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Activity: Herbicide (sulfonylurea)
Structure:

Adverse Effects:
Anemia
Blood
Body Weight Decrease
Bone
Brain
Cancer: Possible Human Carcinogen - BLOOD, TESTES, LIVER
Endocrine: Testicular
Gastrointestinal
Genotoxicity
Liver
Sciatic nerve
Teratogenic
Environmental

Anemia (click on for all fluorinated pesticides)

Two 90-day studies were conducted in the rat. In one study, rats were fed dosages of 6.2, 127, 646, or 965 mg/kg/day (males) or 7.54, 150, 774, or 1,070 mg/kg/day (females). Triflusulfuron methyl exhibited subchronic toxicity at dietary concentrations of 2,000 ppm (127 and 150 mg/kg/day for males and females) or greater in the form of decreased body weights, decreased body weight gains, decreased food efficiency, increased mean relative liver weights, and regenerative anemia. The NOAEL was 6.2 mg/kg/day (males) and 7.54 mg/kg/day (females).
Ref: Federal Register: August 8, 2001 (Volume 66, Number 153)] [Notices] [Page 41593-41597]. Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food.
http://www.fluoridealert.org/pesticides/Triflusulfuron.M.FR.Aug8.01.htm

Blood (click on for all fluorinated pesticides)

-- Carcinogenicity rats NOAEL = 2.44 mg/kg/day LOAEL = 30.6 mg/kg/day based on decreased body weight and body weight gain, alteration in hematology (mainly males) and increased incidences of interstitial cell hyperplasia in the testes. (Possible) evidence of carcinogenicity
Ref: Federal Register: June 12, 2002 (Volume 67, Number 113). Triflusulfuron Methyl; Pesticide Tolerance. Final Rule.
http://www.fluorideaction.org/pesticides/triflusulfuron.m.fr.june.02.htm

CHRONIC STUDIES: Triflusulfuron methyl Chronic Feeding Study in Rats - Non-oncogenic in female rats. Increased incidence of Leydig cell adenomas were observed in males following chronic and excessive exposures at 750 and 1500 ppm. The NOELs for male and female rats were 100 and 750 ppm, respectively. These were based on increased adenomas and reduced circulating red cell mass among higher-dosed males and reduced body weights and increased incidence or severity of species- and age-specific effects among male and female rats at higher doses...
Ref: Nov 2001 - Material Safety Data Sheet for DuPont "UPBEET" HERBICIDE.
http://www.fluorideaction.org/pesticides/triflusulfuron.methyl.msds.pdf

In another 90-day subchronic study, dogs were fed dosages of 3.87, 146.1, or 267.6 mg/kg/day (males) or 3.72, 159.9, or 250.7 mg/kg/day (females). Triflusulfuron methyl was found to be hepatotoxic at 4,000 ppm (146.1 mg/kg/day males and 159.9 mg/kg/day females), and greater elevated hepatic enzyme levels and postmortem evidence, including elevation in liver weights and microscopic evidence of bile stasis. Other microscopic findings considered to be treatment related were testicular atrophy and decreased testicular weights and hypercellularity of the sternal and femoral bone marrow, with a corresponding increase in reticulocyte and leukocyte counts seen in the high-dose males and females. Based on the microscopic findings in the liver and testes of the 4,000 ppm and greater treated animals, the NOAEL was 3.87 mg/kg/day (males) and 3.72 mg/kg/day (females).
Ref: Federal Register. August 8, 2001. [PF-1036; FRL-6795-4]
http://www.fluoridealert.org/pesticides/Triflusulfuron.M.FR.Aug8.01.htm

Body Weight Decrease (click on for all fluorinated pesticides)

