Bone - Adverse Effects
Fluorinated and Fluoride Pesticides

beginning with
A-E • F-G H-P Q-Z
 
 

See short description and defintions on bone

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

Acute neurotoxicity. The NOEL was 2 mg/kg, based on decreases in body weight gain and food consumption in males and females during the week following treatment, decreases in locomotor activity, hind-limb splay and rectal temperature 6-hour post dosing in males and females, and decreases in the proportion of males with an immediate righting reflex on days 7 and 14, at 12 mg/kg/day. In a rat developmental toxicity study, the NOEL was 1 mg/kg/day, based on the slight increase in fetal and litter incidence of reduced ossification of several bones at 2.5 mg/kg/day.
Ref: August 24, 2005. Federal Register. Fipronil; Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food.

http://www.fluorideaction.org/pesticides/fipronil.fr.aug.24.2005.html

The Developmental Toxicity LOEL was 2.5 mg/kg/day and the NOEL was 1.0 mg/ kg/day based on the slight increase in fetal and litter incidence of reduced ossification of several bones... (hyoid, 5th/6th sternebrae, 1st thoracic vertebral body, pubic bone, and one or two metatarsi)...
Ref: Federal Register. July 17, 1998. Fipronil; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/fipronil.fr.july.17.1998.htm

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

• Target / critical effect - Developmental toxicity: Developmental effects at maternal toxic doses (foetal mortality, reduced foetal weight, skeletal variations) in rats. Lowest relevant developmental NOAEL / 100 mg/kgbw/day.

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. The developmental LOAEL was 500 mg/kg/ day based on the increases in placental weights and incidences of fetal skeletal variations seen only at maternally toxic doses of 500 mg/kg/ day.
-- 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 the 18-month mouse study, effects were observed in the lung, liver, spleen and bone marrow at 250 ppm or higher. Findings included, centrilobular hepatocellular hypertrophy, extramedullary hematopoiesis and pigment deposition in the spleen and decreased cellularity (hypocellularity) in the bone marrow...
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

-- Developmental. NOAEL is 100 mg/kg bw/day. LOAEL is 500 mg/kg bw/day, based on the increased incidence of cervical rib
--
Carcinogenicity (mice). NOAEL was not established. LOAEL is 250 ppm (equivalent to 29/38mg/kg/ day [M/F]), based on minimal to moderate centrilobular hepatocellular hypertrophy, minimal to severe extramedullary hematopoiesis, minimal to moderate pigment deposition in the sternal bone marrow, and increased incidence of tissue masses/nodules in the lungs in the males, and minimal to moderate decreased cellularity in the femoral bone marrow and hyperplasia/hypertrophy of the epithelial cells of the terminal bronchioles of the females At the doses tested, the carcinogenic potential of IKI-220 (flonicamid) is positive at 250 ppm in males and females based on the increased incidence of alveolar/bronchiolar adenomas, carcinomas, and combined adenomas/carcinomas. Dosing was considered adequate based on increased incidence of tissue masses/nodules in the lungs and microscopic findings in the liver, spleen, bone marrow, and lungs. However, data were provided suggesting this effect is specific to sensitive strains of mice. Carcinogenic in mice.
--
Aggregate cancer risk for U.S. population... The only other tumor response was nasolacrimal duct tumors which occurred in female rats at the high dose which were considered to be possibly treatment-related, but a clear association with treatment could not be made. Unlike male rats, the nasal tumor response in females could not be clearly associated with spontaneous inflammation related to malocclusion of incisor teeth, due to the low incidence of both the neoplastic and non-neoplastic lesions.

Ref: August 31, 2005. Flonicamid; Pesticide Tolerance. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/
flonicamid.fr.aug.31.2005.html

“IKI-220 Technical: Combined Chronic Toxicity and Carcinogenciity Study in Rats,” (M. Kuwahara; IET 98-0142; 8/16/04). This volume contains discussion of questions concerning the bone/bone marrow effects and cerebellar granular tumors observed in the original study. This document was a response to U.S. EPA questions about an apparent increase incidence in hematopoiesis in bone marrow (femur). This effect was observed primarily as a compensatory response for a decrease in blood cell components due to spontaneous lesions at other sites and observed mainly in animals receiving unscheduled necropsies. Tables 1 and 2 (pages 10 - 11) in the volume list the causes or probable causes for increased hematopoiesis in the bone marrow (femur). The U.S. EPA reviewer asked whether fluorine from flonicamid could cause the bone effects. Metabolism studies have shown that free fluorine is not released and therefore the bone effects were not related to free fluorine. ... (Silva, 4/11/05)
Reference: April 28, 2005 - Summary of toxicology data. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch.
http://www.fluorideaction.org/pesticides/flonicamid.ca.epa.2005.pdf

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

-- Fluazifop butyl (CAS # 69806-50-4) was evaluated for developmental toxicity in the progeny of Sprague-Dawley CD rats administered oral doses of 0 (corn oil vehicle control), 10, 50 and 200 mg/kg/day by gavage on gestation days 6-20... Delayed fetal ossification and reduced fetal weight were dose-related and evident at all treatment levels, although fetal weights in association with dosages of 10 and 50 mg/kg/day were within the threshold of historical controls... [ICI AMERS INC; Butyl 2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxy) propionate butyl: Effects of Oral Administration Upon Pregnancy in Rats; 05/23/80; EPA Doc No. 88-920006839; Fiche No. OTS0543844]
-- Fluazifop butyl was evaluated for developmental toxicity in adult virgin Sprague-Dawley CD rats (160/group) administered oral doses of 0, 1, 5, 10 and 200 mg/kg/day during gestation days 6-20... Skeletal examinations further revealed retarded ossification that was dosage-related in fetuses of gestational treatment levels of 5 mg/kg/day and above... [ICI AMERS INC; Teratology Study with Fluazifop Butyl in Rats; 06/03/81; EPA Doc No. 88-920007020; Fiche No. OTS0545395]
Ref: TOXNET profile from Hazardous Substances Data Bank for FLUAZIFOP-BUTYL.
http://www.fluoridealert.org/pesticides/fluazifop-butyl.toxnet.hsdb.htm

**411-083 069476 Virgo, D. M., "Fluazifop-butyl: 55 week oral toxicity study in beagle dogs," Life Science Research, Stock, Essex, England, 10/15/82. LSR Report No. 81/ILK019/620. Six dogs/sex/group were dosed for 55 weeks with Fluazifop-butyl, 99.6% purity, by gelatin capsules at dose levels of 0, 5, 25, and 125 mg/kg/day in a chronic study. Test article within capsules was dissolved in 0.4 ml/kg corn oil vehicle. NOEL = 5 mg/kg/day... All other noteworthy findings were limited to the high dose group, as follows. Seven 125 mg/kg/day dogs (5 M, 2 F) were killed in extremis prior to term, generally after at least 29 weeks on study... Bone marrow samples taken at weeks 10 and 52 for smear analyses showed "reduced numbers of megakaryocytes ," suggesting reduced production as a reason for low platelet counts. Other hematology-related findings included increased incidence/degree of thymic involution, decreased lymphocyte counts, increased degree of hemosiderin-laden Kupffer cells, hypercellular sternal marrow, and severe extramedullary hematopoiesis in 4 male and 1 female decedent....
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
• Megakaryocytes - Very large bone marrow cells which release mature blood platelets.
 Hematopoiesis - The formation and development of blood cells, usually takes place in the bone marrow.

