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Activity: Herbicide (triazolone)
Structure:

Adverse Effects:
Blood
Body Weight Decrease
Bone
Endocrine: Prostate
Endocrine: Testicular
Endocrine: Vaginal
Liver
Spleen
Environmental
• Persistent in soils
• Groundwater Contaminant
• Highly Toxic to Estuarine/Marine Organisms
• Phototoxic

Subchronic toxicity. A 90-day subchronic toxicity study was conducted in rats, with dietary intake levels of 0, 3.3, 6.7, 19.9, 65.8, 199.3, or 534.9 mg/kg/day for males and 0, 4, 7.7, 23.1, 78.1, 230.5, or 404.3 mg/kg/day for females respectively. NOAELs of 19.9 mg/ kg/day in males and 23.1 mg/kg/day in females were based on clinical anemia.
Ref: Federal Register, March 7, 2003 (Volume 68, Number 45)] [Notices] [Page 11096-11100]. Notice of Filing Pesticide Petitions to Establish Tolerances for a Certain Pesticide Chemical in or on Food.
http://www.fluoridealert.org/pesticides/Sulfentrazone.FR.Mar.7.2003.htm

-- 90-Day oral toxicity rodents (rats) - [870.3100] NOAEL = 19.9 milligrams/kilogram/day (mg/ kg/day) for males and 23.1 mg/kg/ day for females LOAEL = 65.8 mg/kg/ day for males and 78.1 mg/kg/day for females based on clinical signs of anemia (reduced hematocrit, hemoglobin, mean cell volume, and mean cell hemoglobin values during treatment)
-- Chronic toxicity dogs - [870.4100] NOAEL = 24.9 mg/kg/day for males and 29.6 mg/kg/day for females LOAEL = 61.2 mg/kg/ day for males and 61.9 mg/kg/day for females based on compensated normochromic microcytosis
Ref: Federal Register: September 24, 2003. Sulfentrazone; Pesticide Tolerances. Final Rule.
http://www.fluorideaction.org/pesticides/sulfentrazone.fr.sept24.03.htm

• Definitions:
Normochromic: Being normal in colour; referring especially to red blood cells that possess the normal quantity of haemoglobin.
Microcytosis: a blood disorder characterized by the presence of microcytes (abnormally small red blood cells) in the blood; often associated with anemia.

Blood (click on for all fluorinated pesticides)

-- A 1-year feeding oral study was performed on dogs. The induction of normochromic microcytosis in animals fed diets containing 1800 ppm test material, although compensated by increased red cell production, reflects an adverse treatment-related effect. The microcytosis may have arisen from the inhibition of heme synthesis as indicated by the presence of brown to yellow/brown pigmentation in hepatocytes and reticuloendothelial cells of the liver. The microcytosis induced by sulfentrazone justifies an oral LOEL of 61.2 mg/kg/day for males and 61.9 mg/kg/day for females. The NOEL is 24.9 mg/kg/day for males and 29.6 mg/kg/day for females.
-- A 18-month feeding/carcinogenicity study in mice resulted a LOEL of 160.5 mg/kg/day in males and 198.0 mg/kg/day in females, based upon treatment-related decreases in hemoglobin and hematocrit. The NOEL is 93.9 mg/kg/day in males and 116.9 mg/kg/day in females.
-- A developmental toxicity study in rats resulted in a maternal (systemic) LOEL of 50.0 mg/kg/day based upon increased relative spleen weight and splenic extramedullary hematopoiesis. The maternal (systemic) NOEL is 25.00 mg/kg/day...
Ref: US EPA. Pesticide Fact Sheet. Sulfentrazone Reason for Issuance: Registration of a New Chemical Date Issued: February 27, l997.
http://www.epa.gov/opprd001/factsheets/sulfentrazone.pdf

