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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	95465-99-9
Chemical Name	S,S-Bis(1-methylpropyl) O-ethyl phosphorodithioate (synonym: Cadusafos)
Substance ID	R03-B-035-METI, MOE
Classification year (FY)	FY2021
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)/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	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
6	Flammable liquids	Not classified	- -	-	-	A flash point is 129.4 deg C (closed cup) (HSDB in PubChem(Accessed June 2021)).
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
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	Classification not possible	- -	-	-	No data available.
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to liquid substances are not available.
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified	- -	-	-	It contains a metalloid (P), but it is estimated that it does not react vigorously with water from data obtained: water solubility of 241 mg/L (Ministry of the Environment (2011)).
13	Oxidizing liquids	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 (P). However, the classification is not possible due to no data.
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
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	- -	-	-	No data 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)	Category 2	Danger	H300	P301+P310 P264 P270 P321 P330 P405 P501	[Rationale for the Classification] Based on (1) to (8), it was classified in Category 2. [Evidence Data] (1) LD50 for rats (males): 48 mg/kg (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), JMPR (2009)) (2) LD50 for rats (females): 30 mg/kg (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), JMPR (2009)) (3) LD50 for rats (males): 131 mg/kg (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), JMPR (2009)) (4) LD50 for rats (females): 39 mg/kg (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), JMPR (2009)) (5) LD50 for rats (males): 80 mg/kg (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)) (6) LD50 for rats (females): 42 mg/kg (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)) (7) LD50 for rats: 30.1 mg/kg (EFSA (2009)) (8) LD50 for rats: 39 mg/kg (ACGIH (2017))
1	Acute toxicity (Dermal)	Category 1	Danger	H310	P302+P352 P361+P364 P262 P264 P270 P280 P310 P321 P405 P501	[Rationale for the Classification] Based on (1) to (7), it was classified in Category 1. [Evidence Data] (1) LD50 for rabbits: 10.7 mg/kg (EFSA (2009)) (2) LD50 for rabbits (males): 12 mg/kg (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)) (3) LD50 for rabbits (females): 11 mg/kg (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)) (4) LD50 for rabbits (males): 24 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021)) (5) LD50 for rabbits (females): 42 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021)) (6) LD50 for rabbits: between 11 to 41 mg/kg (ACGIH (2017)) (7) LD50 for rabbits: between 12 to 42 mg/kg (JMPR (2009))
1	Acute toxicity (Inhalation: Gases)	Not classified	- -	-	-	[Rationale for the Classification] Liquid (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)	Category 1	Danger	H330	P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 1. Also, the exposure concentration was higher than the saturated vapor pressure concentration (0.011 mg/L) and it was judged as mist. [Evidence Data] (1) LC50 (4 hours, mist) for rats (males): 0.04 mg/L (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)) (2) LC50 (4 hours, mist) for rats (females): 0.026 mg/L (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)) (3) LC50 (4 hours) for rats: 0.032 mg/L (ACGIH (2017))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) In a skin irritation test (GLP, occlusive, stock solution 0.015 mL or 0.007 mL, 4-hour application, observation for 72 hours) with rabbits (n=6/group), no irritant reactions were observed at any observation time points in either a 0.007 mL application group or a 0.015 mL application group. In the 0.015 mL application group, 4 out of 6 animals died within 24 hours after application. No abnormalities were observed in a gross pathological examination of dead animals. It was reported that no abnormalities in general conditions were observed in the 0.007 mL application group (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) This substance was not a skin irritant (EFSA (2009), ACGIH (7th, 2017), JMPR (2009)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) In an eye irritation test (GLP, stock solution 0.1 mL or 0.01 mL) with rabbits (n=6/group), slight irritant reactions (average score: 3.2 out of 110 points) were observed in a 0.1 mL application group 1 hour after application, and all animals died within 2 hours (there were no abnormalities in a gross pathological examination). In a 0.01 mL application group, slight conjunctival redness was observed in 1 animal 24 hours after application. The average scores (out of 110 points) by time of 24/48/72 hours after application were 0.2/0/0, respectively (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) This substance was not irritating to the eyes of rabbits (ACGIH (7th, 2017), JMPR (2009)).
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] Based on (1), it was classified in Category 1B. Also, based on the new findings, the classification result was changed. [Evidence Data] (1) It was reported that, in a Maximization test (GLP, intradermal administration: 0.5% test substance) with guinea pigs (n=20), the positive rates at 24 and 48 hours after challenge were 35% (7/20 animals) and 40% (8/20 animals), respectively, and the skin sensitization rate was 40% (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). [Reference Data, etc.] (2) It was reported that, in a Buehler test (GLP, local administration: 100% test substance) with guinea pigs (n=20), the positive rates at 24 and 48 hours after challenge were both 5% (1/20 animals), and 1 animal with erythema was re-challenged 48 hours after challenge and no skin reactions were observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) As for in vivo, it was negative in a chromosomal aberration test with the bone marrow cells of rats (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), EFSA (2009)). (2) As for in vitro, negative results were obtained in all of multiple bacterial reverse mutation tests, and a gene mutation test and a chromosomal aberration test with the cultured mammalian cells (CHO cells) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), ACGIH (7th, 2017), EFSA (2009)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) As for the classification results by domestic and international organizations, the EPA classified this substance in Group E (Evidence of Non Carcinogenicity for Humans) (EPA OPP Annual Cancer Report 2020 (Accessed August 2021): Classification in 1992), the ACGIH classified it in A4 (ACGIH (7th, 2017)). (2) As a result of a 2-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, no carcinogenicity was observed at doses up to 5.0 ppm (males/females: 0.222/0.280 mg/kg/day) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), ACGIH (7th, 2017), JMPR (2009), EFSA (2009)). (3) As a result of a 22-month carcinogenicity study with mice dosed by feeding, no carcinogenicity was observed at doses up to 5.0 ppm (males/females: 0.705/1.00 mg/kg/day) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), ACGIH (7th, 2017), JMPR (2009), EFSA (2009)).