4.2.3.2 Fluazifop-butyl - Sprague Dawley Rats In a developmental toxicity study (MRID# 00088857, 92067047 and 92067019), fluazifop-butyl, [PP009 (94.8% a.i., batch/lot # P14)] was administered to 22 female CD Sprague Dawley strain rats/group in a corn oil (2 ml/kg) gavage at dose levels of 0, 10, 50 or 200 mg/kg bw/day from days 6 through 20 of gestation. Animals were sacrificed on day 21 ... Various parameters significant to development were affected relative to concurrent and/or historical controls. Post implantation loss was increased (125%) at 200 mg/kg/day. Examination of the heads of fetuses showed increased large fontanelles at 200 and 50 mg/kg/day (45.9% and 11.9%, respectively, versus 3.4% in concurrent controls. Increased incomplete and/or irregular ossification of cranial sutures at 200 and 50 mg/kg/day (58.9% and 43.7%, respectively, versus 14.3% in concurrent controls. The incidence of fissures into the interparietal bone was increased at 200 mg/kg/day (2.2% versus 0% in concurrent and historical controls. Only the percentages of fetal anomalies were presented with no litter incidence. No statistical analysis was presented for the fetal anomalies. Increased incidence of incomplete ossification of thoracic vertebral centra at 200, 50 and 10 mg/kg/day (75.`5%, 58.7, 48.4, respectively, versus 38.5% in concurrent controls, with a historical control range of 0-70.3%) appeared to be test material related. An increased incidence of absent hyoid bone at 200 and 50 mg/kg/day (23.0% and 17.2% versus 10.8% in concurrent controls) was observed. Increased incidence of incomplete ossification of one or more pelvic bones at 200 and 50 mg/kg/day (7.4% and 2.3%, respectively, versus 1.4% in concurrent control) was also observed. Absent hyoid bone and incomplete and/or irregular ossification of the cranial bones, and incomplete ossification of one or more pelvic bones may have been increased at 50 mg/kg/day, but since concurrent controls were higher than the mean historical control, these effects may have been incidental. The incidence of bilateral hydronephrosis at 200 mg/kg/day exceeded the historical control mean but not the range. The incidence of bilateral hydroureter at 200 mg/kg/day exceeded the historical control range and mean. No hydronephrosis nor hydroureter were seen in concurrent controls. In addition, subcutaneous edema (17.7% at 200 mg/kg/day versus 3.4% in concurrent controls) exceeded the mean of 8.9% in historical controls (the upper range was unreadable). The concurrent controls also were less than the mean of historical controls. Diaphragmatic hernia was seen in 1 fetus at 10 mg/kg/day, none at 50 mg/kg/day, and in 3 fetuses at 200 mg/kg/day, with no incidences in 2970 historical control fetuses. However a subsequent much larger study (MRID# 00088858) with 160 litter/group, showed an incidence of diaphragmatic hernias of 3/1113 in control fetuses, 1/1081 fetuses at 1 mg/kg/day, 3/1073 fetuses at 5 mg/kg/day, 2/1064 fetuses at 10 mg/kg/day, and a statistically significantly increased incidence in 59/1064 fetuses and 45/159 litters at 200 mg/kg/day. Since this anomaly was seen at a higher incidence (3 fetuses) in the controls in this study and was not replicated at the same dose in the second study, the single incidence of diaphragmatic hernia at 10 mg/kg/day was considered to be an aberration and not attributable to treatment. For developmental toxicity, the LOAEL is 10 mg/kg/day based on incomplete and/or irregular ossification of the cranial bones and incomplete ossification of thoracic vertebral centra; a NOAEL was not established.
Ref: December 10, 2004. US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf

4.2.3.4 Fluazifop-P-butyl - Wistar Rats In a developmental toxicity study (MRID 46028903) [Fluazifop-p-butyl, calculated as 90.9% a.i.; batch/lot# BX 247T A10209)] was administered to [(24 females) Alderly Park strain of Wistar rats] rats/dose by gavage at dose levels of 0, 2, 5 or 100 mg a.i./kg bw/day from days 7 through 21 of gestation ... Delayed ossification was seen in skull bones. The incidence of the partially ossified occipital (3.3% to 7.1% versus 0% in control), interparietals (9.5% to 29.5% versus 0.4% in control, historical controls), and in parietal bones (14.2% to 38.2% versus 0.4% in control) were dose related and statistically significant in fetuses and litters at 5.0 mg/kg/day and above. [In this study, historical control data are useful but limited because it was collected on studies with dosing gestational day 7 - 16.] The mean manus [10% to 30% of control] and pes scores [4% to 14% of control] showed a statistically significant dose related increase delayed ossification, starting at 5 mg/kg/day. [Manus and pes scores (1-6) were a subjective index of delayed ossification (1-6) in the fore paws and hind paws of each fetus.] Other indications of delayed ossification were seen at the highest dose tested for cervical vertebral arches and centrum (not ossified) and sternebrae 5 and 6. In addition, the odontoid [tooth related] and calcaneum [heel bone] were not ossified at 100 mg/kg/day. Fetal weight was significantly decreased 7% at 100 mg/kg/day only. Increased incidence of dilated ureter was seen only in litters at 100 mg/kg/day and kinked ureter in was dose related and statistically significant at all doses in fetuses, but not in litters at any dose level. There were no incidences of diaphragmatic hernias seen in this study. For developmental toxicity, the NOAEL is 2.0 mg/kg/day and the LOAEL is 5.0 mg/kg/day based on dose related delayed ossification in skull bones [occipital and parietal] in fetuses and litters (page 34-35).
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

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

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

http://www.fluoridealert.org/pesticides/fluazifop-p-butyl.msds.pdf

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

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

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

Fluazinam - Fungicide - CAS No. 79622-59-6

-- Prenatal developmental toxicity rats. Maternal NOAEL = 50 mg/kg/day LOAEL = 250 mg/kg/ day based on decreased body weight gain and food consumption and increased water consumption and urogenital staining Developmental NOAEL = 50 mg/kg/ day LOAEL = 250 mg/kg/ day based on decreased fetal body weights and placental weights, increased facial/ cleft palates, diaphragmatic hernia, and delayed ossification in several bone types, greenish amniotic fluid and possible increased late resorptions and postimplant
-- Prenatal developmental toxicity rabbits. Maternal NOAEL = 4 mg/kg/day LOAEL = 7 mg/kg/ day based on decreased food consumption and increased liver histopathology. Developmental NOAEL = 7 mg/kg/ day LOAEL = 12 mg/kg/ day based on an increase in total litter resorptions and possible fetal skeletal abnormalities