-- TERATOLOGY, RAT. 51974-030; 119842; "Teratogenic Study of DPX-66037-24 in Rats" (Author: C.A. Mebus; E.I. du Pont de Nemours & Company, Inc., Newark, DE, Project No. HLR 525-91, 11/1/91); DPX-66037-24 (95.6% Triflusulfuron-methyl); 0, 30, 120, 350, 1000 mg/kg/day oral gavage; 25 Crl: CD BR female rats/dose; observations- maternal effects; five animals died due to dosing injuries; significant decreases in maternal weight changes and feed consumption were observed; fetal effects; significantly increased average number of malformed fetuses were observed, the majority of fetal malformations occurred in one fetus, when individual end points of developmental evaluation criteria were grouped a significant increase was noted in the 350 and 1000 mg/kg dose groups primarily due to retarded renal development and partial ossification of skulls, sternebra or vertebra; no adverse effect; Maternal NOEL = 120 mg/kg (based on decreased maternal weight gain and feed consumption), Developmental NOEL = 120number of malformed fetuses, retarded fetal development)
-- TERATOLOGY, RABBIT. 51974-031; 119843; "Teratogenic Study of DPX-66037-24 in Rabbits" (Author: S.M. Murray; E.I. du Pont de Nemours & Company, Inc., Newark, DE, Project No. HLR 575-91, 10/28/91); DPX-66037-24 (95.6% Triflusulfuron-methyl); 0, 15, 90, 270, 800 mg/kg/day oral gavage; 20 Hra:(NZW)SPF female rabbits/dose; observations- maternally toxic at doses of 90 mg/kg and greater, significant increased dose-related mortalities and spontaneous abortions occurred at levels of 270 and 800 mg/kg, during the dosing period the highest two dose groups showed clinical signs of reduced fecal output, reduced fecal size or diarrhea; significant decreases in maternal weight changes and feed consumption were also observed; histopathological changes were noted primarily in the 800 mg/kg group and included gastric mucosal ulcerations and digestive tract gaseous distension; death losses at 800 mg/kg were extreme and data from remaining dams were markedly different therefore these data were excluded from statistical analysis; no physiological or developmental fetal effects were observed at any dose level; no adverse effect; Maternal NOEL = 15 mg/kg (based on animal death, abortions, decreased maternal weight gain and food consumption), = 800 mg/kg (based on no adverse affects).
-- 51974-058; 127247; "Combined Chronic Toxicity/Oncogenicity Study with DPX-66037-24 Two-Year Feeding Study in Rats" (Author: L.B. Biegel; E.I. du Pont de Nemours & Company, Inc., Newark, DE; Project No. HLR 3-93; 5/6/93); DPX-66037-24 (95.6% triflusulfuron-methyl); 0, 10, 100, 750, 1,500 ppm (averaged intake (M) 0, 0.406, 4.49, 30.6, 64.5 and (F) 0, 0.546, 5.47, 41.5, 87.7 mg/kg/day, respectively)in diets; 62 rats/sex/dose; observations- statistically significant decreased body weights and body weight gains of rats in the 1,500 ppm group; in females fed 750 and 1500 ppm a decreased incidence of mammary masses was noted when compared to controls, in the highest dosed females statistically significant increases of sciatic nerve myelin/axon degeneration occurred, the 1500 ppm males had no increased incidence of this lesion but showed increased lesion severity; males in 750 and 1500 ppm groups had decreased erythrocyte counts and mean serum triglyceride concentrations; high dosed males showed decreased serum calcium concentrations, an increase in the absolute and relative testes weight and statistically significant increases of both Leydig cell hyperplasia and adenomas; NOEL(M)= 100 ppm (based on decreased erythrocyte counts, decreased body weights, decreased body weight gain, increased severity of sciatic nerve lesions, Leydig cell hyperplasia and Leydig cell adenomas); NOEL(F)= 750 ppm (based on decreased body weight and increased incidence of sciatic nerve degeneration); Possible Adverse Effect: Leydig cell hyperplasia and adenomas; Acceptable. (Miller, 12/13/93)
-- REPRODUCTION, RAT ** 51974-057; 126843; "Reproductive and Fertility Effects with DPX-66037-24 Multigeneration Reproduction Study in Rats" (Author: M. E. Hurtt; E.I. du Pont de Nemours & Company, Inc., Newark, DE, Project No. HLR 231-92, 4/20/93); DPX-66037-24 (95.6% Triflusulfuron-methyl); 0, 10, 100, 750, 1,500 ppm dietary; 30 Crl: CD BR rats/dose both P1 and F1; observations- no dose related mortalities were observed, statistically significant lower body weights and body weight gains were observed in P1 (two highest doses) and F1 (1500 ppm) males, body weight effects were accompanied by statistically significant decreases in food consumption (1500 ppm group), in female P1 rats statistically significant lower mean body weight gains were noted (750, 1500 ppm groups) during premating, statistically significant lower mean body weights during gestation and lactation (two highest groups) were also observed, statistically significant decreases in overall food consumption was present in F1 female rats during premating (750, 1500 ppm groups), no additional statistically significant differences were found in other adult parameters; compound related decreases in mean F1 and F2 pup weights (highest two dose groups) were observed but were not statistically significant, there were no significant differences in any other clinical observations in the F1 and F2 pups; generally gross necropsy and histomorphologic findings of adults and offspring were few and were not considered treatment related; Adult and Developmental NOEL = 100 ppm of a.i. (based on decreased body weight, body weight gain, food efficiency and decreased pup weights); Acceptable (Miller, 11/18/93).
-- Subchronic Neurotoxicity, Rat **51974-099; 147828; "Subchronic Neurotoxicity Study of DPX-66037-24 (Triflusulfuron methyl) Administered Orally via the Diet to Crl:CDBR VAF/Plus Rats" J.A. Foss; E.I. du Pont de Nemours & Company, Newark, DE; Project No. DuPont HLO 127-93; 9/29/94; DPX-66037-24 (95.6%, Triflusulfuron-methyl); male doses (consumed mean doses [mg/kg/day] range) 0, 100 (4.4-9.7), 750 (72.1-32.8), 1500 (143.1-66.5), 3000 (272.1-133.8) ppm in diets, female doses (consumed mean doses [mg/kg/day] range) 0, 100 (5.5-9.7), 750 (67.7-40.0), 1500 (136.2-79.0), 3000 (258.3-163.4) ppm in diets ; 11 rats/sex/dose; observations-No specific evidence of behavioral or histological neurotoxicity at any level. The 750 ppm and higher dietary concentrations significantly reduced body weight gains and feed consumption values and the two highest concentrations significantly reduced the average body weights in females. The 3000 ppm concentration significantly reduced body weight gains and showed a trend to reduce average body weights and feed consumption values in male rats. NOEL(F)= 100 ppm (based on decreased body weight gain); NOEL(M)= 1500 ppm (based on decreased body weight gain); No adverse effects.
-- Rabbit 21-Day Repeated Dosing Dermal Toxicity Study 51974-093; 147897; Subacute Dermal Toxicity; 822; Rabbit; "Repeated Dose Dermal Toxicity: 21-Day Study with DPX-66037-24 (Triflusulfuron Methyl) in Rabbits"; S.A. MacKenzie; E.I. du Pont de Nemours and Co., Haskell Lab. for Tox. and Ind. Med., Newark, DE; Laboratory Report No. HRL 552-93; 9/27/93 ; Triflusulfuron Methyl (DPX-66037-24, 95.6% purity); 0, 50, 300, 1000 mg/kg applied dermally 6 hrs/day for 21 days ; 822; 5 New Zealand White rabbits/sex/dose; observations- There were no test article related mortalities or clinical signs of systemic toxicity. Slight or mild erythema was observed in animals of all groups (including controls). Mild skin trauma was noted in a few animals but was not considered compound-related. Microscopic skin lesions observed in both treated and control groups included, minimal to mild inflamation and acanthosis. Lesions were attributed to testing procedure. Statistically significant differences in mean body weight gain were observed over a few intervals in female rabbits but did not exibit a dose-response and were not considered compound related. No other compound related changes were noted any other parameter including body weight or body weight gain, food consumption, hematology or clinical chemistry analysis. Systemic and Dermal NOEL(M/F)= NOAEL(M/F)=1000 mg/kg b.w. (based on no effects at HDT).
-- Dog Subchronic Dietary Toxicity Study 51974-029; 119838; "A Subchronic (3-month) Toxicity Study of DPX-66037-24 in the Dog Via Dietary Administration" (Author: J.E. Atkinson; Bio/dynamics, Inc., East Millstone, NJ, Project No. 91-3653, 12/20/91); DPX-66037-24(95.6% triflusulfuron-methyl); 0, 100, 4,000 and 8,000 ppm (averaged intake (M) 3.9, 146.1, 267.6 and (F) 3.7, 159.9 and 250.7 mg/kg/day) in diets; 4 Beagle dogs/sex/dose; observations- two high dose females were sacrificed in extremis showing marked body weight loss with low food consumption and frank anemia, other high dose animals exhibited little to no weight gain with food consumption slightly decreased in the early weeks of the study; decreased erythrocyte count and associated hematocrit and hemoglobin levels were noted at 1 1/2 and 3 months with a compensatory elevated reticulocyte count; hepatotoxcity was demonstrated by elevated levels of serum aspartate aminotransferase, serum alanine aminotransferase, alkaline phosphatase and elevated liver weights and microscopic evidence of bile stasis in the 4,000 and 8,000 ppm groups; in mid and high dose males testicular atrophy and decreased testicular weights were characterized by aspermatogenesis, decreased seminiferous tubule thickness and germinal epithelial cytoplasmic vacuolation; sternal and femoral bone marrow hypercellularity was seen in high dose animals; NOEL(M/F)= 100 ppm (based on microscopic findings in the liver and testes); Possible Adverse Effect: testicular atrophy, aspermatogenesis.
Reference: Nov 18, 2005 - Summary of Toxicology Data. California Environmntal Protection Agency. Department of Pesticide Regulation. Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/triflusulfuron-m.ca.epa.2005.pdf

