Adverse Effects
Fluometuron
CAS No.
2164-17-2
 
 

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Activity: Herbicide (phenylurea)
Structure:



Adverse Effects:
Ataxia
Blood
Body Weight Decrease
Bone
Brain
Cancer: Possible Human Carcinogen: Lung,
Lymphocytic lymphomas, (Liver?)
CNS
Endocrine: Pituitary
Endocrine: Testicular
Eye
Kidney
Leukemia
Liver
Lung
Reproductiv/Developmental
Spleen
Environmental

The significant cancer risk contributors have been identified as drinking water (direct and indirect, all sources), and several rotational crops with wheat (flour), soybean (oil), and rice (white) having the highest contributions.
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. (page 7)
http://www.fluorideaction.org/pesticides/fluometuron.opp-2004-0372-0008.pdf

Twelve of the 26 most widely used pesticides in the U.S. are classified as possible or probable carcinogens by the EPA based on studies of laboratory animals, with an annual use that totals 380 million pounds. (atrazine (C=possible), metolachlor (C), metarn sodium (B2=probable), dichloropropene (B2), cyanazine (C), pendimethalin (C), trifluralin (C), acetochlor (B2), chlorothalonil (likely), mancozeb (B2), fluometuron (C), and parathion (C)... (Journal of Pesticide Reform, Summer 1999, at 5).
Ref: Testimony of the Maine Organic Farmers and Gardeners Association In support of L.D. 1540. March 29, 2001.
http://www.mofga.org/ge_pesticide_test.html

-- Note from FAN: Trifluralin, cited above, is another organofluorine pesticide.

Ataxia (click on for all fluorinated pesticides)

TERATOGENICITY RAT **021 054905, "A Teratology Study of Fluometuron Technical in the Albino Rat." (Ciba-Geigy, 6-19-86) Fluometuron technical, batch FL-821838, was administered to mated Crl. COBS CD (SD) (BR) rats at 0 (3% cornstarch, 0.5% Tween 80), 10, 100, or 1000 mg/kg/day on days 6 to 15 of gestation, with 27 animals per group. Decreased food consumption, weight gain, (transient at 100 mg/kg/day) and darkened spleen were observed at 100 and 1000 mg/kg/day. Lethargy, ataxia, pale eyes and extremities, encrustments around eyes/nose/mouth, salivation, blood on vulva, enlarged spleen and darkened kidneys and liver were observed at 1000 mg/kg/day. Maternal NOEL = 10 mg/kg/day. Delayed renal development was observed at 100 mg/kg/day. At 1000 mg/kg/day reduced litter size, fetal weight, and increased incidence of centrum/vertebra not ossified were observed. Developmental NOEL = 10 mg/kg/day. Originally reviewed as unacceptable (M. Silva, 12/15/88), upon receipt of the requested information regarding analysis of fluometuron in diet, the study was re-reviewed and found acceptable. M. Silva, 7/25/89.
Ref: Summary of Toxicology Data. California Department of Food and Agriculture, Medical Toxicology Branch. Revised October 29, 1989.
http://www.fluoridealert.org/pesticides/Fluometuron.CA.EPA.Tox.data.pdf

Blood (click on for all fluorinated pesticides)

E. Subchronic Studies. Subchronic feeding studies were conducted to determine the two concentrations (referred to in this report as "low" and "high" doses) to be used in the chronic studies. Fluometuron was administered in the diet for 90 days at doses of 0, 250, 500, 1,000, 2,000, 4,000, 8,000, or 16,000 ppm to groups consisting of 10 males and 10 females of each species (Tables 1 and 2) (page 5) ... A second 90-day subchronic study, described in Table 3, was undertaken to investigate in-depth the effects of feed containing 0 to 4,000 ppm fluometuron on the spleens of rats.... Gross lesions observed at necropsy included varying degrees of splenomegaly in all dosed groups. This change was dose related with the spleens being larger, heavier, darker, and firmer than the control spleens. In male rats, an increase in the mean weights of spleens occurred at 1,000 ppm, and the mean spleen weight at 4,000 ppm was twice that of the control. In female rats, the mean weight of spleens in the group receiving 250 ppm was greater than that of the control, and those of the groups receiving 2,000 ppm or 4,000 ppm were respectively twice and almost three times that of the control. A dose-related increased incidence of red blood cells with polychromasia and anisocytosis was observed for both male and female rats. Microscopically, the pathologic changes were congestion of the red pulp with corresponding decrease of white pulp. (page 8)
Reference: 1980. Bioassay of fluometuron for possible carcinogenicty. NCI-CG-TR-195. NTPO-80-11. National Cancer Institute. Carcinogenesis. Technical Report Series No. 195. NTP No. 80-11.
http://www.fluorideaction.org/pesticides/fluometuron.ntp.1980.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).
-- Carcinogenic Effects. EPA has determined that there is not enough evidence that fluometuron causes cancer in animals to justify its classification as a carcinogen. Fluometuron is not classified as a carcinogen by the EPA (20). An increased incidence of liver-cell tumors in male mice
was noted in a study of rats and mice. In the same study, no carcinogenic effects were observed in female mice or in rats of either sex (18). Mice that were given oral doses of 87 mg/kg for two years had evidence of liver tumors and leukemia, a condition characterized by uncontrolled growth in the number of white blood cells in the blood stream (7).
-- ACUTE TOXICITY. ... It may be fatal if inhaled, swallowed, or absorbed through skin, as it is irritating to the mucous membrane lining the skin, gastrointestinal tract, and respiratory system (2). While there have been no reports of cases of fluometuron poisoning in humans, this herbicide is considered a mild inhibitor of cholinesterase. Cholinesterase is an essential enzyme of the nervous system. Cholinesterase inhibition was observed in guinea pigs exposed by inhalation to 588 mg/m3 for 2 hours (18). Fluometuron caused an increased white blood cell count in agricultural workers (3).
Ref: Flumeturon. EXTOXNET. Pesticide Information Profile. March 1994.