Ref: Federal Register: April 18, 2002. Fluazinam; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/fluazinam.fr.apr.18.2002.htm

Developmental. 98.5%, NZW Rabbits, 0, 2, 4, 7, 12 mg/kg/d, 16–18 pregnant females/dose Maternal NOAEL 4 mg/kg/d Maternal LOAEL 7 mg/kg/d Developmental NOAEL 7 mg/kg/d Developmental LOAEL 12 mg/kg/d Qualitative sensitivity of young. 7 mg/kg/d 9 Food consumption. 8 Liver histopath (cellular hypertrophy, single cell necrosis, binucleate hepatocytes, brown pigment deposition, apoptosis). 12 mg/kg/d 9 bwg, food consumption. 8 Liver histopath (cellular hypertrophy, single cell necrosis, binucleate hepatocytes, brown pigment deposition, apoptosis). 8 Incidence total litter resorptions. 8 Incidence placental anomalies. 8 Skeletal abnormalities (slight) (kinked tail tip, fused or incompletely ossified sternebrae, abnormalities of head bones).
Ref: Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.
http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf

Flucarbazone-sodium - Herbicide - CAS No. 181274-17-9

Prenatal development: LOAEL = 500 mg/kg/ day based on decreased fetal weight and increased incidence of delayed fetal ossification...
Ref: Federal Register. September 29, 2000. Flucarbazone-sodium; Time-Limited Pesticide Tolerances. Final Rule. http://www.fluoridealert.org/pesticides/flucarbazone_na.fr.sept2000.htm

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

-- Increases in the incidence of 14th rudimentary ribs and incomplete ossification of sternebrae and other bones were observed at 8 mg/kg. The results of this study indicate that daily treatment up to 4 mg/kg was without effect, while daily treatment up to 8 mg/kg, which produced severe maternal toxicity in the rat, produced no teratogenic effect (Rodwell et al., 1979).

-- Groups of 20 male and 20 female SPF (Sprague-Dawley derived) rats received 0, 30, 60, 120, or 240 ppm technical flucythrinate (85.4% pure) in the diet for 6 months. Males and females that received 240 ppm flucythrinate exhibited symptoms of decreased motor activity and ataxia, characterized by weakness in the extremities and gait disturbances. One control and 1 male and 4 females of the 240-ppm group died during the study. Males receiving 240 ppm and females receiving 240 and 120 ppm flucythrinate exhibited weight loss attributable to decreased food consumption. Water intake was depressed in males and females receiving 240 ppm. Leucocyte counts were slightly depressed in males receiving 120 and 240 ppm. Organ weights were in accord with body weights. An increased incidence of brown pigmentation in the spleen was observed in high- dose males and females (Shirasu, 1983).
-- 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... At autopsy, high-dose females exhibited an increased incidence of cystic uterus. 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. A slight increase in relative heart weight was found in high-dose males. No increase in abnormal histopathology or neoplasia was observed in any group of treated males. The uterine cysts found at autopsy in the high-dose females were characterized as endometrial cysts. In the high-dose females, further slight increases in uterine pathology were described histologically, namely etritis/endometritis, cystic endometrial hyperplasia and uterine fibrovascular polyps. Mammary fibroadenomas occurred at similar incidences in all female groups. The incidence of mammary adenomas in treated females exceeded that of controls, but not in a dose-related manner. Mammary adenocarcinomas occurred at higher incidence at 60 and 120 ppm, but not in a dose-related manner (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 higfemales, 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

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

Reproductive and developmental toxicity:
-- A rat developmental study with a maternal NOAEL of 25 mg/kg/day and with a maternal LOAEL of 125 mg/kg/day based on decreased body weight gain initially and a developmental NOAEL of 25 mg/kg/day and a developmental LOAEL of 125 mg/kg/day based on decreased fetal body weight, delayed development mainly delays in ossification in the skull, vertebrae, sternebrae, and appendages, and an increase in the incidence of extra ribs.
-- A rabbit developmental study with a maternal NOAEL of 5 mg/kg/ day and a maternal LOAEL of 25 mg/kg/day based on histopathological finds in the liver and a developmental NOAEL of 25 mg/kg/day and a developmental LOAEL of 125 mg/kg/day based on increased skeletal variations.
Ref: Federal Register. March 29, 2000. Notice of Filing a Pesticide Petition to Establish a Tolerance for Certain Pesticide Chemicals in or on Food.

http://www.fluoridealert.org/pesticides/flufenacet.fr.mar.29.2000.htm

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

-- Mammalian Toxicokinetics. Oral Administration in the rat. Single high dose. In an adequately conducted study groups of 5/sec Fischer 344 rats received a single dose of 350 mg.kg-1 bw of either unlabelled or [14 C-aniline]-flufenoxuron by gavage... There was a significant sex difference in the concentration of radioactivity found in the gonads (7.9 ppm in the males, 52 ppm in the females) and bone marrow (21.6 ppm in the males and 52.6 ppm in the females) (approximately 13 ppm).
-- Mammalian Toxicokinetics. Oral Administration in the rat. Single low dose. In a preliminary study, 1/sex Fischer 344 rats received a single dose of 3.5 mg.kg-1 bw [14 C-aniline]-flufenoxuron by gavage... Radioactivity was found to be extensively distributed throughout the carcass. Substantial concentrations of radioactivity were associated with the fat, GI tract, bone marrow and skin.
Ref: December 1995. Evaluation of Flufenoxuron use as a public hygiene insecticide. UK: Health and Safety Executive, Biocides & Pesticides Assessment Unit. Available at

http://www.pesticides.gov.uk/citizen/evaluations/143_confirm-box.htm

-- 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

90-Day oral toxicity in dog: LOAEL = 38 mg/kg/day (M/F), based on decreased hemoglobin, hematocrit levels, and erythrocyte counts in males and increased absolute liver weights, bone marrow hyperplasia and methemoglobinemia in males and females.
Reference: August 15, 2006. US EPA Human Health Risk Assessment for proposed tolerances on apples, pears, grapes, organges and livestock commodities imported into US. http://www.fluorideaction.org/pesticides/flufenoxuran.hra.epa.2006.pdf

Flumequine - Microbiocide - CAS No. 42835-25-6

-- Teratology studies were conducted in rats (0, 100, 200 or 400 mg/kg bw), mice (50, 100, 200, and 400 mg/kg bw) and rabbits (100, 200 or 400 mg/kg bw). None of these tests showed flumequine to be teratogenic or embryotoxic, but at doses exceeding 100 mg/kg per day it does have an effect on bone formation. The NOELs for the most sensitive species, rats and mice, were 100 mg/kg bw.
-- the twice daily oral administration of flumequine pellets 200 mg for 3 and 13 weeks at the dose level of 150 mg/kg bw/day induced few clinical signs (vomiting, low food consumption), marked reduction in bodyweight gain for females and minimal to slight arthropathies with cartilage damage. Only slight arthropathy was induced at the dose level of 60 mg/kg bw/day...
Ref: Committee for Veterinary Medicinal Products. Flumequine. Summary Report. EMEA/MRL/104/96-FINAL. June 1996. Study performed by EMEA, London UK for the European Agency for the Evaluation of Medicinal Products. Veterinary Medicines Evaluation Unit.

