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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	7696-12-0
Chemical Name	Cyclohex-1-ene-1,2-dicarboximidomethyl (1RS)-cis-trans-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylate (synonym: Tetramethrin)
Substance ID	R03-C-038-MHLW, MOE
Classification year (FY)	FY2021
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	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	-	- -	-	-	-
2	Flammable gases	-	- -	-	-	-
3	Aerosols	-	- -	-	-	-
4	Oxidizing gases	-	- -	-	-	-
5	Gases under pressure	-	- -	-	-	-
6	Flammable liquids	-	- -	-	-	-
7	Flammable solids	-	- -	-	-	-
8	Self-reactive substances and mixtures	-	- -	-	-	-
9	Pyrophoric liquids	-	- -	-	-	-
10	Pyrophoric solids	-	- -	-	-	-
11	Self-heating substances and mixtures	-	- -	-	-	-
12	Substances and mixtures which, in contact with water, emit flammable gases	-	- -	-	-	-
13	Oxidizing liquids	-	- -	-	-	-
14	Oxidizing solids	-	- -	-	-	-
15	Organic peroxides	-	- -	-	-	-
16	Corrosive to metals	-	- -	-	-	-
17	Desensitized explosives	-	- -	-	-	-

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	-	- -	-	-	-
1	Acute toxicity (Dermal)	-	- -	-	-	-
1	Acute toxicity (Inhalation: Gases)	-	- -	-	-	-
1	Acute toxicity (Inhalation: Vapours)	-	- -	-	-	-
1	Acute toxicity (Inhalation: Dusts and mists)	-	- -	-	-	-
2	Skin corrosion/irritation	-	- -	-	-	-
3	Serious eye damage/eye irritation	-	- -	-	-	-
4	Respiratory sensitization	-	- -	-	-	-
4	Skin sensitization	-	- -	-	-	-
5	Germ cell mutagenicity	-	- -	-	-	-
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] There was no increase in the incidence of tumors in mice in (1), and there was only an increase in benign tumors in rats in (2), which was considered to be limited evidence of carcinogenicity, and therefore, the findings were judged inadequate for the classification in Category 1B, and this substance was classified in Category 2. Besides, when the results in (2) are the modes of action in (6) as shown in (3), it is considered that they cannot be extrapolated to humans, but since there are no sufficient background data showing that they were caused by the modes of action in (6), the possibility of extrapolation of (2) to humans cannot be denied. Based on the new findings, the classification result was changed. [Evidence Data] (1) In a carcinogenicity study with mice dosed by feeding for two years (12 to 1,500 ppm: 2.4 to 430 mg/kg/day), there was no increase in the incidence of tumors (CLH Report (2015), ECHA RAC Opinion (2016), EPA Pesticides (2010)). (2) In a carcinogenicity study by 2-year feeding administration (1,000 to 5,000 ppm: 42 to 300 mg/kg/day) to rats (SD strain) which were dosed in utero from the fetal period and started after weaning, an increase in the incidence of interstitial cell adenomas of the testis was observed in males at or above 3,000 ppm (125 mg/kg/day). Similarly, also in a carcinogenicity study by administration to male rats of two strains (SD, Long Evans) in utero from the fetal period and 2-year feeding administration after weaning, an increased incidence of interstitial cell adenomas of the testis was observed in both animal strains in a high-dose (5,000 ppm) group. The reproducibility of testicular tumors was confirmed (CLH Report (2015), ECHA RAC Opinion (2016), EPA Pesticides (2010)). (3) Many modes of action for interstitial (Leydig) cell tumors of the testis in rats are advocated as shown in (6), but it is judged from existing findings that this substance has no mutagenicity. Other mechanisms cannot be ruled out, but the possibility of their extrapolation to humans is considered low. In conclusion, benign tumors of the testis were observed in two independent studies with rats, but the mode of action and its extrapolation to humans remain unknown, and the carcinogenicity classification was determined to be Carc. 2 (ECHA RAC Opinion (2016)). (4) As for the classification results by domestic and international organizations, the EPA classified this substance in Group C (Possible Human Carcinogen) (EPA Annual Cancer Report 2020 (Accessed Oct. 2021): Classification in 1989) or S (Suggestive Evidence of Carcinogenic Potential: classification criteria in 2005) (EPA Pesticides (2010)) and the EU classified it in Carc. 2 (EU-CLP Classification Results (Accessed Oct. 2021)). [Reference Data, etc.] (5) As a result of a carcinogenicity study with SD rats, a dose-related increase in the incidence of interstitial cell adenomas in the testes was observed in mid- and high-dose males. These results were reproducible in SD rats and Long-Evans rats. This increase was outside the historical control range for SD rats. In a carcinogenicity study with B6C3F1 mice, there was no increase in the incidence of tumors. The testicular tumors in rats were benign tumors that occurred at a later stage of the study, and the incidence of tumors was not accelerated even by starting the exposure from the fetal period. Therefore, it was judged that the testicular tumors did not progress to malignant tumors (EPA Pesticides (2010)). (6) At least nine different modes of action based on hypothalamic-pituitary-testicular axis impairments are known for the Leydig cell tumor in rats. These mechanisms are: 1) GnRH (gonadotropin-releasing hormone) agonism; 2) dopamine agonism/enhancement; 3) mutagenicity; 4) androgen receptor antagonism; 5) 5-alpha-reductase inhibition; 6) estrogen receptor agonism/antagonism; 7) aromatase inhibition; 8) reduced testosterone biosynthesis; and 9) increased testosterone metabolism. From this list, only mutagenicity can be considered completely relevant for humans. Mechanisms number 1 and 2 are considered as of no relevance for humans while the rest of the proposed mechanisms are considered of low relevance for humans. (ECHA RAC Opinion (2016)).
7	Reproductive toxicity	-	- -	-	-	-
8	Specific target organ toxicity - Single exposure	-	- -	-	-	-
9	Specific target organ toxicity - Repeated exposure	-	- -	-	-	-
10	Aspiration hazard	-	- -	-	-	-

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 96-hour LC50 = 0.0037 mg/L for fish (Oncorhynchus mykiss) (EPA Pesticides RED, 2010, EU CLP CLH, 2015, OPP Pesticide Ecotoxicity Database).
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 2 due to being not rapidly degradable (a degradation rate by BOD: 1.6% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, METI, 2005)) and 72-hour NOErC = 0.25 mg/L for algae (Raphidocelis subcapitata) (EU CLP CLH, 2015). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained (crustacea, fish), then it is classified in Category 1 due to being not rapidly degradable and 96-hour LC50 = 0.0037 mg/L for fish (Oncorhynchus mykiss) (EPA Pesticides RED, 2010). By drawing a comparison between the above results, it was classified in Category 1.
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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