• See Table of dramatic weight loss effects in laboratory animals exposed to fluoride and/or fluorinated pesticides.
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
Australia: ANIMAL SAFETY
ISSUES. Adverse experiences involving veterinary chemical products
containing fipronil have been reported regularly since the products
were first registered. Patterns that appear to have emerged involve
the development of certain clinical signs including skin reactions,
neurological signs, lethargy, anorexia
and in some cases death. In Australia there have been 56 suspect
adverse experience reports for dogs classified as being either
probably or possibly associated with fipronil. In 21 of those
reports (38%) there was concurrent infestation with the dog paralysis
tick, Ixodes holocyclus. Of these reports, 9 involved death of
the dog...
Ref:
September
2003 - The Reconsideration of Approvals and Registrations Relating
to FIPRONIL. REVIEW SCOPE DOCUMENT. Australian Pesticides & Veterinary
Medicines Authority Canberra Australia.
http://www.fluorideaction.org/pesticides/fipronil.australia.sept2003.pdf
•
Reproductive and developmental toxicity. The
developmental toxicity NOELs in the rat
and rabbit were 20 mg/kg/day (HDT) and 1 mg/kg/day (HDT),
respectively.
Maternal toxicity was observed in the rat at the HDT as evidenced
by decreased body weight gain and
food efficiency. In
the rabbit, the maternal toxicity
NOAEL was less than 0.1 mg/kg/day, based
on reduced body weight gain and food efficiency at all
dose levels tested. The NOEL for reproductive toxicity
was 30 ppm (2.64 mg/kg/day for both sexes combined), based on
clinical signs of toxicity in pups,
decreased litter size, decreased pup body weights, decreased
mating, decreased fertility index, reduced pre- and postnatal
survival, and delays in physical development at
300 ppm (26.03 and 28.40 mg/kg/day for males and females, respectively).
• In
a developmental neurotoxicity study in the rat,
the NOAEL for maternal toxicity was 10 ppm
(0.91 mg/kg/day), based on decreased body weights and body
weight gain at 200 ppm (HDT; 15 mg/kg/day).
Considerable maternal toxicity at the HDT prevented adequate neurotoxicity
evaluation of pups at this dose level.
There was no evidence of neurotoxicity at 10 ppm (0.91
mg/kg/day), which was the NOAEL for developmental neurotoxicity.
The NOAEL for general developmental toxicity
was 0.5 ppm (0.05 mg/kg/day), based on systemic effects consisting
of decreases in pup weights during
lactation and increases in time of preputial
separation in males at 10 ppm.
• Subchronic
toxicity.The
NOAELs in the dog
were 2 and 0.5 mg/kg/day for male and female,
respectively, based on clinical signs of toxicity in males at
10 mg/kg/day and clinical signs of toxicity and decreased
body weight gain in females at 2 mg/kg/day.
The NOAEL for mice was 10 ppm (1.27
and 1.72 mg/kg/day for males and females, respectively), based
on a possible decreased body weight
gain at 25 ppm (3.2 and 4.53 mg/kg/day for males and females,
respectively). A repeated dose dermal study in the rabbit
had a systemic NOAEL of 5 mg/kg/day, based on decreased
body weight gain and food consumption at 10 mg/kg/day,
and a dermal irritation NOEL of 10.0 mg/kg/day (HDT).
•
Chronic toxicity.
The NOAEL for systemic toxicity in mice
was 0.5 ppm (0.06 mg/kg/day) based on decreased
body weight gain, decreased food conversion efficiency in males,
increased liver weights, and liver histopathology
at 10 ppm (1.3 mg/kg/day).
• 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.
•
Subchronic toxicity. The
NOAEL in the rat was 3 ppm (0.18
and 0.21 mg/kg/day in males and females, respectively), based
on clinical signs of toxicity in both sexes and decreased
body weight and body weight gain in males at 10 ppm.
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
-- An acceptable subchronic
oral toxicity [capsule] study in the dog
established that the LOEL is 10.0 mg/kg/day for males (based on
clinical signs of toxicity) and 2.0 mg/kg/day for females (based
on clinical signs of toxicity and decreased
body-weight gain). The NOEL is 2.0 mg/kg/day for males
and 0.5 mg/kg/day for females.
-- An acceptable repeated dose dermal study using the
rat found that the systemic LOEL was 10 mg/kg/day based
on decreased body-weight gain and
food consumption; the dermal irritation LOEL is greater than 10.0
mg/kg/day. The systemic NOEL was 5.0 mg/kg/day; the dermal irritation
NOEL was greater than or equal to 10.0 mg/kg/day.