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

Human Toxicity Excerpts: ... Mild cholinesterase inhibitor & /causes/ ... an increased leukocyte count in circulating blood in exposed agricultural workers. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-331]
Ref: Hazardous Substance Data Bank for Fluometuron. Available at Toxnet

-- 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.

Body Weight Decrease (click on for all fluorinated pesticides)

-- 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).
-- Teratogenic Effects. Pregnant rabbits were given doses of 50, 500 or 1,000 mg/kg/day by gavage during days 6 through 19 of gestation. An increase in the number of resorbed fetuses was found at all treatment doses. Reduction in maternal body weight and food consumption occurred at doses of 500 and 1,000 mg/kg/day (20).
-- 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

Chronic Study ** 025 068693, "Fluometuron Technical: 1-Year Oral Adminstration to Dogs (Min 832047)", (CIBA-Geigy Corporation Pharmaceuticals Div., Laboratory Study No.832047, May 25, 1988). Fluometuron, purity 95.8%, administered in the feed at concentrations of 0, 20, 400 or 7000 ppm to Beagle dogs, 5/sex/group for 52 weeks. Three extra/sex dogs in the control and the high dose groups were continued an additional 4 weeks without further treatment and served as the recovery group. No adverse effect. NOEL = 400 ppm (Increased incidence of emesis; stool irregularities - diarrhea, mucous, soft and bloody stools; reduced body weight (14-19% less than control at week 52), body weight gain and feed consumption; reduced erythrocytic parameters and indices - HGB, RBC, HCT, MCV and MCHC; and increases in percent Heinz bodies, Howell-Jolly bodies and reticulocytes; reduced biochemical parameters - SGPT, glucose and increased cholesterol, bilirubin, potassium and inorganic phosphorous levels). Reduced HGB, increased platelet count and WBC for the recovery group. ACCEPTABLE. (JSK & M. Silva, 8/30/89).
Ref: Summary of Toxicology Data. California Department of Food and Agriculture, Medical Toxicology Branch. Revised October 29, 1989.
http://www.fluoridealert.org/pesticides/Fluometuron.CA.EPA.Tox.data.pdf

Bone (click on for all fluorinated pesticides)

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

TERATOGENICITY RAT **021 054905, "A Teratology Study of Fluometuron Technical in the Albino Rat." (Ciba-Geigy, 6-19-86) Fluometuron technical, batch FL-821838, was administered to mated Crl. COBS CD (SD) (BR) rats at 0 (3% cornstarch, 0.5% Tween 80), 10, 100, or 1000 mg/kg/day on days 6 to 15 of gestation, with 27 animals per group. Decreased food consumption, weight gain, (transient at 100 mg/kg/day) and darkened spleen were observed at 100 and 1000 mg/kg/day. Lethargy, ataxia, pale eyes and extremities, encrustments around eyes/nose/mouth, salivation, blood on vulva, enlarged spleen and darkened kidneys and liver were observed at 1000 mg/kg/day. Maternal NOEL = 10 mg/kg/day. Delayed renal development was observed at 100 mg/kg/day. At 1000 mg/kg/day reduced litter size, fetal weight, and increased incidence of centrum/vertebra not ossified were observed. Developmental NOEL = 10 mg/kg/day. Originally reviewed as unacceptable (M. Silva, 12/15/88), upon receipt of the requested information regarding analysis of fluometuron in diet, the study was re-reviewed and found acceptable. M. Silva, 7/25/89.
Ref: Summary of Toxicology Data. California Department of Food and Agriculture, Medical Toxicology Branch. Revised October 29, 1989. http://www.fluoridealert.org/pesticides/Fluometuron.CA.EPA.Tox.data.pdf

Brain (click on for all fluorinated pesticides)

-- Organ Toxicity. Toxic injury to the liver, kidneys, gut and brain is induced when lethal doses of fluometuron are administered experimentally (TOXNET. 1986. National library of medicine's toxicology data network. Hazardous Substances Databank. Public Health Service. National Institute of Health, U. S. Department of Health and Human Services. Bethesda, MD: NLM.).

National Toxicology Program. Records with Morphology = Gliosis, Code = 4802.
http://magenta.niehs.nih.gov/cftdms/CBDS_apps/demo/CBDS/ResultsMorphTABLE.cfm?tumor_code4=4802
Chemical Name C No. Contract Grp Role Dose Grp An. No Spec/Strain Sex Route Organ Site
FLUOMETURON C08695 GULF SOUTH VEHI 45VF 040 RAT
F
FEED Brain Nos
FLUOMETURON C08695 GULF SOUTH TEST 45HM 041 RAT
M
FEED Brain Nos

National Toxicology Program. Records with Morphology = Meningioma, Benign, Code = 9530.
http://magenta.niehs.nih.gov/cftdms/CBDS_apps/demo/CBDS/ResultsMorphTABLE.cfm?tumor_code4=9530
Chemical Name C No. Contract Grp Role Dose Grp An. No Spec/Strain Sex Route Organ Site
FLUOMETURON C08695 GULF SOUTH VEHI 45VM 003 RAT
M
FEED Cerebellum Nos

Cancer. Possible Human Carcinogen: LUNG, LYMPHOCYTIC LYMPHOMAS (click on for all fluorinated pesticides)

Group C -- Possible Human Carcinogen. Statistically significant increases in combined adenomas/carcinomas of the lung (M); Malignant lymphocytic lymphomas (F); CD-1 mice.
Ref:
April 26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the Office of Pesticide Programs. From: Jess Rowland, Chief Science Information Management Branch Health Effect Division (7509C) Office of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf

Group C--Possible Human Carcinogen. Reviewed 8/ 28/ 96.
Ref: List of Chemicals Evaluated for Carcinogenic Potential. Science Information Management Branch, Health Effects Division, Office of Pesticide Programs, U. S. Environmental Protection Agency. March 15, 2002.
http://www.biomuncie.org/chemicals_evaluated_for_carcinog.htm

The significant cancer risk contributors have been identified as drinking water (direct and indirect, all sources), and several rotational crops with wheat (flour), soybean (oil), and rice (white) having the highest contributions. (page 7)
• A re-examination and statistical analysis of the rates of all lymphocytic lymphomas in female mice and all alveolarhronchiolar hyperplasia, adenomas, and carcinomas in male mice from the carcinogenicity study in mice (0, 10,500, or 2000 ppm [83-2b]) indicated that male mice had a significant increasing trend in alveolar/bronchiolar adenomas andor carcinomas combined at p < 0.05. There were no significant differences in the pair-wise comparisons of the dosed groups with the controls. The male alveolarhonchiolar tumor rates were 15/56, 16/59, 19/56, and 24/58, respectively (L. Taylor Memorandum 9/13/95, TXR 012742). Female mice had a significant increasing trend and a significant difference in pair-wise comparison of the high-dose group (2000 ppm) with the controls for lymphocytic lymphomas at p < 0.05. The lymphatic tissue tumor rates were 4/5 1, 10124, 6/17, and 12/53, respectively (L. Taylor Memorandum 9/13/95, TXR 012742).(page 9)
• D. Classification of Carcinogenic Potential.
The Health Effects Division Carcinogenicity Peer Review Committee (CPRC) met on Oct. 11, 1995 to discuss and evaluate the weight-of-the-evidence on fluometuron with particular reference to its carcinogenic potential. The consensus of the CPRC was that fluometuron should be classified as Group C -possible human carcinogen and for the purpose of risk characterization, both a low dose extrapolation model (Q,’) applied to the animal data (lung tumors in male mice) and the Reference Dose (RfD) approach should be used. This was based on statistically significant increases in combined adenomadcarcinomas of the lungs in male mice and malignant lymphocytic lymphomas in female mice, at a dose which was less than adequate for fully assessing the carcinogenic potential of fluometuron ( L. Taylor Memorandum 8/28/96, TXR 012049).
A quantitative risk assessment-Q,* was performed for fluometuron (B. Fisher Memorandum 12/24/96, TXR 012809). The unit risk, QI*(mg/kg/day)-’of fluometuron, based upon male mouse combined lung (adenomas and/or carcinomas) tumor rates is 1.80 x lo-*in human equivalents (converted from animals to humans by use of the 314‘s scaling factor-1994, Tox Risk, 3.5-K. Crump) (Ref. 1). The dose levels used from this 2-year study were 0, 10,500, and 2000 ppm of fluometuron. The corresponding tumor rates (from re-read slide data, 7/92) for the male mice were 15/56, 16/59, 19/56, and 24/58 respectively.
The estimate of unit risk, Q1*was based upon lung (adenoma and/or carcinoma) tumor rates in male mice. Since male mice had statistically significant increases in mortality with dose increments of fluometuron, the estimate of the unit risk, Q1*,was obtained by the application of the time-to-tumor Weibull model (Tox-Risk program, version 3.5-K. Cnunp). The resulting estimate of unit risk, Q1*,was converted to human equivalents by the use of weights of 0.03 kg for the mice and 70 kg for the humans and the 3/4’s scaling factor for interspecies extrapolation. It is to be noted that Q,* (mg/kg/day)-’ is an estimate of the upper bound on risk and that (as stated in the EPA Risk Assessment Guidelines) “the true value of the risk is unknown, and may be as low as zero. (page 11-12).
(1). See memo-Deriving Q,*s Using the Unified Interspecies Scaling Factor, P.A. Fenner-Crisp. Director-HED, 7/1/94.
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

Twelve of the 26 most widely used pesticides in the U.S. are classified as possible or probable carcinogens by the EPA based on studies of laboratory animals, with an annual use that totals 380 million pounds. (atrazine (C=possible), metolachlor (C), metarn sodium (B2=probable), dichloropropene (B2), cyanazine (C), pendimethalin (C), trifluralin (C), acetochlor (B2), chlorothalonil (likely), mancozeb (B2), fluometuron (C), and parathion (C). Four frequently used pesticides have been associated with increased risk of cancer for exposed humans in epidemiological studies. 190 million pounds of these four pesticides are used annually in the U.S., including 120 million household applications every year. (atrazine, 2,4 D, glyphosate, diazinon). (Journal of Pesticide Reform, Summer 1999, at 5). Last year, the EPA moved under the Food Quality Protection Act to phase out residential uses of diazinon, but agricultural uses remain legal.
Ref: Testimony of the Maine Organic Farmers and Gardeners Association In support of L.D. 1540. March 29, 2001.

http://www.mofga.org/ge_pesticide_test.html

1980 Abstract: ... A bioassay of the phenylurea herbicide fluometuron for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of 50 rats of each sex were fed diets containing 125 or 250 ppm of fluometuron for 103 weeks, and groups of 50 mice of each sex were fed diets containing 500 or 1,000 ppm of fluometuron for 103 weeks. Matched controls consisted of groups of 50 untreated rats and 25 untreated mice of each sex. All surviving animals were killed at 103 to 105 weeks. Splenomegaly observed in rats in the subchronic studies influenced selection of the doses for the chronic study; however, no splenic effects were observed in the chronic study. Mean body weights of the dosed groups of male and female rats and mice were essentially the same as those of the corresponding control groups. Survival of dosed groups of rats and mice was similar to that of the corresponding control groups. Similarities between mean body weights and survival between dosed and control animals in thechronic study suggest that these animals could have tolerated higher doses. The only possible carcinogenic effects from compound administration were in male mice. Incidences of hepatocellular carcinomas or adenomas in male mice were dose related, and the incidence in the high-dose group was marginally higher than that in the corresponding matched controls or pooled controls from concurrent studies. Under the conditions of this bioassay, fluometuron was not carcinogenic for F344 rats or for female B6C3F1 mice. Equivocal results were obtained for male B6C3F1 mice which may have had an increased incidence of hepatocellular tumors. Because of the equivocal findings and because both rats and mice may have been able to tolerate higher doses, it is concluded that additional testing of fluometuron for carcinogenicity is warranted. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Equivocal Female Mice: Negative Synonym: 1,1-dimethyl-3-(a,a,a-trifluoro-m-tolyl) urea
Ref: Bioassay of Fluometuron for Possible Carcinogenicity (CAS No. 2164-17-2). National Toxicology Program. Natl Toxicol Program Tech Rep Ser. 1980 Aug;195:1-99. [Abstract from Toxline at Toxnet]

