Adverse Effects
Fluazifop-P-butyl
CAS No. 79241-46-6
 
 

Return to Fluazifop-P-butyl Index Page

Activity: Herbicide (arylphenoxy ether ester)
Structure:

Adverse Effects:
Blood
Body Weight Decrease

Bone
Endocrine: Ovary
Endocrine: Pituitary
Endocrine: Prostate
Endocrine: Testicular
Endocrine: Uterine
Eye
Fetotoxic
Kidney
Liver
Lung
Reproductive
Spleen
Stomach
Teratogenic

Environmental

The estimate for total domestic use (annual average) is approximately 250,000 lbs. active ingredient. More than 90% of fluazifop-P-butyl’s total usage is on soybeans (75%) and cotton (21%) (page 2).
Ref: October 29, 2003. Tier 1 Drinking Water Assessment for Fluazifop-P-butyl
. EPA Federal Register Docket No. OPP-2004-0347-0011.
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0011.pdf

• Fluazifop-P-butyl is the resolved isomer ® enantiomer) of fluazifop-butyl [(R,S)-2-(4((5-(trifluoromethyl)-2-pyridinyl)oxy)phenoxy)propanoic acid, butyl ester]. The fluazifop-butyl isomers are List B chemicals. Fluazifop-butyl (PC code 122805) has been canceled and only fluazifop-P-butyl is being supported for reregistration (page 5).
• Based on their structures, the Metabolism Assessment Review Committee (MARC) was unable to conclude that the major metabolites of fluazifop-P-butyl will be significantly less toxic than the parent and therefore, recommended that for risk assessment purposes, the residues of concern are parent, fluazifop acid (free and conjugated), 5-trifluoromethyl-2-pyridone, and 2-(4hydroxyphenoxy) propionic acid (free and conjugated)... (page 13)

Ref: December 10, 2004. US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf

• As of February 16, 2005, Fluazifop-butyl and Fluazifop-p-butyl, are both permitted in or on over 30 food commodities in the United States - see list at http://www.fluorideaction.org/pesticides/mrls-fluazifop.htm

As of January 2005: "Fluazifop-butyl (PC code 122805) has been canceled and only fluazifop-P-butyl is being supported for reregistration." - Ref: December 10, 2004. US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf


Blood (click on for all fluorinated pesticides)

Chronic/Subcrhonic Toxicity Studies: Chronic toxicity studies in rodents have shown liver changes (cellular hypertrophy). The No Effect Level (LEL) in rats is 10 ppm (0.5 mg/kg/day). Long term feeding studies in dogs produced a range of potentially serious effects at high dose rates (red cell, bone marrow and lymphadenopathy changes and liver and spleen damage) with a No Effect Level of 25 mg/kg/day. Target Organs: Liver, skin, kidney, eye, bone marrow, blood, reproductive system.
Ref: Material Safety Data Sheet for Fusilade DX (active indredient Fluazifop-P-Butyl). Syngenta. January 21, 2002.

http://www.fluoridealert.org/pesticides/Fluazifop-P-Butyl.MSDS.pdf

Body Weight Decrease (click on for all fluorinated pesticides)

411-110 135236 Moxon, M. E., "Fluazifop-p-butyl: Developmental toxicity study in the rabbit," Zeneca Central Toxicology Laboratory, Alderley Park, 3/23/93. Report # CTL/P/3862. Twenty mated NZW rabbits were dosed by gavage in 1 ml/kg corn oil at 0, 2, or 10 mg/kg/day Fluazifop-p-butyl technical (90.1% purity) between days 8 and 20 of gestation (natural mating day was designated “day 1”). There were also 40 mated does given 50 mg/kg/day of test article, to ensure adequate numbers of surviving litters. Maternal toxicity was generally low: mean body weight was unaffected and there were no characteristic clinical signs. There was one maternal death (killed in extremis) among the high dose females. Abortion frequencies were 1/18, 2/17, 2/13, and 4/37 in controls through increasing dose groups, thus not independently indicative of treatment effects at any dose. Nevertheless, a combination of marked body weight losses (average loss of 654 g) and associated signs of “few feces” or “no feces” among the 4 of the 5 aborted/killed moribund does is considered treatment-related, setting the maternal NOEL = 10 mg/kg/day..
Ref: May 20, 2002. SUMMARY OF TOXICOLOGY DATA FLUAZIFOP-P-BUTYL. California EPA. Department of Pesticide Regulation. Medical Toxicology Branch.

http://www.fluoridealert.org/pesticides/Fluazifop-P-butyl.CAepa.02.pdf

Reproductive Effects: In a 3-generation reproductive study in rats, effects included reductions in weight gain, fetal weight, ossification, testicular weight, spleen weight, increased prostate weight and gestational length. No Effect Level (NEL) was 1 mg/kg/day. Fetotoxic effects seen in the rabbit, including reduced fetal weight and reduced ossification at higher doses. No Effect Level (NEL) was 30 mg/kg/day in rabbits. The NEL for teratogenic effects is at least 10/mg/day in the rat, with diaphragmatic hernia at higher doses. Not teratogenic at highest dose tested in rabbits (90 mg/kg/day). While fluazifop-p-butyl is fetotoxic when fed to pregnant rats, human exposure data has concluded that female formulation workers are not at increased risk of fetotoxic effects when skin protection measures are applied.
Ref: Material Safety Data Sheet for Fusilade DX (active indredient Fluazifop-P-Butyl). Syngenta. January 21, 2002.
http://www.fluoridealert.org/pesticides/Fluazifop-P-Butyl.MSDS.pdf

