Kidney - Adverse Effects
Fluorinated and Fluoride Pesticides

beginning with
A-E • F-G H-P Q-Z
 
 
See short description and definitions on kidney

The use of high doses increases the likelihood that potentially significant toxic effects will be identified. Findings of adverse effects in any one species do not necessarily indicate such effects might be generated in humans. From a conservative risk assessment perspective however, adverse findings in animal species are assumed to represent potential effects in humans, unless convincing evidence of species specificity is available.

-- Food and Agricultural Organization of the United Nations

Note: This is not an exhaustive list.
When time allows more information will be added.

Fipronil - Acaricide, Insecticide - CAS No. 120068-37-3

An acceptable chronic rat feeding study identified the following effects: seizures, including seizures resulting in death, decreased body weight gain, decreased food consumption and food conversion efficiency, decreased hematology measures, alterations in clinical chemistry (cholesterol, calcium, and protein), alterations in thyroid hormones, alterations in urine chemistry, changes on gross necropsy, increase in liver and thyroid weights, and progressive senile nephropathy (kidney effects). The NOEL for systemic toxicity was 0.5 ppm.
Ref: US EPA Pesticide Fact Sheet. May 1996.
http://www.fluoridealert.org/pesticides/fipronil.epa.facts.may.1996.htm

--2 year dietary study in rats. The carcinogenic potential of fipronil was determined in a 2-year study carried out in the rat (CD strain). Animals (50/sex/dose) received dietary administration of fipronil (batch number PGS, 95.4% purity) at either 0.5, 1.5, 30 or 300 ppm; equivalent to 0.02, 0.06, 1.3 and 13 mg/kg/d (males) and 0.03, 0.08, 1.6 and 17 mg/kg/d (females). (page 89)
-- At study termination histopathological findings were confined to a statistically signifiicant increase in progressive senile nephropathy in males and thyroid "follicular cysts" (growth anomaly) at ≤30 ppm in females. (page 91)

Ref: April 204. Evaluation on : Fipronil (Horticultural Uses). No. 212. UK Dept. for Environment, Food and Rural Affairs, Pesticides Safety Directory.
http://www.fluorideaction.org/pesticides/fipronil.uk.report.apr.2004.pdf

Flazasulfuron - Herbicide - CAS No. 104040-78-0

• Long term toxicity and carcinogenicity . Target / critical effect: Liver (centrolobulillar hypertrophy) in mice and kidney (chronic nephropathy) in rats. Lowest relevant NOAEL: 1.3mg/kg bw/day: 2-years rats. No evidence for carcinogenic potential.

Flonicamid - Insecticide - CAS No. 158062-67-0

-- Reproductive and developmental toxicity. A developmental toxicity study in rats resulted in the maternal and developmental no observed adverse effect levels (NOAELs) of 100 mg/kg/day. The maternal lowest observed adverse effect level (LOAEL) was 500 mg/kg/day based on the treatment-related effects observed on the liver and kidney of the dams in the highest dose group...
-- In the multi-generation rat reproduction study, the NOAEL was 300 ppm for both parental animals (13.5-32.8 and 16.3-67.0 mg/kg/day, respectively, for males and females) and their offspring. The effects at the highest dose of 1,800 ppm included the following: increased kidney weights and gross and histopathological alterations in the kidney...
-- In a 90-day rat feeding study the NOAEL was established at 200 ppm (12.11 mg/kg/day) for males and 1,000 ppm (72.3 mg/kg/day) for females. The NOAELs were based on effects on hematology, triglycerides, and pathology in the liver and kidney.
-- In a 13-week mouse study, the NOAEL was 100 ppm (15.25 mg/kg/day in males and 20.1 mg/kg/day in females). The LOAEL is 1,000 ppm (153.9 mg/kg/day in males and 191.5 mg/kg/day in females) based on hematology effects and changes in glucose, creatinine, bilirubin, sodium, chloride and potassium levels, increased liver and spleen weights and histopathology findings in the bone marrow, spleen and kidney.
-- In a rat 24-month combined chronic and oncogenicity study, flonicamid technical was not carcinogenic in rats. The NOAEL was 200 ppm (7.32 mg/kg/day) for males and 1,000 ppm (44.1 mg/kg/day) for females. The LOAEL was 1,000 ppm for males and 5,000 ppm for females based on histopathology in the kidney, hematology effects, hepatic effects including changes in biochemical parameters, increased organ weights, and histopathological changes. Atrophy of striated muscle fibers, cataract and retinal atrophy observed in the high dose females were considered to be due to acceleration of spontaneous age-related lesions.
Ref: Federal Register: May 23, 2003 (Volume 68, Number 100)] [Notices] [Page 28218-28222]. Flonicamid; Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food.
http://www.fluorideaction.org/pesticides/flonicamid.fr.may23.2003.htm

-- 90-Day oral toxicity rodents (rats). 28-day range-finding. NOAEL is 100 ppm (7.47 mg/kg/day) for males and 1,000 ppm (81.9 mg/kg/day) for females.
LOAELs were 500 ppm (36.45 mg/kg/day) for males based on changes in the kidney (hyaline deposition) and 5,000 ppm for females (372.6mg/kg/day) based on kidney (hyaline deposition), liver changes (centrilobularhypertrophy), hematological effects (anemia) and clinical chemistry (increased cholesterol)
-- 90-Day oral toxicity (nonrodents- dogs). NOAEL is 8 mg/kg/day in males and 20 mg/kg/day for female. LOAEL is 20 mg/kg/day in males and 50 mg/kg/day in females, based on acute clinical signs in males and females (vomiting, first observed on Day 1 and last observed on Day 90), clinical pathology at 7 weeks (increased total protein levels in males, lower red blood cells and higher reticulocytes counts in females), increased adrenal weights in males, decreased thymus gland weights in males, and increased kidney tubular vacuolation in females at study termination
--
Prenatal developmental toxicity (rats). Maternal. NOAEL is 100 mg/kg bw/day. LOAEL is 500 mg/kg bw/day, based on increased liver weight, and liver and kidney pathological changes (hypertrophy of centrilobular hepatocytes in liver and vacuolation of proximal tubular cell in kidneys)
-- Chronic dietary. 2-Generation Reproduction rat. Parental LOAEL = 22 mg/kg/day based on increased kidney weights, kidney hyaline deposition, increased blood serum LH (F1 females).
Ref: August 31, 2005. Flonicamid; Pesticide Tolerance. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/
flonicamid.fr.aug.31.2005.html

Floransulam - Herbicide - CAS No. 145701-23-1

-- Short term toxicity. Target / critical effect: Anemia, hepatotoxicity , renal hypertrophy epithelial cells, collecting ducts, adrenal vacuolation(dog ) Lowest relevant oral NOAEL / NOEL: 1 y & 90 d dog (oral feed) ; 5 mg/kg bw/d;...
-- Long term toxicity and carcinogenicity. Target / critical effect: kidney collecting duct hypertrophy, papillary mineralisation, necrosis and inflammation (rat and/or mice) Lowest relevant NOAEL: 2 yr rat (oral feed): 10 mg/kg bw/d. no carcinogenic potential. Other toxicological studies Renal cells affected are probably Type A intercalated cells, involved in acid-base regulation.
Ref: September 18, 2002 - Review report for the active substance florasulam. European Commission Health & Consumer Protection Directorate-General.