-- 90-Day oral toxicity rodents (mice) - [870.3100] NOAEL = 60 mg/kg/day for males and 79.8 mg/kg/day for females LOAEL = 108.4 mg/ kg/day for males and 143.6 mg/kg/ day for females based on decreased body weights, body weight gains, red blood cells, hemoglobin, hematocrit, and severity of splenic micropathology (increased incidence and severity of extramedullary hematopoiesis)
-- 90-Day oral toxicity in nonrodents (dogs) - [870.3150] NOAEL = 28 mg/kg/day LOAEL = 57 mg/kg/ day for males and 73 mg/kg/day for females based on decreased body weights (7-10%) and body weight gains during first 5 weeks of study; decreased hemoglobin, hematocrit, mean cell volume, mean cell hemoglobin and mean cell hemoglobin concentration, and increased absolute liver weights and alkaline phosphatase levels, and microscopic changes in the liver and spleen (pigmented sinusoidal microphages in the liver, swollen centrilobular hepatocytes and pigmented reticuloendotheli al cells in the spleen)
-- Carcinogenicity mice - [870.4200] NOAEL = 93.9 mg/kg/ day for males and 116.9 mg/kg/day for females LOAEL = 160.5 mg/ kg/day for males and 198.0 mg/kg/ day for females based on dose- related decreases in hemoglobin and hematocrit by study termination. No evidence of carcinogenicity
-- Combined chronic toxicity/carcinogenicity rats - [870.4300] NOAEL = 40 mg/kg/day for males and 36.4 mg/kg/day in females LOAEL = 82.2 mg/kg/ day for males and 67 mg/kg/day for females based on dose-related decreased body weights (11 and 19%), body weight gains (13 and 26%), food consumption (13 and 19%), hemoglobin, hematocrit, mean cell volume, and mean cell hemoglobin. Increased nucleated red blood cells and reticulocytes in bone of females at 124.7 mg/kg/ day. No evidence of carcinogenicity
Ref: Federal Register: September 24, 2003. Sulfentrazone; Pesticide Tolerances. Final Rule.
http://www.fluorideaction.org/pesticides/sulfentrazone.fr.sept24.03.htm

Body Weight Decrease (click on for all fluorinated pesticides)

-- A developmental toxicity study in rats resulted in a maternal (systemic) LOEL of 50.0 mg/kg/day based upon increased relative spleen weight and splenic extramedullary hematopoiesis. The maternal (systemic) NOEL is 25.00 mg/kg/day. The developmental (fetal) LOEL is 25.0 mg/kg/day based upon 1) decreased mean fetal weight and 2) retardation in skeletal development as evidenced by an increased number of litters with any variation and by decreased numbers of caudal vertebral and metacarpal ossification sites. The developmental (fetal) NOEL is 10.0 mg/kg/day. Evidence of treatment-related developmental toxicity consisted of decreased fetal viability, decreased fetal body weight, and increased incidence of fetal alterations, comprised, for the most part, of skeletal malformations and variations. A supplementary prenatal oral developmental toxicity study in rats confirmed the maternal and fetal findings of the previously conducted study and did not alter the study conclusions.
Ref: US EPA. Pesticide Fact Sheet. Sulfentrazone Reason for Issuance: Registration of a New Chemical Date Issued: February 27, l997.
http://www.epa.gov/opprd001/factsheets/sulfentrazone.pdf