CNS (click on for all fluorinated pesticides)

-- ACUTE TOXICITY. ... It may be fatal if inhaled, swallowed, or absorbed through skin, as it is irritating to the mucous membrane lining the skin, gastrointestinal tract, and respiratory system (2). While there have been no reports of cases of fluometuron poisoning in humans, this herbicide is considered a mild inhibitor of cholinesterase. Cholinesterase is an essential enzyme of the nervous system. Cholinesterase inhibition was observed in guinea pigs exposed by inhalation to 588 mg/m3 for 2 hours (18). Fluometuron caused an increased white blood cell count in agricultural workers (3).
Ref: Flumeturon. EXTOXNET. Pesticide Information Profile. March 1994.

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

Endocrine: Adrenal (click on for all fluorinated pesticides)

-- 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

Endocrine: Pituitary (click on for all fluorinated pesticides)

A histological re-examination and statistical analysis of pituitary adenomas in Fischer 344 rats from a combined chronic toxicity/oncogenicity study (0, 10, 300, or 1000 ppm [83-51) indicated no significant increasing trends in male rats, but a significant difference was observed in a pairwise comparison of the 10 and 1000 ppm dose groups with the controls for pituitary adenomas was significant at p < 0.05, and a significant difference observed in the pair-wise comparison of the 300 ppm dose group with the controls for pituitary adenomas at p < 0.01. The pituitary adenoma tumor rates in male rats were 3/47,9/51, 1 1/51, and 9/58, respectively (L. Taylor Memorandum 9/13/95. TXR 012742). There were no compound related tumors observed in female rats. Two other studies submitted by the National Cancer Institute (NCI) for both mice and rats were either unremarkable or the results equivocal. However, genotoxicity studies with fluometuron were negative. (page 9)
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

Endocrine: Testicular (click on for all fluorinated pesticides)

-- Mutagenic Effects. In two separate assays, one on yeast and the other on bacterial cell cultures, fluometuron failed to cause mutations. Fluometuron interfered with DNA synthesis in the testes of mice given a single oral dose of 2,000 mg/kg (20).
Ref: Flumeturon. EXTOXNET. Pesticide Information Profile. March 1994.

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

Eye (click on for all fluorinated pesticides)

Primary eye irritation: Induces corneal opacity, Toxicity Category I. Fluometuron (Cotoran, Lanex) Herbicide Profile 12/85.
Ref: Chemical Fact Sheet for Fluometuron. Fact Sheet Number 88. December 1985.

http://pmep.cce.cornell.edu/profiles/herb-growthreg/fatty-alcohol-monuron/fluometuron/herb-prof-fluometuron.html

• Fluometuron is of low to moderate toxicity with toxicity categories of III and IV, except for dermal and eye irritation (II). (page 2)
• Primary eye irritation studies indicate fluometuron produces corneal opacity, iris irritation, redness, chemosis, and discharge, all of which cleared from day 4 to day 10 (Tox Category II) (page 8)
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

TERATOGENICITY RAT **021 054905, "A Teratology Study of Fluometuron Technical in the Albino Rat." (Ciba-Geigy, 6-19-86) Fluometuron technical, batch FL-821838, was administered to mated Crl. COBS CD (SD) (BR) rats at 0 (3% cornstarch, 0.5% Tween 80), 10, 100, or 1000 mg/kg/day on days 6 to 15 of gestation, with 27 animals per group. Decreased food consumption, weight gain, (transient at 100 mg/kg/day) and darkened spleen were observed at 100 and 1000 mg/kg/day. Lethargy, ataxia, pale eyes and extremities, encrustments around eyes/nose/mouth, salivation, blood on vulva, enlarged spleen and darkened kidneys and liver were observed at 1000 mg/kg/day. Maternal NOEL = 10 mg/kg/day. Delayed renal development was observed at 100 mg/kg/day. At 1000 mg/kg/day reduced litter size, fetal weight, and increased incidence of centrum/vertebra not ossified were observed. Developmental NOEL = 10 mg/kg/day. Originally reviewed as unacceptable (M. Silva, 12/15/88), upon receipt of the requested information regarding analysis of fluometuron in diet, the study was re-reviewed and found acceptable. M. Silva, 7/25/89.
Ref: Summary of Toxicology Data. California Department of Food and Agriculture, Medical Toxicology Branch. Revised October 29, 1989. http://www.fluoridealert.org/pesticides/Fluometuron.CA.EPA.Tox.data.pdf

Fluometuron is a mild skin and eye irritant. It has caused skin sensitization in guinea pigs and in humans. It affects the cornea of the eye in such a way that light cannot pass through it. This condition is referred to as corneal opacity. Skin or eye contact with it may cause burning... Prolonged or repeated exposure to fluometuron may cause conjunctivitis.
Ref: Pesticide Informationnn Profile. Fluometuron. March 1994. EXTOXNET.