http://www.fluoridealert.org/pesticides/florasulam.eu.sept.2002.pdf

-- In the rat 90-d dietary study, other histopathological findings in the kidney included degeneration with regeneration in the descending portion of the proximal tubules (females at 500 mg/kg bw/d and above) which was considered to be typical of acute necrosis with regeneration rather than a 90-d old lesion and multi-focal mineralization in the papilla (females at 800 mg/kg bw/d). These lesions did not appear to be reversible. In the rat 2- year dietary study, other histopathological findings in the kidneys included a possible slight decreased incidence of age-related tubular degeneration/regeneration and a decreased severity of spontaneous geriatric renal degeneration (chronic progressive glomerularnephropathy) in males at 250 mg/kg bw/d and above, slight decreased incidence of spontaneous geriatric renal disease in females at 250 mg/kg bw/d and minimal reactive hyperplasia of the transitional epithelium and unilateral necrosis of the papilla in males at 500 mg/kg bw/d. The high-dose males also exhibited decreased proteinuria, which was considered to represent less severe chronic renal disease although the decreased specific gravity suggest that dilution may have also contributed to lower values. Body weight and body-weight gain were significantly lower in males at 1000 mg/kg bw/d and in females at 500 mg/kg bw/d and above in the 90-d dietary study and in males at 500 mg/kg bw/d (highest dose tested [HDT]) and in females at 250 mg/kg bw/d (HDT) in the 2-year dietary study. This was associated with concomitant lower food consumption in the high-dose animals in the both 90-d and 2-year dietary study.
-- The subchronic and chronic toxicity of florasulam was investigated in the mouse, rat and dog. A 28-d repeat dose dermal toxicity study was also carried out in rats. In the subchronic and chronic studies, treatment-related findings were observed in the kidney in all species and in the liver and adrenal glands in dogs. In the kidney, hypertrophy of the epithelial
cells of the collecting ducts occurred in all species tested.
-- In subchronic and chronic dietary studies, treatment-related findings were observed in the kidneys in mice, rats and dogs and in the liver and adrenal glands in the dog
. In the kidney, hypertrophy of the epithelial cells of the collecting duct was observed in all species tested. In rats, hypertrophy of the epithelial cells correlated with elevated serum bicarbonate levels, urinary acidification, decreased urinary specific gravity and increased kidney weights. In dogs, treatment-related findings associated with the liver included increased ALP activity, decreased serum albumin and protein levels, increased liver weights and increased incidence or severity of hepatic vacuolation. Dogs also exhibited slight vacuolization of the zona reticularis and zona fasciculata in the adrenal glands; however, in the absence of any associated inflammation, necrosis or other changes, the toxicological significance was uncertain. The most appropriate NOAEL for subchronic and chronic toxicity end points is 5.0 mg/kg bw/d in the 90-d and 1-year dietary studies in dogs. At the LOAEL, 50 mg/kg bw/d, treatment-related findings were observed in the kidneys and liver in the 90-d and 1-year dietary studies and in the adrenal glands in the 1-year dietary study.
Ref: Florasulam EF-1343 Suspension Concentrate Herbicide. REF2001-12. September 21, 2001. Canadian Pest Management Regulatory Agency. Health Canada.

http://www.hc-sc.gc.ca/pmra-arla/english/pdf/reg/reg2001-12-e.pdf

Fluazifop-butyl - Herbicide - CAS No. 69806-50-4

-- Fluazifop-butyl (CAS # 69806-50-4) was evaluated for subchronic dietary toxicity in Wistar rats (20/sex/group) receiving 0, 10, 100 and 2000 ppm by dietary inclusion for 13 weeks. Mean achieved dosages during 13-week treatment were 0, 0.7, 7.1 and 144.5 mg/kg/day in males of the respective treatment groups and 0, 0.8, 8.0 and 161.9 mg/kg/day in females... Upon terminal necropsy, only high-dose males had evidence of hepatic enlargement or swelling (7/20), although higher absolute and relative liver weights were significant (p < 0.01, Student's t-test) in both males and females of the 2000 ppm group. Also, relative kidney weights were also significantly elevated in the high-dose males. Histopathology confirmed a specific liver toxicity in male rats, marked by significant dose-related hepatocytic hypertrophy with isolated instances of vesicular nuclei and or periacinal hepatocytic necrosis. Renal tubular degeneration, 70% and 20% in 2000 and 100 ppm males respectively, correlated with elevated kidney weights in these groups. [ICI AMERICAS INC; 13 Week Dietary Toxicity Study with PP009 in Rats (Final Report); 05/29/80; EPA Doc No. 88-920006943; Fiche No. OTS0545346]
-- Fluazifop butyl was evaluated for reproductive and developmental effects in 2 successive generations of Charles River Wistar strain rats (30/sex/group) exposed continuously to 0, 10, 80 and 250 ppm in the diet. Each respective parent generation had received treatment for a minimum of 100 days (F0) and 120 days (F1) prior to mating. F0 and F1 dams weaned their progeny for 25 days postpartum to time of offspring selection for mating and continued study (F1) or sacrifice (F1, F2). Thirty days after sacrifice of their offspring, the surviving F1 females and select F1 males were sacrificed and with representative F1 and F2 offspring were examined histologically... F1 parents were found with gross indications of toxicity. Liver
and kidney weights were significantly high (250 ppm) relative to controls, while spleen weights were low in both sexes (80, 250 ppm).Upon necropsy, these F1 progeny were found with dose-related increased hydronephrosis [kidney]... Upon histological investigation, increased incidence geriatric nephropathy [kidney] (both sexes, 80 and 250 ppm), distension of mesenteric and/or cervical lymph nodes (250 ppm) and increased severity of nephrocalcinosis (females, 80 and 250 ppm), .. [ICI AMERS INC; Fluazifop butyl: Effects Upon Reproductive Performance of Rats Treated Continuously Through 2 Generations (Final Report); 03/17/81; EPA Doc No. 88-920006849; Fiche No. OTS05543854]
--- Definition for nephrocalcinosis
: A form of renal stone disease where the kidney tissue is characterised by foci of calcification in addition to numerous deposits of calcium phosphate and calcium oxalate.
Ref: TOXNET profile from Hazardous Substances Data Bank for FLUAZIFOP-BUTYL.
http://www.fluoridealert.org/pesticides/fluazifop-butyl.toxnet.hsdb.htm

Fluazifop-P-butyl - Herbicide - CAS No. 79241-46-6

... 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

Flucythrinate - Acaricide, Insecticide - CAS No. 70124-77-5

-- Groups of 50 male and 50 female CD (Sprague-Dawley derived) rats received technical flucythrinate (80% pure) in the diet at 0, 30, 60 or 120 ppm daily for 24 months... Absolute and relative kidney weights were significantly elevated in mid- and high- dose males while only the relative kidney weight was elevated in high- dose females.... (Brewer et al., 1981).
-- Groups of 6 male and 6 female Beagle dogs received technical flucythrinate (87.3% pure) in the diet at 0, 30, 100, or 300 ppm daily for 24 months... At sacrifice, the relative liver, kidney, and pituitary weights were increased in both high-dose males and females, while increases in relative spleen, testis and lung weights were noted for high-dose males only... ((Spicer et al., 1984).
Ref: 1985 World Health Organization Review for Flucythrinate.