In a rat reproduction study (2-generation, 1 litter/generation), the NOEL for systemic (parental) toxicity was 5.81 mg/kg bw/d based on lower body weights and food consumption. The NOEL for reproductive toxicity was 44 mg/kg bw/d (750 ppm) based on lower pup body weights and histopathological effects on the cerebellum consistent with undernutrition (decreased cellularity in the internal granular layer and increased cellularity in the external germinal layer) in the 2500 ppm group. In the rat developmental toxicity study, the NOEL for maternal toxicity was 120 mg/kg bw/d (based on reduced body-weight gain during dosing period at 350 and 1000 mg/kg bw/d) and for developmental toxicity was 120 mg/kg bw/d (based on delayed ossification). There was no evidence of teratogenicity. In the rabbit developmental toxicity study, the NOEL for maternal toxicity was 15 mg/kg bw/d based on decreased body-weight gain during the treatment period at 90 mg/kg bw/d and clinical signs of toxicity at 270 mg/kg bw/d. The NOEL for developmental toxicity was 90 mg/kg bw/d, based on abortions at 270 mg/kg bw/d. There was no evidence of any teratogenic potential of triflusulfuron-methyl in the rabbit up to 800 mg/kg bw/d.
Ref: Dec 3, 1999 - Report on Triflusulfuron methyl. Regulatory Note REG99-03. Pest Management Regulatory Agency, Health Canada, Ottawa.
http://www.fluorideaction.org/pesticides/triflusulfuron.methy.canada.pdf