-- A acceptable carcinogenicity [feeding] study in the mouse
using fipronil found that the LOEL is 10 ppm (1.181 mg/kg/day
for males and 1.230 mg/kg/day for females) based on decreased
body-weight gain, decreased food conversion efficiency
(males), increased liver weights and increased incidence of hepatic
histopathological changes. The NOEL is 0.5 ppm (0.055 mg/kg/day
for males and 0.063 mg/kg/day for females). The study demonstrated
that fipronil is not carcinogenic to CD-1 mice when administered
at doses of 30 ppm.
-- Fipronil. a. An acceptable prenatal developmental study in
the rat found that the maternal toxicity
LOEL was 20 mg/kg/day based on reduced body-weight
gain, increased water consumption, reduced food consumption,
and reduced food efficiency. The maternal toxicity NOEL was 4
mg/kg/day. The developmental toxicity LOEL was greater than 20
mg/ [[Page 38486]] kg/day. Developmental toxicity NOEL was 20
mg/kg/day or higher.
-- An acceptable prenatal developmental study in the rabbit
found that the maternal toxicity LOEL was 0.1 mg/kg/day
or lower, based on reduced body-weight gain,
reduced food consumption and efficiency. Maternal toxicity NOEL
was less than 0.1 mg/kg/day. The developmental toxicity LOEL was
greater than 1.0 mg/kg/day. The developmental toxicity NOEL was
1.0 mg/kg/day or higher.
-- An acceptable acute neurotoxicity study in the rat
concluded that the NOEL was 2.5 mg/kg. The LOEL is 7.5
mg/kg, based on decreased body-weight gains,
food consumption and feed efficiency in females, decreased hindlimb
splay in males (at 7-hours post test) and decreased grooming in
females (14-days post test).
-- MB46513. An acceptable prenatal developmental study using the
rat found that the maternal toxicity LOEL was 2.5 mg/kg/day
and the NOEL was 1.0 mg/kg/day based an increase in clinical signs
of toxicity (reduced body-weight gain,
food consumption and food efficiency). 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.
-- The LOEL for reproductive toxicity was 300 ppm (26.03 mg/kg/day
for males and 28.40 mg/kg/day for females) based on clinical signs
of toxicity in the F1 and F2 offspring;
decreased litter size in the F1 and F2 litters;
decreased body weights in the F1
and F2 litters; decrease in the percentage of F1
parental animals mating; reduction in fertility index in F1
parental animals; reduced post- implantation survival and offspring
postnatal survivability in the F2 litters; and delay in physical
development in the F1 and F2 offspring.
The NOEL for reproductive toxicity was 30 ppm (2.54 mg/kg/day
for males and 2.74 mg/kg/day for females).
-- In a developmental neurotoxicity study, fipronil was administered
to 30 female rats/group in the diet
at dose levels of 0, 0.5, 10, or 200 ppm (0.05, 0.90, or 15 mg/kg/day,
respectively) from gestation day 6 to lactation day 10. This study
found that the maternal LOEL was 200 ppm (15 mg/kg/day), based
on decreased body weight, body- weight gain,
and food consumption. The maternal NOEL was 10 ppm (0.90 mg/kg/day).
The developmental toxicity LOEL is 10 ppm (0.9 mg/kg/day), based
on a marginal but statistically significant
decrease in group mean pup weights during lactation and
significant increase in time of preputial separation in males.
The NOEL for developmental toxicity is 0.5 ppm (0.05 mg/kg/day).
The developmental neurotoxicity LOEL is 200 ppm (15 mg/kg/day)
based on: Decreased auditory startle response; reduced swimming
direction scores, group mean angle measurements, and water ``Y''
maze times trails; and decreased absolute-brain weights. The NOEL
for developmental neurotoxicity is 10 ppm (0.90 mg/kg/day).
-- MB46513. An acceptable acute neurotoxicity study in the rat
concluded that the neurobehavioral LOEL for rats is 12
mg/kg based on decreases in body-weight
gains and food consumption for males and females during
the week following treatment, significant decreases in locomotor
activity 6-hours post dosing for both males and females, decreases
in hind-limb splay and rectal temperature at 6-hours post dose
in males and females, decreases in the proportion of high-dose
males with an immediate righting reflex on days 7 and 14. Decreased
forelimb grip strength in males on day 7 and increased forelimb
grip strength in high-dose females at 6-hours post dosing was
possibly related to the treatment, because there were also slight
increases in forelimb grip strength in high-dose males at 6 hours
and slight
-- MB46513. An acceptable 28-day dietary range-finding study in
the rat measured thyroid hormone
levels as well as standard study parameters. It found that the
LOEL is 30 ppm (2.20 and 2.32 mg/kg/day for males and females,
respectively), based on clinical signs including piloerection,
curling up and thin appearance; and decreased
body weights in both sexes. The NOEL is 3 ppm (0.23 and
0.24 mg/kg/day for males and females, respectively).