-- 90-Day oral toxicity rodents (mice) - [870.3100] NOAEL = 60 mg/kg/day for males and 79.8 mg/kg/day for females LOAEL = 108.4 mg/ kg/day for males and 143.6 mg/kg/ day for females based on decreased body weights, body weight gains, red blood cells, hemoglobin, hematocrit, and severity of splenic micropathology (increased incidence and severity of extramedullary hematopoiesis)
-- 90-Day oral toxicity in nonrodents (dogs) - [870.3150] NOAEL = 28 mg/kg/day LOAEL = 57 mg/kg/ day for males and 73 mg/kg/day for females based on decreased body weights (7-10%) and body weight gains during first 5 weeks of study; decreased hemoglobin, hematocrit, mean cell volume, mean cell hemoglobin and mean cell hemoglobin concentration, and increased absolute liver weights and alkaline phosphatase levels, and microscopic changes in the liver and spleen (pigmented sinusoidal microphages in the liver, swollen centrilobular hepatocytes and pigmented reticuloendotheli al cells in the spleen)
-- 2-Generation reproduction and fertility effects (rats) - [870.3800] Parental/Systemic NOAEL = 14 mg/kg/day for males and 16 mg/kg/day for females LOAEL = 33 mg/kg/ day for males and 40 mg/kg/day for females based on decreased maternal body weight/body weight gain during gestation in both generation (P and F1) and reduced premating body weight gain in second generation (F1) males Reproductive NOAEL = 14 mg/kg/ day for males and 16 mg/kg/day for females LOAEL = 33 mg/kg/ day for males and 40 mg/kg/day for females based on increased duration of gestation in females and degeneration and/ or atrophy of the germinal epithelium of the testes and oligospermia and intratubular degenerated seminal material in the epididymis of F1 males Offspring NOAEL = 14 mg/kg/ day for males and 16 mg/kg/day for females LOAEL = 33 mg/kg/ day for males and 40 mg/kg/day for females based on reduced prenatal viability (fetal and litter), reduced litter size, increased number of stillborn pups, reduced pup and litter postnatal survival and decreased pup body weights throughout lactation
-- Reproduction and fertility effects (rat). Nonguideline - [870.3800] Parental/Systemic NOAEL = 20 mg/kg/day LOAEL = 51 mg/kg/ day (F1 females) based on decrease in pre-mating body weight gain (10%) Offspring and Reproductive NOAEL = 16 mg/kg/ day LOAEL = 40 mg/kg/ day based on reduced gestation day 20 fetal weights; decreased postnatal day 0, 4 and 7 pup weights; decreased pup survival; delayed vaginal patency; reduced epididymal, prostate, and testicular weights Additional information supports the conclusions reached in the 2- generation reproduction study in rats
-- Combined chronic toxicity/carcinogenicity rats - [870.4300] NOAEL = 40 mg/kg/day for males and 36.4 mg/kg/day in females LOAEL = 82.2 mg/kg/ day for males and 67 mg/kg/day for females based on dose-related decreased body weights (11 and 19%), body weight gains (13 and 26%), food consumption (13 and 19%), hemoglobin, hematocrit, mean cell volume, and mean cell hemoglobin. Increased nucleated red blood cells and reticulocytes in bone of females at 124.7 mg/kg/ day. No evidence of carcinogenicity
-- Subchronic neurotoxicity screening battery - [870.6200]. NOAEL = 30 mg/kg/day for males and 37 mg/kg/day for females LOAEL = 150 mg/kg/ day for males and 180 mg/kg/day for females based on increased incidence of clinical signs; decreased body weight, body weight gains, and food consumption in females; and increased motor activity in females. At 5,000 ppm, included increased mortality; decreased body weights, and body weight gains in males; decreased hindlimb grip strength and increased tail flick latency in males at week 8; distended bladders with red fluid and enlarged spleen. No evidence of neuropathology at 2,500 and 5,000 ppm.
Ref: Federal Register: September 24, 2003. Sulfentrazone; Pesticide Tolerances. Final Rule.
http://www.fluorideaction.org/pesticides/sulfentrazone.fr.sept24.03.htm

Bone (click on for all fluorinated pesticides)

-- A developmental toxicity study in rats resulted in a maternal (systemic)... The developmental (fetal) LOEL is 25.0 mg/kg/day based upon 1) decreased mean fetal weight and 2) retardation in skeletal development as evidenced by an increased number of litters with any variation and by decreased numbers of caudal vertebral and metacarpal ossification sites. The developmental (fetal) NOEL is 10.0 mg/kg/day. Evidence of treatment-related developmental toxicity consisted of decreased fetal viability, decreased fetal body weight, and increased incidence of fetal alterations, comprised, for the most part, of skeletal malformations and variations. A supplementary prenatal oral developmental toxicity study in rats confirmed the maternal and fetal findings of the previously conducted study and did not alter the study conclusions.
Ref: US EPA. Pesticide Fact Sheet. Sulfentrazone Reason for Issuance: Registration of a New Chemical Date Issued: February 27, l997.
http://www.epa.gov/opprd001/factsheets/sulfentrazone.pdf

-- Developmental Study in rats. Developmental LOAEL = 25 mg/kg/day based on decreased fetal weight and retarded skeletal development as evidenced by an increased number of litters with any variation and by decreased numbers of caudal vertebral and metacarpal ossification sites.
-- In the dermal developmental study in rats, the maternal (systemic) NOAEL was 250 mg/kg/day and a LOAEL was not determined. The developmental (fetal) NOAEL was 100 mg/kg/day, based on decreased fetal weight and increased fetal variations (hypoplastic or wavy ribs, incompletely ossified lumbar vertebral arches, incompletely ossified ischia or pubes, and reduced numbers of thoracic vertebral and rib ossification sites) at the LOAEL of 250 mg/kg/day.
Ref: Federal Register. August 1, 2001. Sulfentrazone; Pesticide Tolerances for Emergency Exemptions. Final Rule.
http://www.fluoridealert.org/pesticides/sulfentrazone.fr.aug1.2001.htm

