Ataxia - Adverse Effects
Fluorinated and Fluoride Pesticides

 
 

What is Ataxia? Ataxia is a symptom, not a specific disease or diagnosis. Ataxia means clumsiness, or loss of coordination. Ataxia may affect the fingers and hands, the arms or legs, the body, speech or eye movements. This loss of coordination may be caused by a number of different medical or neurologic conditions; for this reason, it is important that a person with ataxia seek medical attention to determine the underlying cause of the symptom and to get the appropriate treatment.

What causes Ataxia? Most often, ataxia is caused by loss of function in the part of the brain which serves as the "coordination center", which is the cerebellum. The cerebellum is located toward the back and lower part of the head. The right side of the cerebellum controls coordination on the right side of the body, and the left side controls coordination on the left. The central part of the cerebellum is involved in coordinating the very complex movements of gait, or walking. Other parts of the cerebellum help to coordinate eye movements, speech and swallowing.

Ataxia may also be caused by dysfunction of the pathways leading into and out of the cerebellum. Information comes into the cerebellum from the spinal cord and other parts of the brain, and signals from the cerebellum go out to the spinal cord and to the brain. Although the 0cerebeirectly control strength ("motor function") or feeling ("sensory function"), the motor and sensory pathways must work properly to provide the correct input into the cerebellum. Thus, a person with impaired strength or sensation may notice clumsiness or poor coordination, and the doctor may say that person has ataxia.
Ref: http://amazinggrace.org/richard/ataxia.htm


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.

Benfluralin - Herbicide - CAS No. 1861-40-1

Animal Toxicity Studies: ... ATAXIA, WEAKNESS, FALLING. REGURGITATION ALSO OCCURRED IN FIRST 2 HR AFTER TREATMENT. THE OTHER SIGNS OCCURRED 2 TO 14 DAYS AFTER TREATMENT. ALTHOUGH NO BIRDS DIED, CONSIDERABLE WT LOSSES HAD OCCURRED BY THE END OF THE 14 DAY OBSERVATION PERIOD. /FEMALE MALLARDS, ACUTE ORAL/ [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. 13]
Ref: TOXNET profile from Hazardous Substances Data Bank. http://www.fluoridealert.org/pesticides/benfluralin.toxnet.hsdb.htm

Bifenthrin - Acaracide, Insecticide - CAS Numbers: 82657-04-3 (Cis); 83322-02-5 (Trans)

A 13-week feeding study in dogs (by capsule) of doses at nominal dose levels of 0, 2.5, 5, 10, or 20 milligram/kilogram/day (mg/kg/day) (equivalent to 2.21, 4.42, 8.84, and 17.7 mg/kg/day, based on percent active ingredient (a.i.)) for 13 weeks... Ataxia was noted in 4 dogs/sex at 8.84 and 17.7 mg/kg/ day and in one female at 4.42 mg/kg/day. Languidness occurred primarily at 17.7 mg/kg/day in both sexes, but also occasionally at 8.84 mg/kg/ day. All of these symptoms occurred more frequently during the last 3 weeks of the study. Other dose-related clinical signs included blinking, mydriasis, nystagmus, lacrimation, and polypnea.
Ref: Federal Register: November 26, 1997. Bifenthrin; Pesticide Tolerances. Final Rule. http://www.fluoridealert.org/pesticides/bifenthrin.fr.nov.1997.htm

Bromethalin - Rodenticide - CAS No. 63333-35-7

Ten random source male domestic shorthair cats, 2 to 6 years old and 3.0-4.4 kg body weight, were each given a single oral dose (1.5 mg/kg) of bromethalin (cat Nos. 1-5) or bait vehicle carrier (cat Nos. 6-10). Bromethalin-dosed cats developed a toxic syndrome characterized by ataxia, focal motor seizures, vocalization, decerebrate posture, decreased conscious proprioception, recumbency, depression, and semicoma.
Ref: Neuropathologic findings of bromethalin toxicosis in the cat, by Dorman DC, Zachary JF, Buck WB. Vet Pathol 1992 Mar;29(2):139-44.