Ref: Federal Register: July 17, 1998. Fipronil;
Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Fipronil.FR.July.17.1998.htm
Flonicamid
- Insecticide - CAS No.
158062-67-0
-- In the rabbit developmental
toxicity study, the maternal and developmental NOAELs were 7.5
mg/kg/day and 25 mg/kg/day highest dose tested (HDT), respectively.
The maternal LOAEL was 25 mg/kg/day based on decreased
body weights and food consumption. No adverse effects on
the fetuses were observed at the highest dose.
-- Chronic toxicity.
In the chronic dog study with administration via using capsules,
the NOAEL was 8 mg/kg/day. The LOAEL was 20 mg/kg/ day based on
reduced body weights in females and
effects on the circulating red blood cells.
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
--
Combined Chronic/ carcinogenicity (rats).
NOAEL is 200
ppm (equivalent to 7.32/8.92mg/ kg/day in males/females). LOAEL
is 1,000 ppm (equivalent to 36.5/44.1mg/ kg/day in males/females)
based on decreased body weights and body
weight gains, and increased incidences
of keratitis in males and striated muscle
fiber atrophy in females. At the high dose there was an incidence
(12%)of nasolacrimal duct squamous cell carcinomas
slightly outside the historical control
range (0-10%) in male rats. A correlation between the incidence
of inflammation and the fluctuating incidence of nasal tumors
was made across dose groups. EPA did not consider the nasolacrimal
duct tumors to be treatment-related. Female rats had a significant
increasing trend in nasolacrimal duct squamous cell carcinomas
at < 0.05, and at the high dose was slightly above the historical
control mean (0.8%) and range (0-4%). EPA considered the nasolacrimal
duct squamous cell carcinomas to be possibly treatment related,
but that a clear association with treatment could not be made.
--
Subchronic
neurotoxicity screening battery (rats).
NOAEL is 200/1,000 ppm (equivalent to 13/81mg/kg/day [M/F].
LOAEL is 1,000/10,000 ppm (equivalent to 67/722 mg/kg/day [M/F]
based on decreased motor activity, rearing,
and foot splay in males, decreased body
weights, body weight gains,
and food consumption in males and females.
Ref:
August 31, 2005. Flonicamid; Pesticide Tolerance. Final Rule.
Federal Register.
http://www.fluoridealert.org/pesticides/flonicamid.fr.aug.31.2005.html
--
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. Incidences of diarrhea and
excessive salivation were observed for the females in the high
dose group. The females in the high dose group were so affected
as to refuse to eat the certified dog chow. One
female in the 50 mg/kg was euthanized due to severe anorexia on
study day 20. Food consumption was
significantly lower for the females in the 50 mg/kg group (p<0.05).
...
-- Definitive Study: 52964 - 0064 216038 “A 52-Week Oral
Toxicity Study in Dogs With IKI-220 Technical, Amended Report,”
(Ridder, W.E., Watson, M.; Toxicology and Pharmacology, Ricerca
Biosciences, LLC, Painesville, OH; Document #: 012075-1-1; 11/15/02
(amended report 1/2/03)). Flonicamid technical (IKI-220, N-cyanomethyl-4-trifluoromethyl
nicotinamide: 98.7% pure) was administered by capsules to beagle
dogs (6/sex/dose) at 0 (capsule only), 3, 8 and 20 mg/kg/day
for 1 year (365 consecutive days). NOEL
= 8 mg/kg/day (Body weight gains were significantly decreased
in females at 20 mg/kg/day during weeks 2-4.
Although the body weight gains were not statistically different
from controls for the remainder of the study, the body
weight gain decrease was 30% at termination for females at 20
mg/kg/day (4.90 kg for controls vs. 3.41 kg at 20 mg/kg/day).
Males at 9 and 12 months had statistically significantly increased
MCV and MCH and at 12 months increased reticulocytes (%) at 20
mg/kg/day. NOTE that at pretest males at 20 mg/kg/day had a statistically
significantly decreased RBC, HGB and HCT. Throughout the test,
however these parameters were comparable to controls.
