FY2006
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	Classification not possible	- -	-	-	There is a chemical group associated with explosive properties (nitro group) present in the molecule, and the calculated oxygen balance is -179, higher than the criteria: -200, but the classification is not possible due to no data.
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, and there is a risk of a dust explosion (GESTIS (Access on May 2020)).
8	Self-reactive substances and mixtures	Classification not possible	- -	-	-	There is a chemical group associated with explosive properties (nitro group) present in the molecule, but the classification is not possible due to no data.
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 > 200 deg C (GESTIS (Access on May 2020)).
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Classification is not possible because test methods applicable to solid (melting point <= 140 deg C) substances are not 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	Classification not possible	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine), which is chemically bonded to the element other than carbon or hydrogen (N). However, the classification is not possible due to no data.
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	Classification not possible	- -	-	-	There is a chemical group associated with explosive properties (nitro group) present in the molecule, but the classification is not possible due to no data.

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) - (4). [Evidence Data] (1) LD50 for rats: > 2,000 mg/kg (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)) (2) LD50 for rats: males: 4,665 mg/kg, females: 5,000 mg/kg (corn oil was used as a medium) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)) (3) LD50 for rats: males: 4,670 mg/kg, females: 5,000 mg/kg (corn oil was used as a medium) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012)) (4) LD50 for rats: > 10,000 mg/kg (0.5% CMC was used as a medium) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011), Japanese Journal of Pesticide Science Vol. 11, No. 4 (Pesticide Science Society of Japan, 1986)) [Reference Data, etc.] (5) LD50 for rats: 1,050 mg/kg (Environmental Risk Assessment for Chemical Substances vol. 8, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2010), GESTIS (Access on May 2020), HSDB (Access on May 2020)) (6) LD50 for rats: females: 1,050 mg/kg, males: 1,250 mg/kg (Canada Pesticides (2007), HSDB (Access on May 2020))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (5). [Evidence Data] (1) LD50 for rats: > 2,000 mg/kg (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)) (2) LD50 for rats: > 2,500 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011), Japanese Journal of Pesticide Science Vol. 11, No. 4 (Pesticide Science Society of Japan, 1986)) (3) LD50 for rats: > 5,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)) (4) LD50 for rabbits: 2,260 mg/kg (GESTIS (Access on May 2020)) (5) LD50 for rabbits: > 5,000 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)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (4). Besides, the classification result was changed from the previous classification due to the use of new information sources. Because exposure concentrations were higher than the saturated vapor pressure concentration (1.4E-004 mg/L), a reference value in the unit of mg/L was applied as dust. [Evidence Data] (1) LC50 for rats (nose exposure, 4 hours): > 6.73 mg/L (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)) (2) LC50 for rats (nose exposure, 4 hours): > 320 mg/L (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011), HSDB (Access on May 2020)) (3) LC50 for rats (nose exposure, 4 hours): > 0.343 mg/L (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)) (4) LC50 for rats (nose exposure, 4 hours): > 1.21 mg/L (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)) (5) Vapor pressure of this substance: 9.4E-006 mmHg (25 deg C) (HSDB (Access on May 2020)) (converted value for the saturated vapor pressure concentration: 1.4E-004 mg/L)
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (4). [Evidence Data] (1) In a skin irritation test with rabbits on this substance, no irritation was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)). (2) It was not irritating in a skin irritation test with rabbits according to EPA OPP 81-5 (EPA Pesticides RED (1997)). (3) In a skin irritation test with rabbits by 4-hour semi-occlusive application of this substance, no irritation changes were seen, and it was judged as not irritating (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)). (4) This substance is a mild skin irritant (HSDB (Access on May 2020)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (4). [Evidence Data] (1) In an eye irritation test with rabbits on this substance, slight to moderate irritation was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012)). (2) In an eye irritation test with rabbits according to EPA OPP 81-4, it caused slight conjunctival irritation (EPA Pesticides RED (1997)). (3) In an eye irritation test with rabbits on this substance, iritis and conjunctival irritation were seen but completely disappeared by 48 hours (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)). (4) In an eye irritation test with rabbits on this substance, reactions with a score of 1 - 2 were observed for conjunctival redness, chemosis, and discharge at 1 hour after application but fully disappeared by 48 hours (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)).
