Return to Acifluorfen Index Page

Activity: Herbicide (diphenyl ether)
Structure for "Acifluorfen":

Adverse Effects:
Anemia
Body Weight Decrease
Bone
Brain
Cancer: Probable Human Carcinogen - LIVER
Endocrine: Testicular
Eye
Kidney
Liver
Stomach
Environmental

Anemia (click on for all fluorinated pesticides)

Increased liver and kidney weights occurred in chronic rat, mouse, and dog studies and were accompanied by microscopic liver and kidney changes in the chronic rat and dog studies. Anemia was present in chronic rat and dog studies. Stomach ulcers were found in chronic rat and mouse studies. Testicular atrophy occurred in the chronic rat study. Increased mortality occurred in the high-dose group in rat and mouse studies.
Ref: January 15, 2002. Preliminary Human Health Risk Assessment. MEMORANDUM SUBJECT: SODIUM ACIFLUORFEN. HED Chapter for the Reregistration Eligibility Decision Document. US EPA, Office of Prevention, Pesticides and Toxic Substances. http://www.fluorideaction.org/pesticides/acifluorfen.na.a.red.jan.02.pdf

Body Weight Decrease (click on for all fluorinated pesticides)

STUDY TYPE Ð DOSE LEVELS	NOAEL (mg/kg/day)	LOAEL (mg/kg/day)
Chronic/Carcinogenicity - Rat (1983) 0, 25, 150, 500, 2500, or 5000 ppm. (0, 1.25, 7.50, 25.0, 125, or 250 mg/kg/day based on 1 ppm=0.05 mg/kg/day) (MRID No. 00128253; Accession NoÕs. 071315 through 071317 and 250289 through 250792)	25	125 based on reduced body weight, increased absolute and relative liver weights and increased kidney weights, increased incidence of nephritis/pyelonephritis, increased incidence of acidophilic cells in the liver, and related changes in clinical chemistry parameters .
Carcinogenicity in Mice (1982). 0, 625, 1250, or 2500 ppm (males: 0, 119, 259, 655 mg/kg/day; females: 0, 143, 313, 711 mg/kg/day) (MRID No. 00122732; Accession NoÕs.071312, 071313, 071314, 250463, and 250464)	< 119	• • 119 . • • 143 based on reduced body weight, increased absolute and relative liver weights, and changes in hematologic parameters (decreased MCV counts, decreased segmented neutrophil counts, increased RBC counts, and increased lymphocyte counts).
Chronic Feeding Study in Dogs (1983). Tackle Ò2SÓ (Acifluorfen, purity was unspecified). 0, 20, 300, or 4500 ppm (0, 0.5, 7.5 or 112.5 mg/kg/day based on 1 ppm = 0.025 mg/kg/day) for 2 years (MRID No. 00131162; Accession NoÕs.251297 and 251298)	7.5	112.5 based on decreased body weight gain, increased absolute and relative liver and kidney weights, changes in hematology, biochemistry, and urinalysis parameters and increased incidence of microscopic changes in the liver.
Developmental Toxicity Study in Rats (1981) 0, 20, 90, or 180 mg/kg/day from gestation days 6 through 19 (MRID No.00122743; Accession No. 071319)	Maternal: 20 Development al: 20	Maternal: 90 based on increase in clinical signs (excessive salivation and piloerection). Developmental: 90 based on the decreased fetal body weight and the increase in anatomical variations.
Developmental Toxicity Study in Rabbits (1979) 0, 20, 60, 180 mg/kg/day (MRID 00107485)	Maternal: 20 Development al: 60	Maternal: 60 based on clinical signs (anorexia, depression and dyspnea). Developmental: 180 based on fetal resorptions.
Ref: April 27, 2001. MEMORANDUM. SUBJECT: SODIUM ACIFLUORFEN. HED Chapter for the Reregistration Eligibility Decision Document. US EPA. Office of Prevention, Pesticides, and Toxic Substances. http://www.fluorideaction.org/pesticides/acifluorfen.epa.01.healtrsk.pdf
-- For "females 13-50 years," a NOAEL of 20 mg/kg/day was established based on effects of decreased fetal weight and increased incidence of dilated lateral ventricles of the brain observed in a rat developmental toxicity study. Both the decreased fetal weight and the brain malformations are presumed to occur after a single exposure (dose), and thus, are appropriate for this acute risk assessment. These effects were observed at 90 mg/kg/day (LOAEL). Ref: Overview of Sodium Acifluorfen Risk Assessment April 4, 2002. USEPA. http://www.fluorideaction.org/pesticides/acifluorfen.na.epa.apr.02.pdf
-- Carcinogenic Effects. Some studies show acifluorfen to be carcinogenic, while others do not; the main differences among the studies were the dose levels administered and the lengths of the studies. One study of mice fed high doses for 18 months showed decreases in body weight and increases in both benign and malignant liver tumors (2). As a result, acifluorfen is classified as a probable human carcinogen by the U.S. Environmental Protection Agency. Ref: Pesticide Information Profile. Extoxnet. Cornell Univeristy. http://www.fluoridealert.org/pesticides/Acifluorfen.Extoxnet.htm