A developmental toxicity study in rabbits was conducted at gavage dose levels of 0, 100, 250, or 375 mg/kg/day... The maternal (systemic) NOEL is 100 mg/kg/day. Skeletal evaluation in fetuses revealed dose- and treatment-related findings at the 375 mg/kg/day dose level. These included significant increases in both the fetal and litter incidences of fused caudal vertebrae (a malformation) and of partially fused nasal bones (a variation). In addition, at 375 mg/kg/day, significant treatment-related reductions in ossification site averages were observed for metacarpals and both fore- and hindpaw phalanges
Ref: Federal Register: March 10, 1997. Sulfentrazone; Establishment of Tolerances. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/Sulfentrazone.FR.Mar10.1997.htm

Prenatal developmental in rodents (rats) - [870.3700] LOAEL = 25 mg/kg/ day based on decreased mean fetal weights, and retardation in skeletal development evidenced by an increased number of litters with any variation and by decreased number of caudal vertebral and metacarpal ossification sites Maternal NOAEL = 250 mg/kg/day LOAEL was not established. Developmental NOAEL = 100 mg/kg/ day LOAEL = 250 mg/kg/ day based on decreased fetal body weight; increased incidence of fetal variations: hypoplastic or wavy ribs, incompletely ossified lumbar vertebral arches, and incompletely ossified ischia or pubis [see definitions below]; and reduced number of thoracic vertebral and rib ossification sites.
-- Combined chronic toxicity/carcinogenicity rats - [870.4300] NOAEL = 40 mg/kg/day for males and 36.4 mg/kg/day in females LOAEL = 82.2 mg/kg/ day for males and 67 mg/kg/day for females based on dose-related decreased body weights (11 and 19%), body weight gains (13 and 26%), food consumption (13 and 19%), hemoglobin, hematocrit, mean cell volume, and mean cell hemoglobin. Increased nucleated red blood cells and reticulocytes in bone of females at 124.7 mg/kg/ day. No evidence of carcinogenicity
Ref: Federal Register: September 24, 2003. Sulfentrazone; Pesticide Tolerances. Final Rule.
http://www.fluorideaction.org/pesticides/sulfentrazone.fr.sept24.03.htm

• Definitions:
Ischia (plural of Ischium): The ventral and posterior of the three principal bones composing either half of the pelvis; seat bone; the huckle bone.
Pubis: one of the three sections of the hipbone; together the two pubic bones form the front of the pelvis

52988-0047 220351 (EPA MRID#: unknown), Freeman, C., “F6285 Technical: Teratology study in rats (oral),” FMC Corporation Toxicology Laboratory, Princeton, NJ; and Argus Research Laboratories, Inc., Horsham, PA, Aug. 4, 1993. Laboratory Study #: FMC Study No. A91-3410. Pregnant Crl:CD®BR VAF/Plus® dams, 25/group, were dosed by gavage (5 ml/kg corn oil vehicle) with 0, 1, 10, 25, or 50 mg/kg/day Sulfentrazone (F6285 Technical), purity 94.2%, during gestation days 6-15 in a standard developmental toxicity study. Maternal NOEL = 25 mg/kg/day. At 50 mg/kg/day there were decreased maternal body weight gains during late gestation, attributable to decreased gravid uterine weights due to increased resorptions (6.0 resorptions/dam in the 50 mg/kg/day group, compared to a range of 0.3 to 0.9/dam in controls and lower dose groups). About 22% of 50 mg/kg/day group resorptions were late resorptions, which normally occur only in about 0.02% of implantations (based on historical control data). There were three fetal deaths at 50 mg/kg/day, also an uncommon occurrence in historical controls. Vaginal bleeding was observed in ten 50 mg/kg/day dams compared to 0 controls (considered by investigators as associated with the increased resorptions). Also, 50 mg/kg/day dams had increased spleen weights and increased severity of splenic extramedullary hematopoiesis compared to controls and lesser dose groups. Developmental toxicity NOEL = 10 mg/kg/day. Dose related findings at 25 and 50 mg/kg/day included diminished body weights of fetuses (reductions of 7% and 19%, respectively, compared to concurrent controls). Statistically significant skeletal observations at 25 and 50 mg/kg/day were reduced ossification sites of caudal vertebrae and metacarpals. Developmental toxicity at 50 mg/kg/day was marked by malformations [whole body edema (anasarca) in 4 fetuses (4 litters), short ribs in 2 fetuses (1 litter), and bent radius and ulna in 3 fetuses (2 litters): all of these considered treatment-related because of low concurrent and historical control incidences]. Also common at 50 mg/kg/day were wavy ribs [30 fetuses (16 litters), compared with 1 or 0 fetuses per group in controls and lower dose groups] and wide-spread additional ossification delays. This study indicates a “possible adverse effect” and was flagged as such by investigators under 40 CFR 158.34, because the fetal NOEL is lower than the maternal NOEL. Overall, developmental toxicity findings at 25 mg/kg/day were modest, and the dose-response between 25 and 50 mg/kg/day was quite sharp. Study is acceptable. Aldous, 11/29/05.
Ref: January 13, 2006: Summary of toxicology data: Sulfentrazone (F2685). California EPA. Department of Pesticide Regulation. Medical Toxicology Branch.
http://www.fluorideaction.org/pesticides/sulfentrazone.ca.epa.2006.pdf