http://www.fluoridealert.org/pesticides/Fluometuron.Extoxnet.1994.htm

Kidney (click on for all fluorinated pesticides)

• 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

TERATOGENICITY RAT **021 054905, "A Teratology Study of Fluometuron Technical in the Albino Rat." (Ciba-Geigy, 6-19-86) Fluometuron technical, batch FL-821838, was administered to mated Crl. COBS CD (SD) (BR) rats at 0 (3% cornstarch, 0.5% Tween 80), 10, 100, or 1000 mg/kg/day on days 6 to 15 of gestation, with 27 animals per group. Decreased food consumption, weight gain, (transient at 100 mg/kg/day) and darkened spleen were observed at 100 and 1000 mg/kg/day. Lethargy, ataxia, pale eyes and extremities, encrustments around eyes/nose/mouth, salivation, blood on vulva, enlarged spleen and darkened kidneys and liver were observed at 1000 mg/kg/day. Maternal NOEL = 10 mg/kg/day. Delayed renal development was observed at 100 mg/kg/day. At 1000 mg/kg/day reduced litter size, fetal weight, and increased incidence of centrum/vertebra not ossified were observed. Developmental NOEL = 10 mg/kg/day. Originally reviewed as unacceptable (M. Silva, 12/15/88), upon receipt of the requested information regarding analysis of fluometuron in diet, the study was re-reviewed and found acceptable. M. Silva, 7/25/89.
Ref: Summary of Toxicology Data. California Department of Food and Agriculture, Medical Toxicology Branch. Revised October 29, 1989. http://www.fluoridealert.org/pesticides/Fluometuron.CA.EPA.Tox.data.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.

Leukemia (click on for all fluorinated pesticides)

EPA has determined that there is not enough evidence that fluometuron causes cancer in animals to justify its classification as a carcinogen. Fluometuron is not classified as a carcinogen by the EPA (20). An increased incidence of liver-cell tumors in male mice was noted in a study of rats and mice. In the same study, no carcinogenic effects were observed in female mice or in rats of either sex (18). Mice that were given oral doses of 87 mg/kg for two years had evidence of liver tumors and leukemia, a condition characterized by uncontrolled growth in the number of white blood cells in the blood stream (National Institute for Occupational Safety and Health (NIOSH). 1986. Registry of toxic effects of chemical substances (RTECS). Cincinnati, OH: NIOSH.)
Ref: 1994 Pesticide Information Profile. EXTOXNET.
http://www.fluoridealert.org/pesticides/fluometuron.extoxnet.1994.htm

Liver (click on for all fluorinated pesticides)

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)
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

Groups of 50 /B6C3F1/ mice of each sex were fed diets containing 500 or 1,000 ppm of fluometuron for 103 weeks. Matched controls consisted of groups of 25 untreated mice of each sex. All surviving animals were killed at 103 to 105 weeks. Mean body weights of the dosed groups of male and female mice were essentially the same as those of the corresponding control groups. Survival of dosed groups of mice were similar to that of the corresponding control groups. Similarities between mean body weights and survival between dosed and control animals in the chronic study suggest that these animals could have tolerated higher doses. The only possible carcinogenic effects from compound administration were in male mice. Incidences of hepatocellular carcinomas or adenomas in male mice were dose related, and the incidence in the high-dose group was marginally higher than that in the corresponding matched controls or pooled controls from concurrent studies. Under the conditions of this bioassay, fluometuron was not carcinogenic for F344 rats or for female B6C3F1 mice. Equivocal results were obtained for male B6C3F1 mice which may have had an increased incidence of hepatocellular tumors. Because of the equivocal findings and because both rats and mice may have been able to tolerate higher doses, it is concluded that additional testing of fluometuron for carcinogenicity is warranted. (Summary page v)
Reference: 1980. Bioassay of fluometuron for possible carcinogenicty. NCI-CG-TR-195. NTPO-80-11. National Cancer Institute. Carcinogenesis. Technical Report Series No. 195. NTP No. 80-11.
http://www.fluorideaction.org/pesticides/fluometuron.ntp.1980.pdf

PubMed abstract: The experiments on the investigation of pesticide fluometuron (cotoran) influence on nuclease sensitivity and template activity of rat liver chromatin were carried out. Cotoran was found to bind specifically with non-histone proteins of chromatin. It was shown that this pesticide considerably decreases template activity of chromatin and its sensitivity to the action of nucleases. It suggests, that certain conformation changes occur in chromatin upon the action of cotoran.
Ref: Biull Eksp Biol Med 1992 Mar;113(3):261-3. [Effects of pesticide fluometuron (cotoran) on template synthesis of RNA] [Article in Russian] Khamidov DKh, Mirakhmedov AK, Sagatova GA, Azimova ShS. PMID: 1384777 [PubMed - indexed for MEDLINE]

-- 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).
-- Carcinogenic Effects. EPA has determined that there is not enough evidence that fluometuron causes cancer in animals to justify its classification as a carcinogen. Fluometuron is not classified as a carcinogen by the EPA (20). An increased incidence of liver-cell tumors in male mice was noted in a study of rats and mice. In the same study, no carcinogenic effects were observed in female mice or in rats of either sex (18). Mice that were given oral doses of 87 mg/kg for two years had evidence of liver tumors and leukemia, a condition characterized by uncontrolled growth in the number of white blood cells in the blood stream
(7).
-- 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: Fluometuron. 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.

-- PubMed abstract: The experiments on the investigation of pesticide cotoran-effect on RNA synthesis and transport were carried out. Cotoran was shown to destroy considerably the processes of RNA biosynthesis in rat liver, that results in the decrease of RNA transport from nuclei into cytoplasm. By special experiments it was established that functional activity and the integrity of nuclear membrane (according to the alteration in the activity of nuclear membrane enzyme Mg2-dependent ATP-ase) was not destroyed.
Ref: Biull Eksp Biol Med 1992 Jan;113(1):40-2.
[RNA synthesis and transport in the rat liver under the effects of pesticide cotoran (fluometuron)]. [Article in Russian]; by Khamidov DKh, Marakhmedov AK, Sagatova GA, Azimova ShS.