http://www.fluoridealert.org/pesticides/flumequine.report.1996.pdf

• Arthropathy: A rare form of chronic arthritis, reported to occur after attacks of acute rheumatic fever, characterised by an unusual form of bone erosion of the metacarpal heads and by ulnar deviation of the fingers; it resembles rheumatoid arthritis, but with less overt inflammation, and rheumatoid factor is absent. Synonym: Jaccoud's arthropathy.
Defintion from: http://www.books.md/J/dic/Jaccoudsarthropathy.php

Flumethrin - Acaricide - CAS No. 69770-45-2

Studies conducted with flumethrin in mice showed induction of chromosomal aberrations in bone marrow cells after a single dermal application of 5,325 mg/kg to a shaved area or a single intraperitoneal injection of 2,083 mg/kg, but not after repeated intraperitoneal injections of 128 mg/kg (Nakano et al. 1996). In contrast, micronuclei frequency was not significantly elevated after a single dermal dose of 5,325 mg/kg, but was increased after repeated intraperitoneal doses of 128 mg/kg (Nakano et al. 1996). (P 61)
Ref: September 2001. Draft Toxicological Profile for Pyrethrins and Pyrethroids. US Department of Health and Human Services. Public Health Service Agency for Toxic Substances and Disease Registry.

-- Groups of 28 mated female rats received doses of 0, 0.5, 1.0 r 2.0 mg/kg bw per day orally by gavage from days 6 to 15 of gestation. The test substance was administered in a vehicle of 2% aqueous Emulphor. Signs of toxicity (hypoactivity, ptosis, ataxia and salivation) were observed in the dams given 1.0 and 2.0 mg/bw day. Body weight and food consumption were significantllly reduced in the 2.0 mg/kg bw group. The incidence of foetal delayed ossification was significantly increased in the 2.0 mg/kg bw group... The NOELs were 0.5 mg/kg bw per day for maternal toxicity and 1.0 mg/kg bw per day for foetotoxicity.
Ref: Committee for Veterinary Medicinal Products. Flumethrin. Summary Report (1). June 1998. EMEA/MRL/469/98-FINAL. The European Agency for the Evaluation of Medicinal Products.

http://www.fluorideaction.org/pesticides/flumethrin.eu.june.1998.pdf

Abstract: The genotoxic potential of the pyrethroid flumethrin was evaluated by using the combined protocol of metaphase analysis and micronucleus test in vivo in mouse bone marrow. The dermal route was tested in a single treatment and the intraperitoneal (i.p.) route in a single and a multiple treatment. Flumethrin showed a cytotoxic effect on both myelopoiesis and erythropoiesis, as evidenced by a reduction in the mitotic index and in polychromatic erythrocyte values. An increase in the frequency of gaps after the dermal exposure and of breaks only at the highest dose tested in the i.p. treatment indicates a weak clastogenic potential of the compound. A significant increase in the frequency of micronucleated polychromatic erythrocytes was observed after single and multiple i.p. treatments. In the latter, the induction of micronuclei was highly significant but not accompanied by an increase in breaks. This may indicate that the clastogenic effect might not account by itself for the induction of micronuclei, which could also have arisen from an aneugenic potential of flumethrin.
Ref: Nakano E et al. (1996). Evaluation of the Genotoxic Potential of Flumethrin in Mouse Bone Marrow by Chromosomal Analysis and Micronucleus Test. Teratogenesis, Carcinogenesis, and Mutagenesis, Vol. 16, No. 1, pages 37-48.

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

Abstract: An N-phenylimide herbicide, S-53482, inhibits protoporphyrinogen oxidase, an enzyme common to chlorophyll and heme biosynthesis, and produces embryolethality, teratogenicity [mainly ventricular septal defects (VSD) and wavy ribs], and growth retardation in rats. In order to elucidate the mechanism of the developmental toxicity, in particular VSD, effects of the herbicide on rat embryonic blood cells were investigated histologically at the light and electron microscopic levels at 6, 12, 24, 36, and 48 h after oral administration of the chemical to pregnant rats on day 12 of gestation, the most sensitive day for toxicity. Electron and light microscopy demonstrated mitochondrial lesions, including abnormal iron deposits that were probably due to inhibition of heme biosynthesis, in erythroblasts derived from the yolk sac. Subsequently, degeneration of these erythroblasts occurred followed by erythrophagocytosis. Histologically hearts from exposed embryos had a thin ventricular wall, which may reflect a compensatory reaction to a loss of embryonic blood cells. Thus, the herbicide may induce VSD due to hematological dysfunction caused by the inhibition of heme biosynthesis rather than by direct injurious effects on the heart.
Ref: Kawamura S et al (1996). Histological changes in rat embryonic blood cells as a possible mechanism for ventricular septal defects produced by an N-phenylimide herbicide. Teratology. Nov;54(5):237-44.