http://www.fluoridealert.org/pesticides/flucythrinate.1985.who.htm

Fludioxonil - Fungicide - CAS No. 131341-86-1

Fludioxonil safety. a. Ciba has submitted over 25 separate toxicology studies in support of tolerances for fludioxonil. According to Ciba, fludioxonil has a low order of acute toxicity by the oral, dermal, and inhalation exposure routes. The compound is slightly irritating to the eye, non-irritating to skin, and is not a dermal sensitizer. It is not a teratogen and does not affect reproduction or fertility. The kidney and liver have been identified as target organs in subchronic and chronic toxicity studies. No mutagenic activity has been seen in vivo.
Ref: Federal Register. February 5, 1997. [PF-695; FRL-5584-1]

http://www.fluoridealert.org/pesticides/f
ludioxonil.fr.feb.5.1997.htm

A combined chronic toxicity/carcinogenicity study in rats fed 0, 10, 30, 100, 1,000 and 3,000 ppm for either 12 or 24 months (males: 0, 0.37, 1.1, 3.7, 37 and 113 mg/kg/day, respectively; females: 0, 0.44, 1.3, 4.4, 44 and 141 mg/kg/day respectively)... At necropsy, [[Page 56078]] males at the 3,000 ppm dose level exhibited an increased incidence of enlarged livers, and kidneys with discolored foci or general discoloration and an increased severity of progressive nephropathy; kidneys with cysts were reported at both the 1,000 and 3,000 ppm dose levels. For females in the 1,000 and 3,000 ppm dose levels there was an increase incidence of general discoloration of the the kidneys.
Ref: Federal Register.October 29, 1997. 4-(2,2-difluoro-1,3-benzodioxol-4-yl)-1H-pyrrole-3-carbonitrile; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/fludioxonil.fr.oct.29.1997.htm

-- 13 Week Oral Feeding Study - rat. Systemic. NOAEL= 64 mg/kg/day. LOAEL = 428 mg/kg/day based on decreased body weight gain in both sexes, chronic nephropathy in males, and centrilobular hepatocyte hypertrophy in females.
Ref: Federal Register: September 12, 2001. Fludioxonil; Pesticide Tolerances for Emergency Exemptions. Final Rule.

http://www.fluoridealert.org/pesticides/fludioxonil.fr.sept.12.2001.htm

Flufenacet - Herbicide - CAS No. 142459-58-3

NOEL = 40 ppm [1.29 mg/kg/day in males and 1.14 mg/kg/day in females] LOEL = 800 ppm [27.75 mg/kg/day in males and 26.82 mg/kg/day in females] based on increased alkaline phosphatase, kidney, and liver weight in both sexes, increased cholesterol in males, decreased T3, T4 and ALT values in both sexes, and increased incidence of microscopic lesions in the brain [axonal degeneration], eye [vacuolization of the ciliary body epithelium], kidney [hyperplasia of the epithelial cells], spinal cord [axonal degeneration], sciatic nerve [axonal degeneration] and liver [hepatocytomegaly].
Ref: EPA Pesticide Fact Sheet, April 1998

http://www.epa.gov/opprd001/factsheets/flufenacet.pdf

Flufenoxuron - Acaricide, Insecticide, Herbicide - CAS No. 101463-69-8

Abstract: Flufenoxuron (Benzoylphenyl urea derivative) - antimoulting insecticide is recently used for controlling insect reproduction in cultivated areas. The study determined the hazardous effects of the applied dose-treatment during the critical period of rat embryonic development and the induction of growth retardation. In the present work, flufenoxuron was intragastrically administered by stomach intubation to pregnant rats at concentration levels 0 & 20 mg/kg b.wt. in saline solution every other day on gestation day 7 till parturition. Experimental and control pregnant rats were sacrificed on days 13 & 16 of gestation and the foetuses were fixed in 10 percent formol saline. Histological abnormalities of thyroid, liver and kidneys of mothers as well as of skeletal axial and appendicular regions of foetuses were investigated. Foetuses maternally treated with flufenoxuron exhibited delayed differentiation of chondrification and ossification of axial and appendicular regions. The observed defects in foetuses may be attributed to the histological abnormalities of thyroid, liver and kidneys of maternal tissues as well as to the direct effect of the parents as a result of the insecticide or its metabolites on the affected structures during early morphogenesis and differentiation.
Ref: J. Egypt. Ger. Soc. Zool., Vol. 25(B), 65-81, 1998.
PATTERNS OF DEVELOPMENTAL DEFECTS OF RAT FOETUSES MATERNALLY TREATED WITH AN ENVIRONMENTAL ANTIMOULTING INSECTICIDE FLUFENOXURON; by Karim, S.A. http://www.egsz.org/BiologicalCurrentContent/Zoology/Comparative%20Physiology/TOXICOLOGY.htm

Flufenpyr-ethyl - Herbicide - CAS No. 188489-07-8

-- The kidney and liver appear to be the target organs of flufenpyr-ethyl. EPA has not had the opportunity to review the toxicity studies on flufenpyr-ethyl and has not established toxic endpoints.
-- Reproduction. In the rat reproduction study, flufenpyr-ethyl technical was administered in the diet at levels of 0, 200, 2,000, and 20,000 ppm for 2-generations. Parental toxicity was observed at all dose levels, although the effects at the low dose were minimal. Parental toxicity was exhibited by dose-related microscopic changes in the kidney in high dose F0 animals, in all treated F1 males, and in high dose F1 females. There were also 2 high dose F1 males that died possibly as a result of treatment...
-- A second 1-generation reproduction study was performed to establish a clear NOAEL for adult kidney lesions using the dose levels of 20, 50 and 100 ppm. The results of the study indicate that the NOAEL for histological changes in the kidneys of F1 male rats was 100 ppm. No other treatment related findings were noted at any dose level indicating 100 ppm as the NOAEL for treatment and reproductive effects evaluated in the study.
-- A mechanistic study was also conducted to investigate the reproducibility and reversibility of the kidney lesions observed in the initial 2-generation reproduction study. In the first study, the effects observed at 200 ppm in the F1 males, basophilic tubules and interstitial inflamation, were minimal but slightly increased in incidence and severity and a slight increase in interstitial fibrosis of the cortex was also observed. In this mechanistic study, using dose levels of 0 and 2,000 ppm, the NOAEL for histological changes in the kidneys of F0 and F1 male rats and reproductive effects was 2,000 ppm. The histological changes seen in the kidneys in the original study was not reproducible.
-- Subchronic toxicity. Subchronic oral toxicity studies conducted with flufenpyr-ethyl in the rat, mouse and dog indicate a low level of toxicity. i. Rats. Pure (99.4%) flufenpyr-ethyl was tested in rats at dose levels of 0, 600, 2,000, 6,000, and 20,000 ppm in the diet for 13 weeks. Effects observed included urinary incontinence, increased food and water consumption, slight hematological and blood biochemistry changes, decreased spleen weights, an increase in the incidence and severity of basophilic tubules of the kidneys and slight to mild diffusely distributed vacuolation in the liver. Based on these results, the NOAEL was 2,000 ppm (134.2 mg/kg/day) for the males and 20,000 ppm (1,509.6 mg/kg/day) for the females.
-- Mice. In a 78-week oncogenicity study with mice, flufenpyr- ethyl technical was administered at dose levels of 0, 350, 3,500, and 7,000 ppm. Male animals exhibited slight anemia. Females had increased liver and kidney weights (week 53 only). Slight to moderate hepatocellular fatty vacuolation and necrosis were observed. There were no increases in incidence of pre-neoplastic or neoplastic lesions. Based on these results, the NOAEL was 350 ppm for both sexes (39.9 mg/ kg/day for males and 43.7 mg/kg/day for females).
Ref: Federal Register: June 25, 2003 (Volume 68, Number 122)] [Notices] [Page 37813-37820]. Flufenpyr-ethyl; Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food.
http://www.fluorideaction.org/pesticides/flufenpyr-ethyl.fr.june.03.htm