-- Reproduction and fertility effects. Parental/Systemic NOAEL = 5.81/7.75 (m/f) mg/kg/day LOAEL = 44/58 mg/kg/day based on decreased body weight, decreased body weight gain, decreased food consumption, and decreased- food efficiency. Reproductive NOAEL = 89.5/115 (m/f) mg/kg/ day based on the absence of reproductive effects at the highest dose tested (HDT). LOAEL = 3115 mg/kg/day. Offspring NOAEL = 5.81/7.75 (m/f) mg/kg/day LOAEL = 44/58 (m/f) mg/kg/day based on decreased F1 pup body weight on days 14 and 21 due to exposure via milk and in the diet.
-- Subchronic neurotoxicity screening battery. NOAEL = 92.7/7.1 (m/f) mg/kg/day LOAEL = 186.2/51.6 (m/f) mg/kg/day based on decreased body weight and body weight gain.
Ref: Federal Register: June 12, 2002 (Volume 67, Number 113). Triflusulfuron Methyl; Pesticide Tolerance. Final Rule.
http://www.fluorideaction.org/pesticides/triflusulfuron.m.fr.june.02.htm

Two 90-day studies were conducted in the rat. In one study, rats were fed dosages of 6.2, 127, 646, or 965 mg/kg/day (males) or 7.54, 150, 774, or 1,070 mg/kg/day (females). Triflusulfuron methyl exhibited subchronic toxicity at dietary concentrations of 2,000 ppm (127 and 150 mg/kg/day for males and females) or greater in the form of decreased body weights, decreased body weight gains, decreased food efficiency, increased mean relative liver weights, and regenerative anemia. The NOAEL was 6.2 mg/kg/day (males) and 7.54 mg/kg/day (females).
Ref: Federal Register: August 8, 2001 (Volume 66, Number 153)] [Notices] [Page 41593-41597]. Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food.
http://www.fluoridealert.org/pesticides/Triflusulfuron.M.FR.Aug8.01.htm

-- Chronic toxicity rodents NOAEL = 2.44 mg/kg/day LOAEL = 30.6 mg/kg/day based on decreased body weight and body weight gain, alteration in hematology (mainly males) and increased incidences of interstitial cell hyperplasia in testes.
-- Carcinogenicity rats NOAEL = 2.44 mg/kg/day LOAEL = 30.6 mg/kg/day based on decreased body weight and body weight gain, alteration in hematology (mainly males) and increased incidences of interstitial cell hyperplasia in the testes. (Possible) evidence of carcinogenicity
Ref: Federal Register: June 12, 2002 (Volume 67, Number 113). Triflusulfuron Methyl; Pesticide Tolerance. Final Rule.
http://www.fluorideaction.org/pesticides/triflusulfuron.m.fr.june.02.htm

Bone (click on for all fluorinated pesticides)

In a rat reproduction study (2-generation, 1 litter/generation), the NOEL for systemic (parental) toxicity was 5.81 mg/kg bw/d based on lower body weights and food consumption. The NOEL for reproductive toxicity was 44 mg/kg bw/d (750 ppm) based on lower pup body weights and histopathological effects on the cerebellum consistent with undernutrition (decreased cellularity in the internal granular layer and increased cellularity in the external germinal layer) in the 2500 ppm group. In the rat developmental toxicity study, the NOEL for maternal toxicity was 120 mg/kg bw/d (based on reduced body-weight gain during dosing period at 350 and 1000 mg/kg bw/d) and for developmental toxicity was 120 mg/kg bw/d (based on delayed ossification). There was no evidence of teratogenicity...
Ref: Dec 3, 1999 - Report on Triflusulfuron methyl. Regulatory Note REG99-03. Pest Management Regulatory Agency, Health Canada, Ottawa.
http://www.fluorideaction.org/pesticides/triflusulfuron.methy.canada.pdf

