Return to Fluthiacet-methyl Index Page

Activity: Herbicide (unclassified)
Structure for "Fluthiacet":

Adverse Effects:
Anemia
Blood
Body Weight Decrease
Bone
Cancer: Likely to be a human carcinogen - PANCREAS (males) and LIVER
Clastogenic
Endocrine: Uterus
Liver
Pancreas
Environmental

Carcinogenicity in rats. NOAEL males = 2.1 mg/kg/day LOAEL in males = 130 mg/kg/day NOAEL in females = 2.5 mg/kg/day LOAEL in females = 154 mg/kg/day. In males there were decreased body weight, liver toxicity, pancreatic toxicity and microcytic anemia. In females there were liver toxicity, uterine toxicity and slight microcytic anemia. In males only at 130 and 219 mg/kg/day there was respectively, an increase in the trend toward pancreatic exocrine adenomas and pancreatic islet cell adenomas.
Ref: Federal Register. December 21, 2001. Fluthiacet-methyl; Pesticide Tolerance. Final Rule.
http://www.epa.gov/fedrgstr/EPA-PEST/2001/December/Day-21/p31497.htm

Blood (click on for all fluorinated pesticides)

-- 90-day oral Toxicity, rats and mice. Rats: NOAEL = 6.19 milligrams/ kilograms day (mg/ kg/day) in males 6.80 mg/ kg/day in females LOAEL = 216 mg/ kg/day in males 249 mg/ kg/day in females Mice: NOAEL = 1.3 mg/kg/ day in males 1.6 mg/ kg/day in females LOAEL = 66 mg/kg/ day in males 83 mg/kg/ day in females. Based on decreased body weight gains as well as effects on hematology, clinical chemistry, urinalysis parameters, liver weights and microscopic pathology in rats; and on effects on the erythropoietic system and liver in mice.
-- Carcinogenicity rats. NOAEL in males = 2.1 mg/kg/day LOAEL in males = 130 mg/kg/day NOAEL in females = 2.5 mg/kg/day LOAEL in females = 154 mg/kg/dayIn males there were decreased body weight, liver toxicity, pancreatic toxicity and microcytic anemia. In females there were liver toxicity, uterine toxicity and slight microcytic anemia. In males only at 130 and 219 mg/kg/day there was respectively, an increase in the trend toward pancreatic exocrine adenomas and pancreatic islet cell adenomas.
-- In a 90-day rat feeding study the NOAEL was 6.19 mg/kg/day for males and 6.80 mg/kg/day for females. In a 6-week dog dietary study the NOAEL was 236 mg/kg/day for males and 77.7 mg/kg/day for females. In a 28-day rat dermal study the NOAEL was 1000 mg/kg/day [HDT]. In a 1-year dog chronic feeding study, the NOAEL was 57.6 mg/kg/day for males and 30.3 mg/kg/day for females and the Lowest Observed Adverse Effect Level (LOAEL) was 582 mg/kg/day for males and 145 mg/kg/day for females based on effects observed in the erythropoietic system [red blood cells] and the liver.
-- Chronic toxicity NOAEL in males = dogs 57.6 mg/kg/day LOAEL in males = 582 mg/kg/day NOAEL in females = 30.3 mg/kg/day LOAEL in females = 145 mg/kg/day The LOAELs were based on effects observed in the erythropoietic system and liver.
Ref: Federal Register: December 21, 2001. Fluthiacet-methyl; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/Fluthiacet.M.FR.Dec.21.2001.htm

Body Weight Decrease (click on for all fluorinated pesticides)