** 52964
- 0061 216035 “IKI-220 Technical: A Teratogenicity Study
in Rabbits,” (Takahashi, K.; Institute of Environmental
Toxicology, Ibaraki, Japan; Laboratory Study #: IET 00-0025; 2/21/02
& final report amended 11/28/02). Flonicamid technical (98.7%
pure) was administered via oral gavage to artificially inseminated
SPF Japanese White rabbits (Kbl:JW) (25/dose) at 0 (1% sodium
carboxymethyl cellulose), 2.5, 7.5 and 25 mg/kg/day during gestation
days 6 through 27. Maternal NOEL = 7.5 mg/kg/day
(Body weight gains at 25 mg/kg/day were statistically significantly
decreased during the interval of GD 6 - 28 (throughout treatment).
At 25 mg/kg/day there was statistically significantly decreased
food consumption on GD 9 - 12, 12 - 15, 15 - 18 and 18 - 21. Developmental
NOEL = 25 mg/kg/day (There were no treatment-related effects at
any dose.) Acceptable. No adverse effect. (Silva, 2/11/05)
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
Floransulam
- Herbicide - CAS No. 145701-23-1
-- In the rat 90-d
dietary study, other histopathological findings in the kidney
included degeneration with regeneration in the descending portion
of the proximal tubules (females at 500 mg/kg bw/d and above)
which was considered to be typical of acute necrosis with regeneration
rather than a 90-d old lesion and multi-focal mineralization in
the papilla (females at 800 mg/kg bw/d). These lesions did not
appear to be reversible. In the rat 2- year dietary study, other
histopathological findings in the kidneys included a possible
slight decreased incidence of age-related tubular degeneration/regeneration
and a decreased severity of spontaneous geriatric renal degeneration
(chronic progressive glomerularnephropathy) in males at 250 mg/kg
bw/d and above, slight decreased incidence of spontaneous geriatric
renal disease in females at 250 mg/kg bw/d and minimal reactive
hyperplasia of the transitional epithelium and unilateral necrosis
of the papilla in males at 500 mg/kg bw/d. The high-dose males
also exhibited decreased proteinuria, which was considered to
represent less severe chronic renal disease although the decreased
specific gravity suggest that dilution may have also contributed
to lower values. Body weight and body-weight
gain were significantly lower in males at 1000 mg/kg bw/d
and in females at 500 mg/kg bw/d and above in the 90-d dietary
study and in males at 500 mg/kg bw/d (highest dose tested [HDT])
and in females at 250 mg/kg bw/d (HDT) in the 2-year dietary study.
This was associated with concomitant lower food consumption in
the high-dose animals in the both 90-d and 2-year dietary study.
-- In the dog, an increased incidence and
severity of hypertrophy of the epithelial cells was observed in
both sexes at 50 mg/kg bw/d and above in both the 90-d and 1-year
dietary study. There were no treatment-related urinalysis findings
in either the 90-d or 1-year dietary study. The severity (slight)
of the hypertrophy did not appear to increase with prolonged exposure.
In the 90-d dietary study treatment-related findings associated
with the liver included increased alkaline phosphatase (ALP) activity
in both sexes at 50 and 100 mg/kg bw/d, increased liver weights
in both sexes at 100 mg/kg bw/d and a slight increased incidence
or severity of hepatic vacuolation in both sexes at 50 and 100
mg/kg bw/d. Increased liver weights and hepatic vacuolation were
not observed in the 1-year dietary study. In the 1-year dietary
study, treatment-related findings associated with the liver, included
increased alanine aminotransferase (ALAT) and ALP activity and
decreased serum albumin and protein levels in both sexes at 100
mg/kg bw/d. After the high dose was reduced to 50 mg/kg bw/d (week
15), ALP activity remained elevated and serum albumin and protein
levels remained lower in both sexes. In the 1-year dietary study,
no histopathological findings were evident in the liver. In the
1-year dietary study, slight vacuolization of the zona reticularis
and zona fasciculata in the adrenal glands was observed in the
high-dose males and females; however, in the absence of any associated
inflamation, necrosis or other changes, the toxicological significance
of this finding was uncertain. The vacuolization was consistent
with fatty changes. Body weight,
body-weight gain and food consumption were significantly lower
in both sexes at 100 mg/kg bw/d and remained lower in the high-dose
females after the high dose was reduced in the 1-year dietary
study. Body weight, body-weight gain and food consumption were
unaffected by treatment in the 90-d dietary study.