Brain (click on for all fluorinated pesticides)

TERATOLOGY, RABBIT **52988-0038 217369, “F6285 Technical, Teratology Study in Rabbits (Oral)”, ©. Freeman, FMC Corporation, Toxicology Laboratory, Princeton, NJ., Study No. A92-3540, 22 June 1993). 20 mated female New Zealand White rabbits per group received F6285 Technical (94.2 ± 0.5% sulfentrazone) by oral gavage at 0 (corn oil), 100, 250, and 375 mg/kg/day on gestation days 7 through 19. There were no treatment-related deaths. Two dams per group at 100 and 250 mg/kg/day died due to misdosing. One 375 mg/kg/day dam was sacrificed due to misdosing. Five dams at 375 mg/kg/day aborted (two on day 21 and one each on days 22, 23, and 24). The mean number of implants and the mean number of early resorptions were significantly increased at 250 and 375 mg/kg/day. 13, 13, 16, and 18 dams at 0, 100, 250, and 375 mg/kg/day respectively exhibited decreased feces during the study and hematuria was recorded for 1 and 16 dams at 250 and 375 mg/kg/day respectively. Significantly reduced bodyweights were recorded for dams at 250 and 375 mg/kg/day on gestation days 19 and 29 compared to controls and bodyweight gains were significantly reduced during the dosing period and overall for days 0 through 29. Fetal weights were significantly reduced at 250 and 375 mg/kg/day. No treatment-related findings for fetal external and internal exams. Two treatment related skeletal malformations were noted at 375 mg/kg/day. One fetus had incompletely or not ossified frontals, parietals, interparietals, suppraoccipital bones, and execenphaly. Although not statistically significant, the findings were considered treatment-related since they occurred only at the high dose and because execenphaly is uncommon in the rabbit strain. Additionally, 3 fetuses from 3 different dams had fused caudal vertebrae. The incidence was statistically significant and was higher than the historical control values. Treatment-related skeletal variations included statistically significant litter and fetal incidences of partially fused nasal bones at 375 mg/kg/day. Also, 4 litter mates at 375 mg/kg/day had unossified pubes. Finally, the average number of ossified sternal centers, tarsal bones, forepaw and hindpaw phlanges and metacarpal bones was significantly reduced in fetuses at 375 mg/kg/day. Maternal NOEL = 100 mg/kg/day (reduced bodyweight). Developmental NOEL = 100 mg/kg/day (reduced fetal weight, increased early resorptions). No teratogenicity. Acceptable. (Green and Leung, 12/13/05)

Was execenphaly a spelling error? Should it read exencephaly? Definition exencephaly - A condition in which the skull is defective, causing exposure or extrusion of the brain.