Bone (click on for all fluorinated pesticides)

Reproductive Effects: In a 3-generation reproductive study in rats, effects included reductions in weight gain, fetal weight, ossification, testicular weight, spleen weight, increased prostate weight and gestational length. No Effect Level (NEL) was 1 mg/kg/day. Fetotoxic effects seen in the rabbit, including reduced fetal weight and reduced ossification at higher doses. No Effect Level (NEL) was 30 mg/kg/day in rabbits. The NEL for teratogenic effects is at least 10/mg/day in the rat, with diaphragmatic hernia at higher doses. Not teratogenic at highest dose tested in rabbits (90 mg/kg/day). While fluazifop-p-butyl is fetotoxic when fed to pregnant rats, human exposure data has concluded that female formulation workers are not at increased risk of fetotoxic effects when skin protection measures are applied.
Chronic/Subcrhonic Toxicity Studies: Chronic toxicity studies in rodents have shown liver changes (cellular hypertrophy). The No Effect Level (LEL) in rats is 10 ppm (0.5 mg/kg/day). Long term feeding studies in dogs produced a range of potentially serious effects at high dose rates (red cell, bone marrow and lymphadenopathy changes and liver and spleen damage) with a No Effect Level of 25 mg/kg/day.
Target Organs: Liver, skin, kidney, eye, bone marrow, blood, reproductive system.
Ref: Material Safety Data Sheet for Fusilade DX (active indredient Fluazifop-P-Butyl). Syngenta. January 21, 2002.
http://www.fluoridealert.org/pesticides/Fluazifop-P-Butyl.MSDS.pdf

-- 411-110 135236 Moxon, M. E., "Fluazifop-p-butyl: Developmental toxicity study in the rabbit," Zeneca Central Toxicology Laboratory, Alderley Park, 3/23/93. Report # CTL/P/3862. Twenty mated NZW rabbits were dosed by gavage in 1 ml/kg corn oil at 0, 2, or 10 mg/kg/day Fluazifop-p-butyl technical (90.1% purity) between days 8 and 20 of gestation (natural mating day was designated “day 1”). There were also 40 mated does given 50 mg/kg/day of test article, to ensure adequate numbers of surviving litters... Other maternal and general developmental toxicity indices did not indicate treatment effects, however modest ossification delays (2 nd and 5 th sternebrae) and increased incidence of extra 13 th rib (all at 50 mg/kg/day) placed the developmental toxicity NOEL = 10 mg/kg/day.
-- 018 994244: Tesh, J. M., Ross, F. W. and Tesh, S. A. "PP009: Effects of Oral Administration upon Pregnancy in the Rabbit, Final report". Life Science Research report No. 80/ILK 027/498 [November 28, 1980]. PP009, purity 94.8%, administered via gavage at concentrations of 10, 30 or 90 mg/kg/day to 20-24 artificially inseminated female New Zealand rabbits during gestation days 6 through 28. Adverse effects: increased incidence of cloudy eyes (12.7%), small fetuses, delayed ossification and enlarged anterior and posterior fontanelle. Maternal NOEL = >90 mg/kg/day (no toxicity). UNACCEPTABLE (No MTD, too few pregnant dams at scheduled sacrifice). (C. Aldous, 8/27/85).
Ref: May 20, 2002. SUMMARY OF TOXICOLOGY DATA FLUAZIFOP-P-BUTYL. California EPA. Department of Pesticide Regulation. Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/Fluazifop-P-butyl.CAepa.02.pdf

4.2.3.1 Developmental Toxicity Study Conclusions. The LOAEL is 5.0 mg/kg/day based on decreased fetal weight and increased incidence of hydroureter in fetuses and litters, and delayed ossification in a 160 litter/group developmental toxicity study (MRID# 00088858). This LOAEL is also supported by a dose related increased fetal incidence in partially ossified sternebrae and sternebrae bipartite, 5 th (MRID# 46082913, 46082903), and statistically significant increased incidence of fetuses and litters with interparietals, occipitals and parietals partially ossified, calcaneum not ossified and increased manus and pes scores at 5.0 mg/kg/day (MRID#46082903 and 46158401). The NOAEL of 1.0 mg/kg/day in the 160 litter per group study was not selected and a NOAEL of 2.0 mg/kg/day from the Wistar rat studies was selected. Since apparent effects noted at 0.05 and 1.0 mg/kg/day were either not dose related, concurrent controls were low, the effects were lower than the historical control range, or were not statistically significant in litters, and 2 developmental studies that included a 2 mg/kg/day dose group failed to elicit a dose dependant response, a NOAEL of 2.0 mg/kg/day was selected (page 31).
Ref: December 10, 2004. US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf

4.2.3.6 Fluazifop-P-butyl - Wistar Rats. In a developmental toxicity study (MRID 46158401)[Fluazifop-p-butyl, calculated as 90.1% a.i.; batch/lot# P12; CTL Ref.# Y02746/021/003] was administered to [(24 females) Alderly Park strain of Wistar rats] rats/dose by gavage at dose levels of 0, 0.5, 1.0, 20, or 300 mg a.i./kg bw/day from days 7 through 16 of gestation. ... Developmental effects were shown by delayed ossification in many parameters at ≥20 mg/kg/day. The incidence of parietals partially ossified were statistically significant and dose related in fetuses and litters at 20 mg/kg/day. The statistically significant increase in interparietals partially ossified in fetuses at 20 mg/kg/day exceeded historical controls and support the delayed ossification of the parietal bones. Cervical vertebral arches 4 and 5 partially ossified and centrum (4 th not ossified) at 20 mg/kg/day showed statistically significantly increased incidence in fetuses and litters. Manus Scores were statistically significantly increased at 1.0, 20, and 300 mg/kg/day. Pes score were statistically significantly increased at 20 and 300 mg/kg/day. ... For developmental toxicity, the NOAEL is 1.0 mg/kg/day and the LOAEL is 20 mg/kg/day based on dose related delayed ossification in skull bones [parietal], delayed ossification of the cervical arches and centrum (not ossified) in fetuses and litters and delayed ossification of the manus and pes. (Page 36-37).
Ref: December 10, 2004. US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf

Endocrine: Ovary (click on for all fluorinated pesticides)

ONCOGENICITY, MOUSE [OR HAMSTER] 411-125 180756 Rattray, N. J., "Fluazifop-p-butyl: 80 week carcinogenicity study in hamsters," Central Toxicology Laboratory (CTL), Alderley Park Macclesfield, 2/1/01. Lab Study ID: Syngenta No.1606-01. Golden Syrian hamsters, 51/sex/group, were dosed in diet with 0, 0, 200, 750, or 3000 ppm fluazifop-p-butyl (91.6%) for 81-83 weeks. The dual control groups were treated identically. An additional 12/sex/group (same doses) were allocated for 1-yr sacrifice (for hematology only). Estimated achieved doses were 12.5, 47, and 194 mg/kg/day (M) and 12.1, 46, and 181 mg/kg/day (F). No NOEL was established... Findings at the higher two dose levels only included decreased testes weights, reduced spermatozoa counts in epididymides and increased cataract development in males. Stromal cell/sex cord hyperplasia was elevated in high dose females. Benign stromal cell/sex cord tumors were slightly but significantly elevated in 3000 ppm females (incidences of 1, 1, 3, 4, and 5 in controls through high dose groups, respectively). Study is not acceptable, but presumed upgradeable (there is a need to explain why this species was selected for this study, and individual data for hamsters should be provided). The ovarian tumor findings, in addition to the several noted histopathology findings without NOEL's, are possible adverse effects. Contemporary historical control data are needed if the registrant desires to re-visit DPR conclusions about findings of this study. The DPR review briefly discusses some ramifications of ovarian and testicular findings. Aldous, 5/20/02.
Ref: May 20, 2002. SUMMARY OF TOXICOLOGY DATA FLUAZIFOP-P-BUTYL. California EPA. Department of Pesticide Regulation. Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/Fluazifop-P-butyl.CAepa.02.pdf

Target Organs: Liver, skin, kidney, eye, bone marrow, blood, reproductive system.
Ref: Material Safety Data Sheet for Fusilade DX (active indredient Fluazifop-P-Butyl). Syngenta. January 21, 2002.
http://www.fluoridealert.org/pesticides/Fluazifop-P-Butyl.MSDS.pdf

Endocrine: Pituitary

The chronic dietary (all populations), intermediate-term dermal and inhalation, and intermediateterm incidental oral endpoints were selected from the 2-generation reproduction study in rats based on decreased spleen, testes and epididymal weights in males, and decreased uterine and pituitary weights in females (page 5) ... Reproduction and fertility effects (rats). Reproductive NOAEL = M/F 0.74/0.88mg/kg/day LOAEL = M/F 5.8/7.1 mg/kg/day based on decreased abs. & rel testes & epididymal weight and in females decreased pituitary & uterine weights (age 23) ... F1 adult females showed an absolute (28%) and relative (18%) statistically significant increase in ovarian weight at 250 ppm. In F1 adult females, absolute pituitary weights (13%20%) and uterine weights (18%-25%) were statistically significantly reduced at 80-250 ppm. Relative pituitary weights (18%-27%) and uterine weights (19%-29%) were reduced in F1 adult females at 80-250 ppm.
• Comments about Study/Endpoint/Uncertainty Factor: The study/dose/endpoint is appropriate for the route (oral) and duration (chronic) of concern. Although the endpoint of concern in based on male reproductive effects, decreases in pituitary and uterine weights were seen in females at a comparable NOAEL (0.88 mg/kg/day) and LOAEL (7.1 mg/kg/day) (page 45).
Ref: December 10, 2004. US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf

Endocrine: Prostate (click on for all fluorinated pesticides)