http://www.fluorideaction.org/pesticides/flumioxazin.abstracts.htm

-- "Teratology Study of S-53482 Administered Dermally to Rats"; (S. Kawamura; Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Osaka, Japan; Project ID 2018; 3/14/91); The skin of twenty four mated Slc:SD® female rats was treated with 0, 30 or 100 mg/kg/day of S-53482 (lot no. PYG-89021-M, purity: 94.8%) for 6 hours/day from day 6 through day 15 of gestation. An additional group of 25 females were treated in the same manner with 300 mg/kg/day of the test material... There was an increased incidence of a minor skeletal anomaly of wavy ribs for the 300 mg/kg group (0:0/23 vs. 10/17)... (Moore, 6/7/02)
-- "Preliminary Teratology Study of SB-1297, SB-1335 or SB-1855 Administered Orally to Rats"; (S. Kawamura; Environmental Health Science Laboratory, Sumitomo Chemical Co. Ltd, Osaka, Japan; Project ID 599; 1/9/89); Six mated female SPF Slc:SD rats/group were dosed by oral gavage with 0, 30, 100, 200, or 500 mg/kg of SB-1855 (lot no. OK-86-01, purity: 98.2%, also identified as S-53482 in vol. 52894-082) from gestation day 6 through day 15... Teratologic abnormalities for the 30 mg/kg group included ventricular septal defects in the heart (0:0/38 vs. 30:11/25, p<0.01)), persistent left umbilical artery (0:0/38 vs. 30:3/25), and wavy ribs (0:0/42 vs. 30:9/28)... (Moore, 7/29/02)
-- "Pathogenesis of Developmental Effects Produced by S-53482, an N-phenylimide Herbicide, in Rats"; (S. Kawamura; Environmental Health Science Laboratory, Sumitomo Chemical Co. Ltd, Osaka, Japan; Project ID DSB06; 2/20/97); Pregnant female Crj:CD rats were dosed by oral gavage with 0 (0.5% methylcellulose) or 400 mg/kg of S-53482 (lot no. PYG-89021- M, purity: 94.8%) on day 12 of gestation... Examination of the embryonic blood revealed massive deposits of iron in the treated embryos by 24 hours post-dose... 17. In the skeletal examination, delayed ossification of the ribs was noted for the treated fetuses on day 17 (0: 0 vs. 400: 5.6%). On day 20, the incidence of wavy ribs (23.9%) and bent scapula (8.5%) was noted for the treated group in comparison with 0 incidence for the control. Physiologically, the anemia suffered by the treated fetuses preceded the effects of enlarged heart and edema and likely contributed to these effects. Likewise, the author of the report surmised that the skeletal abnormalities may have been due to reduced serum protein levels with delayed development of osteoblast progenitors and low fetal serum alkaline phosphatase levels. Study supplemental (non-guideline study). (Moore, 7/3/02)
-- "Three-Month Subacute Toxicity Study of S-53482 by Dietary Administration in Rats"; (Haruhiko Adachi; Sumitomo Chemical Co., Environmental Health Science Laboratory,, Ltd., Osaka, Japan; Study No. 1760; 4/26/91); Sixteen Crj:CD (SD) rats/sex/group were treated in the diet with 0, 30, 300, 1000 or 3000 ppm of S-53482 (lot no. PYG-89021-M, purity: 94.8%). Six of these animals/sex/group were treated for 5 weeks. The remaining 10 animals/sex/group were treated for 13 weeks ((M): 0, 1.94, 19.4, 65.2, 197.3 mg/kg/day, (F) 0, 2.22, 22.4, 72.8, 218.4 mg/kg/day)... Hypercellularity in the bone marrow was evident for the 1000 and 3000 ppm females at 13 weeks (0: 0/10, 1000: 6/10, 3000: 7/10). Other noted lesions for the 3000 ppm females were focal or generalized necrosis in the liver (0:0/10 vs. 3000: 4/10), extramedullary hematopoiesis in the liver (0: 0/10 vs. 3000: 5/10), myocardial fibrosis in the heart (0: 0/10 vs. 3000: 2/10), myelofibrosis and osteosis in the bone marrow (0: 0/10 vs. 3000: 3/10)...
-- "Teratology Study of S-53482 Administered Orally to Rats (Amendment Included)"; (S. Kawamura; Sumitomo Chemical Co., Ltd., Biochemistry and Toxicology Laboratory, Osaka, Japan; Project ID 1759; 8/28/90, (addendum) 12/26/95); Twenty two mated Slc:SD® female rats were treated by oral gavage with 0, 1, 3, 10, or 30 mg/kg/day of S-53482 (lot no. PYG-89021-M, purity: 94.8%) from day 6 through day 15 of gestation... There was an increased incidence/litter of cardiac (0:2/22 vs. 10:6/22, 30:12/18 (p<0.01)) and skeletal (0:0/22 vs. 30:4/18) malformations. The predominant cardiac and skeletal malformations were ventricular septal defect and double aortic arch and
curvature of the scapula and ulna. There was also an increased incidence/litter of the minor skeletal anomaly, wavy ribs, in the 30 mg/kg group (0: 1/22 vs. 30: 12/18, p<0.01). Adverse effect indicated: malformations in cardiac and skeletal development; Maternal NOEL: 30 mg/kg/day (based upon a lack of treatment-related effects at the highest dose tested); Developmental NOEL: 3 mg/kg/day (based upon the increased incidence of cardiac malformations in the fetuses of the 10 mg/kg treatment group); Study acceptable. (Moore, 6/5/02)
Ref: January 2003 (revised) - Summary of Toxicological Data. California EPA, Department of Pesticides Regulation, Medical Toxicology Branch.

-- Subchronic toxicity. Subchronic toxicity studies conducted with flumioxazin technical in the rat (oral and dermal), mouse and dog indicate a low level of toxicity. Effects observed at high dose levels consisted primarily of anemia and histological changes in the spleen, liver and bone marrow related to the anemia.
-- 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

Fluorocarbon propellants -
(not used as pesticide; though in the past they were used as propellants for pesticides)
Aerosol sprays containing fluorocarbon propellants are another source of solvent intoxication. Prolonged exposure or daily use may result in damage to several organ systems. Clinical problems include cardiac arrhythmias, bone
marrow depression, cerebral degeneration, and damage to liver, kidney, & peripheral nerves. Death occasionally has been attributed to inhalant abuse, probably via the mechanism of cardiac arrhythmias, especially accompanying exercise or upper airway obstruction.

Ref:
Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996. 575]

http://www.fluoridealert.org/pesticides/dichlorodifluorometh.toxnet.htm

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

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

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

Reproductive and developmental toxicity (page 3)
• In a developmental toxicity study in rats gavage dosed from gestation days 7 to 20 at levels of 0, 5, 60 or700 mg/kg/day, evidence of maternal and fetal toxicity was observed at 700 mg/kg/day, the highest dose tested. The maternal and fetal NOAEL was 60 mg/kg/day based on statistically lower body weights in dams an fetuses, and skeletal findings in fetuses that included delayed ossification of some bones and slight increases in the incidences of various rib and thoracic vertebrae anomalies.
• In a developmental toxicity study with rabbits, pregnant animals were given oral doses of 0, 5, 20 or 60 mg/kg/day on gestation days 6 to 28. At the high dose, 15 animalls were sacrificed following spontaneous abortions and 3 animals were found dead. The few surviving animals in this group had live fetuses at cesarean sectioning but other than lower fetal weight and crown/rump length, no treatment-related findings were observed upon external, visceral and skeletal examinations of these fetuses. The NOAEL for maternal and fetal toxicity was 20 mg/kg/day.
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

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

In the main study, fluoroglycofen-ethyl (97.8% pure) was administered by gavage to groups of 18 New Zealant White rabbits at concentrations of 1 (water and vehicle controls), 10, 30 and 90 mg/kg bw/day on days 8-18 of gestation. The animals were killed on day 29.... Overt signs of toxicity seen from days 10-29 in the 90 mg/kg bw/day groups were an increased incidence of scant, red and/or soft faeces, thin appearance, red vaginal discharge, ataxia and lethargy. Maternal body weights in the 90 mg/kg bw/day group were decreased from day 12 to the end of gesttion... Two animals in the 90 mg/kg bw/day group died on day 19, ten aborted their litters between days 21 - 26, and one litter was entirely resorbed at necropsy. Most of the resorptions in this dose group were late resorptions. In the 90 mg/kg bw/day group there was an increased number or resorptions and a decrease in the number of viable fetuses, although the latter was not statistically significant. As a result of this, the viability index (No. viable fetuses/ No. corpora lutea) were reduced. The sex ratio of the fetuses was not altered by fluoroglycofen-ethyl, but the mean weights and crown-to-rump lengths were decreased in fetuses of both sexes at 90 mg/kg bw/day. The decrease in fetal weight was reflected in a decrease in the weight of the gravid uterus in the high dose group. There was a treatment related increase in the incidence of unossified talus in the high dose group, but overall, fluoroglycofen-ethyl did not alter the incidences of developmental variations or malformations. When administered to New Zealand White rabbis by gavage on days 8-18 of gestation at 90 mg/kg bw/day, fluoroglycofen-ethyl was abortifacient, maternally toxic, and feto- and embryotoxic. The NOEL for embryo/fetotoxicity was 30 mg/kg bw/day, based on increased resorptions and abortions and decreased fetal size and viability at 90 mg/kg bw/day. The NOEL for maternal toxicity was 30 mg/kg bw/day, based on overt signs of toxicity, decreased maternal body weights, and maternal deaths at 90 mg/kg bw/day.
Definition of Talus: the bone in the ankle that articulates with the leg bones to form the ankle joint.
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