In another 90-day subchronic study, dogs were fed dosages of 3.87, 146.1, or 267.6 mg/kg/day (males) or 3.72, 159.9, or 250.7 mg/kg/day (females). Triflusulfuron methyl was found to be hepatotoxic at 4,000 ppm (146.1 mg/kg/day males and 159.9 mg/kg/day females), and greater elevated hepatic enzyme levels and postmortem evidence, including elevation in liver weights and microscopic evidence of bile stasis. Other microscopic findings considered to be treatment related were testicular atrophy and decreased testicular weights and hypercellularity of the sternal and femoral bone marrow, with a corresponding increase in reticulocyte and leukocyte counts seen in the high-dose males and females. Based on the microscopic findings in the liver and testes of the 4,000 ppm and greater treated animals, the NOAEL was 3.87 mg/kg/day (males) and 3.72 mg/kg/day (females).
Ref: Federal Register. August 8, 2001. [PF-1036; FRL-6795-4]
http://www.fluoridealert.org/pesticides/Triflusulfuron.M.FR.Aug8.01.htm

51974-030; 119842; "Teratogenic Study of DPX-66037-24 in Rats" (Author: C.A. Mebus; E.I. du Pont de Nemours & Company, Inc., Newark, DE, Project No. HLR 525-91, 11/1/91); DPX-66037-24 (95.6% Triflusulfuron-methyl); 0, 30, 120, 350, 1000 mg/kg/day oral gavage; 25 Crl: CD BR female rats/dose; observations- maternal effects; five animals died due to dosing injuries; significant decreases in maternal weight changes and feed consumption were observed; fetal effects; significantly increased average number of malformed fetuses were observed, the majority of fetal malformations occurred in one fetus, when individual end points of developmental evaluation criteria were grouped a significant increase was noted in the 350 and 1000 mg/kg dose groups primarily due to retarded renal development and partial ossification of skulls, sternebra or vertebra; no adverse effect; Maternal NOEL = 120 mg/kg (based on decreased maternal weight gain and feed consumption), Developmental NOEL = 120 number of malformed fetuses, retarded fetal development).
Reference: Nov 18, 2005 - Summary of Toxicology Data. California Environmntal Protection Agency. Department of Pesticide Regulation. Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/triflusulfuron-m.ca.epa.2005.pdf

Brain (click on for all fluorinated pesticides)

In a rat reproduction study (2-generation, 1 litter/generation), the NOEL for systemic (parental) toxicity was 5.81 mg/kg bw/d based on lower body weights and food consumption. The NOEL for reproductive toxicity was 44 mg/kg bw/d (750 ppm) based on lower pup body weights and histopathological effects on the cerebellum consistent with undernutrition (decreased cellularity in the internal granular layer and increased cellularity in the external germinal layer) in the 2500 ppm group...
Ref: Dec 3, 1999 - Report on Triflusulfuron methyl. Regulatory Note REG99-03. Pest Management Regulatory Agency, Health Canada, Ottawa.
http://www.fluorideaction.org/pesticides/triflusulfuron.methy.canada.pdf

Cancer: Possible Human Carcinogen - BLOOD, TESTES, LIVER (click on for all fluorinated pesticides)

Group C--Possible Human Carcinogen. Reviewed 5/ 28/ 96.
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

-- Carcinogenicity rats NOAEL = 2.44 mg/kg/day LOAEL = 30.6 mg/kg/day based on decreased body weight and body weight gain, alteration in hematology (mainly males) and increased incidences of interstitial cell hyperplasia in the testes. (Possible) evidence of carcinogenicity
-- Carcino-genicity mice NOAEL = 14.6 mg/kg/day LOAEL = 349 mg/kg/day based on increased liver weight and increased hepatic cell tumors (adenomas and/or carcinomas combined. (Possible) evidence of carcinogenicity
Ref: Federal Register. June 12, 2002. Triflusulfuron Methyl; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Triflusulfuron.M.FR.June.02.htm

Endocrine: Testicular (click on for all fluorinated pesticides)