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) - (4). Besides, in data of (5), which was the rationale for EU's classification in Category 1, it was reported to be moderately sensitizing from a reaction rate (55%) after 24 hours, but because the reactions were decreased to 5% (1/20 animals) after 48 hours, it was considered as appropriate to regard them as irritation reactions. [Evidence Data] (1) In a guinea pig skin sensitization test on this substance (Buehler test), no sensitization was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)). (2) In a guinea pig skin sensitization test according to EPA OPP 81-6 (Buehler test, application concentration 100%) and a guinea pig skin sensitization test according to OECD TG406 (maximization test, intradermal administration 5%). it was reported to be negative (CLP Report (2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)). (3) In a guinea pig skin sensitization test according to EPA OPP 81-6, it was reported to be negative (EPA Pesticides RED (1997)). (4) In a guinea pig skin sensitization test (maximization test, intradermal administration 5%), it was reported to be negative (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)). [Reference Data, etc.] (5) In a guinea pig skin sensitization test according to EPA OPP 81-6 (maximization test, intradermal administration 10%), slight erythema was observed in 11/20 animals at 24 hours after the challenge (25%), a reaction was seen only in 1/20 after 48 hours, and it was reported to be moderately sensitizing from a reaction rate (55%) after 24 hours (CLP Report (2019)). (6) It was classified in Skin Sens. 1 (H317) in EU-CLP classification (EU CLP classification (Access on August 2020)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1), (2). [Evidence Data] (1) As for in vivo, it was reported to be negative in a dominant lethal test with rats, a chromosomal aberration test with rat bone marrow cells, and a micronucleus test with mouse bone marrow cells (EPA Pesticides RED (1997), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)). (2) As for in vitro, it was reported to be positive and negative in bacterial reverse mutation tests and negative in a chromosomal aberration test in cultured mammalian cells (same as the above).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] It was classified in Category 2 from (1) - (3). An investigation was conducted by using new information sources, and the classification result was changed. [Evidence Data] (1) As for classification results by domestic and international organizations, EPA classified it in Group C (Possible Human Carcinogen) (EPA Pesticides RED (1997)). (2) In a combined chronic toxicity/carcinogenicity test by 2-year diet administration of this substance to male and female rats, significant increases in thyroid adenoma were observed in males and females (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012)). (3) In a carcinogenicity test by 18-month diet administration of this substance to male and female mice, no increase in treatment-related tumor incidences was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] There were reports of (1) to (4), and based on (3) and (4), it was classified in Category 2. As a result of examination using the new information source, the classification results were changed from the previous classification. [Evidence Data] (1) In a two-generation reproductive study with rats dosed by feeding, a decrease in body weight and a slight decrease in newborn litter size without significant difference were observed in offspring at a dose at which reduced body weight gain and a decrease in food consumption were observed in parent animals (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), CLH Report (2019)). (2) In a developmental toxicity study with female rats dosed by gavage on days 6 to 15 of gestation, no maternal toxicity or fetal toxicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), CLH Report (2019)). (3) In a developmental toxicity study with female rabbits dosed by gavage on days 6 to 18 of gestation, no effect was observed in fetuses even at a dose at which a decrease in food and water consumption and reduced body weight gain were observed in the dams (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012)). The CLH Report (2019) stated that, in this study, no maternal toxicity was observed, but an increased incidence of less than twelve pairs of ribs and missing/incomplete vertebrae was observed in fetuses. (4) In the CLH Report (2019), based on the observed developmental effects in the absence of clear maternal toxicity in (3), and considering the limitation of the study (only Alizarin Red staining was performed (which stained only the ossified parts of the bones in skeletal preparations) and no staining for cartilage was included. It was therefore difficult to conclude if less than twelve pairs of ribs truly reflected missing ribs. However, there were no other indications of fetal skeletal ossification being affected), it was proposed to classify this substance in reproductive toxicity Category 2 (Repr. 2).
8	Specific target organ toxicity - Single exposure	Not classified	- -	-	-	[Rationale for the Classification] There was no report on acute exposure effects of this substance in humans. In experimental animals, based on (1) to (3), any of the oral, dermal, and inhalation routes did not show any findings by which target organs could be identified, and therefore, it was classified as "Not classified." [Evidence Data] (1) In an acute oral toxicity test with rats, salivation, inactivity, change of color of urine, prostration, and an increase in urinary volume were observed at or above 2,500 mg/kg (exceeding Category 2); and in another acute oral toxicity test with rats, a decrease in locomotor activity was observed at or above 5,000 mg/kg (exceeding Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)). (2) In an acute dermal application test with rats, reddish tear (1 animal), change of color of urine, and yellow stained fur (all treated groups) were observed at 5,000 mg/kg (exceeding Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)). (3) It was reported that, in a 4-hour acute inhalation exposure test (nasal) with rats, dyspnea, lacrimation, gasping, and wet rales were observed at 6.73 mg/L (exceeding Category 2), however, since they were also observed in a vehicle control group, they were symptoms by inhalation exposure, and not toxic symptoms by this substance (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (liver)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 1 (liver). In (1), effects on the blood were also observed, but they were changes observed only in females and lacked consistency because no effects on the blood were observed in other similar tests, and therefore, the blood was not adopted as a target organ. In (2), effects on the thyroid were also observed, however, since they were considered to be secondary effects of hepatic metabolic activation, the thyroid was not adopted as a target organ. As a result of examination using the new information, the classification results were changed from the previous classification. [Evidence Data] (1) It was reported that in a 90-day feeding study with rats, at or above 1,800 ppm (90 mg/kg/day, within the range for Category 2), reduced body weight gain and decreases in red blood cell count, hemoglobin, and hematocrit were observed in females (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012)). (2) In a two-year oral toxicity test with rats, periportal hepatocyte hypertrophy, and ground-glass cytoplasmic degeneration and fatty degeneration of the hepatocytes were observed in males and females at or above 100 ppm (5 mg/kg/day, within the range for Category 1); concentrically laminated cytomorphology and increased secretory granules of the thyroid follicular epithelium in males and females, and an increase in liver weight in males were observed at or above 500 ppm (25 mg/kg/day, within the range for Category 2); and reduced body weight gain, an increase in thyroid weight, and hepatic nodular hyperplasia in males and females, and a decrease in food consumption and an increase in liver weight in females were observed at 2,500/5,000 ppm (125/250 m/kg/day, exceeding Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012)). (3) It was reported that in a two-year oral toxicity test with dogs, chronic inflammation of the liver and cholestasis in males and females, an increase in ALP in males, and bile duct hyperplasia, and hepatocyte necrosis in females were observed at or above 50 mg/kg/day (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), EPA Pesticides RED (1997)).
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 EC50 = 0.0125 mg/L for aquatic plants (Lemna gibba) (EPA RED, 1997).
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 in Category 1 because it is not rapidly degradable (BIOWIN) and due to 14-day NOEC = 0.0056 mg/L for aquatic plants (Lemna gibba) (EPA RED, 1997).
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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