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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	2164-08-1
Chemical Name	3-Cyclohexyl-5,6-trimethyleneuracil; Lenacil
Substance ID	R01-A-008
Classification year (FY)	FY2019
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE)
New/Revised	New
Classification result in other fiscal year
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
UN GHS document (External link)	UN GHS document
Definitions/Abbreviations (Excel file)	Definitions/Abbreviations
Model Label by MHLW (External link)
Model SDS by MHLW (External link)
OECD/eChemPortal (External link)	eChemPortal

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Explosives	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified (Not applicable)."
2	Flammable gases	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
3	Aerosols	*	- -	-	-	Not aerosol products. It was classified as "Not classified (Not applicable)."
4	Oxidizing gases	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
5	Gases under pressure	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
6	Flammable liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
7	Flammable solids	*	- -	-	-	No data available. Besides, there is information that it is combustible (GESTIS (Access on June 2019)).
8	Self-reactive substances and mixtures	*	- -	-	-	There are no chemical groups associated with explosive or self-reactive properties present in the molecule. It was classified as "Not classified (Not applicable)."
9	Pyrophoric liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
10	Pyrophoric solids	*	- -	-	-	It was classified as "Not classified" because it is estimated that it does not ignite at normal temperatures from information that it is stable at up to a melting point (315 deg C) (Agricultural Chemicals Times supplement "Agricultural chemicals technology information" No. 8 (Japan Crop Protection Association, 1991)).
11	Self-heating substances and mixtures	*	- -	-	-	No data available.
12	Substances and mixtures which, in contact with water, emit flammable gases	*	- -	-	-	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 (Not applicable)."
13	Oxidizing liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
14	Oxidizing solids	*	- -	-	-	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 (Not applicable)."
15	Organic peroxides	*	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified (Not applicable)."
16	Corrosive to metals	*	- -	-	-	Classification is not possible because test methods applicable to solid substances are not available.
17	Desensitized explosives	*	- -	-	-	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)	*	- -	-	-	[Rationale for the Classification] Based on (1)-(3), it was classified as "Not classified." [Evidence Data] (1) LD50 for both rodents and nonrodents: >5,000 mg/kg (PATTY (6th, 2012)) (2) LD50 for rats: >8,000 mg/kg (Agricultural Chemicals Times supplement "Agricultural chemicals technology information" Vol.8 (Japan Crop Protection Association, 1991)). (3) LD50 for rats: >5,000 mg/kg (CLH Report (2013)) [Reference Data, etc.] (4) LD50 for mice: >11,988 mg/kg (Agricultural Chemicals Times supplement "Agricultural chemicals technology information" Vol.8 (Japan Crop Protection Association, 1991)).
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Based (1) and (2), it was classified as "Not classified." [Evidence Data] (1) LD50 for rabbits: >5,000 mg/kg (PATTY (6th, 2012)) (2) LD50 for rats: >2,000 mg/kg (Agricultural Chemicals Times supplement "Agricultural chemicals technology information" Vol.8 (Japan Crop Protection Association, 1991), CLH Report (2013))
1	Acute toxicity (Inhalation: Gases)	*	- -	-	-	[Rationale for the Classification] Solid (GHS definition). It was classified as "Not classified (Not applicable)."
1	Acute toxicity (Inhalation: Vapours)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." Besides, since LC50 values were higher than the saturated vapor concentration (0.0000000189 mg/L), the reference value in units of mg/L was applied as the dust. [Evidence Data] (1) LC50 (4 hours) for rats: 4.4-5.2 mg/L (PATTY (6th, 2012)) (2) LC50 (4 hours) for rats: >5.12 mg/L (CLH Report (2013))
2	Skin corrosion/irritation	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) In a skin irritation test (equivalent to OECD TG 404, GLP) with rabbits (n=3, female), since both mean scores of erythema and edema were 0 at 24/48/72 hours, it was judged to be non-irritating to the skin (CLH Report (2013)). (2) This substance is not irritating to the skin (PATTY (6th, 2012)).
