GHS Classification Results by the Japanese Government

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GENERAL INFORMATION
Item Information
CAS RN 400882-07-7
Chemical Name 2-Methoxyethyl 2-[4-(tert-butyl)phenyl]-2-cyano-3-oxo-3-[2-(trifluoromethyl)phenyl]propanoate; Cyflumetofen
Substance ID R02-A-050-METI, MOE
Classification year (FY) FY2020
Ministry who conducted the classification Ministry of Economy, Trade and Industry (METI)/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 (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. Besides, there is information that it is combustible (GESTIS (Accessed Sep. 2020)).
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 fluorine and oxygen (but not chlorine), 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
-
-
- - 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 (females): > 2,000 mg/kg (OECD TG 420, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), JMPR (2014), ECHA RAC Opinion (2017))
1 Acute toxicity (Dermal) Not classified
-
-
- - [Rationale for the Classification]
It was classified as "Not classified" from (1).

[Evidence Data]
(1) LD50 for rats: > 5,000 mg/kg (OECD TG 402, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), JMPR (2014), ECHA RAC Opinion (2017))
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) Classification not possible
-
-
- - [Rationale for the Classification]
Classification is not possible due to lack of data because the category could not be determined from (1).

[Evidence Data]
(1) LC50 for rats (4 hours): > 2.65 mg/L (OECD TG 403, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), JMPR (2014), ECHA RAC Opinion (2017))
2 Skin corrosion/irritation Not classified
-
-
- - [Rationale for the Classification]
It was classified as "Not classified" from (1), (2).

[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 reactions were observed in any animal (erythema/eschar score: 0/0/0, edema score: 0/0/0) (ECHA RAC Opinion (2017), CLH Report (2016)).
(2) It is reported that in a skin irritation test with rabbits (n = 3) (GLP, semi-occlusive, 4-hour application, 72-hour observation), no skin irritation reactions were seen in any animal (erythema/eschar score: 0/0/0, edema score: 0/0/0) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)).
3 Serious eye damage/eye irritation Not classified
-
-
- - [Rationale for the Classification]
It was classified as "Not classified" from (1), (2).

[Evidence Data]
(1) It is reported that in an eye irritation test with rabbits (n = 3) (OECD TG 405, GLP, 22-day observation), conjunctival redness persisted for 15 days but disappeared after 22 days (corneal opacity score: 0/0/0, iritis score: 0/0/0, conjunctival redness score: 1/1.3/0.7, chemosis score: 0/0/0) (ECHA RAC Opinion (2017), CLH Report (2016)).
(2) It is reported that in an eye irritation test with rabbits (n = 4) (GLP, 21-day observation), very slight or slight conjunctival redness was observed by 14 days in the unwashed eye group (3 animals) but disappeared after 21 days (in 3 in the unwashed eye group: mean corneal opacity score: 0.0, mean iritis score: 0.0, mean conjunctival redness score: 1.8, mean chemosis score: 0.0) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)).
4 Respiratory sensitization Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
4 Skin sensitization Category 1A


Warning
H317 P302+P352
P333+P313
P362+P364
P261
P272
P280
P321
P501
[Rationale for the Classification]
It was classified in Category 1A from (1).

[Evidence Data]
(1) It is reported that in a maximization test with guinea pigs (n = 10) (OECD TG 406, GLP, intradermal administration: 1% suspension), erythema was seen as sensitization reactions in all the animals (100%) at 24, 48 hours after a challenge (ECHA RAC Opinion (2017), CLH Report (2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)).
5 Germ cell mutagenicity Not classified
-
-
- - [Rationale for the Classification]
Based on (1) to (5), it was classified as "Not classified."

[Evidence Data]
(1) In a micronucleus test with the bone marrow cells of mice (OECD TG 474, GLP, dosed twice by gavage), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), CLH Report (2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017), RAC Opinion (2017)).
(2) In a UDS test using the rat hepatocytes (OECD TG486, GLP, dosed once by oral gavage), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), CLH Report (2016), RAC Opinion (2017)).
(3) In a bacterial reverse mutation test (OECD TG471, GLP), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), CLH Report (2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017), RAC Opinion (2017)).
(4) In a mouse lymphoma TK test using the L5178Y mouse lymphoma cells (OECD TG476, GLP), positive results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), CLH Report (2016), RAC Opinion (2017)).
(5) In a mammalian cell (CHL, CHL (V79)) chromosome aberration test (OECD TG473, GLP), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), CLH Report (2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017), RAC Opinion (2017)).
6 Carcinogenicity Category 2


Warning
H351 P308+P313
P201
P202
P280
P405
P501
[Rationale for the Classification]
Based on (1) to (5), it was classified in Category 2.