Cyfluthrin - Insecticide - CAS No. 68359-37-5

Chronic toxicity-- i. 1 Year dog study. Cyfluthrin was fed to beagle dogs at 0, 40, 160, or 640 ppm (equivalent to 0, 1, 4, or 16 mg/ kg/day) for 52 weeks. The NOEL was 4 mg/kg bw/day. The LOEL was 16 mg/ kg/day for both sexes, based on slight ataxia in two dogs on single occasions, decreased body weight in males, and on observations of increased vomiting and diarrhea at the high dose. The NOEL is 4 mg/kg/ day. This study was classified as core minimum.
Ref: Federal Register: November 26, 1997. Cyfluthrin; Pesticide Tolerances. Final Rule.

http://www.fluoridealert.org/pesticides/cyfluthrin.fr.nov.26.1997.htm

Cyhalothrin - Acaracide, Insecticide - CAS No. 68085-85-8

Cyhalothrin administered orally (in capsules) to dogs at 10 mg/kg/day for 26 weeks produced occasional disturbances of the nervous system (unsteadiness and/or muscular trembling). The NOEL for these effects was not defined. In a 1-year dog study, ataxia, muscle tremors, and convulsions were observed following oral administration at 3.5 mg/kg/day. Abnormal gait and convulsions were observed at 0.5 mg/kg/day. The LOEL of the study was 0.5 mg/kg/day and the NOEL was 0.1 mg/kg/day. EPA believes that there is sufficient evidence for listing cyhalothrin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available neurological toxicity data.
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.

Cyhalothrin, lambda - Insecticide - CAS No. 91465-08-6

A 12-month feeding study in dogs fed dose (by capsule) levels of 0, 0.1, 0.5, 3.5 milligrams(mg)/kilogram (kg)/day with a no-observedeffect level (NOEL) of 0.1 mg/kg/day. The lowest-observed-effect-level (LOEL) for this study is established at 0.5 mg/kg/day based upon clinical signs of neurotoxicity ataxia, muscle tremors, convulsions.
Ref: Federal Register: March 27, 1995. Lambda-Cyhalothrin; Pesticide Tolerances. Final Rule. http://www.fluoridealert.org/pesticides/lambda-cyhal.fr.mar.27.1995.htm

DFP: Diisopropyl fluorophosphate - Insecticide - CAS No. CAS No. 55-91-4

Abstract: A single dose of diisopropyl phosphorofluoridate (DFP), an organophosphorus ester, produces delayed neurotoxicity (OPIDN) in hen. DFP produces mild ataxia in hens in 7–14 days, which develops into severe ataxia or paralysis as the disease progresses. Since, OPIDN is associated with alteration in the expression of several proteins (e.g., Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) [alpha]-subunit, tau, tubulin, neurofilament (NF) protein, vimentin, GFAP) as well as their mRNAs (e.g., NF, CaM kinase II [alpha]-subunit), we determined the effect of a single dose of DFP on the expression of one of the best known immediate-early gene (IEG), c-fos. C-fos expression was measured by Northern hybridization in cerebrum, cerebellum, brainstem, midbrain, spinal cord, and the sciatic nerves of hens at 0.5 hr, 1 hr, 2 hr, 1 day, 5 days, 10 days, and 20 days after a single 1.7 mg/kg, sc. injection of DFP. All the tissues (cerebrum, 52%; cerebellum, 55%; brainstem, 49%; midbrain, 23%; spinal cord, 80%; sciatic nerve, 157%;) showed significant increase in c-fos expression in 30 min and this elevated level persisted at least up to 2 hr. Expressions of [beta]-actin mRNA and 18S RNA were used as internal controls. The significant increase in c-fos expression in DFP-treated hens suggests that c-fos may be one of the IEGs involved in the development of OPIDN.
Ref: C-fos mRNA Induction in the Central and Peripheral Nervous Systems of Diisopropyl Phosphorofluoridate (DFP)-Treated Hens; by RP Gupta et al. Neurochemical Research 25 (3): 327-334, March 2000.