Flumetsulam - Herbicide - CAS No. 98967-40-9

-- 90-Day oral toxicity, Rat - NOAEL (M/F) 250 mg/kg/day. LOAEL (M/F) 1000 mg/kg/day based on severe bilateral tubular-interstitial nephritis.
-- -- The kidney appears to be the primary target organ of rats and dogs following subchronic to chronic exposures.
Ref: August 31, 2004: Flumetsulam: HED Risk Assessment for the Tolerance Reassessment Eligibility Document (TRED).

Chronic toxicity. In a 1-year dietary study in dogs, the NOEL was 100 mg/kg/day and the LOEL was 500 mg/kg/day. The animals were administered feed containing 0, 20, 100, and 500 mg/kg/day. Reduced body weights and inflammatory and atrophic changes in the kidneys occurred in the 500 mg/kg/day dose groups. In a combined feeding carcinogenicity/chronic study in mice there were no treatment-related effects and there was no evidence of a carcinogenic response. Systemic NOEL was greater than or equal to 1,000 mg/kg/day (limit dose); a LOEL was not established. In a combined feeding carcinogenicity/chronic study in rats, renal pathological alterations were seen in males. No treatment-related effects were seen in females at the highest dose (1,000 mg/kg/day) which is the limit dose. There was no carcinogenic response. The NOELs were 500 mg/kg/day in males and 1,000mg/kg/day in females. The LOEL was 1,000 mg/kg/day in males; a LOEL was not established in females. Based on the chronic toxicity data, EPA has established the RfD for flumetsulam at 1.0 milligram (mg)/kilogram (kg)/day. The RfD for flumetsulam is based on the 1-year chronic study in dogs with a NOEL of 100 mg/kg/day and an uncertainty (or safety) factor of 100. Thus, it would not be necessary to require the application of an additional uncertainty factor above the 100-fold factor already applied to the NOEL.
Ref: Federal Register: September 17, 1997 [Notices] [Page 48842-48848]. Notice of Filing of Pesticide Petitions.

http://www.fluoridealert.org/pesticides/f
lumetsulam.fr.sept.17.1997.htm

Flumiclorac-pentyl - Herbicide - CAS No. 87546-18-7

In the rat, the kidney is a potential target organ at high dose levels. Effects included urinary incontinence, increased water consumption, increased urine volume, and increased kidney weights in the females, and increased squamous epithelial cells in urinary sediment and increased kidney weights in the males. Nephropathy was evident in male rats in a two-generation reproduction study following administration of high dose levels.
Reference: June 28, 2005. US EPA. Health Effects Division Chapter of the Tolerance Reassessment Eligibility Decision Document (TRED).
http://www.fluorideaction.org/pesticides/flumiclorac-p.opp-2005-0229-0003.pdf

-- Chronic Toxicity (Including Cancer): Studies with Flumiclorac Pentyl Technical indicate that repeated high exposures produced changes in liver, kidney, and red blood cells but did not produce cancer in test animals.
-- Potentially Aggravated Condition: Individuals with preexisting diseases of the liver,
kidney, or red blood cells may have increased susceptibility to the toxicity of excessive exposures.
-- SUBCHRONIC: Compound-related effects noted at very high dose levels of Flumiclorac Pentyl Technical in rodents and/or dogs included: increased liver and kidney weights; histological changes in the kidney and liver; slight changes in blood biochemistry parameters; decreased red blood cell count, hemoglobin, and hematocrit; and slight decreases in body weight. The NOEL in rats and mice was 1000 ppm.
-- CHRONIC/CARCINOGENICITY: Effects of long-term high dose exposures to Flumiclorac Pentyl Technical in rodents and/or dogs consisted primarily of increases in kidney and liver weights, slight changes in blood biochemistry, and histological changes in the liver. The lowest NOEL was 300 ppm in the mouse study. Flumiclorac Pentyl Technical was not carcinogenic in either rats or mice.
Ref: Material Safety Data Sheet for RESOURCE TM Herbicide.
http://www.fluoridealert.org/pesticides/flumiclorac-pentyl.msds.htm

Flumioxazin - Herbicide - CAS No. 103361-09-7

-- Combined chronic carcinogenicity - rat: NOAEL = mg/kg/day: males = 1.8, females = 2.2 LOAEL = mg/kg/day: males = 18.0, females = 21.8 based on increased chronic nephropathy [kidney] in males and decreased hematological parameters in females (Hgb, MCV, MCH and MCHC) No evidence of carcinogenicity
Ref: Federal Register: April 18, 2001. Flumioxazin; Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/flumioxazin.fr.apr.18.2001.htm

-- Rats. A 90-day subchronic toxicity study was conducted in rats, with dietary intake levels of 0, 30, 300, 1,000 and 3,000 ppm flumioxazin technical (98.4% purity). The NOAEL of 300 ppm was based on decreased bwts; anemia; increases in absolute and/or relative liver, kidney, brain, heart, and thyroid weights, and histological changes in the spleen, liver, and bone marrow related to the anemia.
-- A second 90-day subchronic toxicity study was conducted with a sample of flumioxazin technical of typical purity (94.8%) at dietary concentrations of 0, 30, 300, 1,000, and 3,000 ppm. The NOAEL was 30 ppm based on anemia and related hematological changes; increases in liver, heart, kidney, and thyroid weights; and histological changes in the spleen, liver, and bone marrow related to the anemia.
Ref: Federal Register: February 14, 2001 [Notices] [Page 10292-10301]. Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food.
http://www.fluoridealert.org/pesticides/flumioxazin.fr.feb.14.2001.htm