Ref: January 13, 2006: Summary of toxicology data: Sulfentrazone (F2685). California EPA. Department of Pesticide Regulation. Medical Toxicology Branch. http://www.fluorideaction.org/pesticides/sulfentrazone.ca.epa.2006.pdf

Endocrine: Prostate (click on for all fluorinated pesticides)

Reproduction and fertility effects (rat) Nonguideline - [870.3800] Parental/Systemic NOAEL = 20 mg/kg/day LOAEL = 51 mg/kg/ day (F1 females) based on decrease in pre-mating body weight gain (10%) Offspring and Reproductive NOAEL = 16 mg/kg/ day LOAEL = 40 mg/kg/ day based on reduced gestation day 20 fetal weights; decreased postnatal day 0, 4 and 7 pup weights; decreased pup survival; delayed vaginal patency; reduced epididymal, prostate, and testicular weights Additional information supports the conclusions reached in the 2- generation reproduction study in rats
Ref: Federal Register: September 24, 2003. Sulfentrazone; Pesticide Tolerances. Final Rule.
http://www.fluorideaction.org/pesticides/sulfentrazone.fr.sept24.03.htm

Endocrine: Testicular (click on for all fluorinated pesticides)

-- Toxicological Profile... A two-generation reproduction study in the rat at dietary levels of 14, 33, or 46 mg/kg/day in males and 16, 40, or 56 mg/kg/day in females established a NOEL for systemic and reproductive/ developmental parameters of 14 mg/kg/day for males and 16 mg/kg/day for females. The LOEL for systemic and reproductive/development parameters was 33 mg/kg/day for males and 40 mg/kg/day for females. Systemic effects were comprised of decreased body weight gains, while reproductive/developmental effect at the LOEL included degeneration and/or atrophy in the testes, with epididymal sperm deficits, in the second (F1) generation males. Male fertility in the F1 generation was reduced at higher doses; litter size, pup survival, and pup body weight for both generations were also effected at higher doses.
Ref: Federal Register: March 10, 1997. Sulfentrazone; Establishment of Tolerances. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/Sulfentrazone.FR.Mar10.1997.htm

-- Chronic dietary (all populations) NOAEL= 14.0 mg/kg/day. 2-Generation Reproduction in Rats. LOAEL = 33/44 mg/kg/day in males and females, respectively, based on: (1) Decreased maternal body weight and/or body weight gain during gestation in both P and F1 generations, (2) reduced premating body weight gains in the second generation (F1 adults), (3) increased duration of gestation in both F1 and F2 dams, (4) reduced prenatal viability (fetal and litter), (5) reduced litter size, (6) increased number of stillborn pups, (7) reduced pup and litter postnatal survival, and (8) decreased pup body weights throughout gestation. In males, effects included decreased fertility in F1 generation and/or atrophy of the germinal epithelium of the testes, oligospermia and intratubular degeneration of the seminal product in the epididymis.
Ref: Federal Register. August 1, 2001. Sulfentrazone; Pesticide Tolerances for Emergency Exemptions. Final Rule.
http://www.fluoridealert.org/pesticides/Sulfentrazone.FR.Aug1.2001.htm

-- Reproduction and fertility effects (rat) Nonguideline - [870.3800] Parental/Systemic NOAEL = 20 mg/kg/day LOAEL = 51 mg/kg/ day (F1 females) based on decrease in pre-mating body weight gain (10%) Offspring and Reproductive NOAEL = 16 mg/kg/ day LOAEL = 40 mg/kg/ day based on reduced gestation day 20 fetal weights; decreased postnatal day 0, 4 and 7 pup weights; decreased pup survival; delayed vaginal patency; reduced epididymal, prostate, and testicular weights. Additional information supports the conclusions reached in the 2- generation reproduction study in rats
-- 2-Generation reproduction and fertility effects (rats) - [870.3800] Parental/Systemic... Reproductive NOAEL = 14 mg/kg/ day for males and 16 mg/kg/day for females LOAEL = 33 mg/kg/ day for males and 40 mg/kg/day for females based on increased duration of gestation in females and degeneration and/ or atrophy of the germinal epithelium of the testes and oligospermia and intratubular degenerated seminal material in the epididymis of F1 males...
Ref: Federal Register: September 24, 2003. Sulfentrazone; Pesticide Tolerances. Final Rule.
http://www.fluorideaction.org/pesticides/sulfentrazone.fr.sept24.03.htm

Endocrine: Vaginal (click on for all fluorinated pesticides)