-- 90-Day oral toxicity in nonrodents. NOAEL = 3.9/3.7 (m/f) mg/kg/day LOAEL = 146.9/159.9 (m/f) mg/kg/day based on decreased mean body weight and body weight gain, decreased hematocrit, hemoglobin, RBC`s, SGOT, SGPT, ALP, absolute and relative liver and testes weight; microscopic abnormalities of the liver and testes.
-- Chronic toxicity rodents NOAEL = 2.44 mg/kg/day LOAEL = 30.6 mg/kg/day based on decreased body weight and body weight gain, alteration in hematology (mainly males) and increased incidences of interstitial cell hyperplasia in testes.
-- Carcinogenicity rats NOAEL = 2.44 mg/kg/day LOAEL = 30.6 mg/kg/day based on decreased body weight and body weight gain, alteration in hematology (mainly males) and increased incidences of interstitial cell hyperplasia in the testes. (Possible) evidence of carcinogenicity
-- Special studies: In vivo and in vitro mechanic studies. The purpose of these studies was to investigate the mechanism of Leydig cell tumor induction in the testes of male rats. A dose-dependent decrease in aromatase enzyme activity was seen in vitro, but was inconclusive in vivo.
Ref: Federal Register: June 12, 2002 (Volume 67, Number 113). Triflusulfuron Methyl; Pesticide Tolerance. Final Rule.
http://www.fluorideaction.org/pesticides/triflusulfuron.m.fr.june.02.htm

Dog Subchronic Dietary Toxicity Study 51974-029; 119838; "A Subchronic (3-month) Toxicity Study of DPX-66037-24 in the Dog Via Dietary Administration" (Author: J.E. Atkinson; Bio/dynamics, Inc., East Millstone, NJ, Project No. 91-3653, 12/20/91); DPX-66037-24(95.6% triflusulfuron-methyl); 0, 100, 4,000 and 8,000 ppm (averaged intake (M) 3.9, 146.1, 267.6 and (F) 3.7, 159.9 and 250.7 mg/kg/day) in diets; 4 Beagle dogs/sex/dose; observations- two high dose females were sacrificed in extremis showing marked body weight loss with low food consumption and frank anemia, other high dose animals exhibited little to no weight gain with food consumption slightly decreased in the early weeks of the study; decreased erythrocyte count and associated hematocrit and hemoglobin levels were noted at 1 1/2 and 3 months with a compensatory elevated reticulocyte count; hepatotoxcity was demonstrated by elevated levels of serum aspartate aminotransferase, serum alanine aminotransferase, alkaline phosphatase and elevated liver weights and microscopic evidence of bile stasis in the 4,000 and 8,000 ppm groups; in mid and high dose males testicular atrophy and decreased testicular weights were characterized by aspermatogenesis, decreased seminiferous tubule thickness and germinal epithelial cytoplasmic vacuolation; sternal and femoral bone marrow hypercellularity was seen in high dose animals; NOEL(M/F)= 100 ppm (based on microscopic findings in the liver and testes); Possible Adverse Effect: testicular atrophy, aspermatogenesis.
Reference: Nov 18, 2005 - Summary of Toxicology Data. California Environmntal Protection Agency. Department of Pesticide Regulation. Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/triflusulfuron-m.ca.epa.2005.pdf