Reproductive Effects: In a 3-generation reproductive study in rats, effects included reductions in weight gain, fetal weight, ossification, testicular weight, spleen weight, increased prostate weight and gestational length. No Effect Level (NEL) was 1 mg/kg/day. Target Organs: Liver, skin, kidney, eye, bone marrow, blood, reproductive system.
Ref: Material Safety Data Sheet for Fusilade DX (active indredient Fluazifop-P-Butyl). Syngenta. January 21, 2002.

http://www.fluoridealert.org/pesticides/Fluazifop-P-Butyl.MSDS.pdf

Endocrine: Testicular (click on for all fluorinated pesticides)

4.1.3 Dose-response. A statistically significant, but marginally adequate dose-response was shown in the testes weight, and epididymal weight, decrement in the parental and F1 generation in the adult rat, potentially due to reduced sperm content. The cancer study in hamsters showed a good dose response in testes weight decrement. Since the statistically significant effects were seen in the male P0 and F1 parents and in the hamster study, the effects were considered treatment related. The testicular endpoint from the reproduction study was selected for the chronic RfD, intermediate-term oral incidental exposure, intermediate and long-term dermal and inhalation exposure. Other studies showed testes weight decrement and epididymal effects at higher dose levels, but there were only equivocal histological effects shown. Although extensive short-term studies on the testes weight decrement and epididymal effects were conducted, all failed to show that the effect was incidental or find an explanation for the effect. However, the more sensitive studies on sperm count were not among the extra studies conducted. An acceptable negative study of sufficient duration on sperm parameters would add confidence to the possibility that the testes and epididymal weight decrement seen in the rat reproduction study were incidental and not reproducible. The uterine weight decrement seen in the reproduction study showed a good dose-response and was supported by a dose-response in the pituitary weight decrement at the same doses. In addition, in the hamster, hyperplasia in the ovary was seen at high dose levels. One of the subchronic studies in the rat with fluazifop-P-butyl showed testicular weight decrement, while the other one with fluazifop-butyl did not at approximately the same doses as in the reproduction study; at the highest dose tested in the subchronic study with fluazifop-butyl absolute testes weights were increased 30%. The reason is unknown, but may be due to animal variation or other unknown factors such as edema. The testes and epididymal weight decrement and uterine and ovarian effects suggest possible endocrine related effects. However, negative in vitro studies suggest estrogen and androgen hormones were not involved. Agonistic and antagonistic studies with fluazifop-butyl, fluazifop-P-butyl and the fluazifop acid metabolite were conducted in yeast cells containing human estrogen and androgen receptors. No receptor activity was found with any of the test materials over a sufficiently wide concentration range (page 18-19).
Ref: December 10, 2004. US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf

ONCOGENICITY, MOUSE [OR HAMSTER] 411-125 180756 Rattray, N. J., "Fluazifop-p-butyl: 80 week carcinogenicity study in hamsters," Central Toxicology Laboratory (CTL), Alderley Park Macclesfield, 2/1/01. Lab Study ID: Syngenta No.1606-01. Golden Syrian hamsters, 51/sex/group, were dosed in diet with 0, 0, 200, 750, or 3000 ppm fluazifop-p-butyl (91.6%) for 81-83 weeks. The dual control groups were treated identically. An additional 12/sex/group (same doses) were allocated for 1-yr sacrifice (for hematology only). Estimated achieved doses were 12.5, 47, and 194 mg/kg/day (M) and 12.1, 46, and 181 mg/kg/day (F). No NOEL was established... Findings at the higher two dose levels only included decreased testes weights, reduced spermatozoa counts in epididymides and increased cataract development in males. Stromal cell/sex cord hyperplasia was elevated in high dose females... Aldous, 5/20/02.
Ref: May 20, 2002. SUMMARY OF TOXICOLOGY DATA FLUAZIFOP-P-BUTYL. California EPA. Department of Pesticide Regulation. Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/Fluazifop-P-butyl.CAepa.02.pdf

-- Reproductive Effects: In a 3-generation reproductive study in rats, effects included reductions in weight gain, fetal weight, ossification, testicular weight, spleen weight, increased prostate weight and gestational length. No Effect Level (NEL) was 1 mg/kg/day.
Target Organs: Liver, skin, kidney, eye, bone marrow, blood, reproductive system.
Ref: Material Safety Data Sheet for Fusilade DX (active indredient Fluazifop-P-Butyl). Syngenta. January 21, 2002.

http://www.fluoridealert.org/pesticides/Fluazifop-P-Butyl.MSDS.pdf

The chronic dietary (all populations), intermediate-term dermal and inhalation, and intermediateterm incidental oral endpoints were selected from the 2-generation reproduction study in rats based on decreased spleen, testes and epididymal weights in males, and decreased uterine and pituitary weights in females (page 5).
Ref: December 10, 2004. US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf

Endocrine: Uterine

The chronic dietary (all populations), intermediate-term dermal and inhalation, and intermediateterm incidental oral endpoints were selected from the 2-generation reproduction study in rats based on decreased spleen, testes and epididymal weights in males, and decreased uterine and pituitary weights in females (page 5). ... The uterine weight decrement seen in the reproduction study showed a good dose-response and was supported by a dose-response in the pituitary weight decrement at the same doses. In addition, in the hamster, hyperplasia in the ovary was seen at high dose levels. One of the subchronic studies in the rat with fluazifop-P-butyl showed testicular weight decrement, while the other one with fluazifop-butyl did not at approximately the same doses as in the reproduction study; at the highest dose tested in the subchronic study with fluazifop-butyl absolute testes weights were increased 30%. The reason is unknown, but may be due to animal variation or other unknown factors such as edema. The testes and epididymal weight decrement and uterine and ovarian effects suggest possible endocrine related effects. However, negative in vitro studies suggest estrogen and androgen hormones were not involved. Agonistic and antagonistic studies with fluazifop-butyl, fluazifop-P-butyl and the fluazifop acid metabolite were conducted in yeast cells containing human estrogen and androgen receptors. No receptor activity was found with any of the test materials over a sufficiently wide concentration range (page 19).
Ref: December 10, 2004. US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf

Eye (click on for all fluorinated pesticides)

-- 018 994244: Tesh, J. M., Ross, F. W. and Tesh, S. A. "PP009: Effects of Oral Administration upon Pregnancy in the Rabbit, Final report". Life Science Research report No. 80/ILK 027/498 [November 28, 1980]. PP009, purity 94.8%, administered via gavage at concentrations of 10, 30 or 90 mg/kg/day to 20-24 artificially inseminated female New Zealand rabbits during gestation days 6 through 28. Adverse effects: increased incidence of cloudy eyes (12.7%), small fetuses, delayed ossification and enlarged anterior and posterior fontanelle. Maternal NOEL = >90 mg/kg/day (no toxicity). UNACCEPTABLE (No MTD, too few pregnant dams at scheduled sacrifice). (C. Aldous, 8/27/85).
-- ONCOGENICITY, MOUSE [OR HAMSTER] 411-125 180756 Rattray, N. J., “Fluazifop-p-butyl: 80 week carcinogenicity study in hamsters,” Central Toxicology Laboratory (CTL), Alderley Park Macclesfield, 2/1/01. Lab Study ID: Syngenta No.1606-01. Golden Syrian hamsters, 51/sex/group, were dosed in diet with 0, 0, 200, 750, or 3000 ppm fluazifop-p-butyl (91.6%) for 81-83 weeks. The dual control groups were treated identically. An additional 12/sex/group (same doses) were allocated for 1-yr sacrifice (for hematology only). Estimated achieved doses were 12.5, 47, and 194 mg/kg/day (M) and 12.1, 46, and 181 mg/kg/day (F). No NOEL was established... Findings at the higher two dose levels only included decreased testes weights, reduced spermatozoa counts in epididymides and
increased cataract development in males...
Ref: May 20, 2002. SUMMARY OF TOXICOLOGY DATA FLUAZIFOP-P-BUTYL. California EPA. Department of Pesticide Regulation. Medical Toxicology Branch.

http://www.fluoridealert.org/pesticides/Fluazifop-P-butyl.CAepa.02.pdf

4.2.3.8 Fluazifop-P-butyl - Rabbit In a developmental toxicity study [MRID 46082904] [fluazifop-p-butyl (90.1% a.i., batch/lot # P12)] was administered to [(20 females) New Zealand White] rabbits/group by gavage in corn oil vehicle [1 ml/kg] at dose levels of 0, 2, 10 or 50 mg a.i./kg bw/day from days 8 through 20 of gestation. Day sperm was found was designated as day 1. On day 30 of gestation, dams were killed and the uterine contents examined for live and dead fetuses. Fetuses were weighed, examined for external and visceral abnormalities, sexed, eviscerated and stained for skeletal examination. ... Treatment related effects on development were seen in the 50 mg/kg/day group only. Statistically significant extra 13 th rib and delayed ossification was seen in sternebrae 2 and 5. An increase in partially ossified 5 sternebrae was seen at 10 mg/kg/day, but the litter incidence was not increased. A nominal increase in malformations were seen at 50 mg/kg/day, such as acephaly [1 fetus/1 litter], cebocephaly [1 fetus/1 litter], cleft palate [1 fetus/1 litter], microphthalmia [1 fetus/1 litter], gastroschisis [1 fetus/1 litter], and multiple anomalies in 1 fetus/1 litter. None were duplicated and all could have occurred 1 to 3 times in the same litter, with 0 in control. Since individual animal data was not submitted, this incidence in litters could not be verified. For developmental toxicity, the NOAEL is 10 mg/kg/day and the LOAEL is 50 mg/kg/day based on increased 13 th rib and increased incidence of delayed ossification of sternebrae 2 and 5. (page 39).
Ref: December 10, 2004. US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf

Definitions:

Acephaly: literally means absence of the head. The acephalic fetus is a parasitic twin attached to an otherwise intact fetus. The acephalic fetus has a body but lacks a head and a heart; the fetus’s neck is attached to the normal twin. The blood circulation of the acephalic fetus is provided by the heart of the twin. The acephalic fetus can not exist independently of the fetus to which it is attached.
Ref: http://www.icomm.ca/geneinfo/acep.htm

Cebocephaly: A facial anomaly, characterized by a small, flattened nose with a single nostril situated below incomplete or underdeveloped closely set eyes.
Ref: http://www.icomm.ca/geneinfo/cephaly.htm

Gastroschisis: is an abdominal wall defect located to the side of the umbilical cord (umbilicus). The infant is born with intestines protruding through this defect and no protective sac is present.
Ref: http://www.nlm.nih.gov/medlineplus/ency/article/002924.htm

Microphthalmia - small eye syndrome. Microphthalmia is a disorder in which one or both eyes are abnormally small.