-- 90-day oral Toxicity, rats and mice. Rats: NOAEL = 6.19 milligrams/ kilograms day (mg/ kg/day) in males 6.80 mg/ kg/day in females LOAEL = 216 mg/ kg/day in males 249 mg/ kg/day in females Mice: NOAEL = 1.3 mg/kg/ day in males 1.6 mg/ kg/day in females LOAEL = 66 mg/kg/ day in males 83 mg/kg/ day in females. Based on decreased body weight gains as well as effects on hematology, clinical chemistry, urinalysis parameters, liver weights and microscopic pathology in rats; and on effects on the erythropoietic system and liver in mice.
-- 6-week oral toxicity in dogs. NOAEL = 236 mg/kg/ day in males 77.7 mg/ kg/day in females LOAEL = 709 mg/kg/ day in males 232 mg/ kg/day in females based on decreased body weight gain.
-- 2-generation Reproduction and fertility effects. Parental/systemic NOAEL = 1.59 mg/kg/ day in males LOAEL = 31.8 mg/kg/ day in males NOAEL = 1.73 mg/kg/ day in females LOAEL = 35.2 mg/kg/ day in females based on reduction in male body weights/ gains and hepatic pathology Reproductive in males: NOAEL = 31.8 mg/kg/ day LOAEL =313 mg/kg/ day Reproductive in females: NOAEL = 37.1 mg/kg/ day LOAEL = 388 mg/kg/ day based on decreases in mean litter body weights.
-- Carcinogenicity rats. NOAEL in males = 2.1 mg/kg/day LOAEL in males = 130 mg/kg/day NOAEL in females = 2.5 mg/kg/day LOAEL in females = 154 mg/kg/dayIn males there were decreased body weight, liver toxicity, pancreatic toxicity and microcytic anemia. In females there were liver toxicity, uterine toxicity and slight microcytic anemia. In males only at 130 and 219 mg/kg/day there was respectively, an increase in the trend toward pancreatic exocrine adenomas and pancreatic islet cell adenomas.
Ref: Federal Register: December 21, 2001. Fluthiacet-methyl; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/Fluthiacet.M.FR.Dec.21.2001.htm

Bone (click on for all fluorinated pesticides)

-- Prenatal Maternal developmental in rats and rabbits. Maternal in rats: NOAEL = 1,000 mg/ kg/day, HDT Maternal in rabbits: NOAEL = 1,000 mg/ kg/day, HDT Developmental in rabbits: NOAEL = 300 mg/kg/ day Developmental in rabbits: LOAEL of 1,000 mg/ kg/day based on slight non- significant increased incidence of irregularly shaped sternebrae attributed to a delay in fetal development. (See following.)
-- In rabbits, in utero exposure did not result in maternal toxicity at 1,000 mg/kg/day. Developmental toxicity, however, was seen at this dose characterized as an increase in irregular sternebrae (a variation which is reversible). The occurrence of developmental toxicity at which no maternal toxicity was noted indicates an apparent increase in susceptibility. The Office of Pesticide Program's Hazard Identification Assessment Review Committee (HIARC), however, determined that the apparent susceptibility is not convincing because of the equivocal nature of the effect based on:
(1) The increased incidence of irregular sternebrae was not statistically significant when compared to concurrent controls;
(2) the increase occurred at the Limit-Dose (1,000 mg/kg/day;
(3) it was the only anomaly seen (i.e., a single variation);
(4) the dose response was not strong because there was only a small increase in the litter incidence between the low- (5 mg/kg/day) and the high-dose (1,000 mg/kg/day), with the mid- and high-dose groups having 8 litters with this variation;, and
(5) this endpoint is appropriate to establish a LOAEL and not appropriate for risk assessments. Based on these factors, the HIARC concluded that there is no increased susceptibility in the rabbit study. Therefore, the 10X FQPA safety factor to ensure the protection of infants and children was not applied in the risk assessments.
Ref: Federal Register: December 21, 2001. Fluthiacet-methyl; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/Fluthiacet.M.FR.Dec.21.2001.htm

Cancer: Likely to be a human carcinogen - PANCREAS (males) and LIVER (click on for all fluorinated pesticides)

Likely to be Carcinogenic to Humans. Pancreatic cell tumors (exocrine adenomas, islet cell adenomas, and combined islet cell tumors); Sprague-Dawley rats (M). Hepatocellular tumors (adenomas and combined adenoma/carcinoma); CD-1 mice (M & F). CD-1 mice (M & F).
Ref: April 26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the Office of Pesticide Programs. From: Jess Rowland, Chief Science Information Management Branch Health Effect Division (7509C) Office of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf

Likely to be carcinogenic to humans. Reviewed 12/ 8/ 98.
Ref: List of Chemicals Evaluated for Carcinogenic Potential. Science Information Management Branch, Health Effects Division, Office of Pesticide Programs, U. S. Environmental Protection Agency. March 15, 2002.
http://www.biomuncie.org/chemicals_evaluated_for_carcinog.htm

-- Fluthiacet-methyl is classified as a "likely to be a human carcinogen" based on the presence of pancreatic tumors (exocrine adenomas, islet cell adenomas and combined islet cell adenomas + carcinomas) in male rats and liver tumors (adenomas and combined adenomas + carcinomas) in male and female mice.
Ref: US EPA. Pesticide Fact Sheet. Fluthiacet-methyl Reason for Issuance: Conditional Registration Date Issued: April 1999.
http://www.epa.gov/opprd001/factsheets/fluthiacet.pdf