Ref: Florasulam EF-1343 Suspension Concentrate
Herbicide. REF2001-12. September 21, 2001. Canadian Pest Management
Regulatory Agency. Health Canada.
http://www.hc-sc.gc.ca/pmra-arla/english/pdf/reg/reg2001-12-e.pdf
Fluazifop-butyl
- Herbicide - CAS No. 69806-50-4
-- Fluazifop butyl
(CAS # 69806-50-4) was evaluated for 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]
Ref: TOXNET profile from Hazardous Substances
Data Bank for FLUAZIFOP-BUTYL.
http://www.fluoridealert.org/pesticides/Fluazifop-butyl.TOXNET.HSDB.htm
In a teratogenicity
study in Sprague-Dawley rats exposed via oral gavage, delayed
ossification and an increased incidence of hydroureter were observed
in fetuses (the fetotoxic LOEL was 5 mg/kg/day; the NOEL 1 mg/kg/day)
and a teratogenic LOEL of 200 mg/kg/day (the NOEL was 10 mg/kg/day)
was determined based on the incidence of diaphragmatic hernia.
Maternal toxicity was observed in this study at doses higher than
those causing fetotoxicity and included reduced
body weight gain and decreased gravid uterus (the maternal
LOEL was 200 mg/kg/day; the NOEL was 10 mg/kg/day). In a 2-generation
reproductive toxicity dietary study in Wistar rats, the reproductive
LOEL of 250 ppm (12.5 mg/kg/day; the NOEL was 80 ppm or 4 mg/kg/day)
was based on reduced litter sizes,
reduced viability, reduced testis and epididymis weights and tubular
atrophy in offspring. Fetotoxicity (delayed ossification and eye
opacities) was also demonstrated in New Zealand White rabbits
(the LOEL was 30 mg/kg/day; the NOEL was 10 mg/kg/day). EPA believes
that there is sufficient evidence for listing fluazifop butyl
on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based
on the available hepatic and developmental 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.
Fluazifop-P-butyl
- Herbicide - CAS No. 79241-46-6
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 Òday 1Ó). There were also 40 mated does
given 50 mg/kg/day of test article, to ensure adequate numbers
of surviving litters. Maternal toxicity was generally low: mean
body weight was unaffected and there were no characteristic clinical
signs. There was one maternal death (killed in extremis) among
the high dose females. Abortion frequencies were 1/18, 2/17, 2/13,
and 4/37 in controls through increasing dose groups, thus not
independently indicative of treatment effects at any dose. Nevertheless,
a combination of marked body weight losses
(average loss of 654 g) and associated signs of "few
feces" or "no feces" among the 4 of the 5 aborted/killed
moribund does is considered treatment-related, setting the maternal
NOEL = 10 mg/kg/day..
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
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.
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
Fluazinam
- Fungicide - CAS No. 79622-59-6
In subchronic and chronic
toxicity studies, fluazinam targeted the following organs: liver,
lung, uterus, testes, pancreas, thymus, thyroid, stomach, eyes
and brain. Generalized toxicity was observed
in rats, mice and dogs as decreases in body weight, body-weight
gain, food consumption and/or food efficiency.
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
Prenatal developmental
toxicity -rats. 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 postimplantation loss...
Prenatal developmental toxicity -rabbits. LOAEL = 12 mg/kg/day
based on an increase in total litter resorptions and possible
fetal skeletal abnormalities.
Ref: Federal Register. September 7, 2001.
Fluazinam; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/Fluazinam.FR.Sept.7.2001.htm
-- 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 postimplantation loss
-- Reproduction and fertility effects rats. Parental/Systemic
NOAEL = 1.9 mg/kg/day LOAEL = 9.7 mg/kg/day based on liver pathology
in F1 males Reproductive NOAEL = 10.6 mg/kg/day LOAEL = 53.6 mg/kg/day
based on decreased number of implantation sites and decreased
litter sizes to day 4 post-partum for F1 females (F2 litters).
Offspring NOAEL = 8.4 mg/kg/day LOAEL = 42.1 mg/kg/day based on
reduced F1 and F2 pup body weight gains
during lactation.
-- Specicial study. 4-Week dietary (range-finding) rats. NOAEL
= M: 5.1 mg/kg/day; F: 5.3 mg/kg/day LOAEL = M: 26.4 mg/kg/day;
F: 25.9 mg/kg/day based on decreased body
weight gain and food consumption,
increased serum phospholipids, increased total cholesterol, increased
relative liver weights, and liver histopathology.
-- Specicial study. 4-Week dietary (Range-finding) mice NOAEL
= M: 7.6 mg/kg/day; F: 8.2 mg/kg/day LOAEL = M: 36 mg/kg/day;
F: 43 mg/kg/day based on decreased body
weight gain, increased serum glucose, increased kidney
weights.