Reproduction and fertility effects (rat) Nonguideline - [870.3800] Parental/Systemic NOAEL = 20 mg/kg/day LOAEL = 51 mg/kg/ day (F1 females) based on decrease in pre-mating body weight gain (10%) Offspring and Reproductive NOAEL = 16 mg/kg/ day LOAEL = 40 mg/kg/ day based on reduced gestation day 20 fetal weights; decreased postnatal day 0, 4 and 7 pup weights; decreased pup survival; delayed vaginal patency; reduced epididymal, prostate, and testicular weights Additional information supports the conclusions reached in the 2- generation reproduction study in rats
Ref: Federal Register: September 24, 2003. Sulfentrazone; Pesticide Tolerances. Final Rule.
http://www.fluorideaction.org/pesticides/sulfentrazone.fr.sept24.03.htm

Liver (click on for all fluorinated pesticides)

-- Chronic toxicity. A 12-month feeding study in dogs was dosed at levels of 0.0, 24.9, or 61.2 mg/kg/day for male dogs and 0.0, 10.4, 29.6, or 61.9 [[Page 11100]] mg/kg/day for female dogs in the control through high-dose groups, respectively, with a NOAEL of 24.9 mg/kg/day for males and 29.6 mg/kg/ day for females based on hematology effects and microscopic liver changes.
-- In a 90-day subchronic feeding study in dogs administered by dietary admix at doses of 0, 10, 28, or 57 mg/kg/day for males and 0, 10, 28, or 73 mg/kg/day for females, a NOAEL of 28 mg/kg/day was determined for both males and females based on decreases in Hgb and HCT, elevated alkaline phosphatase levels, increased liver weights and microscopic liver as well as splenic changes.
Ref: Federal Register, March 7, 2003 (Volume 68, Number 45)] [Notices] [Page 11096-11100]. Notice of Filing Pesticide Petitions to Establish Tolerances for a Certain Pesticide Chemical in or on Food.
http://www.fluoridealert.org/pesticides/Sulfentrazone.FR.Mar.7.2003.htm

-- 90-Day oral toxicity in nonrodents (dogs) - [870.3150] NOAEL = 28 mg/kg/day LOAEL = 57 mg/kg/ day for males and 73 mg/kg/day for females based on decreased body weights (7-10%) and body weight gains during first 5 weeks of study; decreased hemoglobin, hematocrit, mean cell volume, mean cell hemoglobin and mean cell hemoglobin concentration, and increased absolute liver weights and alkaline phosphatase levels, and microscopic changes in the liver and spleen (pigmented sinusoidal microphages in the liver, swollen centrilobular hepatocytes and pigmented reticuloendotheli al cells in the spleen)
Ref: Federal Register: September 24, 2003. Sulfentrazone; Pesticide Tolerances. Final Rule.
http://www.fluorideaction.org/pesticides/sulfentrazone.fr.sept24.03.htm

Spleen (click on for all fluorinated pesticides)

A prenatal oral developmental toxicity study in the rat with dose levels at 25.0 or 50.0 mg/kg/day established a maternal NOEL of 25 mg/kg/day based on decreased body weight gain, increased spleen weight, and microscopic changes in the spleen, and a fetal NOEL of 10 mg/kg/day was based on fetal death, reduced body weights, and alterations in skeletal development at higher doses... Risk to infants and children was determined by use of developmental toxicity studies in rats and a two-generation reproduction study in rats. The oral developmental toxicity studies resulted in a maternal NOEL of 25 mg/kg/day based on decreased body weight gain, increased spleen weight, and microscopic changes in the spleen, and a fetal NOEL of 10 mg/kg/day based on fetal death, reduced body weights, and alterations in skeletal development at higher doses.
Ref: Federal Register: March 10, 1997. Sulfentrazone; Establishment of Tolerances. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/Sulfentrazone.FR.Mar10.1997.htm