Fluorouracil - Former insect Chemosterilant; now used as a pharmaceutical -
CAS No. 51-21-8

-- A major use of fluorouracil is in the palliative treatment of carcinoma of the colon, rectum, breast, stomach, and pancreas that is not amenable to surgery or irradiation. The major toxic effects of fluorouracil are on the normal, rapidly proliferating tissues particularly of the bone marrow and lining of the gastrointestinal tract. Leukopenia , predominantly of the granulocytopenic type, thrombocytopenia, and anemia occur commonly with intravenous fluorouracil therapy at doses ranging from 6 to 12 mg/kg. Pancytopenia and agranulocytosis also have occurred...
-- EPA believes that there is sufficient evidence for listing fluorouracil on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the toxicity of this substance to bone marrow, and on the developmental and chronic neurotoxicity data for this chemical.
Ref: USEPA/OPPT. Support Document for the Health and Ecological Toxicity Review of TRI Expansion Chemicals. U. S. Environmental Protection Agency, Washington, DC (1993). As cited by US EPA in: Federal Register: January 12, 1994. Part IV. 40 CFR Part 372. Addition of Certain Chemicals; Toxic Chemical Release Reporting; Community Right-to-Know; Proposed Rule.
Definition for Leukopenia - an abnormal lowering of the white blood cell count

Potential Adverse Effects on Fetus: Exposure in first trimester: skeletal abnormalities; hypoplasia of aorta, lungs, thymus, and gastrointestinal tract; and urinary tract abnormalities. Fetus exposed in third trimester had cyanosis and clonus... the incidence of malformations, particularly those affecting the tail, hindlimb bud, and brain, was increased.
Ref: TOXNET profile from Hazardous Substances Data Base.

http://www.fluoridealert.org/pesticides/Fluorouracil.TOXNET.HSDB.htm

Fluoxastrobin - Fungicide - CAS No. 193740-76-0

Reproduction and fertility - rats. Offspring systemic: decreased body weights, delayed preputial separation, and incomplete ossification in the F1 and/or F2 males and females.
Ref: Federal Register. September 16, 2005. Fluoxastrobin; Pesticide Tolerances. Final Rule.

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

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

Abstract: This report describes the first part of a study which was undertaken to examine the teratogenic potential of triazole compounds used as fungicides in agriculture. Pregnant Wistar rats were given single oral dosages of flusilazole or bitertanol on days 9, 10, 11 or 13th of gestation (positive vaginal smear=day 1) at levels of 1/5, 1/10 and 1/50 LD50. The dosages were calculated from the reported LD50 values of 1272 mg/kg for flusilazole and 5000 mg/kg for bitertanol. The results of the study demonstrated that both compounds induce congenital anomalies when given on days 9, 10 or 11th at levels corresponding to 1/5 and 1/10 LD50. The types of the registered malformations after flusilazole treatment were exophthalmus, hypognathia, macroglossia and cleft palate and after bitertanol treatment micro- and acaudia and in rare cases exophthalmus, hypognathia and cleft palate. A clear dose effect relationship was established for both compounds.
Ref: Vergieva T (1990). Vergieva T. eratology 1990 Aug;42(2):27A-28A. Abstract from Toxnet.

• Definitions:
Exophthalmia (n.) The protrusion of the eyeball so that the eyelids will not cover it, in consequence of disease.
Hypognathus - Unequal conjoined twins in which the rudimentary parasite is attached to the mandible of the autosite.
Macroglossia - Excessively large tongue.

Fluosilicic acid - Wood Preservative - CAS No. 16961-83-4

-- The effects of long-term exposure to fluorosilicic acid are changes in bone, corrosivity of the mucous membranes (e.g., ulceration of the nose, throat, and bronchial tubes), coughing, shock, pulmonary edema, fluorosis, coma, and even death (LCI, Ltd., undated-a). In a study of 50 workers engaged for approximately 30 years in the production of phosphate fertilizers, the concentration of gaseous fluoride (hydrogen fluoride, silicon tetrafluoride, and fluorosilicic acid) ranged from 0.04 to 0.17 mg/m 3 . Nine workers had increased bone densities (Fabbri et al., 1978; cited by HSDB, 2000a).
Ref: Sodium Hexafluorosilicate [CASRN 16893-85-9] and Fluorosilicic Acid [CASRN 16961-83-4]. Review of Toxicological Literature. October 2001. Prepared for Scott Masten, Ph.D. National Institute of Environmental Health Sciences P.O. Box 12233 Research Triangle Park, North Carolina 27709 Contract No. N01-ES-65402. Submitted by Karen E. Haneke, M.S. (Principal Investigator) Bonnie L. Carson, M.S. (Co-Principal Investigator) Integrated Laboratory Systems P.O. Box 13501 Research Triangle Park, North Carolina 27709.

http://www.fluoridealert.org/pesticides/Fluorosilicates.NIH.2001.pdf

Flupyrsulfuron-methyl - Herbicide - CAS No. 144740-54-5

- Reproductive toxicity. Target/critical effect - Developmental toxicity. Reduced foetal weight, retarded ossification.
Ref: FINAL European Commission Review report for the active substance flupyrsulfuron-methyl. Finalised in the Standing Committee on Plant Health at its meeting on 27 April 2001 in view of the inclusion of flupyrsulfuron-methyl in Annex I of Directive 91/414/EEC-
.
http://europa.eu.int/comm/food/fs/ph_ps/pro/eva/newactive/list2_flupyrsulfi_en.pdf

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

-- Developmental toxicity studies. (a) Oral teratology study in rats. In a study (1992), groups of 30 mated outbred albino Sprague-Dawley CRL:COBS CD(SD)BR rats were administered by gavage fluqinconazole (96% purity) in a 1% w/v aqueous methylcellulose solution at concentrations of 0, 0.4, 2 and 20 mg/kg bw/day (based on a range-finding study) from day 6 to 15 of presumed gestation... An increase in abnormal sternebrae was seen in the low dose group (27%) and the high dose group (31%, p<0.05) but not at the mid dose group (15%) when compared to controls (13%) - as the incidence, of this relatively common anomaly, in the low dose group is not statistically significant and not party of a dose response it is considered to be of no biological significance. Fluquinconazole was clearly maternally toxic, producing abortion and mortality at 8 mg/kg bw/day. There was evidence of mild fetotoxicity (abnormal sternebrae) but not teratogenicity at 9 mg/kg bw/day. The NOAEL for maternal and fetotoxicity was 2 mg/kg bw/day based on increased incidence of abortions in dams and increased mortality.
-- In the rabbit the NOEL for maternal and fetal toxicity was 2 mg/kg bw/day. Fluquinconazole was not teratogenic in the rabbit in the presence of maternal toxicity. Fluquinconazole was clearly maternally toxic, producing abortion and mortality at 8 mg/kg bw/day. There was evidence of mild fetotoxicity (abnormal sternebrae) but not teratogenicity at 8 mg/kg bw/day.
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 - Herbicide - CAS No. 59756-60-4