Fluometuron - Herbicide - CAS No. 2164-17-2

• The spleen, kidney, and liver appear to be the organs consistently affected following exposure to moderate doses of fluometuron in rats and dogs in subchronic, chronic, developmental, and reproductive studies. (page 8)
• 3. Dermal Exposure. Short-Term (1-30 days) However, the developmental rat study (MRID 00163710) can be used for the short-term dermal exposure based on the developmental NOAEL of 10 mg/kg/day and LOAEL of 100 mg/kg/day, based on delayed urinary system development (shortened renal papillae). This effect can be assumed to have occurred during the dosing period but delayed until later in development. This provides a conservative endpoint for short-term exposure.
• 4. Inhalation Exposure (All Durations). A. Short -Term (1-30 Days) The developmental rat study (MRID 00 163710) encompasses the appropriate exposure duration (gestation days 6-15) with developmental NOAEL of 10 mg/kg/day and LOAEL of 100 mg/kg/day, based on delayed urinary system development (shortened renal papillae). This study is also supported by the developmental rabbit study (MRID 00147554) in which the maternal NOAEL was also 10 mg/kg/day and LOAEL 100 mg/kg/day, based on increased incidence of stool variations, increased incidence of abortions, reduced food consumption and decreased maternal body weight gain.
• Developmental Toxicity, Rat (83-3a) MRID: 00163710,42397601 CITATION: T. Arthur. 1986. A teratoiogy study of fluometuron technical in the albino rat. Study Number MI# 832125; Tox and Path. Report No. 199-84. Reproductive and Genetic Toxicology Subdivision Ciba Geigy Corporation, Summit, NJ 07901. In a developmental study (MRID 00163710,32397601) fluometuron (95.2% ai, batch # FL 821838) was administered to 27 female Cr1:COB CD BR rats/dose by gavage at dose levels of 0, 10, 100, or 1000 mg/kg/day (dosage volume 10 ml/kg/day was adjusted daily for each rats body weight) from gestation days 6 through 15, inclusive. A dose-related decrease in fetal weights were observed only in the high-dose group (58% M, 57% F). No gross observable malformations were observed in any of the 857 fetuses examined. The fetal M/F sex ratios were comparable among the groups. A significant increase in the incidence of shortened or absent renal papillae was observed in the mid-dose (shortened: 9/82 control, 23/83 high; absent: 3/82 control, 2/83 high) compared to control. It should be noted that a statistical analysis was not performed on the high-dose-due to growth retardations, and reduced fetal weights. Significant fetal skeletal variations were observed only in the high-dose group and included incomplete ossification and widened sutures of the skull, wavy ribs, and bipartite and fused sternebrae, unossified teeth, vertebral centra, ischium/Os pubis, metatarsal and the distal phalanges of the fore-and hind-paws. (pages 51-52).
Ref. February 1, 2005. US EPA: Fluometuron: Revised HED Risk Assessment for Phase III of the Reregistration Eligibility Decision. Docket Identification Number: OPP-2004-0372-0008. 
http://www.fluorideaction.org/pesticides/fluometuron.opp-2004-0372-0008.pdf

-- Organ Toxicity. Toxic injury to the liver, kidneys, gut and brain is induced when lethal doses of fluometuron are administered experimentally (10). An increase in spleen weight and in the incidence of abnormalities in red-blood cells, and decreased weight gain in females were observed in a 90-day study of rats (18).
-- CHRONIC TOXICITY. Rats were fed 7.5, 75, or 750 mg/kg/day for 90 days. At the 750 mg/kg dose, decreased body weight and congestion in the spleen, adrenals, liver, and
kidneys were evident. The NOAEL for this study was 7.5 mg/kg/day (100 ppm). When doses of 1.5, 15 or 150 mg/kg/day were fed to puppies for 90 days, congestion of the liver, kidneys and spleen occurred at the 150 mg/kg dose. No effects were seen at 15 mg/kg/day (400 ppm) (20).
Ref: Flumeturon. EXTOXNET. Pesticide Information Profile. March 1994.

http://pmep.cce.cornell.edu/profiles/extoxnet/dienochlor-glyphosate/fluometuron-ext.html

-- PubMed abstract: Twelve of fifteen 6-9-mo-old clinically healthy Desert sheep were given single or repeated daily doses of 25 to 4000 mg cotoran/kg by drench. Cotoran poisoning was characterized by grinding of the teeth, ruminal tympany, mydriasis, dyspnea, staggering, paresis of the hind and forelimbs, and recumbency. Lesions were widespread congestion and hemorrhage, hepatic fatty change, catarrhal enteritis and degeneration of the epithelial cells of the renal proximal convoluted tubules. These were accompanied by significant increases in the activities of GOT, LDH and GGT and decreases in serum total protein and calcium.
Ref: Vet Hum Toxicol 1995 Jun;37(3):214-6.
Toxicity of cotoran (fluometuron) in Desert sheep; by Mohamed OS, Ahmed KE, Adam SE, Idris OF.

Fluopicolide - Fungicide - CAS No. 239110-15-7

Chronic toxicity (page 4)
ii. Chronic toxicity/carcinogenicity was assessed in rats at dietary levels of 50, 200, 750 and 2500 ppm. The NOAEL was 200 ppm (8.4 mg/kg/day in males and 10.8 mg/kg/day in females) based on microscopic changes in the liver and kidneys similar to those observed in the 90-day rat study. No evidence of carcinogenicity was observed in rats up to 2500 ppm.

Subchronic toxicity (pages 3-4)
Ninety-day feeding studies were conducted in dogs, mice and rats.
iii. In a 90-day rat study with dietary levels of 100, 1400 and 20,000 ppm, the maximum tolerated dose (MTD) was exceeded at 20,000 ppm based on body weight gain of 30 to 40% below control. The target organs identified in rats were the liver (centrilobular hypertrophy) in both sexes and the kidneys in males (accumulation of hyaline droplets, single cell death at the proximal tubule epithelium, slight foci of basophilic tubules and granular casts) at 1400 ppm and 20,000 ppm. The NOAEL was 100 ppm, equivalent to 7.4 and 8.4 mg/kg/day, in males and females, respectively.

Reference: January 1, 2005, submission to US EPA from Valent U.S.A. Company. Federal Register Docket EPA-HQ-OPP-2006-0481-0002.
http://www.fluorideaction.org/pesticides/fluocopicolide.valent.june.2005.pdf

Fluoroacetamine - Rodenticide, Insecticide - CAS No. 640-19-7
(also known as Fluoroacetamide or Compound 1081)

Sodium fluoroacetate and fluoroacetamide are readily absorbed by the gut, but only to a limited extent across skin. The toxic mechanism is distinct from that of fluoride salts. Three molecules of fluoroacetate or fluoroacetamide are combined in the liver to form a molecule of fluorocitrate, which poisons critical enzymes of the tricarboxylic acid (Krebs) cycle, blocking cellular respiration. The heart, brain, and kidneys are the organs most prominently affected... Crimidine and sodium fluoroacetate are no longer registered for use as pesticides.
Ref: US EPA.
http://www.epa.gov/oppfead1/safety/healthcare/handbook/Chap17.pdf

Fluoroacetic Acid - Rodenticide - CAS No. 144-49-0

IN RATS, MITOCHONDRIA FROM KIDNEY CORTEX ACTIVELY PRODUCED FLUOROCITRATE MORE THAN 700% ABOVE CONTROL. 2 PATHWAYS OF FLUOROCITRATE ACTIVATION IDENTIFIED. 1 ASSOC WITH PYRUVATE METAB & NOT DEPENDENT ON OXIDATIVE PHOSPHORYLATION ENERGY; 2ND ASSOC WITH ACETATE METAB & IS ATP DEPENDENT.
[BUFFA P ET AL; FLUORIDE 12 (3): 114 (1979)]
Ref: TOXNET profile from Hazardous Substances Data Bank.