-- Carcinogenicity rats. NOAEL in males = 2.1 mg/kg/day LOAEL in males = 130 mg/kg/day NOAEL in females = 2.5 mg/kg/day LOAEL in females = 154 mg/kg/dayIn males there were decreased body weight, liver toxicity, pancreatic toxicity and microcytic anemia. In females there were liver toxicity, uterine toxicity and slight microcytic anemia. In males only at 130 and 219 mg/kg/day there was respectively, an increase in the trend toward pancreatic exocrine adenomas and pancreatic islet cell adenomas.
-- Carcinogenicity mice. NOAEL in males and females = 0.1 mg/ kg/day LOAEL in males and females = 0.1 and 1.2 mg/kg/day, respectively, based on non- neoplastic liver findings. In males, and possibly females, at 10 mg/kg/day for males and 12 mg/kg/day for females; and at 32 gm/kg/day for males and 37 mg/ kg/day for females, there was an increase in the number of mice with hepatocellular adenomas, carcinomos and or adenomas/ carcinomas.
-- Chronic Dietary General population. 18-month carcinogenicity in the mouse. NOAEL = 0.1 mg/kg/day Non-neoplastic liver findings (increase in absolute and relative liver weights, fatty changes, chronic inflammation, karyomegaly, single cell necrosis and ceroid/lipofuscin pigmentation).
-- Cancer. Fluthiacet-methyl has been classified as ``likely to be a human carcinogen'' by EPA. The Office of Pesticide Programs, Heath Effects Division, Cancer Assessment Review Committee recommended a linear low-dose approach (Q1*) for human risk assessment. The Q1* is 0.207 (mg/kg/day)-1 in human equivalents and is based upon the combined hepatocellular tumors (adenomas and carcinomas) in male mice. EPA conducted a cancer assessment analysis (food) using DEEM software and Tier 2 chronic dietary exposure assumptions. The assumptions of this Tier 2 chronic dietary analysis are as specified above. The cancer risk estimate (food only) for the U.S. population (total) is 3.93 x 10-8. This risk estimate translates to a dietary exposure of 1.90 x 10-7 mg/kg/day. This dietary exposure value was back-calculated based upon the cancer risk estimate and the Q1*. As cancer risk = Exposure x Q1 * Thus, Exposure = cancer risk estimate/ Q1 * or Exposure = 3.93 x 10-8/0.207.
Ref: Federal Register: December 21, 2001. Fluthiacet-methyl; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/Fluthiacet.M.FR.Dec.21.2001.htm

Clastogenic (click on for all fluorinated pesticides)

-- Cytogenetics. In vitro cytogenetic assays performed with two different mammalian cell lines demonstrated that fluthiacet-methyl is clastogenic both in the presence and absence of S9 activation.
Ref: Federal Register: December 21, 2001. Fluthiacet-methyl; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/Fluthiacet.M.FR.Dec.21.2001.htm

Endocrine: Uterus (click on for all fluorinated pesticides)

-- Carcinogenicity rats. NOAEL in males = 2.1 mg/kg/day LOAEL in males = 130 mg/kg/day NOAEL in females = 2.5 mg/kg/day LOAEL in females = 154 mg/kg/dayIn males there were decreased body weight, liver toxicity, pancreatic toxicity and microcytic anemia. In females there were liver toxicity, uterine toxicity and slight microcytic anemia. In males only at 130 and 219 mg/kg/day there was respectively, an increase in the trend toward pancreatic exocrine adenomas and pancreatic islet cell adenomas.
Ref: Federal Register: December 21, 2001. Fluthiacet-methyl; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/Fluthiacet.M.FR.Dec.21.2001.htm

Liver (click on for all fluorinated pesticides)

Likely to be Carcinogenic to Humans. Pancreatic cell tumors (exocrine adenomas, islet cell adenomas, and combined islet cell tumors); Sprague-Dawley rats (M). Hepatocellular tumors (adenomas and combined adenoma/carcinoma); CD-1 mice (M & F). CD-1 mice (M & F).
Ref: April 26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the Office of Pesticide Programs. From: Jess Rowland, Chief Science Information Management Branch Health Effect Division (7509C) Office of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf

A chronic reference dose (RfD) (0.001 mg/kg/day) was identified for fluthiacet-methyl, based on non-neoplastic liver findings (increase in absolute and relative liver weights, fatty changes, chronic inflammation, karyomegaly, single cell necrosis and ceroid/lipofuscin pigmentation).
Ref. Federal Register. December 21, 2001. Fluthiacet-methyl; Pesticide Tolerance. Final Rule.
http://www.epa.gov/fedrgstr/EPA-PEST/2001/December/Day-21/p31497.htm

-- Carcinogenicity rats. NOAEL in males = 2.1 mg/kg/day LOAEL in males = 130 mg/kg/day NOAEL in females = 2.5 mg/kg/day LOAEL in females = 154 mg/kg/dayIn males there were decreased body weight, liver toxicity, pancreatic toxicity and microcytic anemia. In females there were liver toxicity, uterine toxicity and slight microcytic anemia. In males only at 130 and 219 mg/kg/day there was respectively, an increase in the trend toward pancreatic exocrine adenomas and pancreatic islet cell adenomas.
-- Carcinogenicity mice. NOAEL in males and females = 0.1 mg/ kg/day LOAEL in males and females = 0.1 and 1.2 mg/kg/day, respectively, based on non- neoplastic liver findings. In males, and possibly females, at 10 mg/kg/day for males and 12 mg/kg/day for females; and at 32 gm/kg/day for males and 37 mg/ kg/day for females, there was an increase in the number of mice with hepatocellular adenomas, carcinomos and or adenomas/ carcinomas.
-- Chronic Dietary General population. 18-month carcinogenicity in the mouse. NOAEL = 0.1 mg/kg/day Non-neoplastic liver findings (increase in absolute and relative liver weights, fatty changes, chronic inflammation, karyomegaly, single cell necrosis and ceroid/lipofuscin pigmentation).
-- Cancer. Fluthiacet-methyl has been classified as ``likely to be a human carcinogen'' by EPA. The Office of Pesticide Programs, Heath Effects Division, Cancer Assessment Review Committee recommended a linear low-dose approach (Q1*) for human risk assessment. The Q1* is 0.207 (mg/kg/day)-1 in human equivalents and is based upon the combined hepatocellular tumors (adenomas and carcinomas) in male mice. EPA conducted a cancer assessment analysis (food) using DEEM software and Tier 2 chronic dietary exposure assumptions. The assumptions of this Tier 2 chronic dietary analysis are as specified above. The cancer risk estimate (food only) for the U.S. population (total) is 3.93 x 10-8. This risk estimate translates to a dietary exposure of 1.90 x 10-7 mg/kg/day. This dietary exposure value was back-calculated based upon the cancer risk estimate and the Q1*. As cancer risk = Exposure x Q1 * Thus, Exposure = cancer risk estimate/ Q1 * or Exposure = 3.93 x 10-8/0.207.
Ref: Federal Register: December 21, 2001. Fluthiacet-methyl; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/Fluthiacet.M.FR.Dec.21.2001.htm

• Definition: Karyomegaly: the condition of a cells nucleusbeing abnormally enlarged (i.e., for reasons other than it being polyploid).

Pancreas (click on for all fluorinated pesticides)

Likely to be Carcinogenic to Humans. Pancreatic cell tumors (exocrine adenomas, islet cell adenomas, and combined islet cell tumors); Sprague-Dawley rats (M). Hepatocellular tumors (adenomas and combined adenoma/carcinoma); CD-1 mice (M & F). CD-1 mice (M & F).
Ref: April 26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the Office of Pesticide Programs. From: Jess Rowland, Chief Science Information Management Branch Health Effect Division (7509C) Office of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf

-- Fluthiacet-methyl is classified as a "likely to be a human carcinogen" based on the presence of pancreatic tumors (exocrine adenomas, islet cell adenomas and combined islet cell adenomas + carcinomas) in male rats and liver tumors (adenomas and combined adenomas + carcinomas) in male and female mice.
Ref: US EPA. Pesticide Fact Sheet. Fluthiacet-methyl Reason for Issuance: Conditional Registration Date Issued: April 1999.
http://www.epa.gov/opprd001/factsheets/fluthiacet.pdf

-- Carcinogenicity. NOAEL in males = rats 2.1 mg/kg/day LOAEL in males = 130 mg/kg/day NOAEL in females = 2.5 mg/kg/day LOAEL in females = 154 mg/kg/day. In males there were decreased body weight, liver toxicity, pancreatic toxicity and microcytic anemia. In females there were liver toxicity, uterine toxicity and slight microcytic anemia. In males only at 130 and 219 mg/kg/day there was respectively, an increase in the trend toward pancreatic exocrine adenomas and pancreatic islet cell adenomas.
Ref: Federal Register: December 21, 2001. Fluthiacet-methyl; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Fluthiacet.M.FR.Dec.21.2001.htm