LYMPHOMAS (click on for all fluorinated pesticides)

Group C -- Possible Human Carcinogen. Statistically significant increases in combined adenomas/carcinomas of the lung (M); Malignant lymphocytic lymphomas (F); CD-1 mice.
Ref:
April 26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the Office of Pesticide Programs. From: Jess Rowland, Chief Science Information Management Branch Health Effect Division (7509C) Office of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf

Lung (click on for all fluorinated pesticides)

Group C -- Possible Human Carcinogen. Statistically significant increases in combined adenomas/carcinomas of the lung (M); Malignant lymphocytic lymphomas (F); CD-1 mice.
Ref:
April 26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the Office of Pesticide Programs. From: Jess Rowland, Chief Science Information Management Branch Health Effect Division (7509C) Office of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf

• A re-examination and statistical analysis of the rates of all lymphocytic lymphomas in female mice and all alveolarhronchiolar hyperplasia, adenomas, and carcinomas in male mice from the carcinogenicity study in mice (0, 10,500, or 2000 ppm [83-2b]) indicated that male mice had a significant increasing trend in alveolar/bronchiolar adenomas andor carcinomas combined at p < 0.05. There were no significant differences in the pair-wise comparisons of the dosed groups with the controls. The male alveolarhonchiolar tumor rates were 15/56, 16/59, 19/56, and 24/58, respectively (L. Taylor Memorandum 9/13/95, TXR 012742). Female mice had a significant increasing trend and a significant difference in pair-wise comparison of the high-dose group (2000 ppm) with the controls for lymphocytic lymphomas at p < 0.05. The lymphatic tissue tumor rates were 4/5 1, 10124, 6/17, and 12/53, respectively (L. Taylor Memorandum 9/13/95, TXR 012742).(page 9)
• D. Classification of Carcinogenic Potential.
The Health Effects Division Carcinogenicity Peer Review Committee (CPRC) met on Oct. 11, 1995 to discuss and evaluate the weight-of-the-evidence on fluometuron with particular reference to its carcinogenic potential. The consensus of the CPRC was that fluometuron should be classified as Group C -possible human carcinogen and for the purpose of risk characterization, both a low dose extrapolation model (Q,’) applied to the animal data (lung tumors in male mice) and the Reference Dose (RfD) approach should be used. This was based on statistically significant increases in combined adenomadcarcinomas of the lungs in male mice and malignant lymphocytic lymphomas in female mice, at a dose which was less than adequate for fully assessing the carcinogenic potential of fluometuron ( L. Taylor Memorandum 8/28/96, TXR 012049).
A quantitative risk assessment-Q,* was performed for fluometuron (B. Fisher Memorandum 12/24/96, TXR 012809). The unit risk, QI*(mg/kg/day)-’of fluometuron, based upon male mouse combined lung (adenomas and/or carcinomas) tumor rates is 1.80 x lo-*in human equivalents (converted from animals to humans by use of the 314‘s scaling factor-1994, Tox Risk, 3.5-K. Crump) (Ref. 1). The dose levels used from this 2-year study were 0, 10,500, and 2000 ppm of fluometuron. The corresponding tumor rates (from re-read slide data, 7/92) for the male mice were 15/56, 16/59, 19/56, and 24/58 respectively.
The estimate of unit risk, Q1*was based upon lung (adenoma and/or carcinoma) tumor rates in male mice. Since male mice had statistically significant increases in mortality with dose increments of fluometuron, the estimate of the unit risk, Q1*,was obtained by the application of the time-to-tumor Weibull model (Tox-Risk program, version 3.5-K. Cnunp). The resulting estimate of unit risk, Q1*,was converted to human equivalents by the use of weights of 0.03 kg for the mice and 70 kg for the humans and the 3/4’s scaling factor for interspecies extrapolation. It is to be noted that Q,* (mg/kg/day)-’ is an estimate of the upper bound on risk and that (as stated in the EPA Risk Assessment Guidelines) “the true value of the risk is unknown, and may be as low as zero. (page 11-12).
(1). See memo-Deriving Q,*s Using the Unified Interspecies Scaling Factor, P.A. Fenner-Crisp. Director-HED, 7/1/94.
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

Reproductive/Developmental (click on for all fluorinated pesticides)

E. Endpoint Selection or Dose/Response
1. Acute Reference Dose For the general population, no study exists to determine effects from a single dose. Therefore there is no acute reference dose for the general population. However, for females age 13+ (women of child bearing years) there is a study to support this reference dose. In the rat developmental toxicity study (83-3aYMRID 00163710), dose levels of 10, 100, and 1000 mg/kg/day were administered via gavage on days 6-15 of gestation. The NOAEL/LOAEL for developmental toxicity were 10/100 mg/kg/day, based on delayed urinary system development (23/83 [28%] vs. 9/82 [11%] controls). The urinary system of the fetus forms at specific time points during development and therefore could be adversely affected from a single exposure during gestation. Delayed urinary development would not be recognized until later during growth. Maternal NOAEL/LOAEL was 10/100 mg/kg/day, based on decreased food consumption (high-dose: 8%-23% from Day 10 to Day 20 of gestation) and an increased incidence of darkened spleens (mid: 7/27 [26%]; high: 24/27 [89%], controls: 0/27). An uncertainty factor of 100 (1 OX for interspecies extrapolation and 1OX for intraspecies variability) is applied.
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

Spleen (click on for all fluorinated pesticides)

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)
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

