Adverse Effects
Benfluralin also known as Benefin
CAS No. 1861-40-1
 
 

Return to Benfluralin Index Page

Activity: Herbicide (2,6-dinitroaniline)
Structure:

Adverse Effects:
Ataxia
Blood
Body Weight Decrease
Cancer.
Suggestive Evidence of Carcinogenicity: LIVER.
Endocrine: Thyroid
Kidney
Liver
Spleen
Environmental

As of February 15, 2005, this herbicide is permitted to have residues in or on 8 food commodities in the US. They are presented at the bottom of this page.


Ataxia (click on for all fluorinated pesticides)

Animal Toxicity Studies: ... ATAXIA, WEAKNESS, FALLING. REGURGITATION ALSO OCCURRED IN FIRST 2 HR AFTER TREATMENT. THE OTHER SIGNS OCCURRED 2 TO 14 DAYS AFTER TREATMENT. ALTHOUGH NO BIRDS DIED, CONSIDERABLE WT LOSSES HAD OCCURRED BY THE END OF THE 14 DAY OBSERVATION PERIOD. /FEMALE MALLARDS, ACUTE ORAL/ [U.S. Department of the Interior, Fish and Wildlife Service. Handbook of Toxicity of Pesticides to Wildlife. Resource Publication 153. Washington, DC: U.S. Government Printing Office, 1984. 13]
Ref: TOXNET profile from Hazardous Substances Data Bank.
http://www.fluoridealert.org/pesticides/Benfluralin.TOXNET.HSDB.htm

Blood (click on for all fluorinated pesticides)

Increased relative liver weights, decreased red blood cell counts and decreased hematocrit and hemoglobin levels were observed in dogs orally administered benfluralin at a dose of 125 mg/kg/day for 2 years. The NOAEL was 25 mg/kg/day. Based on the NOAEL, EPA has established an oral RfD of 0.003 mg/kg/day. EPA believes that there is sufficient evidence for listing benfluralin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available hematological toxicity data for this chemical.
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.

Body Weight Decrease (click on for all fluorinated pesticides)

-- REPRODUCTION, RAT **208-078 167287, ATwo-Generation Reproduction Study in Rats with Benefin@, (Janet A. Trutter, Hazleton Washington, Inc., Vienna, VA., Report # HWA 174-136, 9 February 1995). Thirty Sprague-Dawley Crl:CD 7 BR rats per sex per group received benefin (95.8% purity) in the diet at concentrations of 0, 100, 1000, and 5000 ppm through 2 generations with one litter per generation. Parental NOEL = 100 ppm (7.1 and 8.8 mg/kg/day for M and F, respectively, based on hepatocellular enlargement, enhanced extent of chronic progressive nephropathy in both sexes, and renal tubule hyaline droplets in males: also associated increased liver and kidney weights). Offspring NOEL = 100 ppm (reduced body weights of pups by day 7, continuing at least through weaning). The high dose caused pup weight reductions at weaning to about 60% of controls. Adult 5000 ppm F1 males (the more sensitive gender and generation of adults) weighed about 80% of controls after 10 to 19 weeks of treatment. Lesser but statistically significant decrements were seen in F0 males and in F0 and F1 females at 5000 ppm. Food consumption was correspondingly reduced in both sexes at this dose level. Offspring effects limited to 5000 ppm included significant reduction of mean live litter size at birth and a reduction of pup viability between day 4 cull and weaning (21% loss in 5000 ppm F2 pups). Acceptable, with no adverse effects. (H. Green and C. Aldous, 4/21/00).
-- TERATOLOGY, RABBIT **208-077 167286, “Teratology Study in Rabbits with Benefin”, (M. D. Mercieca, Springborn Laboratories, Inc., Spencerville, OH, Report # 3130.9, 3 June 1991). Twenty inseminated female New Zealand white rabbits per group received benefin (in 10% aqueous acacia) at concentrations of 0, 25, 50, 100, and 225 mg/kg/day on gestation days 6 through 18 in a guideline teratology study. Maternal NOEL = 50 mg/kg/day (increased incidence of does with few or no feces). Developmental NOEL = 225 mg/kg/day (highest dose tested). The highest dose was clearly maternally toxic, as indicated by significant (p < 0.01) reductions in food consumption and body weight gain, and by the presence of 3 aborted litters and one total litter resorption loss. Acceptable, with no adverse effects (H. Green, and C. Aldous, 4/18/00).
Ref: Summary of Toxicological Data: Benefin. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch. Revised April 21, 2000.