Dichlorodifluoromethane - Insecticide, Fungicide, Propellant, US EPA List 2 Inert - CAS No. 75-71-8

DOGS, MONKEYS, & GUINEA PIGS EXPOSED TO 20% OF GAS IN AIR FOR SEVERAL HR A DAY FOR SEVERAL DAYS SHOWED TEMPORARY INTOXICATION WITH TREMORS, ATAXIA, AND TENDENCY TO STARE, SALIVATE, & LACRIMATE, BUT NO CUMULATIVE TOXIC EFFECT & NO SPECIFIC OCULAR DISTURBANCE. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986. 322]
Ref: TOXNET profile from Hazardous Substances Data Bank for DICHLORODIFLUOROMETHANE
http://www.fluoridealert.org/pesticides/dichlorodifluorometh.toxnet.htm

Dichlorofluoromethane (CFC-21) - Propellant - CAS No. 75-43-4

DOGS, MONKEYS, & GUINEA PIGS EXPOSED TO 20% OF GAS IN AIR FOR SEVERAL HR A DAY FOR SEVERAL DAYS SHOWED TEMPORARY INTOXICATION WITH TREMORS, ATAXIA, AND TENDENCY TO STARE, SALIVATE, & LACRIMATE, BUT NO CUMULATIVE TOXIC EFFECT & NO SPECIFIC OCULAR DISTURBANCE. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986. 322]
Ref: TOXNET profile from Hazardous Substances Data Bank. http://www.fluoridealert.org/pesticides/dichlorodifluorometh.toxnet.htm

Ethalfluralin - Herbicide - CAS No. 55283-68-6

Short-term inhalation (1 to 7 days). Intermediate-term Inhalation (1 week to several months). Long-term inhalation (several months to lifetime). (Residential): Clinical signs included hypoactivity, dyspnea, ataxia, chromodacryorrhea, poor grooming, and yellow urine; these were reversible after 4 days (LC 50 0.94 mg/ L).
Ref: Federal Register. January 17, 2002. Ethalfluralin; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/ethalfluralin.fr.jan17.2002.htm

Flocoumafen - Rodenticide - CAS No. 90035-08-8

Sub-acute Toxicity. ...In a five-day range-finding study, male and female Fischer 344 rats received 0, 0.2, 0.4 or 0.8 ppm of flocoumafen in the diet together with vitamin K3 at 3 ppm. Four out of five males and four out of five females receiving 0.8 pm died after 9-12 days after the initial dose. Clinical signs reported in rats receiving 0.8 ppm included abnormal posture, ataxia, paralysis of the hind legs, swelling, bruising and bleeding from the nose. Body weight gain was reduced in both sexes receiving the top dose and temporarily in some males receiving 0.4 and 0.2 ppm...
Ref: Evaluation on Flocoumafen. April 1987. UK Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool 3 Peasholme Green, York YO1 7PX. Also available at http://www.pesticides.gov.uk/citizen/evaluations/evallist.htm

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

CHRONIC TOXICITY, DOG. Subchronic Oral Toxicity Study: 52964-0013; 208802; “A 90-Day Oral Toxicity Study in Dogs with IKI-220 Technical”; (W.E. Ridder, M. Watson; Toxicology and Pharmacology, Ricerca LLC, Painesville, OH; Report No. 011509-1; 9/5/01); Four beagle dogs/sex/group received 0, 3, 8, or 20 mg/kg/day of IKI-220 Technical (lot no. 9809, purity: 98.7%) in capsules for 13 weeks. An additional group of 4 females received 50 mg/kg/day of the test material for the same duration. Both the males and females in the 20 mg/kg group and the females in the 50 mg/kg group demonstrated treatment-related signs of vomiting. Ataxia was also noted for some of the animals in these groups....
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

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

-- 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)...
-- Short-term studies Rat Groups of CD (Sprague-Dawley derived) rats received technical flucythrinate (86% pure) in the diet daily for 28 days at 0, 6, 30 ppm (8 male and 8 female rats per group) or at 150 or 300 ppm (12 male and 12 female rats per group). Some survivors from the 150 and 300 ppm groups were used to study reversibility of toxicity. Animals receiving 300 ppm exhibited severe hind limb ataxia, diuresis, hypersensitivity and salivation typical of pyrethroid intoxication. Animals receiving 150 ppm were much less affected, while females generally exhibited greater sensitivity to flucythrinate than males. Five females of the 300 ppm group died without apparent cause...
Ref: 1985 World Health Organization Review for FLUCYTHRINATE.