E. Subchronic Studies. Subchronic feeding studies were conducted to determine the two concentrations (referred to in this report as "low" and "high" doses) to be used in the chronic studies. Fluometuron was administered in the diet for 90 days at doses of 0, 250, 500, 1,000, 2,000, 4,000, 8,000, or 16,000 ppm to groups consisting of 10 males and 10 females of each species (Tables 1 and 2) (page 5) ... A second 90-day subchronic study, described in Table 3, was undertaken to investigate in-depth the effects of feed containing 0 to 4,000 ppm fluometuron on the spleens of rats.... Gross lesions observed at necropsy included varying degrees of splenomegaly in all dosed groups. This change was dose related with the spleens being larger, heavier, darker, and firmer than the control spleens. In male rats, an increase in the mean weights of spleens occurred at 1,000 ppm, and the mean spleen weight at 4,000 ppm was twice that of the control. In female rats, the mean weight of spleens in the group receiving 250 ppm was greater than that of the control, and those of the groups receiving 2,000 ppm or 4,000 ppm were respectively twice and almost three times that of the control. A dose-related increased incidence of red blood cells with polychromasia and anisocytosis was observed for both male and female rats. Microscopically, the pathologic changes were congestion of the red pulp with corresponding decrease of white pulp. (page 8)
Reference: 1980. Bioassay of fluometuron for possible carcinogenicty. NCI-CG-TR-195. NTPO-80-11. National Cancer Institute. Carcinogenesis. Technical Report Series No. 195. NTP No. 80-11.
http://www.fluorideaction.org/pesticides/fluometuron.ntp.1980.pdf

-- 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

 

Environmental (click on for all fluorinated pesticides)

D. Environmental Fate and Drinking Water Exposure and Risk Assessment
Fluometuron and its metabolites are mobile and persistent in the environment. The primary route of degradation of fluometuron and its main degradate CGA-41686 [1-methyl-3-(a,a,a-trifluoro-m-tolyl)urea] is microbial metabolism. However, since fluometuron and its degradates are not volatile, and these degradative processes are not rapid enough, these compounds will be available for leaching to ground water and runoff to surface water in many use conditions. Once in ground water or surface water, fluometuron is expected to persist due to its stability to hydrolysis and photolysis. (page 39)
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

Fluometuron is an urea herbicide used for annual grass and annual broadleaf weed control in cotton. Its use on cotton poses risks on an acute basis to both endangered and non-endangered freshwater fish, invertebrates, birds, mammals, and aquatic plants. The Agency was unable to assess the potential chronic risk to birds, and freshwater or estuarine/marine fish and invertebrates due to insufficient data. (page 1)
Major Conclusions
Risks to Terrestrial Organisms
• There are acute risks to avian species that feed on short grass, long grass, and broadleaf plants/small insects. C Chronic risk to birds could not be evaluated due to absence of chronic avian testing.
• There are acute risks to mammals (15 g and 35 g) that forage on short grass, long grass, and broadleaf plants/small insects. There is acute risk to large mammals (1000 g) that feed on short grass.
• There is chronic risk to mammals that forage on short grass, long grass, broadleaf plants/small insects, and fruits/pods/large insects/seeds.
Risk to terrestrial plants on land and in semi-aquatic areas is expected.
Risks to Aquatic Organisms
• The present assessment suggests potential risk on an acute basis to freshwater fish and invertebrates. These estimates were based on Mississippi (MS), Texas (TX) and North Carolina (NC) cotton scenarios (endangered and non-endangered species’ LOCs exceeded). For the California cotton scenario, only endangered species’ LOCs are exceeded for freshwater fish and invertebrates.
• Although estuarine/marine invertebrates endangered species’ LOCs are exceeded, there are currently no federally listed threatened or endangered estuarine/marine invertebrates.
• The Agency was unable to assess the potential chronic risk to freshwater and estuarine/marine fish or freshwater and estuarine/marine invertebrates due to data gaps.
• Risk to aquatic plants is expected for both non-endangered and endangered species.

D. Key Uncertainties and Information Gaps
The following uncertainties and information gaps were identified as part of the problem formulation:
Chronic data for birds were not submitted by the registrant; therefore, measurement endpoints could not be estimated.
Chronic data for freshwater fish were not submitted by the registrant; therefore, measurement endpoints could not be estimated.
Chronic data for freshwater invertebrates were not submitted by the registrant; therefore, measurement endpoints could not be estimated.
Chronic data for estuarine/marine fish were not submitted by the registrant; therefore, measurement endpoints could not be estimated .
Chronic data for estuarine/marine invertebrates and mollusks were not submitted by the registrant; therefore, measurement endpoints could not be estimated.
• Inhalation and dermal pathways for terrestrial mammals and birds were not evaluated because these routes of exposure are considered to be negligible compared to the dietary ingestion pathways. Uncertainties associated with exposure pathways for terrestrial animals are discussed in greater detail in Section IV.D.3.
• Risks to semiaquatic wildlife via consumption of pesticide-contaminated fish were not evaluated. However, given that bioaccumulation of fluometuron is low, ingestion of fish by piscivorus wildlife is not likely to be of concern.
Risks to top-level carnivores were not evaluated due to a lack of data for these receptors. Ingestion of grass, plants, fruits, insects, and seeds by terrestrial wildlife was considered; however, consumption of small mammals and birds by carnivores was not evaluated. In addition, food chain exposures for aquatic receptors (i.e., fish consumption of aquatic invertebrates and/or aquatic plants) were also not considered.
Surrogates were used to predict potential risks for species with no data (i.e., reptiles and amphibians). It was assumed that use of surrogate effects data is sufficiently conservative to apply the broad range of species within taxonomic groups. If other species are more or less sensitive to fluometuron than the surrogates, risks may be under or overestimated, respectively.