Fetotoxic (click on for all fluorinated pesticides)

-- Reproductive Effects: In a 3-generation reproductive study in rats, effects included reductions in weight gain, fetal weight, ossification, testicular weight, spleen weight, increased prostate weight and gestational length. No Effect Level (NEL) was 1 mg/kg/day. Fetotoxic effects seen in the rabbit, including reduced fetal weight and reduced ossification at higher doses. No Effect Level (NEL) was 30 mg/kg/day in rabbits. The NEL for teratogenic effects is at least 10/mg/day in the rat, with diaphragmatic hernia at higher doses. Not teratogenic at highest dose tested in rabbits (90 mg/kg/day). While fluazifop-p-butyl is fetotoxic when fed to pregnant rats, human exposure data has concluded that female formulation workers are not at increased risk of fetotoxic effects when skin protection measures are applied.
Ref: Material Safety Data Sheet for Fusilade DX (active indredient Fluazifop-P-Butyl). Syngenta. January 21, 2002.
http://www.fluoridealert.org/pesticides/Fluazifop-P-Butyl.MSDS.pdf

Kidney (click on for all fluorinated pesticides)

... Subchronic and chronic toxicity studies with fluazifop-butyl or fluazifop-P-butyl show that the rat is more sensitive to toxic effects than the dog, rabbit or hamster, possibly due to longer retention time of the major metabolite (fluazifop acid) in the rat. The kidney and liver are the target organs and the toxicity is expressed as exacerbation of age related kidney toxicity and liver toxicity in the presence of peroxasome proliferation (page 5).
Ref: December 10, 2004.
US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf

ONCOGENICITY, MOUSE [OR HAMSTER] 411-125 180756 Rattray, N. J., "Fluazifop-p-butyl: 80 week carcinogenicity study in hamsters," Central Toxicology Laboratory (CTL), Alderley Park Macclesfield, 2/1/01. Lab Study ID: Syngenta No.1606-01. Golden Syrian hamsters, 51/sex/group, were dosed in diet with 0, 0, 200, 750, or 3000 ppm fluazifop-p-butyl (91.6%) for 81-83 weeks. The dual control groups were treated identically. An additional 12/sex/group (same doses) were allocated for 1-yr sacrifice (for hematology only). Estimated achieved doses were 12.5, 47, and 194 mg/kg/day (M) and 12.1, 46, and 181 mg/kg/day (F). No NOEL was established. Changes seen at all dose levels included chronic progressive nephropathy, factoring both incidence and degree, in kidneys of both sexes; gall stone formation at all dose levels in males; testicular tubular degeneration, factoring both incidence and degree, dose-related in all treated male groups; and elevated liver weights in all female groups.,,
Ref: May 20, 2002. SUMMARY OF TOXICOLOGY DATA FLUAZIFOP-P-BUTYL. California EPA. Department of Pesticide Regulation. Medical Toxicology Branch.

http://www.fluoridealert.org/pesticides/Fluazifop-P-butyl.CAepa.02.pdf

4.2.3.1 Developmental Toxicity Study Conclusions. The LOAEL is 5.0 mg/kg/day based on decreased fetal weight and increased incidence of hydroureter in fetuses and litters, and delayed ossification in a 160 litter/group developmental toxicity study (MRID# 00088858). (page 31).
Ref: December 10, 2004. US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003

Liver (click on for all fluorinated pesticides)

... Subchronic and chronic toxicity studies with fluazifop-butyl or fluazifop-P-butyl show that the rat is more sensitive to toxic effects than the dog, rabbit or hamster, possibly due to longer retention time of the major metabolite (fluazifop acid) in the rat. The kidney and liver are the target organs and the toxicity is expressed as exacerbation of age related kidney toxicity and liver toxicity in the presence of peroxasome proliferation (page 5).
Ref: December 10, 2004.
US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf

Chronic/Subcrhonic Toxicity Studies: Chronic toxicity studies in rodents have shown liver changes (cellular hypertrophy). The No Effect Level (LEL) in rats is 10 ppm (0.5 mg/kg/day). Long term feeding studies in dogs produced a range of potentially serious effects at high dose rates (red cell, bone marrow and lymphadenopathy changes and liver and spleen damage) with a No Effect Level of 25 mg/kg/day. Target Organs: Liver, skin, kidney, eye, bone marrow, blood, reproductive system.
Ref: Material Safety Data Sheet for Fusilade DX (active indredient Fluazifop-P-Butyl). Syngenta. January 21, 2002.

http://www.fluoridealert.org/pesticides/Fluazifop-P-Butyl.MSDS.pdf

Lung (click on for all fluorinated pesticides)