Developmental toxicity–rats 0, 1, 5, 10, or 75 mg/kg/day by gavage
NOAEL - maternal: 10 mg/kg/day.NOAEL - developmental: 10 mg/kg/day.
LOAEL - maternal: 75 mg/kg/day. LOAEL - developmental: 75 mg/kg/day.
Effects: decreased body weight gain and food consumption; decreased fetal viability; decreased fetal weight; significant increase in the incidence of malformations including cephalocele and sternoschisis; increased incidence of incomplete ossification of various skeletal structures.
Developmental toxicity–rabbits 0, 5, 10, or 50 mg/kg/day by gavage
NOAEL - maternal: 10 mg/kg/day. NOAEL - developmental: 10 mg/kg/day.
LOAEL - maternal: 50 mg/kg/day. LOAEL - developmental: 50 mg/kg/day.
Effects: decreased body weight gain and food consumption; decreased fetal viability; decreased fetal weight; malformations including gastroschisis, cephalocele, domed head, flexed paw, and skull and sternum anomalies.

Ref: US EPA. Augustr 17, 2004. Human Health Risk Assessment for Fluridone TRED.

Teratology - Rat: Maternal NOEL=100 mg/kg/day; Maternal LEL=300 mg/kg/day (decreased body weight); Developmental NOEL=300 mg/kg/day; Developmental LEL=1000 mg/kg/day (decreased fetal weight, delayed ossification); Teratogenic NOEL=1000 mg/kg/day (HDT); LEL=none; core grade minimum (Elanco Products, 1986)
Ref: US EPA IRIS for Fluridone. 1990
.
http://www.fluoridealert.org/pesticides/Fluridone.EPA.IRIS.1990.htm

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

The developmental NOAEL is 250 mg/kg/day, the LOEL is 500 mg/kg/day based on reduced ossification... The developmental toxicity NOAEL is 300 mg/kg/day, and the LOEL is 600 mg/ kg/day, based on an increase in two ossification variations incompletely ossified cervical vertebral transverse processes and pubes.
Ref:
Federal Register. September 30, 1998. Fluroxypyr; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/Fluroxypyr.FR.Sept.30.1998.htm

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

Abstract: The objective of this study was to assess the maternal and developmental toxicity potential of fluroxypyr methylheptyl ester (FMHE) in rats. Groups of 28 Sprague-Dawley rats received 0 (corn oil vehicle), 100, 300, or 600 mg/kg/day of FMHE via gavage on gestation days 6-15. In-life parameters evaluated included clinical signs of toxicity, feed consumption, body weights and body weight gains. On gestation day 20, all surviving females were euthanized and examined for gross pathologic changes and alterations in liver, kidney and gravid uterus weights. The number of corpora lutea, implantations and resorptions was determined. The fetuses were removed, weighed, sexed and examined for external, visceral and skeletal alterations. At 600 mg/kg/day, eight rats (29%) died prior to the scheduled necropsy. No specific treatment-related gross pathological lesions were found. Decreased body weight gain, slightly decreased feed consumption and an increased incidence of anogenital staining also were noted at this dose level. No signs of maternal toxicity were observed in rats given 100 or 300 mg/kg/day. In the fetuses obtained from the 600 mg/kg/day group, several skeletal variations (delayed ossification) occurred with increased incidence. Despite the severity of the maternal toxicity at this dose level, there were no other signs of developmental toxicity, nor were there any adverse effects of treatment on any other developmental parameters at the 100 or 300 mg/kg/day dose levels. Thus, the no-observed-effect-level (NOEL) for maternal and developmental toxicity was 300 mg/kg/day.
Ref: Carney EW et al. (1995). Developmental toxicity study in rats with fluroxypyr methylheptyl ester. Author Address: Toxicology Research Laboratory, Dow Chemical Co., Midland, MI. Source: Teratology; Mar;51(3):180. Abstract from Toxnet.

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

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

-- Developmental toxicity. Sprague-Dawley rats (25/dose) were gavaged on days 6 to 15 of pregnancy with doses of 0, 5, 50, 250 or 1000 mg/kg bw/day flurtamone (91.9% pure) in an aqueous suspension of 0.25% CMC containing 1% Tween 80... All rats were terminated on gestation day 20 and received a gross necropsy... The external, soft tissue and skeletal examinations of the foetuses did not reveal any dose-dependent increases in foetal malformations. Foetuses in the 1000 mg/kg/day group showed evidence of delayed development (i.e. significant decreases in the average number of ossified vertebrae, xiphoid centres, and metatarsals when compared to control). In the top dose group there was also an increase in the average number of thoracic ribs. These skeletal variations are generally considered to be reversible delays in development that resolve with continuted growth and could be expected observations in foetuses with decreased body weights... Because of the reduced body weight gain observed at 5 mg/kg bw/day, a clear NOEl for maternal toxicity could not be determined in this study. Therefore, based on reduced body weight gain at 5 mg/kg bw/day, a LOEL of 5 mg/kg bw/day was determined for maternal toxicity in this study. Based on the developmental effects at the top dose, a NOEL of 250 mg/kg bw/day was determined for foetal toxicity...
-- Developmental toxicity. Rabbit. Artificially-inseminated rabbits (20/dose) were gavaged with doses of 0, 20, 200 or 600 mg/kg bw/day flurtamone (91.9%purity) in an aqueous suspension of 0.25% CMC containing 1% Tween 80 on gestation days 6 to 19... All rabbits were terminated on gestation day 29 and received a gross necropsy... The foetal examinations revealed that four foetuses from one top dose litter had interrelated external, soft tissue and skeletal malformations (the dam had 9 implantations with 5 early resorptions). These observations (e.g. open eyelids, cleft palate, syndactylly [see definition below] and irregular shaped skull bones) were considered to be unrelated to treatment because: i) these alterations occurred in 4 litter mates, ii) the litter incidences for these alterations were generally not significantly different from the control group incidences, iii) all other malformations and variations that occurred in high-dose group foetuses, other than those observed in the above 4 litter mates, were single events within the historical control ranges [pages 112-113].
• FAN Note: "Syndactylly" as spelled in this UK report. The definition for "Syndactyly" in an American dictionary: any degree of webbing or fusion of fingers or toes, involving soft parts only or including bone structure. SYN symphalangism (1), symphalangy, syndactylia, syndactylism. Ref: Stedman's Concise Medical Dictionary for the Health Professions. Illustrated 4th Edition. 2001.
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