-- Groups of 62 rats/sex were fed diets containing 0, 10, 100, 750 or 1500 ppm DPX-66037- 24 (95.6% purity) (equal to 0.406, 4.06, 30.6 or 64.5 mg/kg bw/d for males and 0.546, 5.47, 41.5 and 87.7 mg/kg bw/d for females) for 22 months. The NOEL for this study was 100 ppm (4.06 mg/kg bw/d). At 750 ppm, body weights and body-weight gains were lower than controls in both sexes and males had lower erythrocyte counts than controls at most time points and an increased incidence of Leydig cell hyperplasia compared to controls. The incidence of myelin/axonal degeneration of the sciatic nerve was increased compared to controls in the 1500-ppm group of females (25/48 versus [vs] 42/49). Triflusulfuron-methyl was oncogenic in male rats under the conditions of this study, with an increased incidence of Leydig cell adenomas in the 750- and 1500-ppm groups compared to controls.
-- Possible mechanisms of Leydig cell tumour development induced by triflusulfuron-methyl were studied. Ten Crl:CD ¨ BR male rats/group were treated by gavage for 15 days with 0, 1000, 1500 or 2000 mg/kg bw DPX-66037-24 (95.6% purity) in corn oil. An additional group of 10 control rats were pair-fed to the 2000 mg/kg bw group. Satellite groups of 10 rats treated with 0 or 2000 mg/kg bw DPX-66037 were given human chorionic gonadotropin (hCG) one hour before sacrifice. All treated groups had lower body weights and food consumption than controls. Absolute and relative weights of the prostate, seminal vesicles and coagulating glands were lower than controls. Serum estradiol was statistically significantly lower than controls. There were slight, but not statistically significant, increases in luteinizing hormone (LH), follicule-stimulating hormone (FSH) and prolactin in the treated groups compared to controls. In the rats treated with hCG, the 2000 mg/kg bw/d group had increased testosterone and lower estradiol than the controls.
-- Isolated Leydig cells from 11-week old male rats were exposed to 0, 0.1, 0.5, 1.0, 10, 100 or 1000 FM DPX-66037-24 for two hours. Three cultures from each dose were then exposed to two international units of hCG. No effect on hormone levels was observed in the hCG-treated cultures. In the triflusulfuron-methyl-only cultures, testosterone was significantly increased (198%) compared to controls, and estradiol was decreased. Triflusulfuron-methyl appears to inhibit the conversion of testosterone to estradiol by aromatase in vitro; the in vivo results are inconclusive.
-- In long-term rodent dietary studies, the NOEL for chronic (18-mo) systemic toxicity in mice was 20.9 mg/kg bw/d, based on increased absolute and relative liver weights along with histopathological changes in the liver at the LOEL of 349 mg/kg bw/d. Triflusulfuron was not oncogenic in the mouse. The NOEL for chronic (2-yr) systemic toxicity and oncogenicity in rats was 4.06 mg/kg bw/d, based on lower body weight and erythrocyte counts, and an increased incidence of Leydig cell tumours (adenomas) in males at 30.6 mg/kg bw/d. A study was performed that attempted to determine the mechanism of tumour formation. The results indicated that triflusulfuron-methyl appears to inhibit the conversion of testosterone to estradiol by aromatase in vitro, the in vivo results are inconclusive. Disruption of the hypothalmic-pituitary- testicular (HPT) axis is a well-recognized mechanism of Leydig cell adenoma formation in the rat by non-genotoxic compounds. Aromatase inhibition is one of the established mechanisms of disruption. A threshold for this effect exists; doses that do not disrupt the HPT axis should not cause tumours. The relevance of these tumours to humans is questionable, as they are extremely rare in humans.
Ref: Dec 3, 1999 - Report on Triflusulfuron methyl. Regulatory Note REG99-03. Pest Management Regulatory Agency, Health Canada, Ottawa.
http://www.fluorideaction.org/pesticides/triflusulfuron.methy.canada.pdf

Gastrointestinal (click on for all fluorinated pesticides)

Groups of 20 artificially inseminated female rabbits were treated by gavage with 0, 15, 90, 270 or 800 mg/kg bw/d DPX-66037-24 (95.6% purity) on days 7Ð19 of gestation. The NOEL for maternal toxicity was 15 mg/kg bw/d. At 90 mg/kg bw, body-weight gains were lower than controls at the beginning of the treatment period. Clinical signs of toxicity were observed at 270 mg/kg bw/d (stool absent or reduced, small stool), abortions and evidence of gastrointestinal effects were found at gross necropsy (ulceration of gastric mucosa, gaseous distension). Food consumption was also lower than controls in the 270 and 800 mg/kg bw/d groups...
Ref: Dec 3, 1999 - Report on Triflusulfuron methyl. Regulatory Note REG99-03. Pest Management Regulatory Agency, Health Canada, Ottawa.
http://www.fluorideaction.org/pesticides/triflusulfuron.methy.canada.pdf

Genotoxicity (click on for all fluorinated pesticides)

-- A human lymphocyte cytogenetic assay was performed using 0.5, 1.5, 1.7, 1.85, or 2.0 mg/mL DPX-66037-59 (98.7%) with and without metabolic activation. Cytotoxicity was observed at 1.85 mg/mL, indicated by a lower mitotic index than controls. Triflusulfuron-methyl, with metabolic activation, was clastogenic at 2.0 mg/mL under the conditions of this test.
-- A human lymphocyte cytogenetic assay was performed using 0.1Ð2.0 mg/mL DPX-66037-24 (95.6%) with and without metabolic activation. Cytotoxicity was observed at 2.0 mg/mL, indicated by a lower mitotic index than controls. Triflusulfuron-methyl, with metabolic activation, was clastogenic at $1.7 mg/mL in a dose-dependent manner under the conditions of this test.
-- ... It was genotoxic in mammalian in vitro chromosomal aberrations assays (same assay performed twice), but not in a mammalian in vivo assay.
Ref: Dec 3, 1999 - Report on Triflusulfuron methyl. Regulatory Note REG99-03. Pest Management Regulatory Agency, Health Canada, Ottawa.
http://www.fluorideaction.org/pesticides/triflusulfuron.methy.canada.pdf