[Evidence Data]
(1) As for the classification results by domestic and international organizations, EPA classified this substance in S (Suggestive Evidence of Carcinogenic Potential) (EPA Annual Cancer Report 2018 (Accessed Oct. 2020): Classification in 2013).
(2) In a two-year carcinogenicity study with rats (dosed by feeding), a significant increase in the incidence of interstitial cell tumors of the testis, which were neoplastic lesions (48/50 cases: 96%), was observed in males of the highest-dose group (6,000 ppm). The incidence of these tumors was within the range of the 20-year historical control data from the laboratory that conducted the study (28 to 50/50 cases: 56% to 100%: 1993 to 2012) but it exceeded the 10-year historical control data (28 to 43/50 cases: 56% to 86%: 2003 to 2012). Therefore, it was considered to be treatment-related (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), CLH Report (2016), ECHA RAC Opinion (2017)).
(3) From the result of the carcinogenicity study with rats of (2) above, an increased tendency of the incidence of C-cell carcinoma of the thyroid gland was also observed. The incidence of C-cell carcinoma of the thyroid gland exceeded the historical control data range. The incidence of combined C-cell adenoma and carcinoma was statistically significantly increased (CLH Report (2016), ECHA RAC Opinion (2017)).
(4) In an 18-month carcinogenicity study with mice (dosed by feeding), no carcinogenicity was observed at the dose of 10,000 ppm (CLH Report (2016), ECHA RAC Opinion (2017)).
(5) In the EPA Carcinogen Risk Assessment in 2005, this substance was classified as S. This classification was based on the presence of a single tumor type (thyroid c-cell) in one species and one sex (male rat) and the lack of concern for mutagenicity (US Federal Register Vol. 84, No. 89 (2019)).

[Reference Data, etc.]
(6) In a two-year carcinogenicity study with rats (dosed by feeding), no treatment-related increase in the incidence of neoplastic lesions was observed at doses up to 1,500 ppm. No carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)).
(7) In an 18-month carcinogenicity study with mice (dosed by feeding), no treatment-related increase in the incidence of neoplastic lesions was observed at doses up to 5,000 ppm. No carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), CLH Report (2016), ECHA RAC Opinion (2017)).
(8) The EU's CLP classification proposer reported that in the 6,000 ppm dosed group of rats, males showed an increase in testicular interstitial cell tumors and an increase in the combined incidence of thyroid C-cell adenomas and carcinomas. Testicular interstitial cell tumors occurred commonly in the F344 rat. Therefore, it was judged as being unnecessary to take the increased incidence of these tumors into account for classification. On the other hand, the increased incidence of thyroid C-cell adenomas and carcinomas exceeded the latest historical control data range and was considered to be a treatment-related effect. Based on the increased incidence of thyroid C-cell tumors in male rats, it was proposed that this substance should be classified as Carc. 2 in the CLP classification (CLH Report (2016), ECHA RAC Opinion (2017)). The RAC of ECHA considered that although a real signal above background was shown, the evidence for carcinogenicity was weak, therefore, there was sufficient uncertainty for RAC to conclude that classification as Carc. 2 was warranted (ECHA RAC Opinion (2017)).
7 Reproductive toxicity Not classified
-
-
- - [Rationale for the Classification]
Based on (1) to (4), it was classified as "Not classified."

[Evidence Data]
(1) It was reported that in a two-generation reproduction toxicity study with rats dosed by feeding (OECD TG416, GLP), effects on the adrenal gland (increased absolute and relative weights, diffuse cellular hypertrophy of the zona glomerulosa, diffuse cellular hypertrophy of the zona fasciculata) were observed in parental animals and similar findings were observed in pups at 500 ppm and 1,500 ppm. Additionally, reduced follicle-stimulating hormone and reduced progesterone concentrations (F1) in parental animals, and a delay in vaginal opening (F1 females) in pups were observed at 500 ppm; and at 1,500 ppm, in addition to the effects observed at 500 ppm, general toxicity effects (such as increases in absolute or relative pituitary weight and reduced body weight gain), increases in absolute and relative ovary weight (P females), vacuolation of interstitial cells in the ovary, a decrease in 17 beta-estradiol concentrations, and an increase in mean estrous cycle length (F1 females) in parental animals and a delay in preputial separation (F1 males) and reduced body weight gain (F2) in pups were observed. It was reported that no effect on fertility was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)).
(2) In the study of (1), the prolonged estrous cycle length observed in the high-dose group of F1 females was within the historical control data range. Concerning the decreases in serum FSH and progesterone observed at or above the intermediate dose and the decrease in 17 beta-estradiol and vacuolation of interstitial cells in the ovary observed in the high dose group, since the number of animals tested was not sufficient, the relevance of administration of this substance on fertility was debatable. Therefore, it was determined that the classification for the effects of this substance on fertility was not required (CLH Report (2016), ECHA RAC Opinion (2017)).
(3) It was reported that in a developmental toxicity study with rats dosed by gavage (OECD TG414, GLP, gestation days 6 to 19), an increase in adrenal weight and vacuolation of adrenal cortical cells in parental animals and an increase in the number of dams whose fetuses had incomplete ossification of the sternebra were observed but no teratogenicity was observed at 250 mg/kg/day (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017), CLH Report (2016)).
(4) It was reported that in a developmental toxicity study with rabbits dosed by gavage (OECD TG414, GLP, gestation days 6 to 28), a decrease in ossified lumbar vertebras was observed in pups at 250 mg/kg/day, and a decrease in food consumption, reduced body weight gain and lower placenta weight in parental animals and a decrease in ossified lumbar vertebras, lower body weight, an increase in angulated alae of the hyoid, and incomplete ossification of the sternebra in pups were observed but no teratogenicity was observed at 1,000 mg/kg/day (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017), CLH Report (2016)).