http://www.fluoridealert.org/pesticides/fluoroacetic.acid.toxnet.htm

Fluoroglycofen-ethyl - Herbicide - CAS No. 77501-90-7

--In the mouse 1 and 3 month study, the rat 1 month study and the dog 52 week study, reductions in haemoglobin levels, red blood cell numbers and packed cell volume were variously seen, predominantly at the top doses. Nucleated and polychromatic red blood cell numbers were raised in the rat study only. These effects appeared reversible, in both the 1 month rat and mouse studies. It would appear that any potential haemolytic effects, possibly from aniline-derivatives, are of secondary importance to other subchronic effects. In dogs there were initial decreases in body weight and food consumption, which returned to normal with time, and increased liver and kidney weights. There was a brown pigment of unknown aetiology in the renal cortical tubule epithelial cells, which was PAS and iron-negative.
-- The chronic toxicity and oncongenicity of fluoroglycofen-ethyl was investigated in mice (2 studies) and rats. In both species, the systemic toxicity was much the same as had been seen in the sub-acute studies, the main effects being on the liver and kidneys... In the rat study, brown pigment was observed in the renal tubular cells from week 14 to termination in the high dose group. A decrease in packed cell volume, haemoglobin and red cell counts were also seen at the top dose.
-- A satellite group which was treated for 14 weeks and then given a 13 week recovery period showed that the compound related effects were at least partially reversible. The NOEL for chronic oral exposure to fluoroglycofen-ethyl was 0.95 mg/kg bw/da (20 ppm) based on the hepatic and renal effects at 100 ppm.
Ref: Evaluation on: Fluoroglycofen-ethyl. May 1992. Issue No. 50. Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, UK.
http://www.pesticides.gov.uk/citizen/evaluations/050_confirm-box.htm

Fluoxastrobin - Fungicide - CAS No. 361377-29-9

• 90-Day oral toxicity-rats. reduced body weight gain and food intake, vacuolation in the zona fasciculate of the adrenal cortex, calculi in the urethra and kidney, and histological lesions in kidney, urinary bladder, and urethra;
• 90-Day oral toxicity-dogs.
dose-related reductions in net body weight gain and food efficiency in addition to toxicity findings in the liver in both sexes (cholestasis) and in kidneys (increased relative weights in females and degeneration of the proximal tubular epithelium in males).
• 90-Day oral toxicity-mice. There was a dose related increase in liver weight in both sexes and in kidney weight in females, in addition to other effects whose toxicological relevance was considered uncertain. Among these effects were increased hepatocellular hypertrophy with cytoplasmic changes in the high-dose males and minimal to moderate kidney tubular hypertrophy in mid- and high-dose females.
90-Day Subchronic Oral Toxicology-Dog. dose-related reductions in net body weight gain and food efficiency; toxicity findings in the liver (cholestasis) in both sexes; and toxicity findings in the kidneys (increased relative weights in females and degeneration of the proximal tubular epithelium in males).
Ref: Federal Register. September 16, 2005. Fluoxastrobin; Pesticide Tolerances. Final Rule.

http://www.fluorideaction.org/pesticides/fluoxastrobin.fr.sept16.05.html

Fluquinconazole - Fungicide - CAS No. 136426-54-5

-- Oral long-term toxicity and carcinogenicity. 2-year dietary study in rats. groups of 50 male and 50 female outbred albino Sprague-Dawley CRL :COBS CD(SD)BR rats were administered fluquinconazole (93.2% purity) in the diet at concentrations of 0 (control), 1, 20 or 100 ppm. Additionally 20 animals/sex/dose designated for the interim-kill received the test compound at concentrations of 0, 1, 5, 10 or 100 ppm for 12 months... At the interim-kill, organ weights showed moderate significant treatment-realted increase in the absolute liver and kidney weights in males and females at the 100 ppm dose level compared with controls. The relative liver and kidney weights were significantly increased in males at the 100 ppm dose level and in females at 10 ppm. A significant increase in the incidence of hyaline droplet deposition in the proximal tubular epithelium occurred in the kidneys of males (15/20 compared with 6/20 controls) at the 100 ppm dose level. Minimal to moderate hypertrophy of centrilobular hepatocytes was observed in the liver of all top dose animals and at the 10 ppm dose level (10/20 males and 3/20 females). In the thyroid, an increase in the follicular epithelial height in both sexes was noted at the 100 ppm dose level. At the terminal-kill, the absoloute and relative liver and kidney weights of males and females were slightly to moderately increased at 100 ppm dose level...
-- Kidney effects were observed in the rat and mouse and consisted of increases in organ weight and histopathological changes including hyaline droplet nephropathy, focal tubular hyperplasia, increases in the incidence of small and large eosinophilic inclusions, and increase in the incidence and severity of chronic progressive nephropathy. There is no conclusive mechanism for the observed kidney effects.

-- Short Term Toxicity. Oral route. Rat. (b)... Groups of 5 male and 5 female outbrd albino Sprague-Dawley Crl:COBS CD(SD)BR rats were each administered fluquinconazole (100% purity) either in the diet at concentrations of 0 (control), 5, 20, 100 and 400 ppm or by gavage dissolved in 1 % aqueous methlcellulose at a dose level of 10 mg/kg bw/day for 28 days. Due to mortalities at the 400 ppm dose level, a supplementary gorups of 5 male and 5 female animals were administered fluquinconazole at a dose level of 200 ppm... Organ weights showed a dose-related increase in the relative liver weight at dose levels of 20 ppm in males (15-44%) and at 100 ppm and 10 mg/kg bw/day dose levels (25-27%). The relative kidney weight was increased in males only (11-21%) compared with controls at dose levels of 20 ppm. Gross examination at necropsy revealed accentuation of the lobular pattern of the liver at dose levels of 5 ppm in females and at 20 ppm in males. Pale kidneys were observed in males at dose levels of 5 ppm... Histopathology showed significant treatment-related centrilobular hepatocyte hypertrophy in males and females at dose levels of 100 ppm. In the kidney, slight to moderate hyaline droplet mephropathy was observed in males at 20 ppm... The liver, thyroid and kidneys were noted to be the target organs of the test compound and significant changes in these organs indicative of significant hepatic enzyme induction were considered to be relevant for risk assessment.
-- Short Term Toxicity. Oral route. Rat. (c). In a 3-month feeding study, groups of 10 male and 10 female outbred albino Spraque-Dawley CRL:COBS CD(SD)BR rats were administered fluquinconazole (>96.2% purity) at concentrations of 0 (controls), 1, 5, 15, or 100 ppm. Additional groups of animals at the 0 (control) and 100 ppm dose levels were kept on an untreated diet for 4 weeks in order to invetigate the regressivity of effects. Blood samples were taken after 6 and 13 weeks of treatment for haematological and clinical chemistry investigations... Slight signs of intoxication were observed after 2 weeks in both sexes at the 100 ppm dose level. The signs included unsteady gait, tremors, hunched posture, and reduced muscle tone. Lower incidence of reduced activity and twitches in males, and muscular fibrillation and ataxia in females were also observed. Body weight gain was significantly reduced (9%) in males only at the 100 ppm dose level compared with controls during the treatment period and transient significantly lower body weights were recorded... Haematology, clinical chemistry and urinalysis parameters showed incidences of statistically significant changes which were considred to be of limited toxicological significance because they were either not dose-related or were reported to be withing the range of historical data. There was an increase in the absolute liver (35%) and adrenal (36.4%) weights in females at the 100 ppm dose level. The relative kidney (14%) and liver (21%) weights in males and the relative kidney (6.9%) and adrenal (30%) weights in females were significantly increased at the 100 ppm dose level. In females, the relative liver weight was increased at dose levels of 15 ppm (14%) and 100 ppm (32%). At the end of the withdrawal period, the relative kidney weight in males and the relative liver weight in females were still siginficantly elevated compared with controls...
Ref: Evaluation on: Fluquinconazole. May 1999. No. 184. Evaluation of Fully Approved or Provisionally Approved Products. Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7 PX, UK. Available online:

http://www.pesticides.gov.uk/citizen/evaluations/evallist.htm

Fluridone - Aquatic Herbicide - CAS No. 59756-60-4

CHRONIC EXPOSURE (Fluridone Technical). The following effects were reported in chronic, teratogenic, and reproductive toxicity studies in laboratory animals where experimental dosage levels and durations of exposure were far in excess of those likely to occur in humans.
-- Chronic Toxicity - Decreased survival in lifetime feeding study. Increased liver enzyme activity, liver weight, liver cell size, and microscopic liver cell changes. Increased kidney weights, and microscopic kidney cell changes.
Increased serum enzyme levels...
Ref: Material Safety Data Sheet for Sonar SRP Herbicide. SePro Corporation.
http://www.fluoridealert.org/pesticides/fluridone.msds.sepro.1994.PDF

-- Three studies were conducted concurrently, using Fischer rats fed the same dietary levels of Fluridone [0, 200, 650, 2000 ppm (0, 8, 25, 81 mg/kg/day)]. The first study was a 1-year feeding study (R-1126) in which 120 animals were divided into four groups of 15 animals/sex/dietary level. The other two studies were reported to be replicate 2-year oncogenic assays (Nos. R-1136 and R-1146), in which 240 animals per assay were divided into four groups of 30 animals/sex/dietary level. These three studies constitute a 2-year study with 75 animals/sex/dietary level of which 15 animals/sex/dietary level were sacrificed at 12 months. Effects observed at 650 ppm included glomerulonephritis, atrophic testes, eye keratitis, decreased body weight and organ weights. [Elanco Products Company, Division of Eli Lilly and Company. 1980a. MRID No. 00103251, 00103305. Available from EPA. Write to FOI, EPA, Washington, DC 20460.]
Ref: US EPA IRIS for Fluridone. 1990.

http://www.fluoridealert.org/pesticides/fluridone.epa.iris.1990.htm

Fluroxypyr - Herbicide - CAS No. 69377-81-7

-- Chronic toxicity. EPA has established the RfD for fluroxypyr at 0.5 mg/kg/day. This RfD is based on histopathological lesions in the kidneys, decreased testes weights, and increased adrenal weights in both sexes observed in a 4-week range-finding feeding study in the dog with a NOAEL of 50 mg/kg/day. An uncertainty factor of 100 was used in calculating the RfD to account for both inter- and intra-species variations.
Ref: Federal Register: September 30, 1998. Fluroxypyr; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/fluroxypyr.fr.sept.30.1998.htm

-- In a range finding feeding study in dogs, dogs at 500 mg/kg/day exhibited ataxia and hind limb weakness as well as decreases in body weight and food consumption. Histopathology showed moderate acute tubular nephrosis and a slight to moderate acute gastroenteritis. Some early signs of acute tubular nephrosis were also seen in both sexes of dogs at 150 mg/kg/day. The NOEL for the study was 50 mg/kg/day, the LOAEL was 150 mg/kg/day based on histopathological lesions in the kidneys, decreased testes weights, and increased adrenal weights in both sexes.
-- In the carcinogenicity study in mice, there were no adverse effects on survival or clinical signs in either sex. There was no apparent treatment-related increase in the incidence of any tumor type in either sex. The LOAEL is 1000 mg/kg/day, based on decreased body weight/gain in males and an increased incidence of kidney lesions in females. The NOEL is 300 mg/kg/day.
-- In a developmental toxicity study in rats, fluroxypyr administration resulted in 8 deaths at the high-dose level, and decreased body-weight gain and food consumption during the dosing period at this dose level also. Clinical signs observed in those dying on test included staining of the skin/fur in the ano-genital area, lethargy, hypothermia, labored breathing, irregular gait, pale appearance. There were no treatment-related effects on gross pathologic alterations or absolute and relative liver and kidney weights at any dose level. The maternal NOEL is 300 mg/kg/day, the LOAEL is 600 mg/kg/day, based on deaths and decreased body-weight gain and food consumption. The developmental toxicity NOEL is 300 mg/kg/day, and the LOAEL is 600 mg/kg/day, based on an increase in two ossification variations (incompletely ossified cervical vertebral transverse processes and pubes).
Ref: US EPA. Pesticide Fact Sheet. Fluroxypyr. Reason for Issuance: Conditional Registration Date Issued: September 30, 1998.
http://www.epa.gov/opprd001/factsheets/fluroxypyr.pdf

870.4300 Carcinogenicity--Rats NOAEL = 100 mg/kg/day. LOAEL = 500 mg/kg/day based on chronic progressive kidney glomerulonephropathy (M&F).(no) evidence of carcinogenicity.
Ref: Federal Register. December 31, 2003. Fluroxypyr; Pesticide Tolerance. Final Rule.
http://www.epa.gov/fedrgstr/EPA-PEST/2003/December/Day-31/p32007.htm

Fluroxypyr 1-methylheptyl ester - Herbicide - CAS No. 81406-37-3

Reproductive toxicity study. In the 2-generation reproductive toxicity study in rats, the maternal (systemic) NOAEL was 100 mg/kg/ day, based on increased kidney weights and kidney histopathology at the LOAEL of 500 mg/kg/day. The developmental (pup) NOAEL was 500 mg/kg/ day, based on decreased body weight at the LOAEL of 1,000 mg/kg/day. The reproductive NOAEL was 1,000 mg/kg/day (HDT).... Chronic dietary all populations: 28-day dog range- finding feeding study LOAEL = 150 mg/kg/day based on histopathological lesions in the kidneys, decreased testes weights, and increased adrenal weights in both sexes...
Ref: Federal Register. September 17, 2001. Fluroxypyr 1-Methylheptyl Ester; Pesticide Tolerances for Emergency Exemptions. Final Rule.
http://www.fluoridealert.org/pesticides/fluroxypyr.fr.sept.17.2001.htm

Metabolite toxicology. Administration of fluroxypyr, as the acid or methylheptyl ester in a variety of toxicological studies, has produced similar effects. The principal response to sufficiently high dosages, whether administered over the short-term or, in some cases, over a lifetime, was nephrosis.
Ref: Federal Register: May 14, 2003 (Volume 68, Number 93)] [Notices] [Page 25883-25888]. Fluroxypyr; Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food
http://www.fluorideaction.org/pesticides/fluroxypyr.fr.may.14.2003.htm

870.4300 Carcinogenicity--Rats NOAEL = 100 mg/kg/day. LOAEL = 500 mg/kg/day based on chronic progressive kidney glomerulonephropathy (M&F).(no) evidence of carcinogenicity.
Ref: Federal Register. December 31, 2003. Fluroxypyr; Pesticide Tolerance. Final Rule.
http://www.epa.gov/fedrgstr/EPA-PEST/2003/December/Day-31/p32007.htm