Bone (click on for all fluorinated pesticides)

Developmental toxicity in rats... A significant increase (p < 0.0001) in resorptions in the high-dose group and significant reduction (p< 0.01) in mean fetal weights for both the mid- and high-dose groups were observed. A significant increase (p< 0.05 or 0.01) in anatomical variations was seen in the mid- and high-dose groups. The variations included slightly dilated lateral ventricles of the brain, hemorrhage in the eyeball, slight dilation of the renal pelvis, hemorrhage in either the peritoneal cavity or subcutaneous spaces, and minor changes in ossification (such as incomplete ossification of supra-occipital sternebra or thoracic centra). The NOAEL for developmental toxicity is 20 mg/kg/day; the LOAEL for developmental toxicity is 90 mg/kg/day based on the decreased fetal body weight and the increase in anatomical variations.
Ref: November 10, 1999. Toxicology Chapter for RED. MEMORANDUM SUBJECT: ACIFLUORFEN: TOXICOLOGY CHAPTER FOR RED. http://www.epa.gov/pesticides/reregistration/acifluorfen/toxicology_chapter.pdf

Brain (click on for all fluorinated pesticides)

The toxicity database is adequate for selecting toxicity endpoints for risk assessments, although a developmental neurotoxicity study is required because of neurotoxicity which occurred in a developmental rat study (dilated lateral ventricles of the brain)... A developmental toxicity study in rats found qualitative evidence of increased susceptibility of offspring because developmental toxicity (increased resorptions, reduced fetal weights, slightly dilated lateral ventricles of the brain, hemorrhage in the eyeball, slight dilation of the renal pelvis, hemorrhage in peritoneal cavity and subcutaneous spaces, and changes in ossification) was accompanied by minimal maternal toxicity (excess salivation and piloerection)... the Hazard Identification Assessment Review Committee recommended that a developmental neurotoxicity study in rats be conducted based on neurotoxicity observed in a developmental toxicity study in rats (increased incidence of dilated lateral ventricles of the fetal brain, MRID 00122743). In addition, no neurotoxicity studies are available for acifluorfen or for structurally related compounds which might provide an understanding on the effects of acifluorfen on the developing nervous system.
Ref: EPA, Sodium Acifluorfen. HED Chapter for the Reregistration Eligibility Decision. April 27, 2001.
http://www.epa.gov/oppsrrd1/reregistration/acifluorfen/newrisk.pdf

-- For "females 13-50 years," a NOAEL of 20 mg/kg/day was established based on effects of decreased fetal weight and increased incidence of dilated lateral ventricles of the brain observed in a rat developmental toxicity study. Both the decreased fetal weight and the brain malformations are presumed to occur after a single exposure (dose), and thus, are appropriate for this acute risk assessment. These effects were observed at 90 mg/kg/day (LOAEL).
Ref: Overview of Sodium Acifluorfen Risk Assessment April 4, 2002. USEPA. http://www.fluorideaction.org/pesticides/acifluorfen.na.epa.apr.02.pdf