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

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

-- 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.
-- Neurotoxicity was evaluated in the inclined plane test with flumethrin administered as a single dose in Cremophor:water (2%) or corn oil/milk emulsions. The NOELs were 0.3 mg/kg bw and 1.0 mg/kg bw for the Cremophor and milk formulations respectively. Statisticlaly significant effects were found following dosing with 5 mg/kg bw in either vehicle. No positive control group was included and the sensitivity of the study is uncertain.
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

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

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/f
luometuron.ca.epa.tox.data.pdf

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

ACUTE EXPOSURE ... Neurologic sequelae have been noted following acute poisoning, including hypertonicity with arm and leg spasms, severe mental deficits, and moderate residual paresis. Severe cerebellar dysfunction, ataxia, and depression were described in a 15-year-old patient who survived acute fluoroacetate poisoning.
Ref: FLUOROACETAMIDE CASRN: 640-19-7. Hazardous Substances Data Bank.
http://www.fluorideaction.org/pesticides/fluoroacetamide.hsdb.htm

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

Little specific data were available specifically about the toxicity of fluoroacetic acid; its toxicity is expected to be similar to that of FLUOROACETATE. Neurologic sequelae have been noted following acute poisoning, such as hypertonicity with arm and leg spasms, severe mental deficits, and moderate residual paresis. Severe cerebellar dysfunction, ataxia, and depression were described in a 15-year-old patient who survived acute fluoroacetate poisoning.
Ref: TOXNET profile from Hazardous Substances Data Bank. http://www.fluoridealert.org/pesticides/fluoroacetic.acid.toxnet.htm

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

In the 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 gestaion.
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

Human Toxicity Excerpts: ... APHTHOUS ULCERATION MAY OCCUR ... OTHER TOXIC EFFECTS INCL ... HYPERPIGMENTATION, PHARYNGITIS, ESOPHAGITIS, CEREBELLAR ATAXIA, & EPISTAXIS. LASSITUDE & ASTHENIA, LASTING FROM 12-36 HR AFTER INJECTION, MAY OCCUR. WHEN ... DEATH /OCCURS/ IT IS USUALLY FROM SEPTICEMIA ... TOPICALLY, /IT/ ... MAY INDUCE PHOTOSENSITIZATION ... . [Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975. 1079]
Ref: TOXNET profile from Hazardous Substances Data Base. http://www.fluoridealert.org/pesticides/fluorouracil.toxnet.hsdb.htm