Ecological Effects
-- a. Aquatic (Acute/Chronic Hazard Summary) Fluazinam is considered
to be very highly toxic to highly toxic
to fish (freshwater and estuarine/marine) on an acute basis (LC50
= 0.036 - 0.11 ppm). Chronic freshwater NOAEC/LOAEC values were
calculated at 0.0053 - 0.00069 ppm and 0.010 - 0.014 ppm, respectively,
with larval survival, reduced number of spawns, and growth as
the endpoints affected. Acute toxicity values for aquatic invertebrates
suggest that fluazinam is highly toxic to freshwater invertebrates
(Daphnia EC50 = 0.18 - 0.22 ppm) and very highly toxic to estuarine/marine
invertebrates (oyster EC50 = 0.0047 and mysid shrimp EC50 = 0.039
ppm ). Chronic toxicity to invertebrates are only represented
through the Daphnia magna life cycle where the NOAEC was calculated
at 0.068 ppm and the LOAEC at 0.140 ppm.. The
endpoints affected for this study were reproductive (reduced number
of young per female) and growth effects. No acceptable
data have been submitted to assess the chronic effects of fluazinam
to estuarine/marine fish or invertebrates. An estuarine/marine
fish life-stage toxicity test (Guideline 72-4a) and an estuarine/marine
invertebrate life-cycle toxicity test (Guideline 72-4b) are required
to fulfill these requirements.
-- d. Risk to Avian Species (Acute/Chronic) Although acute exposure
should result in minimal toxic effects to birds, the
risk assessment suggests that the proposed uses can cause chronic
(reduced growth in young) effects in birds. RQ values
were calculated for exposure to peanuts (maximum EECs RQ = 1.0
- 1.8 and 56 day average EECs RQ = 1.1 ppm) and potatoes (maximum
EECs RQ = 1.0 - 1.5 and 56 day average(RQ = 1).
Ref: US EPA Pesticide Fact Sheet. Fluazinam.
August 10, 2001.
http://www.epa.gov/opprd001/factsheets/fluazinam.pdf
Flucarbazone-sodium
- Herbicide - CAS No. 181274-17-9
SUBCHRONIC/CHRONIC
TOXICITY
-- Study # 870.3150. 28-Day oral toxicity in nonrodents (dogs)
NOAEL = 164 mg/kg/day in males and 171 mg/kg/day in females. LOAEL
= 1,614 mg/kg/day in males and 1,319 mg/kg/day in females based
on decreased body weight gain, decreased
food consumption, decreased
T4 levels and increased thyroxine-binding capacity, induction
of microsomal enzymes, increased liver weight and liver histopathology
in both sexes.
-- Study # 870.3700b. Prenatal developmental toxicity in rabbits
Maternal NOAEL = 100 mg/kg/day LOAEL = 300 mg /kg/day based on
decreased food consumption and increased
clinical signs Developmental NOAEL = 300 mg/kg/day LOAEL = 500
mg/kg/day based on decreased fetal weight
and increased incidence of delayed fetal
ossification
-- Study # 870.3800. Reproduction and fertility effects in rats
Parental/Systemic NOAEL = 287 mg/kg/day for males and 340 mg/kg/day
for females with a slight, increased incidence of moderate cecal
enlargement occurring as an adaptive response to treatment. LOAEL
= 800 mg/kg/day for males based decreased
liver weight and 991 mg/kg/day for females based on decreased
uterine weight and increased incidence of severe cecal enlargement.
Reproductive/Offspring NOAEL = 287 mg/kg/day for males
and 340 mg/kg/day for females LOAEL = 800 mg/kg/day for males
and 991 mg/kg/day for females based on reduced
pup weights, decreased liver weight
in male pups, marbled liver, air filled stomach
-- Study # 870.4100b. Chronic toxicity in dogs NOAEL = 35.9 mg/kg/day
in males and 37.1 mg/kg/day in females. LOAEL = 183 mg/kg/day
in males and 187 mg/kg/day in females based upon body
weight gain depression and increased N-demethylase levels
in both sexes, decreased T4 levels and marginally increased
liver weight in females.
-- Study # 870.4300. 2-Year Chronic toxicity/carcinogenicity in
rats NOAEL = 125 mg/kg/day in males and females LOAEL = 1,000
mg/kg/day in males and females based on
decreased body weight and increased food
consumption in females,
thickened mucosa of the glandular stomach
in both sexes, inflammatory infiltrates (males), vacuolation of
the squamous epithelium in the fore-stomach (females) and immunological
effects in males. no evidence of carcinogenicity
-- Aquatic:
Flucarbazone-sodium is practically non-toxic to freshwater fish
on an acute basis (96- hour LC50 > 96.7 ppm).