Liver (click on for all fluorinated pesticides)

-- 90-Day oral toxicity in nonrodents. NOAEL = 3.9/3.7 (m/f) mg/kg/day LOAEL = 146.9/159.9 (m/f) mg/kg/day based on decreased mean body weight and body weight gain, decreased hematocrit, hemoglobin, RBC`s, SGOT, SGPT, ALP, absolute and relative liver and testes weight; microscopic abnormalities of the liver and testes.
-- Carcinogenicity mice NOAEL = 14.6 mg/kg/day LOAEL = 349 mg/kg/day based on increased liver weight and increased hepatic cell tumors (adenomas and/or carcinomas combined. (Possible) evidence of carcinogenicity
Ref: Federal Register: June 12, 2002 (Volume 67, Number 113). Triflusulfuron Methyl; Pesticide Tolerance. Final Rule.
http://www.fluorideaction.org/pesticides/triflusulfuron.m.fr.june.02.htm

-- Chronic toxicity dogs NOAEL = 26.9 mg/kg/day LOAEL = 116.6 mg/kg/day based on increased liver weight, alkaline phosphatase, and hepatocellular hypertrophy.
Ref: Federal Register: June 12, 2002 (Volume 67, Number 113). Triflusulfuron Methyl; Pesticide Tolerance. Final Rule.
http://www.fluorideaction.org/pesticides/triflusulfuron.m.fr.june.02.htm

In another 90-day subchronic study, dogs were fed dosages of 3.87, 146.1, or 267.6 mg/kg/day (males) or 3.72, 159.9, or 250.7 mg/kg/day (females). Triflusulfuron methyl was found to be hepatotoxic at 4,000 ppm (146.1 mg/kg/day males and 159.9 mg/kg/day females), and greater elevated hepatic enzyme levels and postmortem evidence, including elevation in liver weights and microscopic evidence of bile stasis. Other microscopic findings considered to be treatment related were testicular atrophy and decreased testicular weights and hypercellularity of the sternal and femoral bone marrow, with a corresponding increase in reticulocyte and leukocyte counts seen in the high-dose males and females. Based on the microscopic findings in the liver and testes of the 4,000 ppm and greater treated animals, the NOAEL was 3.87 mg/kg/day (males) and 3.72 mg/kg/day (females).
Ref: Federal Register. August 8, 2001. [PF-1036; FRL-6795-4]
http://www.fluoridealert.org/pesticides/Triflusulfuron.M.FR.Aug8.01.htm

Sciatic Nerve (click on for all fluorinated pesticides)

Groups of 62 rats/sex were fed diets containing 0, 10, 100, 750 or 1500 ppm DPX-66037- 24 (95.6% purity) (equal to 0.406, 4.06, 30.6 or 64.5 mg/kg bw/d for males and 0.546, 5.47, 41.5 and 87.7 mg/kg bw/d for females) for 22 months. The NOEL for this study was 100 ppm (4.06 mg/kg bw/d). At 750 ppm, body weights and body-weight gains were lower than controls in both sexes and males had lower erythrocyte counts than controls at most time points and an increased incidence of Leydig cell hyperplasia compared to controls. The incidence of myelin/axonal degeneration of the sciatic nerve was increased compared to controls in the 1500-ppm group of females (25/48 versus [vs] 42/49)...
Ref: Dec 3, 1999 - Report on Triflusulfuron methyl. Regulatory Note REG99-03. Pest Management Regulatory Agency, Health Canada, Ottawa.
http://www.fluorideaction.org/pesticides/triflusulfuron.methy.canada.pdf

Teratogenic (click on for all fluorinated pesticides)

TERATOLOGY, RAT. 51974-030; 119842; "Teratogenic Study of DPX-66037-24 in Rats" (Author: C.A. Mebus; E.I. du Pont de Nemours & Company, Inc., Newark, DE, Project No. HLR 525-91, 11/1/91); DPX-66037-24 (95.6% Triflusulfuron-methyl); 0, 30, 120, 350, 1000 mg/kg/day oral gavage; 25 Crl: CD BR female rats/dose; observations- maternal effects; five animals died due to dosing injuries; significant decreases in maternal weight changes and feed consumption were observed; fetal effects; significantly increased average number of malformed fetuses were observed, the majority of fetal malformations occurred in one fetus, when individual end points of developmental evaluation criteria were grouped a significant increase was noted in the 350 and 1000 mg/kg dose groups primarily due to retarded renal development and partial ossification of skulls, sternebra or vertebra; no adverse effect; Maternal NOEL = 120 mg/kg (based on decreased maternal weight gain and feed consumption), Developmental NOEL = 120 mg/kg (based on increased average number of malformed fetuses, retarded fetal development).