http://www.fluorideaction.org/pesticides/benefin.ca.tox.rev.apr.2000.pdf

Animal Toxicity Studies: ... ATAXIA, WEAKNESS, FALLING. REGURGITATION ALSO OCCURRED IN FIRST 2 HR AFTER TREATMENT. THE OTHER SIGNS OCCURRED 2 TO 14 DAYS AFTER TREATMENT. ALTHOUGH NO BIRDS DIED, CONSIDERABLE WT LOSSES HAD OCCURRED BY THE END OF THE 14 DAY OBSERVATION PERIOD. /FEMALE MALLARDS, ACUTE ORAL/ [U.S. Department of the Interior, Fish and Wildlife Service. Handbook of Toxicity of Pesticides to Wildlife. Resource Publication 153. Washington, DC: U.S. Government Printing Office, 1984. 13]
Ref: TOXNET profile from Hazardous Substances Data Bank. http://www.fluoridealert.org/pesticides/Benfluralin.TOXNET.HSDB.htm

Cancer; LIVER (click on for all fluorinated pesticides)

Suggestive Evidence of Carcinogenicity, but Not Sufficient to Assess Human Carcinogenic Potential. Liver tumors (hepatocellular adenomas & carcinomas) in 2 genetically related strains of mice (CD-1 & Swiss SPF) (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

Endocrine: Thyroid (click on for all fluorinated pesticides)

208-079 167288, “Benefin: Two-Year Dietary Chronic Toxicity/Oncogenicity Study in Fischer 344 Rats”, (Michael R. Moore, Corning Hazleton Inc, Vienna, VA., Laboratory ID # CHV 174-133, Sponsor Report # DR-0097-3397-005, 1 July 1996). Fifty CDF ® (F-344)CrlBR rats per sex per group received benefin in the diet at 0, 10, 100, 2500, and 5000 ppm for 2 yr. An additional 10 per sex per group at the same dose levels were designated for 1-yr interim sacrifice. Estimated achieved dosages were 0, 0.5, 5.4, 136, and 275 mg/kg/day in males, and 0, 0.7, 6.8, 168, and 331 mg/kg/day in females, respectively over weeks 1-104....Tumor incidence: thyroid follicular tumors (adenomas and carcinomas) increased in males (incidences of 1, 1, 1, 7, and 8 in controls through high dose, respectively) and females (incidences of 0, 0, 1, 5, and 4)... Tumors are possible adverse effects, which should be evaluated in perspective of the many indications of excessive exposures at effective dose levels. Green and Aldous, 4/11/00.
Ref: Summary of Toxicological Data: Benefin. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch. Revised April 21, 2000.
http://www.fluorideaction.org/pesticides/benefin.ca.tox.rev.apr.2000.pdf

Kidney (click on for all fluorinated pesticides)