7	Reproductive toxicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in a two-generation reproduction toxicity study (GLP) with rats dosed by feeding, at 5 ppm, reduced body weight gain and erythrocyte cholinesterase (ChE) activity inhibition were observed in F1 parent animals, but no effects on fertility were observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), EFSA (2009), JMPR (2009)). (2) It was reported that, in a developmental toxicity study with rats dosed by gavage (GLP, days 6 to 15 of gestation), at or above 6 mg/kg/day, symptoms related to ChE inhibition, such as reduced locomotor activity, diarrhea, lacrimation, and tremor, were observed in parent animals, but only minor developmental effects (delayed ossification, low body weight) were observed in fetuses (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), ACGIH (7th, 2017), EFSA (2009), JMPR (2009)). (3) It was reported that, in a developmental toxicity study with rabbits dosed by gavage (GLP, days 7 to 19 of gestation), no developmental toxicity was observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), JMPR (2009)).
8	Specific target organ toxicity - Single exposure	Category 1 (nervous system)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1 (nervous system). Also, based on the new findings, the classification result was changed. [Evidence Data] (1) It was reported that, in an acute oral toxicity test (acute neurotoxicity test, GLP) with rats, diarrhea, staining of the abdomen and genital areas, discharge from the mouth, decreased feces, hematuria, tremor and depression, erythrocyte ChE activity inhibition (20% or above), brain ChE activity inhibition (20% or above), and decreased locomotor activity (males) were observed at 25 mg/kg (within the range for Category 1); and soiled fur (males), increased mortality (20%) (females), limp when handled (females), lacrimation (females), salivation (females), an increased number of urine pools (females), an increase in tail-flicking latency (females), reduced hindlimb grip strength, and decreased locomotor activity (females) were observed at 40 mg/kg (within the range for Category 1) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), JMPR (2009)). (2) It was reported that, in multiple acute oral toxicity tests with rats (GLP), staining of the lower abdomen, decreased locomotor activity, diarrhea, lacrimation, salivation, tremor, lying on side, erythrocyte ChE activity inhibition (20% or above), etc. were observed at 2.5 to 120 mg/kg (within the range for Category 1) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 1 (nervous system). [Evidence Data] (1) It was reported that, in a repeated dose 90-day oral toxicity study (GLP) with rats dosed by feeding, erythrocyte ChE activity inhibition (20% or above) and death (females: 1/15, cause of death unknown) were observed at 5.0 ppm (0.327 mg/kg/day (males), 0.389 mg/kg/day (females), within the range for Category 1), and death (males: 11/15, females: 13/15) was caused at 800 ppm (59.1 mg/kg/day (males), 67.9 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), ACGIH (2017), JMPR (2009)). (2) It was reported that, in a 90-day subchronic neurotoxicity test (GLP) with rats dosed by feeding, brain and erythrocyte ChE activity inhibition (20% or above), reduced body weight gain, decreased food consumption, decreases in landing foot splay width and forelimb grip strength (males), sensitivity reaction to contact, and decreased feces (females) were observed at 300 ppm (20.0 mg/kg/day (males), 23.1 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), JMPR (2009)). (3) It was reported that, in a 2-year combined chronic toxicity/carcinogenicity study (GLP) with rats dosed by feeding, erythrocyte ChE activity inhibition (20% or above), decreased locomotor activity, and a decrease in Eos (females) were observed at 5.0 ppm (0.222 mg/kg/day (males), 0.280 mg/kg/day (females), within the range for Category 1) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), EFSA (2009), ACGIH (2017), JMPR (2009)). (4) It was reported that, in a 22-month combined chronic toxicity/carcinogenicity study (GLP) with mice dosed by feeding, renal necrotizing arteritis (males) was observed at 1.0 ppm (0.141 mg/kg/day (males), 0.189 mg/kg/day (females), within the range for Category 1), and erythrocyte ChE activity inhibition (20% or above), atrophy of the adrenal cortex, focal hyperplasia of the adrenal cortex (males), and hyperplasia of the duodenal mucosa (females) were observed at 5.0 ppm (0.705 mg/kg/day (males), 1.00 mg/kg/day (females), within the range for Category 1). On the other hand, it was reported that renal necrotizing arteritis and effects on the adrenal glands were less dose-dependent (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), EFSA (2009), ACGIH (2017), JMPR (2009)). [Reference Data, etc.] (5) It was reported that, in a repeated dose 90-day oral toxicity study (GLP) with dogs dosed by gavage, no effects were observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), JMPR (2009), HSDB in PubChem (Accessed Aug. 2021)). (6) It was reported that, in a one-year chronic toxicity study (GLP) with dogs dosed by gavage, no effects were observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2021), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), ACGIH (2017), JMPR (2009)).
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 48-hour EC50 = 0.00257 mg a.i./L for crustacea (Daphnia magna) (Document for registration standards for agricultural chemicals set by the Minister of Environment to prevent harm to animals and plants in areas of public waters, 2014). (a.i.: active ingredient)
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 (BIOWIN) and 72-hour NOErC = 0.907 mg a.i./L for algae (Raphidocelis subcapitata) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 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 48-hour EC50 = 0.00257 mg a.i./L for crustacea (Daphnia magna) (Document for registration standards for agricultural chemicals set by the Minister of Environment to prevent harm to animals and plants in areas of public waters, 2014). From the above results, it was classified in Category 1. (a.i.: active ingredient)
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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