*Acute Toxicity:... Breathing small amounts of the product Fusilade 2000 may cause vomiting and severe lung congestion; larger amounts may ultimately lead to labored breathing, coma, and death [37].
Ref: EXTOXNET. Pesticide Information Profile for Fluazifop-p-butyl. Cornell University.

http://ace.ace.orst.edu/info/extoxnet/pips/fluazifo.htm

Reproductive (click on for all fluorinated pesticides)

Chronic/Subcrhonic Toxicity Studies: Chronic toxicity studies in rodents have shown liver changes (cellular hypertrophy). The No Effect Level (LEL) in rats is 10 ppm (0.5 mg/kg/day). Long term feeding studies in dogs produced a range of potentially serious effects at high dose rates (red cell, bone marrow and lymphadenopathy changes and liver and spleen damage) with a No Effect Level of 25 mg/kg/day. Target Organs: Liver, skin, kidney, eye, bone marrow, blood, reproductive system.
Ref: Material Safety Data Sheet for Fusilade DX (active indredient Fluazifop-P-Butyl). Syngenta. January 21, 2002.

http://www.fluoridealert.org/pesticides/Fluazifop-P-Butyl.MSDS.pdf

"Fluazifop-P-butyl 79241-46-6 Withdrawn. Teratogenic and suspected reproductive effects in experimental animals. 1991."
Definition: "Withdrawn. A substance which the manufacturer has either withdrawn from the market, or for which he has withdrawn his application for registration, approval, or renewed approval and when it is clear that these measures were undertaken due to the health or environmental properties of the substance."

Ref: Euopean Commission. Appendix 5. Substances which may not be included as active ingredients in approved pesticide products, Chapter 15, Section 2, subsection one.
http://www.kemi.se/lagar_eng/pdf/app5_8.pdf

Spleen (click on for all fluorinated pesticides)

Reproductive Effects: In a 3-generation reproductive study in rats, effects included reductions in weight gain, fetal weight, ossification, testicular weight, spleen weight, increased prostate weight and gestational length. No Effect Level (NEL) was 1 mg/kg/day...
Chronic/Subcrhonic Toxicity Studies: Chronic toxicity studies in rodents have shown liver changes (cellular hypertrophy). The No Effect Level (LEL) in rats is 10 ppm (0.5 mg/kg/day). Long term feeding studies in dogs produced a range of potentially serious effects at high dose rates (red cell, bone marrow and lymphadenopathy changes and liver and spleen damage) with a No Effect Level of 25 mg/kg/day., Target Organs: Liver, skin, kidney, eye, bone marrow, blood, reproductive system.
Ref: Material Safety Data Sheet for Fusilade DX (active indredient Fluazifop-P-Butyl). Syngenta. January 21, 2002.
http://www.fluoridealert.org/pesticides/Fluazifop-P-Butyl.MSDS.pdf

The chronic dietary (all populations), intermediate-term dermal and inhalation, and intermediateterm incidental oral endpoints were selected from the 2-generation reproduction study in rats based on decreased spleen, testes and epididymal weights in males, and decreased uterine and pituitary weights in females (page 5).
Ref: December 10, 2004. US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf

Stomach (click on for all fluorinated pesticides)

Acute Toxicity... A single dose of the formulated compound (Fusilade 2000) can cause severe stomach and intestine disturbance.
Ref: EXTOXNET. Pesticide Information Profile for Fluazifop-p-butyl. Cornell University.
http://ace.ace.orst.edu/info/extoxnet/pips/fluazifo.htm

Teratogenic (click on for all fluorinated pesticides)

-- Reproductive Effects: In a 3-generation reproductive study in rats, effects included reductions in weight gain, fetal weight, ossification, testicular weight, spleen weight, increased prostate weight and gestational length. No Effect Level (NEL) was 1 mg/kg/day. Fetotoxic effects seen in the rabbit, including reduced fetal weight and reduced ossification at higher doses. No Effect Level (NEL) was 30 mg/kg/day in rabbits. The NEL for teratogenic effects is at least 10/mg/day in the rat, with diaphragmatic hernia at higher doses. Not teratogenic at highest dose tested in rabbits (90 mg/kg/day). While fluazifop-p-butyl is fetotoxic when fed to pregnant rats, human exposure data has concluded that female formulation workers are not at increased risk of fetotoxic effects when skin protection measures are applied.
Ref: Material Safety Data Sheet for Fusilade DX (active indredient Fluazifop-P-Butyl). Syngenta. January 21, 2002.
http://www.fluoridealert.org/pesticides/Fluazifop-P-Butyl.MSDS.pdf

"Fluazifop-P-butyl 79241-46-6 Withdrawn. Teratogenic and suspected reproductive effects in experimental animals. 1991." Definition: "Withdrawn. A substance which the manufacturer has either withdrawn from the market, or for which he has withdrawn his application for registration, approval, or renewed approval and when it is clear that these measures were undertaken due to the health or environmental properties of the substance."
Ref: Euopean Commission. Appendix 5. Substances which may not be included as active ingredients in approved pesticide products, Chapter 15, Section 2, subsection one.
http://www.kemi.se/lagar_eng/pdf/app5_8.pdf