With chronic exposure, flucarbazone-sodium
reduces fish growth at 2.75 ppm, with a
No Observable Adverse Effects Concentration (NOAEC) established
at 1.25 ppm (1250 ppb). It is practically non-toxic
to freshwater invertebrates on an acute basis (EC50 > 109 ppm)
and does not reduce reproduction of aquatic invertebrates at the
NOAEC of 115 ppm (115,000 ppb). The NOAECs for fish and aquatic
invertebrates are well above the peak estimated environmental
concentration (EEC) in water of 1.42 ppb.
Ref: US EPA Pesticide Fact Sheet for Flucarbazone-sodium.
September 29, 2000.
http://www.epa.gov/opprd001/factsheets/flucarbazone.pdf
Flucythrinate
- Acaracide, Insecticide - CAS No. 70124-77-5
CHRONIC TOXICITY No
adverse effects were observed when rats and dogs were fed flucythrinate
for 90 days at doses of up to 3 mg/kg for rats and 3.75 mg/kg
for dogs (5). Dogs fed 7.5 mg/kg/day
for 2 years exhibited vomiting and decreased
body weight gain. The NOEL for this study was 0.75 mg/kg/day
(12). Rats fed 6 mg/kg/day for 2 years also exhibited decreased
body weight gain. The systemic NOEL for this study was
3 mg/kg/day (12).
Ref: E X T O X N E T Pesticide Information
Profile Flucythrinate.
http://www.fluoridealert.org/pesticides/Flucythrinate.Profile.PMEP.htm
-- In an apparently
treatment-related manner, 1 dam treated at 4 mg/kg died, while
19 died at 8 mg/kg, but the cause of death was not determined.
Absolute body weights were reduced at 4 and 8 mg/kg as were body-weight
gains. Incomplete recovery of body weight had occurred
by day 20 (termination).
-- Groups of twenty female New Zealand white rabbits were artifically
inseminated after induction of ovulation with chorionic gonadotropin
on 2 consecutive days. Technical flucythrinate (80% pure) was
administered in corn oil at 0, 10, 30, or 60 mg/kg daily from
days 6-18 (inclusive) of gestation and were maintained without
treatment until sacrificed at day 29... Depression
of maternal body weight and faecal scouring were observed
in the high-dose (60 mg/kg) group up to day 18. Maternal
weight gain was significantly reduced in the mid- and high-dose
groups and its recovery in the high-dose group was incomplete
at day 29 (termination).
-- 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. Absolute weight
and weight gain were markedly depressed for males and females
in the groups receiving 150 and 300 ppm. All symptoms in the two
highest-dose groups were reversed in 48 hours, while the weight
loss, relative to controls, was regained within 4 weeks after
cessation of exposure. Weight loss
in the two highest-dosage groups was attributable to decreased
food intake. Plasma urea nitrogen was elevated for females receiving
300 ppm. Absolute and relative liver weights were elevated in
females receiving 300 ppm. Based on the findings of weight
loss, a no-effect level of 30 ppm was determined (Fischer,
1979).
- Rat 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. Skin lesions consistent
with scratching of the head, neck and thorax were observed in
all mid- and high-dose groups throughout the study. Mortality
was decreased in high-dose males. Terminal
body weights were decreased in treated animals, but especially
in high-dose males and females. This was possibly related to a
depression of food intake. A very mild anaemia
was observed in the 3rd months for both high-dose males
and females...
Ref: Flucythrinate. 1985 World Health Organization
Review.
http://www.fluoridealert.org/pesticides/Flucythrinate.1985.WHO.htm
Fludioxonil
- Fungicide - CAS No. 131341-86-1
-- 1
Year chronic toxicity study - dog. NOAEL = 3.3 mg/kg/day.
LOAEL = 35.5 mg/kg/day based on decreased
weight gain in female dogs.
-- 13 Week Oral Feeding Study - rat.
Systemic. NOAEL= 64 mg/kg/day. LOAEL = 428 mg/kg/day based on
decreased body weight gain in both sexes,
chronic nephropathy in males, and centrilobular
hepatocyte hypertrophy in females.
Ref: Federal Register: September 12, 2001.
Fludioxonil; Pesticide Tolerances for Emergency Exemptions. Final
Rule. http://www.fluoridealert.org/pesticides/Fludioxonil.FR.Sept.12.2001.htm
A chronic oral toxicity
study in dogs dosed for 52 weeks at 0, 100, 1,000, and 8,000 ppm
in the diet (0, 3.1, 33.1, and 297.8 mg/kg/ day in males; 3.3,
35.5, and 330.7 mg/kg/day in females. The LEL is 297.8 mg/kg/day
for male dogs based on decreased body weight, hematology alterations
(increase in platelets and fibrin), clinical chemistry alterations
(increase in cholesterol and alkaline phosphatase) and
increased liver weight. The LEL is 35.5 mg/kg/day for female
dogs based on a marked decrease in body weight gain for weeks
1 - 13 and weeks 1 - 52 of the study. The NOEL is 33.1
mg/kg/day for male dogs and 3.3 mg/kg/day in female dogs.
