NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	148477-71-8
Chemical Name	3-(2,4-Dichlorophenyl)-2-oxo-1-oxaspiro[4.5]dec-3-en-4-yl 2,2-dimethylbutanoate; Spirodiclofen
Substance ID	R02-A-053-METI
Classification year (FY)	FY2020
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)
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 (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)
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	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
7	Flammable solids	Classification not possible	- -	-	-	No data available.
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.
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
10	Pyrophoric solids	Classification not possible	- -	-	-	No data available.
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).
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	The substance is an organic compound containing chlorine and oxygen (but not fluorine) which are chemically bonded only to carbon or hydrogen.
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule.
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.

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). [Evidence Data] (1) LD50 for rats: > 2,000 mg/kg (OECD TG 423, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), JMPR (2009), ECHA RAC Opinion (2016))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) LD50 for rats: > 2,000 mg/kg (OECD TG 402, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), JMPR (2009), ECHA RAC Opinion (2016))
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). [Evidence Data] (1) LC50 for rats (4 hours): > 5.03 mg/L (OECD TG 403, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), JMPR (2009), ECHA RAC Opinion (2016))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) It is reported that in a skin irritation test with rabbits (n = 3) (OECD TG 404, GLP, semi-occlusive, 4-hour application, 72-hour observation), no skin irritation changes were seen (erythema/eschar score: 0/0/0, edema score: 0/0/0) (ECHA RAC Opinion (2016), CLH Report (2015), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) It is reported that in an eye irritation test with rabbits (n = 3) (OECD TG 405, GLP, 72-hour observation), no eye irritation reactions were seen in any animal (corneal opacity score: 0/0/0, iritis score: 0/0/0, conjunctival redness score: 0/0/0, chemosis score: 0/0/0) (ECHA RAC Opinion (2016), CLH Report (2015), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1B	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] It was classified in Category 1B from (1). [Evidence Data] (1) It is reported that in a maximization test with guinea pigs (n = 10) (OECD TG 406, GLP, intradermal administration: 5% solution), a positive rate was 40% (4/10), 10% (1/10) at 48, 72 hours after the first challenge and 10% (1/10), 40% (4/10) at 48, 72 hours after the second challenge (ECHA RAC Opinion (2016), CLH Report (2015), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (4), it was classified as "Not classified." [Evidence Data] (1) In a micronucleus test using the bone marrow cells of mice, negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012), CLH Report (2015), ECHA RAC Opinion (2017)). (2) In a bacterial reverse mutation test, negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012), CLH Report (2015), ECHA RAC Opinion (2017)). (3) In a mammalian cell (CHL V79) gene mutation test, negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012), CLH Report (2015), ECHA RAC Opinion (2017)). (4) In a chromosomal aberration test using the CHL V79 cells, negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)) or equivocal results (CLH Report (2015), ECHA RAC Opinion (2017)) were obtained.
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 1B. [Evidence Data] (1) As for the classification results by domestic and international organizations, EPA classified this substance in L (Likely to be Carcinogenic to Humans) (EPA Annual Cancer Report (Accessed September 2020): Classification in 2004), and EU classified this substance in Carc. 1B. (2) In a two-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding (OECD TG 453, GLP), increases in the incidence of testicular tumors (Leydig cell tumors) and uterus adenocarcinoma were observed in a group treated at the highest dose of 2,500 ppm (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), CLH Report (2015)). (3) In an 18-month carcinogenicity study with mice dosed by feeding (OECD TG 451, GLP), significant increases in the incidence of hepatocellular adenoma and the combined incidence of hepatocellular adenoma and carcinoma were observed in males of the groups treated at or above the medium dose of 3,500 ppm. In females of the group treated at 3,500 ppm, a significant increase in the combined incidence of hepatocellular adenoma and carcinoma was observed, but in females of the groups treated at 7,000 ppm, although a tendency of an increase in the combined incidence of hepatocellular adenoma and carcinoma was observed, it did not show any significant difference (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), CLH Report (2015)). (4) The EPA classified this substance in L for carcinogenicity based on the evidence for the increased incidence of Leydig cell tumors in male rats, uterus adenocarcinomas in female rats and liver tumors in mice (Federal Register vol. 79, NO. 112 (2014)).
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1), it was classified in Category 1B. In (1), effects on fertility such as atrophy of the reproductive organs and decreased sperm count were observed in F1 males. [Evidence Data] (1) It was reported that in a two-generation reproduction toxicity study with rats dosed by feeding (OECD TG416, GLP), at 1,750 ppm, general toxicity effects (such as reduced body weight gain and signs on the adrenal glands), testicular and epididymal atrophy, decreases in spermatid count and sperm count, and no occurrence of pregnancy due to failure in copulation or infertile copulation (4/25 cases) (F1 males) were observed in parental animals; lower body weight of liveborn pups (F1 and F2), reduced body weight gain (F1) and a delay in preputial separation (F1 males), etc. were observed in pups. The CLH Report reported that reduced spermatogenesis potential was observed in F1 parental animals (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2015)). [Reference Data, etc.] (2) It was reported that in a developmental toxicity study with rats dosed by gavage (OECD TG414, GLP, day 6 to 19 of gestation), no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2015)). (3) It was reported that in a developmental toxicity study with rabbits dosed by gavage (OECD TG414, GLP, day 6 to 28 of gestation), no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2015)). (4) It was reported that in a developmental neurotoxicity study with rats dosed by feeding (GLP, gestation day 0 to F1 lactation day 21), at 1,500 ppm, reduced body weight gain, etc. were observed in parental animals; and reduced body weight gain during the lactation period was observed in pups, but no developmental neurotoxicity 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), CLH Report (2015)). (5) It was reported that in another developmental neurotoxicity study with rats dosed by feeding (GLP, gestation day 0 to F1 lactation day 20), which was a different test from (4), at 1,500 ppm, reduced body weight gain, etc. during the lactation period were observed, but no developmental neurotoxicity was observed in pups (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012), CLH Report (2015)). (6) Under the EU CLP, it was classified in Repr. 2 (CLP classification (Accessed Sep. 2020)).