 

Environmental (click on for all fluorinated pesticides) Phototoxic Pesticide. Light-dependent peroxidizing herbicides (LDPHs). US EPA identified the following organofluorine herbicides Acifluorfen, Azafenidin, Carfentrazone-ethyl, Flumiclorac-penty, Flumioxazin, Fluthiacet-methyl, Fomesafen, Lactofen, Oxadiargyl, Oxadiazon, Oxyfluorfen, Sulfentrazone, Thidiazimin as phototoxic pesticides that act by inhibiting protoporphyringen oxidase in the heme and chlorophyll biosynthetic pathway. [10 out of the 13 pesticides that EPA identified are organofluorines]. SEE http://www.fluoridealert.org/pesticides/PHOTOTOXICITY.PAGE.htm Ref: December 11, 2001 - US EPA. Revised Environmental Fate and Effects Division Preliminary Risk Assessment for the Oxyfluorfen Reregistration Eligibility Decision Document - also at: http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxyefedchap.pdf -- Fluthiacet-methyl was shown to be practically non-toxic to birds, practically non-toxic to small mammals, practically non-toxic to bees and other beneficial insects, very highly toxic to fish, and moderately toxic to fresh water invertebrates. For seedling emergence, onion is the most sensitive non-target plant species and for vegetative, vigor, cucumber is the most sensitive non-target plant species. For aquatic plants, duckweed and nonvascular green algae are the most sensitive aquatic plant species. There are no acute or chronic risk to non-target endangered fish, birds, aquatic invertebrates, terrestrial or aquatic plants or endangered species. Risks to endangered terrestrial and aquatic species are expected to be minimal form the use of Action Herbicide on soybeans. Because surfactant is used with the end-use product, and may enhance the product's phytotoxicity, limited vegetative vigor test with onion, tomato, cucumber and an aquatic test with duckweed are a condition of the registration for Action Herbicide. -- The following statement must appear in the Environmental Hazards section of the label of end use products: This pesticide is toxic to fish and aquatic invertebrates. Do not discharge effluent containing this product into lakes, streams, ponds, estuaries, oceans or other waters unless in accordance with the requirements of a National Pollutant Discharge Elimination System (NPDES) permit and the permitting authority has been notified in writing prior to discharge. Do not discharge effluent containing this product to sewer systems without previously notifying the sewage treatment plant authority. For guidance contact your State Water Board or Regional Office of the Environmental Protection Agency. Ref: US EPA. Pesticide Fact Sheet. Fluthiacet-methyl Reason for Issuance: Conditional Registration Date Issued: April 1999. http://www.epa.gov/opprd001/factsheets/fluthiacet.pdf

A  February 16, 2005, check at the Code of Federal Regulations for Fluthiacet-methyl: this herbicide is permitted in or on 9 food commodities in the United States. The following list identifies these crops for which EPA has set pesticide.
Code of Federal Regulations] [Title 40, Volume 22] [Revised as of July 1, 2004] From the U.S. Government Printing Office via GPO Access [CITE: 40CFR180.551] [Page 501] TITLE 40--PROTECTION OF ENVIRONMENT CHAPTER I--ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PART 180_TOLERANCES AND EXEMPTIONS FROM TOLERANCES FOR PESTICIDE CHEMICALS IN FOOD--Table of Contents Subpart C_Specific Tolerances Sec. 180.551 Fluthiacet-methyl; tolerances for residues. (a) General. A tolerance is established for residues of the herbicide, fluthiacet-methyl, acetic acid [[2-chloro-4-fluoro-5- [(tetrahydro-3-oxo-1H,3H-[1,3,4]thiadiazolo[3,4-[alpha]]pyridazin-1- ylidene)amino]phenyl]thio]-methyl ester, in or on the food commodity:
Commodity	Parts per million
Corn, field, forage	0.050
Corn, field, grain	0.010
Corn, field, stover	0.050
Corn, pop, grain	0.010
Corn, pop, stover	0.050
Corn, sweet, forage	0.050
Corn, sweet, kernel plus cob with husks removed	0.010
Corn, sweet, stover	0.050
Soybean, seed	0.01
(b) Section 18 emergency exemptions. [Reserved] (c) Tolerances with regional registrations. [Reserved] (d) Indirect or inadvertent residues. [Reserved]