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

-- Acute oral toxicity. Rat. Groups of 5 male and 5 female COBS CD Sprague-Dawley rats were each administered by gavage fluquinconazole (99.6% purity) suspended in a 1% w/v aqueous methyl-cellulose solution at dose levels of 10, 50 or 250 mg/kg bw. Animals were killes and necropsied after a 14-day observation period. Five males and 5 females at the 250 mg/kg bw dose were killed in a moribund condition one day after treatment. There were no mortalities in either sex at dose levels of 50 mg/kg bw. The signs of intoxication prior to death were very severely reduced activity and reduced muscle tone, severe hunched posture and slight to moderate ataxia... The acute oral LD 50 of fluquinconazole in the rat was 112 mg/kg bw in both sexes. Fluquinconazole is classified with R25 Toxic if swallowed under current EC criteria.
-- -- Acute oral toxicity. Mouse. Groups of 5 male and 5 female CRLL:CD (ICR) BR mice were each administered by gavage fluqinconazole (99.6% purity) dissolved in a 1% aqueous methyl cellulose solution at nominal dose levels of 0, 100, 200 or 400 mg/kg bw. The test animals were killed and necropsied after a 14-day observation period... Signs of intoxication were observed from 5 h after treatment for up to 5 days in males at dose levels of 200 mg/kg bw and in females at dose levels of 100 mg/kg bw. The severity of the signs was dose related and included reduced activity, laboured respiration, reduced muscle tone (females only), ataxia, piloerection, hunched posture, pale extreminities, urogenital soiling (females). Slight (200 mg/kg bw) to significantly marked (400 mg/kg bw) loss of body weight was recorded in surviving females after week one. Body weight gain was normal in males throughout the study and in females after week one. The acute oral LD 50 of fluquinconazole in the mouse was 325 mg/kg bw in males and 180 mg/kg bw in females.
-- Acute inhalation toxicity. Groups of 5 male and 5 female Crl:CD (SD)BR Spraque-Dawley rats were exposed head-only to a dust aerosol of fluquinconzole (98.7% purity), at mean analytical concentrations of 0, 0.082, 0.24, 1.08 or 4.56 mg/l for four hours. All surviving animals were killed and necropsied after a 14-day observation period... signs of toxicity inclding ataxia, hunched posture and respiratory distress were observed at the 0.24 mg/l dose for up to 4 days and at the higher dose levels until death... The acute inhalation LC50 of fluquinconazole in the rat was 0.75 mg/l (0.83 mg/l in males and 0.51 mg/l in females). Fluquinconazole is classified under current EC criteria with R23 Toxic by inhalation.
-- Short Term Toxicity. Oral route. Rat. (b)... Groups of 5 male and 5 female outbrd albino Sprague-Dawley Crl:COBS CD(SD)BR rats were each administered fluquinconazole (100% purity) either in the diet at concentrations of 0 (control), 5, 20, 100 and 400 ppm or by gavage dissolved in 1 % aqueous methlcellulose at a dose level of 10 mg/kg bw/day for 28 days. Due to mortalities at the 400 ppm dose level, a supplementary gorups of 5 male and 5 female animals were administered fluquinconazole at a dose level of 200 ppm... At the 200 ppm dose level 2 males and 5 females were killed in a moribund condition after 9 and 7 days respectively of treatment. The signs of toxicity observed showed dose-related severity. The signs at dose levels of 100 ppm and above included hunched posture, hypoactivity, ataxia, reduced mucle tone, piloerection, twitches, urogenital staining, ptosis and emaciation...
-- Short Term Toxicity. Oral route. Rat. (c). In a 3-month feeding study, groups of 10 male and 10 female outbred albino Spraque-Dawley CRL:COBS CD(SD)BR rats were administered fluquinconazole (>96.2% purity) at concentrations of 0 (controls), 1, 5, 15, or 100 ppm. Additional groups of animals at the 0 (control) and 100 ppm dose levels were kept on an untreated diet for 4 weeks in order to invetigate the regressivity of effects. Blood samples were taken after 6 and 13 weeks of treatment for haematological and clinical chemistry investigations... Slight signs of intoxication were observed after 2 weeks in both sexes at the 100 ppm dose level. The signs included unsteady gait, tremors, hunched posture, and reduced muscle tone. Lower incidence of reduced activity and twitches in males, and muscular fibrillation and ataxia in females were also observed. Body weight gain was significantly reduced (9%) in males only at the 100 ppm dose level compared with controls during the treatment period and transient significantly lower body weights were recorded...
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

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

A 28-day feeding study in Beagle dogs administered Fluroxypyr 98.0% a.i. in the diet at levels of 0, 50, 150 or 450 mg/kg/day for 28 days. Dogs at 500 mg/kg/day exhibited ataxia and hind limb weakness as well as decreases in body weight and food consumption and were sacrificed on days 16/17 of the study. Histopathology showed moderate acute tubular nephrosis and a slight to moderate acute gastroenteritis. Some early signs of acute tubular nephrosis were also seen in both sexes of dogs at 150 mg/kg/day. The NOAEL for the study was 50 mg/kg/ day, the LOEL was 150 mg/kg/day based on histopathological lesions in the kidneys, decreased testes weights, and increased adrenal weights in both sexes.
Ref: Federal Register: September 30, 1998. Fluroxypyr; Pesticide Tolerance. Final Rule.