3	Serious eye damage/eye irritation	*	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) In an eye irritation test (equivalent to OECD TG 405, GLP) with rabbits (n=3, female), mean scores of conjunctival redness were 0.3 at 24/48/72 hours in 2/3 animals (0 in the other animal), and mean scores of the cornea, the iris and conjunctival edema were 0 in all three animals. Therefore, it was judged to be non-irritating to the eyes (CLH Report (2013)). [Reference Data, etc.] (2) This substance generates no serious eye damage, and the symptoms are mild and transient following instillation into the conjunctival sac (PATTY (6th, 2012)).
4	Respiratory sensitization	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	*	- -	-	-	[Rationale for the Classification] Based on (1)-(3), it was classified as "Not classified." [Evidence Data] (1) In a maximization test (OECD TG 406, GLP) with guinea pigs (20 animals, male and female), no positive reaction was observed (CLH Report (2013)). (2) This substance is generally not a skin sensitizer (PATTY (6th, 2012)). (3) To the abraded skin of guinea pigs, 10% and 50% aqueous solutions were applied for 3 weeks 9 times in total. The challenge application was conducted 2 weeks after the last application, and irritation and sensitization were surveyed. Though slight irritation was observed, sensitization was judged to be negative (Japan Crop Protection Association (Agricultural Chemicals Times supplement "Agricultural chemicals technology information") Vol.8 (1991)).
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), since all standard combination tests, including in vivo and in vitro tests were negative, it was classified as "Not classified." [Evidence Data] (1) As for in vivo, it was negative in a bone marrow micronucleus test with mice (CLH Report (2013)). (2) As for in vitro, it was negative in a bacterial reverse mutation test, a mouse lymphoma TK assay and a chromosomal aberration test with human peripheral lymphocytes (PATTY (6th, 2012), Japan Crop Protection Association (Agricultural Chemicals Times supplement "Agricultural chemicals technology information") Vol.8 (1991), CLH Report (2013)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on the classification results by other organizations in (1) and (2)-(5), by considering the opinion of the ECHA risk assessment committee (ECHA RAC) that there is some evidence for an increased incidence of malignant mammary adenocarcinoma in rats, it was classified as Category 2. [Evidence Data] (1) As for the classification results by domestic and international organizations, it was classified as "Carc.2" in the EU CLP (CLP classification (Access on June 2019)). (2) In a combined repeated toxicity test with a carcinogenicity test in which rats were dosed by feeding at 250-25,000 ppm for 2 years, an increase in the incidence of malignant mammary adenocarcinoma was observed in females. The incidence of the malignant mammary adenocarcinoma was 12% at 2,500 ppm and 10% at 25,000 ppm, slightly higher than the historical control data (6.7%) from this laboratory. However, since it was within the range of the historical control data (13.3%) from the animal supplier, the increased incidence of malignant mammary adenocarcinoma was considered to be an equivocal finding (ECHA RAC Background document (2013)). (3) In a test in which this substance was administered by feeding to rats for 2 years, no incidence of tumors was observed (Japan Crop Protection Association (Agricultural Chemicals Times supplement "Agricultural chemicals technology information") Vol.8 (1991)). (4) In a carcinogenicity test in which mice were dosed at 100-7,000 ppm by feeding for 18 months, increased hepatocellular adenomas in the liver and increased lung alveolar tumors (total of adenomas and carcinomas) were observed in males at 7,000 ppm. Though the incidence of lung alveolar tumors (32%) was higher than the historical control data (18-21%), the difference was small and did not demonstrate decreased latency compared to controls. It was therefore considered to be of equivocal toxicological significance (CLH Report (2013)). (5) In a carcinogenicity test with rats, the incidence of mammary adenocarcinoma significantly increased at the intermediate and high doses in female rats, and a dosage relationship was observed in the combined incidences of adenomas and adenocarcinomas. Therefore, ECHA RAC concluded that there is some evidence of carcinogenicity in the mammary glands in female rats. On the other hand, as for the liver adenomas and lung alveolar tumors in male mice, it was concluded that there is equivocal evidence because they were within the range of the historical control data from this laboratory, or that the relation with administration of this substance was unspecified (CLH Report (2013)).