The preliminary risk assessment for endangered species indicates that fluometuron exceeds the endangered species LOCs [Level of Concern] for the following combinations of analyzed uses and species: (page 39)
• Freshwater fish (acute): Cotton (all scenarios modeled - MS, NC, TX, and CA).
• Freshwater invertebrates (acute): Cotton (all scenarios modeled - MS, NC, TX, and CA).
• Estuarine/marine invertebrates (acute): Cotton (scenarios modeled - MS, NC, and TX). CA cotton scenario does not exceed endangered species’ LOCs.
• Aquatic vascular plants (acute): Cotton (MS, TX, and NC scenarios).
• Aquatic non-vascular plants (acute): Cotton (MS, TX, and NC scenarios).
• Birds (acute) : Cotton (short grass, tall grass, and broadleaf plants/small insects).
• Mammals (acute) : Cotton (short grass, tall grass, broadleaf plants/small insects) for small (15 g) and medium (35 g) mammal and cotton (short grass) for large mammals (1000 g).
• Mammals (chronic) : Cotton ( short grass, tall grass, broadleaf plants/small insects, and fruits/pods/large insects/seeds).
• Non-target terrestrial and semi-aquatic plants (acute): Cotton (dry areas, wetland areas, and drift).
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


/ACUTE SYMPTOMS IN MALLARDS AFTER ORAL ADMIN ARE/ ATAXIA, WING DROP OR WINGS CROSSED HIGH OVER BACK, TAIL POINTED UPWARD, FLUFFED FEATHERS, HYPEREXCITABILITY, PHONATION, FALLING. SIGNS APPEARED 15 MIN AFTER-TREATMENT & PERSISTED FOR UP TO ONE WK. [U.S. Department of the Interior, Fish and Wildlife Service. Handbook of Toxicity of Pesticides to Wildlife. Resource Publication 153. Washington, DC: U.S. Government Printing Office, 1984. 44]

Environmental Fate: TERRESTRIAL FATE: IT IS OF INTERMEDIATE PERSISTENCE WITH A HALF-LIFE OF 60-75 DAYS ACCORDING TO SOIL CONDITIONS. [Worthing, C.R. and S.B. Walker (eds.). The Pesticide Manual - A World Compendium. 8th ed. Thornton Heath, UK: The British Crop Protection Council, 1987. 412]

Environmental Bioconcentration: An estimated BCF of 15 was calculated for fluometuron(SRC), using a log Kow of 2.42 (1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low. However, in a study of unicellular green algae (Chlorella fusca), a log BCF of 1.96(4) was determined for fluometuron, corresponding to a BCF of 91.2 and indicating a moderate potential for bioconcentration in algae. [(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 70 (1995) (2) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999) (3) Franke C et al; Chemosphere 29: 1501-14 (1994) (4) Manthey M et al; pp. 453-459 in The Sci of the Total Environ, Supp. Amsterdam, The Netherlands: Elsevier (1993)]

Environmental Water Concentrations: GROUNDWATER: Based on the records maintained in the STORET database of EPA, fluometuron was not detected in any of the 156 groundwater samples analyzed from 125 locations in the U.S.(1). Fluometuron was not detected (detection limit 0.5 ug/l) in water from 119 wells, springs and municipal drinking water supplies sampled throughout Arkansas, during 1985-1987(2). In a study of groundwater sampled in 1992-1998 from 231 wells in 14 counties in the Arkansas Delta, fluometuron was detected at high and persistent concentrations in two of the wells, at 0.4-0.9 ug/l in a well used for a machine shop and at 19-24 ug/l in a well designated for domestic use(3). [(1) USEPA; Drinking Water Health Advisory: Pesticides, Chelsea, MI: Lewis Publishers, Inc. p. 427-41 (1989) (2) Cavalier TC et al; Ground Water Monit Rev 9: 159-66 (1989) (3) Nichols T et al; Water Res Engr 98: 1242-1247 (1998)]

SURFACE WATER: Based on the records maintained in the STORET database of EPA, fluometuron was not detected in 14 surface water samples from 14 locations in the US(1). In a study of the Mississippi River and its tributaries in July/Aug 1991, fluometuron was detected in three tributaries and at three Mississippi River sites at concns of 9-411 ng/l(2). [(1) USEPA; Drinking Water Health Advisory: Pesticides. Chelsea, MI: Lewis Publishers, Inc. p. 427-41 (1989) (2) Pereira WE, Hostettler FD; Environ Sci Tech 27: 1542-1552 (1993)]

Ref: Hazardous Substance Data Bank for Fluometuron. Available at Toxnet


Abstract: Existing drinking water wells are widely used for the collection of ground water samples to evaluate chemical contamination. A well comparison study was conducted to compare pesticide and nitrate-N data from specially designed stainless steel research monitoring wells with data from nearby existing on-farm drinking water wells. Results could help to determine whether adequate information concerning ground water contamination can be obtained from existing drinking water wells for use in making pollutant control decisions. The study was conducted during 1993-1994 in the Little Coharie Watershed, a 158 square mile area located in the coastal plain of eastern North Carolina. Statistical analysis indicated that research monitoring wells provided a greater probability of detecting pesticides in ground water than existing on-farm wells. Atrazine was the most frequently detected pesticide found in all wells, followed in order by fluometuron, carbofuran, metolachlor, alachlor, carbaryl, butylate, chlorothalonil, linuron and simazine. Ninety-seven percent of all wells had observed concentrations of nitrate-N, ranging from 0.1 to 30.1 mg/L. There was not a significant difference between research wells and existing wells for monitoring nitrate-N. Based on results of this study, existing drinking water wells can be used for monitoring nitrate; however, specialized stainless steel monitoring wells should be used for monitoring pesticides in ground water.
Ref: Smith CN el at. (1999). A field study to compare performance of stainless steel research monitoring wells with existing on-farm drinking water wells in measuring pesticide and nitrate concentrations. Chemosphere. Feb;38(4):875-89.
http://www.fluorideaction.org/pesticides/fluometuron.pubmed.htm.

 
 
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