COMBINED, RAT **208-079 167288, “Benefin: Two-Year Dietary Chronic Toxicity/Oncogenicity Study in Fischer 344 Rats”, (Michael R. Moore, Corning Hazleton Inc, Vienna, VA., Laboratory ID # CHV 174-133, Sponsor Report # DR-0097-3397-005, 1 July 1996). Fifty CDF ® (F-344)CrlBR rats per sex per group received benefin in the diet at 0, 10, 100, 2500, and 5000 ppm for 2 yr. An additional 10 per sex per group at the same dose levels were designated for 1-yr interim sacrifice. Estimated achieved dosages were 0, 0.5, 5.4, 136, and 275 mg/kg/day in males, and 0, 0.7, 6.8, 168, and 331 mg/kg/day in females, respectively over weeks 1-104. Chronic NOEL = 10 ppm (0.5 and 0.7 mg/kg/day in M and F), based on increased hyaline droplets in kidneys of both sexes at 100 ppm and above, increased and tubular cell karyomegaly and transitional cell hyperplasia in kidneys of males, hepatocellular hypertrophy and increased hepatocellular pigmentation in females, and calculus of renal pelvis in females. Substantial toxicity prompted investigators to determine that the two highest dose levels “exceeded the maximum tolerated dose and therefore should not be used for risk assessment”. The study design, with no dose levels between 100 and 2500 ppm, gave no opportunity to characterize dose-response in this range of primary interest. These were major changes at the highest two dose levels (in both sexes, unless indicated), in addition to the findings for the NOEL (above) applying to both sexes. Body weights were reduced over time (in males, primarily in last few weeks of the study), so that at termination the deficits of 2500 and 5000 ppm groups compared to controls were 8 and 17% in males, and 18 and 28% in females, respectively. In females only, this was accompanied by approximately 10% food consumption reductions at each of the higher dose levels. There were reductions in the main hematology parameters (RBC counts, HCT, and Hb levels). Incidence and/or degree of chronic progressive nephropathy was increased. The majority of these rats had “slight” to “minimal” degeneration of sciatic nerve and skeletal muscle (thigh). Males had elevated incidence of single cell necrosis in liver. Chronic inflammation of the lungs was seen in the majority of these rats, whereas low incidences of congestion of the abdominal cavity, and urinary bladder hyperplasia were limited to these dose levels. Numerous clinical chemistry changes mirrored the above pathology in kidneys, liver, and perhaps other tissues at the higher two dose levels. Tumor incidence: thyroid follicular tumors (adenomas and carcinomas) increased in males (incidences of 1, 1, 1, 7, and 8 in controls through high dose, respectively) and females (incidences of 0, 0, 1, 5, and 4). Hepatocellular tumors (primarily adenomas) were increased in males (incidences of 2, 2, 1, 5, and 11 in controls through high dose, respectively). There were no statistically significant increases in epithelial cell tumors in kidneys nor urinary bladder, however the low incidences of transitional cell papilloma and tubule cell adenoma or carcinoma were predominantly found in 2500 and 5000 ppm groups (compare to the congener, trifluralin). Study is acceptable. Tumors are possible adverse effects, which should be evaluated in perspective of the many indications of excessive exposures at effective dose levels. Green and Aldous, 4/11/00.
Ref: Summary of Toxicological Data: Benefin. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch. Revised April 21, 2000.
http://www.fluorideaction.org/pesticides/benefin.ca.tox.rev.apr.2000.pdf

Liver (click on for all fluorinated pesticides)

"Benefin: 13-Week Oral Toxicity Study in Beagle Dogs", (D.W. Dalgard, Hazleton Washington, HWA 174-135, 12/28/93). Benefin, purity 95.8%, administered via capsule at concentrations of 0, 5, 25, 125 mg/kg/day to 4 Beagle dogs/sex/group for 13 weeks. Emesis (compound colored) was slightly increased at all dose levels for females and for mid and high dose males. Liver weights was increased for high dose males; and the incidence of hepatocellular hypertrophy was increased for high dose males and females. Increased incidence of hemosiderin pigment was observed in the liver at the high dose and the spleen at mid and high dose levels. NOAEL = 5 mg/kg/day. Acceptable (Kishiyama, J., and P. Iyer, 5/12/98).
Ref: Summary of Toxicology Data for Benefin. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch

http://www.cdpr.ca.gov/docs/toxsums/pdfs/53.pdf

COMBINED, RAT **208-079 167288, "Benefin: Two-Year Dietary Chronic Toxicity/Oncogenicity Study in Fischer 344 Rats", (Michael R. Moore, Corning Hazleton Inc, Vienna, VA., Laboratory ID # CHV 174-133, Sponsor Report # DR-0097-3397-005, 1 July 1996). Fifty CDF ® (F-344)CrlBR rats per sex per group received benefin in the diet at 0, 10, 100, 2500, and 5000 ppm for 2 yr. An additional 10 per sex per group at the same dose levels were designated for 1-yr interim sacrifice. Estimated achieved dosages were 0, 0.5, 5.4, 136, and 275 mg/kg/day in males, and 0, 0.7, 6.8, 168, and 331 mg/kg/day in females, respectively over weeks 1-104. Chronic NOEL = 10 ppm (0.5 and 0.7 mg/kg/day in M and F), based on increased hyaline droplets in kidneys of both sexes at 100 ppm and above, increased and tubular cell karyomegaly and transitional cell hyperplasia in kidneys of males, hepatocellular hypertrophy and increased hepatocellular pigmentation in females, and calculus of renal pelvis in females. Substantial toxicity prompted investigators to determine that the two highest dose levels “exceeded the maximum tolerated dose and therefore should not be used for risk assessment”. The study design, with no dose levels between 100 and 2500 ppm, gave no opportunity to characterize dose-response in this range of primary interest. These were major changes at the highest two dose levels (in both sexes, unless indicated), in addition to the findings for the NOEL (above) applying to both sexes. Body weights were reduced over time (in males, primarily in last few weeks of the study), so that at termination the deficits of 2500 and 5000 ppm groups compared to controls were 8 and 17% in males, and 18 and 28% in females, respectively. In females only, this was accompanied by approximately 10% food consumption reductions at each of the higher dose levels. There were reductions in the main hematology parameters (RBC counts, HCT, and Hb levels). Incidence and/or degree of chronic progressive nephropathy was increased. The majority of these rats had "slight" to "minimal" degeneration of sciatic nerve and skeletal muscle (thigh). Males had elevated incidence of single cell necrosis in liver. Chronic inflammation of the lungs was seen in the majority of these rats, whereas low incidences of congestion of the abdominal cavity, and urinary bladder hyperplasia were limited to these dose levels. Numerous clinical chemistry changes mirrored the above pathology in kidneys, liver, and perhaps other tissues at the higher two dose levels. Tumor incidence: thyroid follicular tumors (adenomas and carcinomas) increased in males (incidences of 1, 1, 1, 7, and 8 in controls through high dose, respectively) and females (incidences of 0, 0, 1, 5, and 4). Hepatocellular tumors (primarily adenomas) were increased in males (incidences of 2, 2, 1, 5, and 11 in controls through high dose, respectively). There were no statistically significant increases in epithelial cell tumors in kidneys nor urinary bladder, however the low incidences of transitional cell papilloma and tubule cell adenoma or carcinoma were predominantly found in 2500 and 5000 ppm groups (compare to the congener, trifluralin). Study is acceptable. Tumors are possible adverse effects, which should be evaluated in perspective of the many indications of excessive exposures at effective dose levels. Green and Aldous, 4/11/00.
Ref: Summary of Toxicological Data: Benefin. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch. Revised April 21, 2000.
http://www.fluorideaction.org/pesticides/benefin.ca.tox.rev.apr.2000.pdf

Spleen (click on for all fluorinated pesticides)