7	Reproductive toxicity	*	- -	-	-	[Rationale for the Classification] Based on (1)-(4), it was classified as "Not classified." [Evidence Data] (1) In a three-generation reproduction toxicity study with rats by feeding, no effects on growth, fertility and reproduction were observed (PATTY (6th, 2012), Japan Crop Protection Association (Agricultural Chemicals Times supplement "Agricultural chemicals technology information") Vol.8 (1991)). (2) In a two-generation reproduction toxicity study by feeding to rats, decreased body weight gain was observed in pups during lactation at a dose (817 mg/kg/day) where an effect on the thyroid was observed in parental animals. Besides, though the effect on lactation was observed as a reproductive effect at a very high dose, 4,300 mg/kg/day, it exceeded the 1,000 mg/kg/day, the limit dose for standard reproductive toxicity studies. Therefore, it was not considered as a reproductive effect (CLH Report (2013)). (3) No embryo toxicity or teratogenicity was observed in tests in which rats and rabbits were exposed during gestation (PATTY (6th, 2012)). (4) No embryo toxicity or teratogenicity was observed in tests in which rats and rabbits were exposed during gestation (CLH Report (2013)).
8	Specific target organ toxicity - Single exposure	*	- -	-	-	[Rationale for the Classification] There are no reports of single exposure to this substance in humans. As for experimental animals, as described in (1)-(3), no clear adverse effects were observed at doses exceeding Category 2 through all oral, dermal and inhalation routes. Therefore, it was classified as "Not classified." [Evidence Data] (1) In a single oral dose test with rats, there were no mortalities nor notable clinical signs of toxicity at 5,000 mg/kg (exceeding Category 2) (CLH Report (2013)). (2) In a single dermal dose test with rats, there were no mortalities nor notable clinical signs of toxicity at 5,000 mg/kg (exceeding Category 2) (CLH Report (2013)). (3) In a 4-hour single inhalation exposure test with rats, exaggerated breathing and brown staining around the nose were observed during and after exposure to the aerosol of this substance at 5.12 mg/L (exceeding Category 2). However, there were no deaths, and no treatment-related harmful effects were observed at necropsy (CLH Report (2013)).
9	Specific target organ toxicity - Repeated exposure	*	- -	-	-	[Rationale for the Classification] Based on (1)-(4), it was classified as "Not classified" for the oral route. Besides, there was no information on the other routes. Therefore, the classification was not possible due to lack of data. [Evidence Data] (1) In repeated dose toxicity tests in which this substance was administered to rats and mice by feeding for 90 days, increased liver weight at 5,000 ppm (equivalent to 787 mg/kg/day, exceeding Category 2) in only females in mice, and leucopenia, excretion urinary proteins and lipofuscin staining in the thyroid follicular epithelium at 5,000 ppm (equivalent to 412 mg/kg/day, exceeding Category 2) in rats, were observed (CLH Report (2013)). (2) In a test in which this substance was administered to dogs by feeding for 90 days, increased weight of the liver and thyroid (including the parathyroid), and centrilobular/midzonal hepatocyte hypertrophy were observed at 5,000 ppm (equivalent to 221 mg/kg/day, exceeding Category 2) (CLH Report (2013)). (3) In a test in which this substance was administered to rats by feeding for 28 days, no adverse effects that would enable identification of target organs were observed at doses within the range of Category 2 (CLH Report (2013)). (4) In neither a 2-year feeding test with rats nor an 18-month feeding test with mice, nonneoplastic findings that would enable identification of target organs were observed within the range of Category 2 (CLH Report (2013)).
10	Aspiration hazard	*	- -	-	-	[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)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
11	Hazardous to the aquatic environment Long term (Chronic)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	Classification not possible due to lack of data.

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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