TABLE 3. Doses and Toxicological Endpoints Selected for Various Exposure Scenarios
EXPOSURE SCENARIO	DOSE (mg/kg/day)	ENDPOINT	STUDY
Acute Dietary (Female 13-50)	NOAEL=20 UF=100 FQPA SF=10	Decreased fetal weight and increased incidences of dilated lateral ventricles of the brain at 90 mg/kg/day	DevelopmentalÐ rat
		Acute PAD = 0.02 mg/kg/day
(a) Dermal (short and intermediate-term, females 13-50)	NOAEL=20 MOE=100 FQPA SF=10 (Females 13-50)	Decreased fetal weight and increased incidences of dilated lateral ventricles of the brain at 90 mg/kg/day
(b) Inhalation (short and intermediate-term, females 13-50)
(a) = Since an oral NOAEL was selected, a dermal absorption factor of 20% of oral absorption should be used in route-to-route extrapolation.
(b) = Since an oral NOAEL was selected, an inhalation absorption factor of 100% of oral absorption (default value) should be used in route-to-route extrapolation.
Ref: January 15, 2002. MEMORANDUM. SUBJECT: SODIUM ACIFLUORFEN. HED Chapter for the Reregistration Eligibility Decision Document. US EPA. Office of Prevention, Pesticides, and Toxics Substances. http://www.fluorideaction.org/pesticides/acifluorfen.na.a.red.jan.02.pdf

Cancer: Probable Human Carcinogen - LIVER (click on for all fluorinated pesticides)

Likely to be Carcinogenic to Humans at High Doses. Not Likely to be Carcinogenic to Humans at Low Doses. Liver; B6C3F1 & 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

Group B2--Probable Human Carcinogen. Reviewed 3/ 17/ 88.
Ref: March 15, 2002. List of Chemicals Evaluated for Carcinogenic Potential. Science Information Management Branch, Health Effects Division, Office of Pesticide Programs, U. S. Environmental Protection Agency.
http://www.biomuncie.org/chemicals_evaluated_for_carcinog.htm

-- Acifluorfen is classified as a Group B2 compound, i.e., the chemical is a probable human carcinogen. Acifluorfen produced an increased incidence of combined malignant and benign liver tumors in two different strains of mice. The compound also displayed positive mutagenic activity in several non-mammalian test systems, and is structurally similar to four other diphenyl ether herbicide compounds which caused increased incidences of liver tumors in two different strains of mice. EPA believes that there is sufficient evidence for listing acifluorfen sodium salt on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available carcinogenicity data.
Ref. USEPA/OPP. Support Document for the Addition of Chemicals from Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) Active Ingredients to EPCRA Section 313. U. S. Environmental Protection Agency, Washington, DC (1993). As cited by US EPA in: Federal Register: January 12, 1994. Part IV. 40 CFR Part 372. Addition of Certain Chemicals; Toxic Chemical Release Reporting; Community Right-to-Know; Proposed Rule.

There are eight diphenyl ethers that are structurally similar to diclofop-methyl. Of the chemicals, fomesafen sodium, haloxyfop-methyl (Verdict), oxyfluorfen, acifluorfen sodium, nitrofen, and lactofen were reviewed in the initial CPRC report. All of these chemicals induced liver adenomas and carcinomas in rats and/or mice. Except for haloxyfop-methyl, all of the other chemicals produced positive results in at least one of the mutagenicity assays...
May 24, 2000 - Cancer Assessment Document. Evaluation of the Carcinogenic Potential of Diclofop-Methyl. (Second Review). Final Report. Cancer Assessment Review Committee, Health Effects Division, US EPA Office of Pesticide Programs.
Note: Except for Nitrofen, all the pesticides cited above are fluorinated.

Endocrine: Testicular (click on for all fluorinated pesticides)

Increased liver and kidney weights occurred in chronic rat, mouse, and dog studies and were accompanied by microscopic liver and kidney changes in the chronic rat and dog studies. Anemia was present in chronic rat and dog studies. Stomach ulcers were found in chronic rat and mouse studies. Testicular atrophy occurred in the chronic rat study. Increased mortality occurred in the high-dose group in rat and mouse studies.
Ref: January 15, 2002. Preliminary Human Health Risk Assessment. MEMORANDUM SUBJECT: SODIUM ACIFLUORFEN. HED Chapter for the Reregistration Eligibility Decision Document. US EPA, Office of Prevention, Pesticides and Toxic Substances. http://www.fluorideaction.org/pesticides/acifluorfen.na.a.red.jan.02.pdf

Eye (click on for all fluorinated pesticides)

Acute Toxicity: Sodium acifluorfen has been placed in Acute Toxicity Category I for acute eye irritation and in Category II for acute dermal irritation.
Ref: April 4, 2002. Overview of Sodium Acifluorfen Risk Assessment. USEPA. http://www.fluorideaction.org/pesticides/acifluorfen.na.epa.apr.02.pdf