"Benefin: 13-Week Oral Toxicity Study in Beagle Dogs", (D.W. Dalgard, Hazleton Washington, HWA 174-135, 12/28/93). Benefin, purity 95.8%, administered via capsule at concentrations of 0, 5, 25, 125 mg/kg/day to 4 Beagle dogs/sex/group for 13 weeks. Emesis (compound colored) was slightly increased at all dose levels for females and for mid and high dose males. Liver weights was increased for high dose males; and the incidence of hepatocellular hypertrophy was increased for high dose males and females. Increased incidence of hemosiderin pigment was observed in the liver at the high dose and the spleen at mid and high dose levels. NOAEL = 5 mg/kg/day. Acceptable (Kishiyama, J., and P. Iyer, 5/12/98).
Ref: Summary of Toxicology Data for Benefin. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch

http://www.cdpr.ca.gov/docs/toxsums/pdfs/53.pdf

Environmental (click on for all fluorinated pesticides)

Fish  
-- Goldfish (Carassius auratus) -
Highly Toxic
--
Sheepshead minnow (Cyprinodon variegatus) - Highly toxic
--
Bluegill (Lepomis macrochirus) -- Highly toxic to Very Highly Toxic
-- Rainbow trout,donaldson trout (Oncorhynchus mykiss) -
Highly Toxic
--
Fathead minnow (Pimephales promelas) -Highly Toxic
Zooplankton    
--
Opossum shrimp (Americamysis bahia) - Very Highly Toxic
Ref: PAN Pesticides Database - Chemical Toxicity Studies on Aquatic Organisms. Toxicity Studies for Benfluralin on All Organism Groups - Toxicology studies on aquatic organisms from science journals.
http://www.pesticideinfo.org/List_AquireAll.jsp?Rec_Id=PC35043


Fluoride/fluorinated substances identified in Agreement between Canada and the United States on Great Lakes Water Quality, 1978.
Appendix 1 - Hazardous Polluting Substances:

Ammonium Bifluoride * Ammonium Fluoborate * Ammonium Fluoride * Ammonium Silicofluoride * Antimony Trifluoride * Beryllium Fluoride * Ferric Fluoride * Hydrofluoric Acid * Lead Fluoborate * Lead Fluoride * Sodium Bifluoride * Sodium Fluoride * Zinc Fluoride * Zinc Silicofluoride * Zirconium Potassium Fluoride.
Appendix 2 - Potential Hazardous Polluting Substances:

Aluminum Fluoride * Antimony Pentafluoride * Benfluralin * Chlorflurazole * Cobaltous Fluoride * Stannous Fluoride

A February 15, 2005, check at the Code of Federal Regulations for Benfluralin: this herbicide is permitted in or on 8 food commodities in the United States. The following list identifies these crops for which EPA has set pesticide tolerances. 

[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: 40CFR180.208]
[Page 378]

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. 180.208 N-Butyl-N-ethyl-[alpha][middot][alpha][middot][alpha]-tri
fluoro-2,6-dinitro-p-toluidine; tolerances for residues
(a) General. Tolerances are established for residues of the
herbicide N-butyl-N-ethyl-[alpha][middot][alpha][middot][alpha]-
trifluoro-2,6-dinitro-p-toluidine in or on the following food commodities:
Commodity

As of
December 1,

2003

PPM

As of
February 15,

2005

PPM

CFR
Alfalfa, forage
Not Listed in this way 0.05(N) 180.208
Alfalfa, hay
Not Listed in this way 0.05(N) 180.208
Clover, forage Not Listed in this way 0.05(N) 180.208
Clover, hay
Not Listed in this way 0.05(N) 180.208
Lettuce 0.05 0.05(N) 180.208
Peanut 0.05 0.05(N) 180.208
Trefoil, birdsfoot, forage Not Listed in this way 0.05(N) 180.208
Trefoil, birdsfoot, hay Not Listed in this way 0.05(N) 180.208
ALFALFA
0.05 Not Listed in this way 180.208
CLOVER
0.05 Not Listed in this way 180.208
TREFOIL, BIRDSFOOT
0.05 Not Listed in this way 180.208
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
 
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