GHS Classification Results by the Japanese Government

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GENERAL INFORMATION
Item Information
CAS RN 142459-58-3
Chemical Name N-(4-Fluorophenyl)-N-isopropyl-2-{[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]oxy}acetamide; Flufenacet
Substance ID R02-A-089-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
-
-
- - 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) Category 4


Warning
H302 P301+P312
P264
P270
P330
P501
[Rationale for the Classification]
It was classified in Category 4 from (1) - (3).

[Evidence Data]
(1) LD50 for rats (males): 683 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013))
(2) LD50 for rats (males): 1,620 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013))
(3) LD50 for rats (females): 589 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013))

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 (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013))

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]
The classification is not possible because effects are unknown at a dose near the upper limit for Category 4 in (1).

[Reference Data, etc.]
(1) LC50 for rats (4 hours): > 3.74 mg/L (mist) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013))

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 = 6) (GLP, semi-occlusive, 4-hour application, 72-hour observation), no skin irritation changes were seen in any animal (erythema/eschar score: 0/0/0/0/0/0, edema score: 0/0/0/0/0/0) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), 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 = 6) (GLP, 7-day observation), slight conjunctival redness in all the animals and slight chemosis in 5 were observed, but all of these disappeared within 7 days (corneal opacity score: 0/0/0/0/0/0, iritis score: 0/0/0/0/0/0, conjunctival redness score: 0.3/1/1/0.7/0.7/0.7, chemosis score: 0/0.3/0.3/0.3/0.3/0.3) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), 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 = 20) (GLP, intradermal administration: 5% solution), the positive rate was 60% (12/20), 45% (9/20) at 24, 48 hours after the removal of patches when challenged with a 25% solution, and the positive rate was 55% (11/20), 60% (12/20) at 24, 48 hours after the removal of patches when challenged with a 50% solution (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)).

[Reference Data, etc.]
(2) A Buehler test with guinea pigs gave a negative result (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)).
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 (GLP, single intraperitoneal injection), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)).
(2) In a bacterial reverse mutation test (GLP), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)).
(3) In a gene mutation test using the cultured mammalian cells (CHL V79 cells) (GLP), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)).
(4) In a chromosomal aberration test using the cultured mammalian cells (CHO) (GLP), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)).
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 NL (Not Likely to be Carcinogenic To Humans) (EPA Annual Cancer Report (2019): Classification in 1997).
(2) In a two-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, no evidence of carcinogenicity was observed at doses up to 800 ppm (males/females: 39.0/49.8 mg/kg/day) at which apparent toxicity effects were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012), EPA Pesticides FACTS (1998)).
(3) In a 20-month carcinogenicity study with mice dosed by feeding, no evidence of carcinogenicity was observed at doses up to 400 ppm (males/females: 62.2/77.2 mg/kg/day) at which apparent toxicity findings were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012), EPA Pesticides FACTS (1998)).
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 (GLP), no effect on fertility was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)).
(2) It was reported that in a developmental toxicity study with rats dosed by gavage (GLP, days 6-15 of gestation), at 125 mg/kg/day, reduced body weight gain and a reduction in food consumption were observed in parental animals; and lower body weight, delayed ossification, and an increase in extra ribs were observed in pups, but no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)).
(3) It was reported that in a developmental toxicity study with rabbits dosed by gavage (GLP, days 6-18 of gestation), at 125 mg/kg/day, hepatocyte vacuolation (foamy), hypertrophy of hepatocytes, and an increase in frosted glass-like cytoplasm in hepatocytes were observed in parental animals; and an increase in skeletal variations (extra ribs, extra lumbar vertebral arches, and extra lumbar centrums) was observed in pups, but no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)).
(4) It was reported that in a developmental neurotoxicity test with rats dosed by feeding (GLP, from day 6 of gestation to day 11 of lactation, or days 6-24 of gestation), at 100 ppm, reduced body weight gain and a decrease in food consumption were observed in parental animals; and lower body weight, a delay in opening of the eyes, and a delay in preputial separation were observed in pups, but no developmental neurotoxicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)).
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) to (4), the symptoms in the nervous system were observed after administration by the oral route, and in (1), effects were observed in the dose range for Category 1. Therefore, it was classified in Category 1 (nervous system).

[Evidence Data]
(1) It was reported that in an acute neurotoxicity test by oral administration to rats, ataxia, hypoactivity and stained fur around the reproductive organs (females) were observed at or above 75 mg/kg (within the range for Category 1); reductions in locomotor activity and locomotion performance (females) were observed at or above 150 mg/kg (within the range for Category 1); and ataxia, hypoactivity and reductions in locomotor activity and locomotion performance (males) were observed at or above 200 mg/kg (within the range for Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)).
(2) It was reported that in an acute oral toxicity test with rats, hypoactivity, lacrimation, reddish tears, salivation, and staining of the natural cavities were observed in males and the LD50 was 683 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)).
(3) It was reported that in an acute oral toxicity test with rats, ataxia, labored breathing, hypoactivity, stained fur, and increased secretion were observed and the LD50s were 1,620 mg/kg (males) and 589 mg/kg (females) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)).
(4) It was reported that in an acute oral toxicity test with mice, hypoactivity, hyperreactivity, convulsions, unkempt fur, salivation, and lacrimation were observed and the LD50s were 1,330 mg/kg (males) and 1,760 mg/kg (females) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)).
9 Specific target organ toxicity - Repeated exposure Category 2 (nervous system, eye, blood system, liver, kidney)


Warning
H373 P260
P314
P501
[Rationale for the Classification]
The target organs were considered to be the blood, thyroid, liver, and kidney based on (1) to (6), the nervous system based on (3) and (4), and the eyes based on (5) and (6). The findings in the thyroid among these organs were considered to be due to physiological reactions associated with drug hypermetabolism in the liver, and the thyroid was excluded from the target organs. Adverse effects on the target organs were observed in the dose range for Category 2. Therefore, it was classified in Category 2 (nervous system, eyes, blood system, liver, kidney).