Flurprimidol - Plant Growth Regulator - CAS No. 56425-91-3

A rat teratology study using doses of 0, 2.5, 10, 45 or 200 mg/kg/day of flurprimidol had a maternal toxicity NOEL of 10 mg/kg/day and a LEL of 45 mg/kg/day based on decreased body weight gain and food consumption. The developmental NOEL was 10 mg/kg/day and the LEL was 45 mg/kg/day based on decreased fetal weight, increased incidence of hydronephrosis, hydroureter and numerous developmental skeletal anomalies.
Ref: US EPA Pesticide Fact Sheet. February 22, 1989.

http://www.fluoridealert.org/pesticides/flurprimidol.epa.facts.1989.htm
• Hydronephrosis: Pathological chronic enlargement of the collecting channels of a kidney, leading to compression and eventual destruction of kidney tissue, and diminishing kidney functionning. http://www.hyperdictionary.com/medical/hydronephrosis

Flurtamone - Herbicide - CAS No. 96525-23-4

-- Long term toxicity and carcinogenicity. Target / critical effect: Liver: hypertrophy, centrilobular hypertrophy. Kidney: increased amyloidosis in mice. Lowest relevant NOAEL: 2.8 mg/kg bw (2 year rat study) Carcinogenicity: No carcinogenic potential
Ref: July3, 2003. Flurtamone. Sanco/10162/2003-Final. Review report for the active substance flurtamone. Finalised in the [EU] Standing Committee on the Food Chain and Animal Health at its meeting on 4 July 2003 in view of the inclusion of flurtamone in Annex I of Directive 91/414/EEC.
http://www.fluorideaction.org/pesticides/flurtamone.eu.july.2003.pdf

Flurtamone: Table 5.27 The incidence and severity of renal amyloidosis in unscheduled deaths [page 104]
Dose
Males
Females
(ppm)
Incidence
Mean grade
Incidence
Mean grade
0
1/10 (10%)
0.6
2/7 (29%)
0.9
30
3/5 (60%)
2.4
1/8 (14%)
0.9
300
3/11 (30%)
1.2
7/13 (54%)
2.0
3500
10/13 (77%)
2.9
7/12 (64%)
2.8
7000
10/13 (77%)
2.8
9/19 (47%)
2.1

-- Two-year dietary study in mice. In a carcinogenicity study, groups CD-1 mice (60/sex/dose) were fed diets containing 0, 30, 300, 3500 and 7000 ppm flurtamone (91.9% purity) for at least 78 weeks... The mean intake of flurtamone for males and females was estimated to be 4.5, 45, 525 and 1050 mg/kg bwday at 30, 300, 3500 and 7000 ppm, respectively. After 78 weeks of treatment, the mortality rate for the 7000 ppm female mice was significantly higher than controls and a significant negative survival trend was found in both sexes. The test laboratory pathologist considered systemic amyloidosis to be the major cause of death (Table 5.34) [page 102]. Gross necropsy revealed an increased incidence of enlarged livers and liver masses at dose levels 3500 and of irregular shaped kidneys at 7000 ppm. Significant increases in mean liver weight (absolute and relative) were observed in 3500 and 7000 ppm animals (not statistically significant in 3500 ppm males) at both the interim and terminal sacrifices (Table 5.26). Significant decreases in mean absolute kidney weights were observed in males at 7000 ppm at the interim and terminal sacrifices [page 103]. Microscopic examinations revealed an increased incidence of systemic amyloidosis (most severe in the kidneys) in the 3500 and 7000 ppm animals and the 300 ppm females that died or were sacrificed in extremis. The incidence and severity of renal amyloidosis is given in Table 5.27. An increase in the incidence of centrilobular hypertrophy was observed in both sexes at dose levels 3500 ppm. The incidence of hepatic pigment (primarily in the reticuloendothelial cells) was increased in males at dose levels 3500 ppm and in females at 7000 ppm. There was an increase in the incidence of degeneration/inflammation/regeneration in the dorsal nasal turbinates of both sexes at 7000 ppm and in males at 3500 ppm. The severity and incidence of extramedullary haematopoiesis was increased in the spleens of the 7000 ppm males and females [page 104] Based on the incidence and severity of renal amyloidosis associated with early death in females at 300 ppm, the test laboratory proposed a NOEL for non-neoplastic lesions of 30 ppm (equivalent to approximately 4 mg/kg/day) for this study. The NOEL for neoplastic lesions in mice was determined to be 300 ppm (equivalent to approximately 45 mg/kg/day). In the opinion of the applicant [Rhone-Poulenc Agriculture Ltd], the observed amyloidosis in the above study was not a treatment-related effect of flurtamone administration. The incidences of amyloidosis in this study were re-analysed by an independent pathologist but the histopathological slides were not re-examined. It should be noted that systemic amyloidosis is a common age-related condition in CD-1 mice with a tendency to be more frequent as a cause of death in females than in males and the incidence varies widely within laboratories and between laboratories [page 105]... [page 108]
Ref: December 2000 . Evaluation on: Flurtamone. No. 196. Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7PX, UK. Available online at:
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm

Flusilazol / Flusilazole - Fungicide - CAS No. 85509-19-9

-- 2-Generation Reproduction - rat: Parental NOEL=3.5 mg/kg/day; Parental LEL=19 mg/kg/day (decreased body weight and body weight gain in F1 males during the 90 day feeding study); Reproductive NOEL and LEL could not be determined; Developmental NOEL=0.85 mg/kg/day (hydronephrosis noted at weaning of F2b pups - only trial examined); core grade supplementary (E.I. du Pont de Nemours & Co., Inc., 1986b)
-- Teratology - rat: Maternal NOEL=10 mg/kg/day; Maternal LEL=100 mg/kg/day (increased mortality after day 23 of gestation, prolonged gestation, decreased food consumption and weight gain, increased relative and absolute liver weight); Developmental NOEL (pre and post natal)=2 mg/kg/day; Developmental LEL=10 mg/kg/day (increased incidence of small renal papilla, distended ureter, dilated renal pelvis, decreased pup survival); core grade minimum (E.I. du Pont de Nemours & Co., Inc., 1985b)
Ref: US EPA IRIS. NuStar CASRN: 85509-19-9. Available October 6, 2003, at Toxnet.
• Definitions:
-- Hydronephrosis
: Pathological chronic enlargement of the collecting channels of a kidney, leading to compression and eventual destruction of kidney tissue, and diminishing kidney functionning.
--
Renal papilla - Renal Papillary Necrosis Alternate Names : Necrosis - Renal Papillae, Renal Medullary Necrosis Definition A disorder of the kidney involving death of some or all of the renal papillae.

Fluxofenim - Herbicide safener - CAS No. 88485-37-4

-- Chronic/Subchronic Toxicity Studies. Fluxofenim: Liver and kidney effects; Thyroid effects at high doses (dogs).
-- Target Organs Active Ingredients Fluxofenim: Liver, kidney, and thyroid.
Ref: Ciba-Geigy Material Safety Data Sheet for Concep-III.

http://www.fluoridealert.org/pesticides/fluxofenim.msds.ciba.1996.htm

 
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