A developmental toxicity study in rats found qualitative evidence of increased susceptibility of offspring because developmental toxicity (increased resorptions, reduced fetal weights, slightly dilated lateral ventricles of the brain, hemorrhage in the eyeball, slight dilation of the renal pelvis, hemorrhage in peritoneal cavity and subcutaneous spaces, and changes in ossification)
Ref: January 15, 2002. MEMORANDUM. SUBJECT: SODIUM ACIFLUORFEN. HED Chapter for the Reregistration Eligibility Decision Document. http://www.fluorideaction.org/pesticides/acifluorfen.na.a.red.jan.02.pdf

Severe eye irritant; moderate skin irritant (rabbit). /Acifluorfen/ [Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994]
Ref: TOXNET profile from Hazardous Substances Data Base for ACIFLUORFEN-SODIUM..
http://www.fluoridealert.org/pesticides/Acifluorfen.NA.TOXNET.HSDB.htm

Acifluorfen is very toxic and is labeled with a DANGER signal word due to its potential to cause serious eye injury.
Ref: Pesticide Information Profile. Extoxnet from Cornell Univeristy.
http://www.fluoridealert.org/pesticides/Acifluorfen.Extoxnet.htm

Kidney (click on for all fluorinated pesticides)

A 2-generation reproduction study in rats fed diets containing 0, 25, 500 or 2,500 ppm with no adverse effect on adult reproductive performance observed under the conditions of the study. The NOEL was established at 25 ppm (equivalent to 1.25 mg/kg of body weight/day) based on decreased viability and increased incidence of kidney lesions in high dose offspring.
Ref: Federal Register. April 17, 1996. Sodium Salt of Acifluorfen; Pesticide Tolerance. Proposed Rule.
http://www.fluoridealert.org/pesticides/Acifluorfen.Sod.FR.Apr17.96.htm

The chronic feeding toxicity study in rats, mice, and dogs demonstrated that acifluorfen induced liver toxicity (acidophilic cells in the liver and increased liver weight) and kidney toxicity (nephritis/pyelonephritis and increased kidney weight). An increase in the incidence of stomach ulcer was also seen in chronic feeding study in rats.
Ref: US EPA Toxicology Chapter for RED. November 10, 1999
http://www.epa.gov/pesticides/reregistration/acifluorfen/toxicology_chapter.pdf

Liver (click on for all fluorinated pesticides)

Carcinogenicity. Acifluorfen has been classified as a Group B2 (probable human carcinogen) chemical by the OPP Cancer Peer Review Committee (CPRC), based on an increased number of liver tumors in both sexes of mice and a high incidence of uncommonly occurring stomach papillomas in male mice. The Committee recommended using the Q1* approach for quantification of human risk. The Q1* is 0.11 (mg/kg/day)-1.
Ref: Federal Register. July 25, 1997. Sodium Salt of Acifluorfen; Pesticide Tolerances for Emergency Exemptions. Final Rule.
http://www.epa.gov/fedrgstr/EPA-PEST/1997/July/Day-25/p19668.htm

Male mice had a significant increasing trend, and significant differences in the pair-wise comparisons of all dose groups with the controls, for liver adenoma and/or carcinoma tumors combined.
Ref: MEMORANDUM. November 8, 2001. SUBJECT: REVISED Sodium Salt of Aciflourfen (Tackle TM , Blazer TM ) Quantitative Risk Assessment (Q1 * ) Based On B6C3F1 Mouse Dietary Study Using mg/kg b.w.^ 3 /4 's/day Cross Species Scaling Factor.
http://www.fluorideaction.org/pesticides/acifluorfen.na.cancer.nov01.pdf

Stomach (click on for all fluorinated pesticides)

Increased liver and kidney weights occurred in chronic rat, mouse, and dog studies and were accompanied by microscopic liver and kidney changes in the chronic rat and dog studies. Anemia was present in chronic rat and dog studies. Stomach ulcers were found in chronic rat and mouse studies. Testicular atrophy occurred in the chronic rat study. Increased mortality occurred in the high-dose group in rat and mouse studies.
Ref: January 15, 2002. Preliminary Human Health Risk Assessment. MEMORANDUM SUBJECT: SODIUM ACIFLUORFEN. HED Chapter for the Reregistration Eligibility Decision Document. US EPA, Office of Prevention, Pesticides and Toxic Substances. http://www.fluorideaction.org/pesticides/acifluorfen.na.a.red.jan.02.pdf