NITE - Chemical Management Field

Latest GHS Classification Results by the Japanese Government (edited by NITE)

GENERAL INFORMATION

Item	Information
CAS RN	7696-12-0
Chemical Name	(1,3-Dioxo-4,5,6,7-tetrahydroisoindolin-2-yl)methyl 2,2-dimethyl-3-(2-methylprop-1-en-1-yl)cyclopropane-1-carboxylate
Substance ID	m-nite-7696-12-0_v2
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	To Guidance List
UN GHS document (External link)	To UN GHS document
FAQ（GHS classification results by the Japanese Government）	To FAQ
List of Information Sources (Excel file)	List of Information Sources
List of Definitions/Abbreviations	Definitions/Abbreviations
Sample Label by MHLW (External link)	MHLW Website (in Japanese Only)
Sample SDS by MHLW (External link)	MHLW Website (in Japanese Only)
OECD/eChemPortal (External link)	To OECD/eChemPortal (External link)

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Explosives	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecules.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
7	Flammable solids	Classification not possible	- -	-	-	Classification not possible due to lack of data	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
8	Self-reactive substances and mixtures	Classification not possible	- -	-	-	Although the unsaturated bond is included in molecule, classification is not possible with no data.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
10	Pyrophoric solids	Not classified	- -	-	-	It is for agricultural chemicals, and even if it contacts the normal temperature air, it does not ignite spontaneously. It is described that storage with temperature at up to 50degC provides stability (PM (13th, 2003)).	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	The test method applicable for substances becoming liquid or gas at 140degC of test temperature has not been established.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified (Not applicable)	- -	-	-	Metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At) are not included.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Although it is an organic compound including oxygen, not fluorine and chlorine, this oxygen has not chemically bound to any elements other than carbon and hydrogen.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	The organic compound not including peroxy group in molecule.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to solid substances are not available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
17	Desensitized explosives	-	- -	-	-	-	-	-

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Acute toxicity (Oral)	Not classified	- -	-	-	Although LD50 value 4,600 mg/kg of the oral administration test employing a rat (EHC 98 (1990)), which corresponded to the U.N. GHS acute toxicity Category 5, it fell under unadopted category in Japan and was classified into "Not classified".	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
1	Acute toxicity (Dermal)	Not classified	- -	-	-	Since LD50 value of the dermal administration test employing rats was >5,000 mg/kg (EHC 98 (1990)) , it was classified into "Not classified".	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Since it was a solid by the definition of GHS and inhalation in gas was not assumed, it was classified into "Not applicable".	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	Classification not possible due to lack of data	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	This substance is a solid whose saturated vapor pressure level (30degC)is 1.26*10^-5 mg/L. Since LC50 value of 3-hour inhalation exposure test employing rats is >2.74 mg/L (HSDB (2001)), the dust standard is applied. Since 4-hour equivalent LC50 value is >2.06 mg/L, classification cannot be specified, and classification is not possible.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
2	Skin corrosion/irritation	Classification not possible	- -	-	-	Classification is not possible since the exposures time is unknown despite a description of "no irritation" in the results of either case of two skin irritation tests with rabbits (EHC 98 (1990)).	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
3	Serious eye damage/eye irritation	Category 2B	- Warning	H320	P305+P351+P338 P337+P313 P264	There are descriptions of "slight" and "It is a transient condition and recovered after 48 hours," respectively, about the two determinations of the eye irritation test employing rabbits. (EHC 98 (1990)). As mentioned above, it was classified into Category 2B.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification is not possible since there is no data.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
4	Skin sensitization	Classification not possible	- -	-	-	For humans, it has been described that "there is no sensitizing properties" in the half-sealing patch test employing a 1% solution in 200 healthy persons (EHC 98 (1990)). For animals, although it has been described that "racemic mixture and 1R, cis/Tran isomer were not acknowledged to be the sensitization substances in guinea pig" (EHC 98(J), (1990)), the details, such as dosage, have not been described. As mentioned above, classification is not possible due to insufficient data.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
5	Germ cell mutagenicity	Not classified	- -	-	-	From the description of the body cell in vivo mutagenicity test (chromosome aberration test employing a the mouse bone marrow cell) being "negative" (EHC 98 (1990)), it was classified into "Not classified".	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
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)).	FY2021	GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
7	Reproductive toxicity	Classification not possible	- -	-	-	In a reproductive toxicity study in rats it is reported that "there were no effects on the offspring at doses at which increases in liver and kidney weights and decreased weight gain and feed intake were observed in the parent animals. However, effects on the oestrous cycle and inhibition of ovulation were observed at the highest dose of 1,000 mg/kg, but there were no changes in the pregnancy rate" (EHC 98 (1990)). Since this primary document is non-public data and some details are unclear, classification is not possible.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
8	Specific target organ toxicity - Single exposure	Category 2 (central nervous system)	Warning	H371	P308+P311 P260 P264 P270 P405 P501	EHC 98 (1990) has a description that "signs of the toxicity include excessive excitement, tremor (trembling), ataxia, and a functional fall." When one of citation (Degradation, metabolism and toxicity of synthetic pyrethroids. (1976)) is checked, we found a description that "as which irritability, ataxia, and urinary incontinence were regarded" in the single inhalation exposure test which employed the rat and the mouse. This impact was seen within the limits of the guidance value of Category 2. As mentioned above, it was classified into Category 2 (central nervous systems).	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
9	Specific target organ toxicity - Repeated exposure	Classification not possible	- -	-	-	In EHC 98 (1990) it was reported that "weight reduction of the pituitary gland and thyroid/parathyroid gland and reduction of lien weight in males" were observed in a 104-week feeding study in mice. Moreover, in a 6-month feeding study in rats, it was reported that "increased serum calcium levels and reduced hepatic lipid content in males and a slight increase in urinary protein and increases in relative weight of kidneys and liver weights in males and females" within the range of guidance values for Category 2 were observed. For liver symptoms, it is pointed out that "it is an adaptive change related to the addition of corn oil to the feed" (EHC 98 (1990)). Also, for other organs no effects apart from weight loss have not been observed and no serious symptoms are thought to occur. From the above, none of these organs can be considered as target organs, but the possibility cannot be completely ruled out that exposure to this substance will affect human health, so classification is not possible.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
10	Aspiration hazard	Classification not possible	- -	-	-	Classification not possible due to lack of data	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
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).	FY2021	GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
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.	FY2021	GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in the Annexes to the Montreal Protocol.	FY2021	GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))

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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