[Reference Data, etc.]
(5) In developmental toxicity studies with rats and rabbits, no irreversible structural effect for fetal development was reported. It was determined that the classification for effects on development was not required under the EU-CLP regulation (CLH Report (2016)). The RAC also judged that classification was not required for fertility, sexual function and development of the offspring (ECHA RAC Opinion (2017)).
8 Specific target organ toxicity - Single exposure Classification not possible
-
-
- - [Rationale for the Classification]
Based on (1) to (4), it was classified as "Not classified" in the oral and dermal routes. (3) could not be used for classification because the effects at doses near the upper limit of Category 2 were unclear. However, classification was not possible due to lack of data since there was not sufficient information available for classification in the inhalation route.

[Evidence Data]
(1) It was reported that in an acute oral toxicity test with rats (females) (OECD TG 420, GLP), loose feces (one case) was observed and no mortality occurred at 2,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017), CLH Report (2016), ECHA RAC Opinion (2017)).
(2) It was reported that in an acute neurotoxicity test with rats dosed by gavage, no change in general condition and behavior was observed at 2,000 mg/kg (within the range for Category 2) and it was concluded that this substance did not have acute neurotoxic potential (CLH Report (2016), ECHA RAC Opinion (2017)).
(3) It was reported that in an acute dermal toxicity test with rats (OECD TG 402, GLP), no symptom nor death was observed at 5,000 mg/kg (in the range corresponding to “Not classified”) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017), CLH Report (2016), ECHA RAC Opinion (2017)).
(4) It was reported that in an acute (dust) inhalation toxicity test with rats (OECD TG 403, GLP), exaggerated breathing and brown staining around the snout and the lower jaw were observed and no mortality occurred at 2.65 mg/L (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017), CLH Report (2016), ECHA RAC Opinion (2017)).
9 Specific target organ toxicity - Repeated exposure Category 2 (adrenal gland)


Warning
H373 P260
P314
P501
[Rationale for the Classification]
Based on (1) to (4), the target organs were considered to be the adrenal glands, and effects were seen within the dosage range for Category 2, therefore, it was classified in Category 2 (adrenal gland).

[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), adrenal gland effects (diffuse vacuolation of adrenal cortical cells (males), an increase in relative adrenal weight and diffuse hypertrophy of adrenal cortical cells (females)), an increase in relative liver weight (males) and vacuolation of interstitial cells in the ovary (females) were observed at or above 1,000 ppm (54.5 mg/kg/day (males), 62.8 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017), CLH Report (2016), ECHA RAC Opinion (2017)).
(2) It was reported that in a one-year chronic toxicity study with rats dosed by feeding (OECD TG 452, GLP), hematological effects (such as an increase in RBC and decreases in MCH and MCV), adrenal gland effects (females: increases in absolute and relative weight, males and females: diffuse hypertrophy of adrenal cortical cells), liver effects (males: increases in absolute and relative weight, diffuse hepatocellular hypertrophy), and ovary effects (vacuolation of interstitial cells) were observed at 1,500 ppm (56.8 mg/kg/day (males), 69.2 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017), CLH Report (2016), ECHA RAC Opinion (2017)).
(3) It was reported that in one-year chronic toxicity study with dogs dosed by capsules (OECD TG 452, GLP), adrenal gland effects (formation of fine vacuoles in adrenocortical cells, emergence of large vacuoles, focal infiltration of lymphocytes in the zona fasciculata and reticularis and degeneration of adrenal cortical cells, a decrease in TG, and infiltration of brown pigment-laden macrophages in the adrenal cortices (males), adrenal interstitial fibrosis (females)) were observed at 300 mg/kg/day (in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017), CLH Report (2016), ECHA RAC Opinion (2017)).
(4) It was reported that in a two-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding (OECD TG 451, GLP), diffuse hypertrophy of adrenal cortical cells and luminal dilatation of the gland in the uterine horn (females) were observed at 1,500 ppm (49.5 mg/kg/day (males), 61.9 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017), CLH Report (2016), ECHA RAC Opinion (2017)).

[Reference Data, etc.]
(5) It was reported that in a repeated dose dermal toxicity: 28-day study with rats (OECD TG 410, GLP, 6 hours/day, 5 days/week), no effect was observed at 1,000 mg/kg/day (converted guidance value: 222.2 mg/kg/day) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), CLH Report (2016), ECHA RAC Opinion (2017)).
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) Classification not possible
-
-
- - Classification not possible due to lack of data.
11 Hazardous to the aquatic environment Long term (Chronic) Category 1


Warning
H410 P273
P391
P501
It was classified in Category 1 because it is not rapidly degradable (BIOWIN) and due to 72-hour NOEC (Biomass/growth rate) = 0.0396 mg/L for algae (Raphidocelis subcapitata) (EU CLP CLH, 2016).
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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