Fluthiacet-methyl -Herbicide - CAS No. 117337-19-6

-- Prenatal Maternal developmental in rats and rabbits. Maternal in rats: NOAEL = 1,000 mg/ kg/day, HDT Maternal in rabbits: NOAEL = 1,000 mg/ kg/day, HDT Developmental in rabbits: NOAEL = 300 mg/kg/ day Developmental in rabbits: LOAEL of 1,000 mg/ kg/day based on slight non- significant increased incidence of irregularly shaped sternebrae attributed to a delay in fetal development. (See following.)
-- In rabbits, in utero exposure did not result in maternal toxicity at 1,000 mg/kg/day. Developmental toxicity, however, was seen at this dose characterized as an increase in irregular sternebrae (a variation which is reversible). The occurrence of developmental toxicity at which no maternal toxicity was noted indicates an apparent increase in susceptibility. The Office of Pesticide Program's Hazard Identification Assessment Review Committee (HIARC), however, determined that the apparent susceptibility is not convincing because of the equivocal nature of the effect based on:
(1) The increased incidence of irregular sternebrae was not statistically significant when compared to concurrent controls;
(2) the increase occurred at the Limit-Dose (1,000 mg/kg/day;
(3) it was the only anomaly seen (i.e., a single variation);
(4) the dose response was not strong because there was only a small increase in the litter incidence between the low- (5 mg/kg/day) and the high-dose (1,000 mg/kg/day), with the mid- and high-dose groups having 8 litters with this variation;, and
(5) this endpoint is appropriate to establish a LOAEL and not appropriate for risk assessments. Based on these factors, the HIARC concluded that there is no increased susceptibility in the rabbit study. Therefore, the 10X FQPA safety factor to ensure the protection of infants and children was not applied in the risk assessments.
Ref: Federal Register: December 21, 2001. Fluthiacet-methyl; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Fluthiacet.M.FR.Dec.21.2001.htm

Flutolanil - Fungicide - CAS No. 66332-96-5

A rabbit developmental study with a maternal NOEL of 5 mg/kg/day and a maternal LOEL of 25 mg/kg/day based on histopathological finds in the liver and a developmental NOEL of 25 mg/kg/day and a developmental LOEL of 125 mg/kg/day based on increased skeletal variations... Reproductive and developmental toxicity... A rat developmental study with a maternal NOEL of 25 mg/kg/day and with a maternal LOEL of 125 mg/kg/day based on decreased body weight gain initially and a developmental NOEL of 25 mg/kg/day and a developmental LOEL of 125 mg/kg/day based on decreased fetal body weight, delayed development [mainly delays in ossification in the skull, vertebrae, sternebrae, and appendages], and an increase in the incidence of extra ribs. A rabbit developmental study with a maternal NOEL of 5 mg/kg/day and a maternal LOEL of 25 mg/kg/day based on histopathological finds in the liver and a developmental NOEL of 25 mg/kg/day and a developmental LOEL of 125 mg/kg/day based on increased skeletal variations.
Ref: Federal Register. June 23, 1998. [PF-813; FRL-5795-1]
http://www.fluoridealert.org/pesticides/Flutolanil.FR.June.23.1998.htm

Flutriafol - Fungicide - CAS No. 76674-21-0

7.3 Reproductive toxicity. Pregnant rats were administered 0, 10, 50 or 125 mg/kg bw/day from day 5 to 15 of gestation. Maternal toxicity was apparent at the highest dose level. Significant dose-related reductions in fetal ossification were observed in all treatment groups. At the 10 mg/kg bw dosage level, incomplete ossification of the odontoid, calcaneum and occipital bones were noted. In the 50 and 125 mg/kg bw dosage groups, the incidence of fetuses with extra ribs was increased. In a rabbit teratology study, the dams were administered (orally) 9, 2.3, 7.5 or 15 mg/bw from day 6 to 18 of gestation. Reduced maternal body weight gain, increased post implantation loss, and a reduction in viable fetuses were seen at the 15 mg/kg bw dose level. There was a small increase in the number of fetuses with extra ribs in the lumber region in all treatment groups. The NEL in the rabbit study was considered to be 7.5 mg/kg bw/day. Although a NEL was not established for the rat study, it was considered to be in the order of 10 mg/kg bw/day.
Evaluation on: Flutriafol. October 1996. Issue No. 158, UK Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7PX.
http://www.pesticides.gov.uk/citizen/evaluations/158_confirm-box.htm

Definitions:
Odontoid - Having the form of a tooth; toothlike. Of or pertaining to the odontoid bone or to the odontoid process. Odontoid bone, the anterior process of the centrum of the second vertebra, or axis, in birds and mammals. See Axis. Origin: Gr., a tooth + form: cf.F. Odontoide. Source: Websters Dictionary
Calcaneum - Synonym: calcaneus. Origin: L. The heel.
Occipital - Of or pertaining to the occiput, or back part of the head, or to the occipital bone. Occipital bone, the point of the occiput in the mesial plane farthest from the ophryon. Origin: Cf. F. Occipital. The occipital bone. Source: Websters Dictionary

Fluvalinate - Acaracide, Insecticide - CAS No. 69409-94-5

Delayed ossification and decreased weight and length of fetuses were observed in offspring of rats orally administered 50 mg/kg/day (LOEL) on days 6 to 15 of gestation. The NOEL was 10 mg/kg/day. These effects were observed at doses that produced maternal toxicity. Curved tibia and fibula were observed in the offspring of rabbits orally administered 125 mg/kg/day (LOEL). The NOEL was 25 mg/kg/day. In a 2-generation reproduction study, a decrease in pup weight and growth were observed in offspring of rats orally administered 5 mg/kg/day (LOEL). The NOEL was 1 mg/kg/day. Significantly decreased weight and survival were observed in offspring of rats orally administered 25 mg/kg/day... EPA believes that there is sufficient evidence for listing fluvinate on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available developmental, dermal, and hematological toxicity data for this chemical.
Ref: USEPA/OPP. Support Document for the Addition of Chemicals from Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) Active Ingredients to EPCRA Section 313. U. S. Environmental Protection Agency, Washington, DC (1993). As cited by US EPA in: Federal Register: January 12, 1994. Part IV. 40 CFR Part 372. Addition of Certain Chemicals; Toxic Chemical Release Reporting; Community Right-to-Know; Proposed Rule.

Fomesafen - Herbicide - CAS No. 72178-02-0

Acute toxicity. EPA has selected the developmental NOEL of 7.5 mg/kg/day from the oral rat developmental toxicity study for the acute dietary endpoint; at the lowest observed effect level (LOEL) of 50 mg/ kg/day, fetuses had delayed or partial ossification and extra ribs.
Ref: Federal Register. July 9, 1997. [OPP-300512; FRL-5729-5] RIN 2070-AB78 http://www.fluoridealert.org/pesticides/Fomesafen.FR.July.9.1997.htm

 
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