http://www.fluoridealert.org/pesticides/fluroxypyr.fr.sept.30.1998.htm

Indoxacarb - Insecticide - CAS No. 173584-44-6

In a subchronic neurotoxicity study in rats, there was no evidence of neurotoxicity at 11.9 and 6.09 mg/kg/day, the highest dose tested for males and females, respectively. The standard subchronic rat study showed equivocal evidence of neurotoxicity (i.e., ataxia and tremors) but only in moribund animals.
Ref: Federal Register: April 16, 1998 [Page 18912-18919]. Notice of Filing of Pesticide Petitions.

http://www.fluoridealert.org/pesticides/dpx-mp062.fr.apr16.1998.htm

Methanesulfonyl fluoride - Fumigant, Insecticide - CAS No. 558-25-8

Range of Toxicity:
-- Minimum lethal human exposure is unknown. In rats exposed by inhalation to a concentration of 2.2 ppm for 1 hour, only minimal salivation was seen; at 5 ppm for the same duration, copious salivation, eye and nose exudates, diarrhea, depression, ataxia, and tremors were observed.
-- ACUTE EXPOSURE. Methanesulfonyl fluoride is an irreversible inhibitor of acetylcholinesterase in vitro. It also inhibits butyrylcholinesterase and trypsinogen in vitro.
-- NEUROLOGIC. ACUTE EXPOSURE. Symptoms noted in experimental animals included CNS depression, tremors, ataxia, and convulsions. ANTICHOLINESTERASE COMPOUNDS can affect the CENTRAL NERVOUS SYSTEM, producing restlessness, anxiety, headaches, convulsions, and coma.
Ref: TOXNET profile from Hazardous Substances Data Base.
http://www.fluoridealert.org/pesticides/m
ethanesulfonyl.fluo.toxnet.htm

Mipafox - Acaracide, Insecticide - CAS No. 371-86-8

The ability of sarin (107448) to induce delayed neurotoxicity was examined in mice. Female Swiss-albino-mice were exposed to 5mg/m3 sarin vapor 20 minutes/day for 10 days. Other mice were injected subcutaneously with 2.5mg/kg mipafox (371868) daily for 10 days. Mice were observed for clinical signs of toxicity for 14 days starting after the first sarin or mipafox exposure. They were killed on day 14. Brain and spinal cord tissues, and blood platelets were assayed for neurotoxic-esterase (NTE) activity. Spinal cord sections were prepared and examined for histopathological changes. Mice exposed to sarin developed muscular weakness in the limbs and ataxia on day 14. Mipafox exposed mice developed severe ataxia. Both sarin and mipafox inhibited brain, spinal cord, and platelet NTE activity. Sarin was less potent than mipafox. Sarin and mipafox induced spinal cord axonal degeneration. The degree of degeneration was greater in mipafox treated mice. Sarin also caused focal axonal degeneration in the lateral branches of the spinal cord. The authors conclude that sarin seems capable of inducing delayed neurotoxicity in mice following repeat inhalation exposure.
Ref: Husain K et al. (1993). Delayed Neurotoxic Effect of Sarin in Mice after Repeated Inhalation Exposure. Journal of Applied Toxicology, Vol. 13, No. 2, pages 143-145. As cited on Toxnet.

DAILY ADMIN OF MIPAFOX TO RATS FOR 35 DAYS PRODUCED ATAXIA & REDN IN LEVEL OF DOPAMINE IN CORPUS STRIATUM. [FREED VH ET AL; ROLE OF STRIATAL DOPAMINE IN DELAYED NEUROTOXIC EFFECTS OF ORGANOPHOSPHORUS COMPOUNDS; EUR J PHARMACOL 35 (1): 229-32 (1976)]
Ref: TOXNET profile for Mipafox from Hazardous Substances Data Base.