8	Specific target organ toxicity - Single exposure	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (5), it was classified as "Not classified." [Evidence Data] (1) It was reported that in an acute oral toxicity test with rats (OECD TG 423, GLP), no symptom nor death was observed at 2,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012), CLH Report (2015)). (2) It was reported that in an acute oral toxicity test (GLP) with mice, no symptom nor death was observed at 2,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)). (3) It was reported that in an acute neurotoxicity test with rats dosed by gavage (GLP), no general toxicity and no treatment-related effect in an FOB and a motor activity test were observed at 2,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012), CLH Report (2015)). (4) It was reported that in an acute dermal toxicity test with rats (OECD TG 402, GLP), no symptom nor death was observed at 2,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012), CLH Report (2015)). (5) It was reported that in an acute (dust) inhalation toxicity test with rats (4 hours, OECD TG 403, GLP), no symptom nor death was observed at 5.03 mg/L (in the range corresponding to “Not classified”) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012), CLH Report (2015)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (adrenal gland), Category 2 (reproductive organs (male))	Danger Warning	H372 H373	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) to (3), it was considered that the target organs were the adrenal glands and the reproductive organs (males), and adrenal effects were observed in the dose range for Category 1 and reproductive effects (males) were observed in the dose range for Category 2. Therefore, it was classified in Category 1 (adrenal gland) and Category 2 (reproductive organ (males)). [Evidence Data] (1) It was reported that in a repeated dose 90-day oral toxicity study with rats dosed by feeding (OECD TG 408, GLP), small cytoplasmic vacuolation of the adrenal cortex and a decrease in TG (females) were observed at or above 500 ppm (32.1 mg/kg/day (males), 47.1 mg/kg/day (females), within the range for Category 2); and longer PTT, an increase in ALP, decreases in Chol and TG, and small cytoplasmic vacuolation of the adrenal cortex (males) were observed at 2,500 ppm (166.9 mg/kg/day (males), 215.3 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012), CLH Report (2015), ECHA RAC Opinion (2016)). (2) It was reported that in a repeated dose 90-day oral toxicity study with dogs dosed by feeding (OECD TG 409, GLP), vacuolation of zona fasciculata of the adrenal cortex was observed in 2/4 females at or above 200 ppm (7.7 mg/kg/day (males), 8.4 mg/kg/day (females), within the range for Category 1); and liver effects (increases in AST and ALP, increases in absolute and relative weight, and an increase in ALT (males), acidophilic liver cytoplasm (females), inflammatory cellular infiltrate and hepatocyte necrosis (one female)), adrenal effects (vacuolation of zona fasciculata of the adrenal cortex, mononuclear cell infiltration), thymus effects (cortical atrophy, decreases in absolute and relative weight (males)), effects on male reproductive organs (vacuolation and hypertrophy of testicular Leydig cells and degeneration of testicular epithelium, oligospermia/aspermia in the epididymis, a decrease in absolute prostate weight, and immature prostate) were observed at or above 630 ppm (26.6 mg/kg/day (males), 28.0 mg/kg/day (females), within the range for Category 2) and at 2,000 ppm (84.7 mg/kg/day (males), 81.0 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012), CLH Report (2015), ECHA RAC Opinion (2016)). (3) It was reported that in a one-year chronic toxicity study with dogs dosed by feeding (OECD TG 452, GLP), vacuolation of zona fasciculata of the adrenal cortex was observed at 150 ppm (4.33 mg/kg/day (males), 4.74 mg/kg/day (females), within the range for Category 1), and increases in absolute and relative testis weight and vacuolation of Leydig cells (males) were observed at 600 ppm (16.1 mg/kg/day (males), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012), CLH Report (2015), ECHA RAC Opinion (2016)). [Reference Data, etc.] (4) It was reported that in a repeated dose 90-day oral toxicity study with mice dosed by feeding (OECD TG 408, GLP), hypertrophy of Leydig cells (males) and cytoplasmic vacuolation of the adrenal cortex (females) were observed at 1,000 ppm (163.8 mg/kg/day (males), 233.6 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), CLH Report (2015), ECHA RAC Opinion (2016)). (5) It was reported that in a two-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding (OECD TG 453, GLP), reduced body weight gain, an increase in ALP, vacuolation of jejunal epithelial cells, diffuse hypertrophy and vacuolation of fasciculata cells of the adrenal cortex and focal hyperplasia of Leydig cells (males), and a decrease in TG (females) were observed at or above 2,500 ppm (110.1 mg/kg/day (males), 152.9 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), CLH Report (2015), ECHA RAC Opinion (2016)). (6) It was reported that in an 18-month combined chronic toxicity/carcinogenicity study with mice dosed by feeding (OECD TG 451, GLP), increases in absolute and relative adrenal weight and vacuolation of the adrenal cortex, increases in absolute and relative liver weight, an increase in relative testicular weight, hepatocellular hypertrophy and hypertrophy or hyperplasia of testicular Leydig cells (males), and pigmentation of the adrenal glands (females) were observed at 3,500 ppm (610 mg/kg/day (males), 722 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), CLH Report (2015), ECHA RAC Oinion (2016)).
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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