[Evidence Data]
(1) It was reported that in a 90-day oral toxicity test with rats dosed by feeding, at or above 400 ppm (24.3 mg/kg/day (males), at 28.8 mg/kg/day (females), within the range for Category 2), hematological effects (decreases in red blood cell count (RBC) and hemoglobin (Hb), a decrease in hematocrit (Ht) (males)), liver effects (hypertrophy of hepatocytes, an increase in smooth endoplasmic reticula, an increase in relative liver weight (males), single cell necrosis of hepatocytes (females)), and kidney effects (hyaline droplet deposition/degeneration in the proximal renal tubules (males), brown pigmentation of the proximal ureter (females), hyperplasia and foreign bodies of the renal pelvic epithelium (males)), and other effects were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)).
(2) It was reported that in a 90-day oral toxicity test with dogs dosed by feeding, at 800 ppm (27.7 mg/kg/day (males), 28 mg/kg/day (females), within the range for Category 2) and 2,400 ppm (96.9 mg/kg/day (males), 93.2 mg/kg/day (females), within the range for Category 2), hematological effects (decreases in RBC, Hb, and Ht, an increase in platelet count (PLT)), thyroid effects (decreases in T3 and T4, hypertrophy of thyroid follicular cells (females)), liver effects (increases in absolute and relative liver weight, diffuse hypertrophy of hepatocytes, an increase in ALP), kidney effects (an increase in relative kidney weight, hyperplasia of the epithelium of the renal papilla (males), vacuolation of the cytoplasm in the renal collecting tubules (females), hyperplasia of the epithelium of the renal papilla (females)), brain effects (vacuolation of the cerebral cortex), and other effects were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)).
(3) It was reported that in a 90-day repeated oral dose neurotoxicity test with rats dosed by feeding, an increase in the number of swollen axons in the cerebellum and the medulla oblongata and spinal cord was observed at or above 600 ppm (38.1 mg/kg/day (males), 42.6 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)).
(4) It was reported that in a one-year chronic toxicity study with dogs dosed by feeding, hematological effects (decreases in RBC, Hb, and Ht) were observed at 800 ppm (27.8 mg/kg/day (males), 26.8 mg/kg/day (females), within the range for Category 2) and liver effects (vacuolation of hepatocytes, hypertrophy of centrilobular hepatocytes, an increase in ALP), effects on the brain and nervous system (degeneration of axons in the spinal cord and the brain, abnormal brain waves, abnormal gait, abnormal posture, degeneration of axons in the sciatic nerve, hyporeactivity, an increase in muscle tone, and abnormal physiological nystagmus), and cardiac effects (an increase in relative cardiac weight, ventricular extrasystole, electrocardiogram abnormalities (notch in R wave/T wave, peaked T wave)), and other effects were observed at 1,600 ppm (62.2 mg/kg/day (males), 58.8 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)).
(5) It was reported that in a two-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, at 400 ppm (19.3 mg/kg/day (males), 24.4 mg/kg/day (females), within the range for Category 2) and 800 ppm (39 mg/kg/day (males), 49.8 mg/kg/day (females), within the range for Category 2), hematological effects (an increase in methemoglobin (MetHb), an increase in PLT (males)), liver effects (increases in absolute and relative weight, hypertrophy of hepatocytes, single cell necrosis of hepatocytes, hyperplasia of the intrahepatic bile duct (males)), kidney effects (mineral deposits in the renal pelvis, hyperplasia of the epithelium of the renal pelvis (males), an increase in nitrites in urine (males), an increase in pH of urine), effects on the eyes (mineral deposits in the sclera, cataract (females)), effects on the uterus (cystic hyperplasia of the endometrium), and other effects were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)).
(6) It was reported that in a 20-month carcinogenicity study with mice dosed by feeding, an increase in cataract (males) was observed at or above 50 ppm (7.4 mg/kg/day (males), 9.4 mg/kg/day (females), within the range for Category 1); and an increase in MetHb and an increase in cataract (females) were observed at or above 200 ppm (30.4 mg/kg/day (males), 38.4 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2012)).

[Reference Data, etc.]
(7) In the results of various toxicity tests, the effects of the administration of flufenacet were observed mainly on the liver (hypertrophy of hepatocytes), the thyroid (hyperplasia of the follicular epithelium, etc.), the kidney (hyperplasia of the epithelium of the renal pelvis, etc.), the blood (an increase in MetHb, anemia), and the eyes (cataract: mice). In a subacute oral toxicity test (dogs), vacuolation of the cerebral cortex was observed in males and females in the group dosed at 2,400 ppm, and in a subacute neurotoxicity test (rats), swollen axons in the cerebellum and the medulla oblongata and spinal cord were observed in males and females in the group dosed at or above 600 ppm. Thus, neurotoxicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)).
(8) With respect to the effects on the thyroid, an explanation was given that a decrease in thyroid hormone (T3/T4) due to the induction of UDP-glucuronosyltransferase in the liver activated the hypothalamus-anterior pituitary-thyroid axis, resulting in an increase in thyroid weight (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)).
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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