http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB

Nuarimol - Fungicide - CAS No. 63284-71-9

Exposure to nuarimol causes both acute and chronic effects. It is moderately acutely toxic, with a WHO classification of Class III, or "slightly hazardous" and a rat oral LD50 of 1250 mg/kg. (24) DowElanco data indicates a single oral as well as inhalation exposure of the product caused laboratory rats to exhibit reduced activity, clonic convulsion (muscle contraction), ataxia (loss of balance and coordination), labored breathing, reduced weight gain, and coma. Laboratory animals exhibited increases in liver weight and enzyme activity and microscopic liver cell changes when repeatedly exposed to the product. (8) The product is also an eye irritant. (8,16,21) As mentioned above, EPA has concerns over the product's ability to cause cancer and birth defects in lab animals. (10)
Ref: NEVER-REGISTERED PESTICIDES: Rejected Toxics Join the "Circle of Poison." Greenpeace USA Pesticide Campaign report. By Sandra Marquardt, Laura Glassman and Elizabeth Sheldon. February 1992.
http://www.fluoridealert.org/pesticides/nuarimol.greenpeace.1992.htm

Sodium fluorosilicate (Sodium Hexafluorosilicate) - Insecticiide; Wood Preservative; EPA List 3 Inert - CAS No. 16893-85-9

-- Mouse strain, 70 mg/ kg (LD 50 ; 0.37 mmol/ kg); Toxic effects were observed in the peripheral nerves and sensation (flaccid paralysis without anesthesia, generally neuromuscular blockage) and in behavior (ataxia and muscle contraction or spasticity). RTECS* (1997)
Ref: Review of Toxicological Literature. October 2001. Sodium Hexafluorosilicate [CASRN 16893-85-9] and Fluorosilicic Acid [CASRN 16961-83-4]. 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

tau-Fluvalinate - Acaracide, Insecticide - CAS No. 102851-06-9

-- Neurotoxic effects of tau fluvalinate were seen in rats after administration by gavage of 60 mg/kg bw/day in corn oil for 7 days. Body weight decrease, symptoms such as fear, ruffled fur, ataxia, startle response hyperreactivity, spasms, and signs of neurotoxicity (reduced grip strength, irritability, reduced motion, spasms and abnormal gait) were observed, accompanied by nerve fibre degeneration correlating to incidence and severity of the symptoms. Severity and number of the lesions were reduced in animals allowed to recover for 7 days. 10 mg/kg bw/day resulted in a marginal increase in vocalisation when handled and hyperalgesia.
Ref:
Revised Summary Report. EMEA/MRL/021-REV1/95. Committee for Veterinary Medicinal Products. The European Agency for the Evaluation of Medicinal Products.
http://www.fluorideaction.org/pesticides/tau.fluvalinate.1995.review.pdf

Tefluthrin - Insecticide - CAS No. 79538-32-2

-- In a chronic toxicity study, dogs were dosed at dose levels of 0, 0.1, 0.5, and 2 mg/kg/day for 12 months. The LOEL for this chronic study is 2.0 mg/kg/day based on the increased incidence of ataxia in both sexes at the high-dose. The NOEL is 0.5 mg/kg/day.
-- Toxicological Endpoints 1. Acute toxicity. For acute dietary risk assessment, EPA recommends use of a NOEL of 0.5 mg/kg/day based on increased incidence of tremors and ataxia in both sexes of dogs at 2.0 mg/kg/day (LOEL) on day 1 of the study from the 1 year oral chronic toxicity study in dogs.
-- Toxicological Endpoints 2. Short - and intermediate - term toxicity. For short- and intermediate term MOE's, EPA recommends use of a NOEL of 0.5 mg/kg/day based on increased incidence of tremors and ataxia in both sexes of dogs at 2.0 mg/kg/day (LOEL) from the one year oral toxicity study in dogs and use of a dermal absorption rate of 25%. A dermal absorption rate of 25% was recommended based on the weight-of-the-evidence available for structurally related pyrethroids.
-- Chronic toxicity. EPA has established the RfD for tefluthrin at 0.005 milligrams/kilogram/day (mg/kg/day). This RfD is based on increased incidence of tremors and ataxia in both sexes of dogs in a chronic toxicity study and an uncertainty factor of 100 to account for both interspecies extrapolation and intraspecies variability.
Ref: Federal Register: November 26, 1997. Tefluthrin; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/tefluthrin.fr.nov.1997.htm

 
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