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/fluometuron.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 ² 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 ³ 200 mg/kg bw and
in females at dose levels of ³ 100 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/methanesulfonyl.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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