4.2.3.8 Fluazifop-P-butyl - Rabbit In a developmental toxicity study [MRID 46082904] [fluazifop-p-butyl (90.1% a.i., batch/lot # P12)] was administered to [(20 females) New Zealand White] rabbits/group by gavage in corn oil vehicle [1 ml/kg] at dose levels of 0, 2, 10 or 50 mg a.i./kg bw/day from days 8 through 20 of gestation. Day sperm was found was designated as day 1. On day 30 of gestation, dams were killed and the uterine contents examined for live and dead fetuses. Fetuses were weighed, examined for external and visceral abnormalities, sexed, eviscerated and stained for skeletal examination. ... Treatment related effects on development were seen in the 50 mg/kg/day group only. Statistically significant extra 13 th rib and delayed ossification was seen in sternebrae 2 and 5. An increase in partially ossified 5 sternebrae was seen at 10 mg/kg/day, but the litter incidence was not increased. A nominal increase in malformations were seen at 50 mg/kg/day, such as acephaly [1 fetus/1 litter], cebocephaly [1 fetus/1 litter], cleft palate [1 fetus/1 litter], microphthalmia [1 fetus/1 litter], gastroschisis [1 fetus/1 litter], and multiple anomalies in 1 fetus/1 litter. None were duplicated and all could have occurred 1 to 3 times in the same litter, with 0 in control. Since individual animal data was not submitted, this incidence in litters could not be verified. For developmental toxicity, the NOAEL is 10 mg/kg/day and the LOAEL is 50 mg/kg/day based on increased 13 th rib and increased incidence of delayed ossification of sternebrae 2 and 5. (page 39).
Ref: December 10, 2004. US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf

Definitions:

Acephaly: literally means absence of the head. The acephalic fetus is a parasitic twin attached to an otherwise intact fetus. The acephalic fetus has a body but lacks a head and a heart; the fetus’s neck is attached to the normal twin. The blood circulation of the acephalic fetus is provided by the heart of the twin. The acephalic fetus can not exist independently of the fetus to which it is attached.
Ref: http://www.icomm.ca/geneinfo/acep.htm

Cebocephaly: A facial anomaly, characterized by a small, flattened nose with a single nostril situated below incomplete or underdeveloped closely set eyes.
Ref: http://www.icomm.ca/geneinfo/cephaly.htm

Gastroschisis: is an abdominal wall defect located to the side of the umbilical cord (umbilicus). The infant is born with intestines protruding through this defect and no protective sac is present.
Ref: http://www.nlm.nih.gov/medlineplus/ency/article/002924.htm

Microphthalmia - small eye syndrome. Microphthalmia is a disorder in which one or both eyes are abnormally small.

An acute dietary endpoint for females 13-49 years of age was selected from a developmental toxicity study in rats, based on diaphragmatic hernia. ... The overall rat studies showed a NOAEL/LOAEL of 2.0/5.0 mg/kg/day. The NOAEL/LOAEL was chosen from among MRID# 0008858, 46082903, 46082913 and 46518401. For a single dose effect, the NOAEL/LOAELs are 50/200 mg/kg/day based on the diaphragmatic hernia malformations (Page 31).
Ref: December 10, 2004. US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf

Environmental (click on for all fluorinated pesticides)

3.3 Environmental Degradation. Environmental fate studies indicate that fluazifop-P-butyl is not mobile and not persistent. The predominant environmental fate process appears to be microbially-assisted hydrolysis to fluazifop acid and 5-trifluoromethyl-2-pyridone [major metabolites], which are considered to be mobile and therefore, can potentially reach surface and ground waters. Aerobic soil metabolism studies showed that the half-life of the parent ester is on the order of a few hours. The properties of fluazifop acid, namely high mobility and long persistence in water (78-day hydrolysis half-life at pH 7) and anaerobic soil (half-life 1 to 3 years, MRID# 92067033) indicate that it might persist from year to year in the subsurface, and move with flowing ground water. The degradate 5 trifluoromethyl-2-pyridone does not sorb to soil, indicating very high mobility. A minor degradate is 2-(4-hydroxyphenyl)-5-trifluromethylpyridine. There are no data on its mobility, but it is expected to be similar to that of fluazifop acid. ... Water softening, in which the alkalinity is raised to pH 10 or 11 by the addition of lime or soda ash, will rapidly degrade the parent fluazifop-P-butyl to fluazifop acid (page 11-12).
Ref: December 10, 2004. US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf
-- see also: http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0011.pdf

Effects on aquatic organisms: Fluazifop-p-butyl may be highly to moderately toxic to fish, but only slightly toxic to other aquatic species, such as invertebrates. The reported 96-hour LC50 values for the technical product in fish species are 0.53 mg/L in bluegill sunfish and 1.37 mg/L in rainbow trout [5], indicating very high to high toxicity. The 48-hour LC50 in Daphnia magna (an aquatic invertebrate) is reported as greater than 10 mg/L [5], indicating only slight toxicity.
Ref: Fluazifop-p-butyl. E X T O X N E T Pesticide Information Profiles. Revised June 1996.
http://ace.ace.orst.edu/info/extoxnet/pips/fluazifo.htm


 
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