-- 90-Day oral toxicity rodents (mice) - [870.3100] NOAEL = 60 mg/kg/day for males and 79.8 mg/kg/day for females LOAEL = 108.4 mg/ kg/day for males and 143.6 mg/kg/ day for females based on decreased body weights, body weight gains, red blood cells, hemoglobin, hematocrit, and severity of splenic micropathology (increased incidence and severity of extramedullary hematopoiesis)
-- 90-Day oral toxicity in nonrodents (dogs) - [870.3150] NOAEL = 28 mg/kg/day LOAEL = 57 mg/kg/ day for males and 73 mg/kg/day for females based on decreased body weights (7-10%) and body weight gains during first 5 weeks of study; decreased hemoglobin, hematocrit, mean cell volume, mean cell hemoglobin and mean cell hemoglobin concentration, and increased absolute liver weights and alkaline phosphatase levels, and microscopic changes in the liver and spleen (pigmented sinusoidal microphages in the liver, swollen centrilobular hepatocytes and pigmented reticuloendotheli al cells in the spleen)
-- Prenatal developmental in rodents (rats) - [870.3700] Maternal NOAEL = 25 mg/kg/day LOAEL = 50 mg/kg/ day based on increased relative splenic extramedullary hematopoiesis
-- Subchronic neurotoxicity screening battery - [870.6200] NOAEL = 30 mg/kg/day for males and 37 mg/kg/day for females LOAEL = 150 mg/kg/ day for males and 180 mg/kg/day for females based on increased incidence of clinical signs; decreased body weight, body weight gains, and food consumption in females; and increased motor activity in females. At 5,000 ppm, included increased mortality; decreased body weights, and body weight gains in males; decreased hindlimb grip strength and increased tail flick latency in males at week 8; distended bladders with red fluid and enlarged spleen. No evidence of neuropathology at 2,500 and 5,000 ppm.
Ref: Federal Register: September 24, 2003. Sulfentrazone; Pesticide Tolerances. Final Rule.
http://www.fluorideaction.org/pesticides/sulfentrazone.fr.sept24.03.htm

Teratogen (click on for all fluorinated pesticides)

52988-0047 220351 (EPA MRID#: unknown), Freeman, C., “F6285 Technical: Teratology study in rats (oral),” FMC Corporation Toxicology Laboratory, Princeton, NJ; and Argus Research Laboratories, Inc., Horsham, PA, Aug. 4, 1993. Laboratory Study #: FMC Study No. A91-3410. Pregnant Crl:CD®BR VAF/Plus® dams, 25/group, were dosed by gavage (5 ml/kg corn oil vehicle) with 0, 1, 10, 25, or 50 mg/kg/day Sulfentrazone (F6285 Technical), purity 94.2%, during gestation days 6-15 in a standard developmental toxicity study. Maternal NOEL = 25 mg/kg/day. At 50 mg/kg/day there were decreased maternal body weight gains during late gestation, attributable to decreased gravid uterine weights due to increased resorptions (6.0 resorptions/dam in the 50 mg/kg/day group, compared to a range of 0.3 to 0.9/dam in controls and lower dose groups). About 22% of 50 mg/kg/day group resorptions were late resorptions, which normally occur only in about 0.02% of implantations (based on historical control data). There were three fetal deaths at 50 mg/kg/day, also an uncommon occurrence in historical controls. Vaginal bleeding was observed in ten 50 mg/kg/day dams compared to 0 controls (considered by investigators as associated with the increased resorptions). Also, 50 mg/kg/day dams had increased spleen weights and increased severity of splenic extramedullary hematopoiesis compared to controls and lesser dose groups. Developmental toxicity NOEL = 10 mg/kg/day. Dose related findings at 25 and 50 mg/kg/day included diminished body weights of fetuses (reductions of 7% and 19%, respectively, compared to concurrent controls). Statistically significant skeletal observations at 25 and 50 mg/kg/day were reduced ossification sites of caudal vertebrae and metacarpals. Developmental toxicity at 50 mg/kg/day was marked by malformations [whole body edema (anasarca) in 4 fetuses (4 litters), short ribs in 2 fetuses (1 litter), and bent radius and ulna in 3 fetuses (2 litters): all of these considered treatment-related because of low concurrent and historical control incidences]. Also common at 50 mg/kg/day were wavy ribs [30 fetuses (16 litters), compared with 1 or 0 fetuses per group in controls and lower dose groups] and wide-spread additional ossification delays. This study indicates a “possible adverse effect” and was flagged as such by investigators under 40 CFR 158.34, because the fetal NOEL is lower than the maternal NOEL. Overall, developmental toxicity findings at 25 mg/kg/day were modest, and the dose-response between 25 and 50 mg/kg/day was quite sharp. Study is acceptable. Aldous, 11/29/05.
Ref: January 13, 2006: Summary of toxicology data: Sulfentrazone (F2685). California EPA. Department of Pesticide Regulation. Medical Toxicology Branch.
http://www.fluorideaction.org/pesticides/sulfentrazone.ca.epa.2006.pdf