Ref: Federal Register: October 29, 1997
[Page 56075-56082]. 4-(2,2-difluoro-1,3-benzodioxol-4-yl)-1H-pyrrole-3-carbonitrile;
Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Fludioxonil.FR.Oct.29.1997.htm
Flufenacet
- Herbicide - CAS No. 142459-58-3
-- Developmental Toxicity
(rat): Maternal NOEL = 25 mg/kg/day Maternal LOEL = 125 mg/kg/day
based on decreased body weight gain initially.
Developmental NOEL = 25 mg/kg/day Developmental LOEL = 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.
Ref: US EPA. Pesticide Fact Sheet. Flufenacet
Reason for Issuance: Conditional Registration Date Issued: April
1998.
http://www.epa.gov/opprd001/factsheets/flufenacet.pdf
Flumequine
- Microbiocide - CAS No. 42835-25-6
-- 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
Flumethrin
- Acaricide, Insecticide
- CAS No. 69770-45-2
Groups of 15/sex/dose
Wistar rats were fed diets containing
0, 10, 50 or 250/150 mg/kg feed for 13 weeks. The test substance
was a 50% premix with colloidal SiO2 carrier. Due to severe
weight loss the dose level of 250 mg/kg feed was reduced
to 150 mg/kg feed during week 3. Body weight
gain was significantly reduced in the rats given 150 mg/kg
feed compared with the controls. Skin lesions,
described as ulcerative dermatitis, were observed in the 50 and
150 mg/kg feed groups and were dose-related in severity. The
NOEL was 10 mg/kg feed, equivalent to 0.7/0.8 mg/kg bw per day...
-- IN GLP repeated-dose toxicity study, groups of 20/sex/dose
Wistar rats were fed diets containing
0, 10, 40 or 160 mg/kg feed flumethrin for up to 15 weeks. During
mixing of the diets, 1% peanut oil was added to minimise dust
formation. At 160 mg/kg feed, body weight
gain was significantly reduced...
-- Groups of 4/sex/dose Beagle dogs
were fed diets containing 0, 50, 100 or 200 mg/kg feed flumethrin
for 13 weeks. The test substance was a 45.3% premix with colloidal
SiO2 carrier. Skin lesions and emesis
were observed in the groups receiving 50 mg/kg feed and above
and were dose-related in incidence and severity. Over the 13 weeks,
the mean body weight of males given 200
mg/kg feed was decreased and females in this group gained
less weight than the controls...
-- In a 2-generation reproduction study in rats with 2 litters
per generation, flumethrin was administered in the diet at concentrations
of 0, 1, 5 or 50 mg/kg feed. The test substance was a 45.6% premix
with colloidal SiO2 carrier. Food consumption and
body weight gain were reduced in parental animals of the P and
F1 generations... In the 50 mg/kg feed group, pup viability
on days 1 to 4 post-partum and pup body
weights were depressed and signs of pyrethroid-poisoning were
observed in the pubs of the F1a and F 1b litters. The NOEL
was 5 mg/kg feed, equivalent to 0.36 and 0.40 mg/kg bw per day,
in males and females respectively...
-- 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
Flumioxazin
- Herbicide - CAS No. 103361-09-7
Subchronic, Chronic,
and Other Toxicity
-- 870.3800 Reproduction and fertility effects - rat. Parental/Systemic
NOAEL = mg/kg/day: males = 12.7, females = 15.1 LOAEL = mg/kg/day:
males = 18.9, females = 22.7 based on increase in clinical signs
(red substance in vagina) and increased female mortality
as well as decreased body weight, body weight
gain and food consumption
Reproductive NOAEL = mg/kg/day: males = 18.9 (HDT), females
= 22.7 (HDT) LOAEL = mg/kg/day: males = >18.9 (HDT), females =
>22.7 (HDT) Offspring NOAEL = mg/kg/day: males = 6.3, females
= 7.6 LOAEL = mg/kg/day: males = 12.7, females = 15.1 based on
a decrease in the number of liveborn and a decrease
in pup body weight
-- 870.3700b Prenatal developmental - rabbit (oral) Maternal NOAEL
= 1000 mg/kg/day LOAEL = 3000 mg/kg/day (HDT) based on decrease
in body weight and food consumption
during dosing Developmental NOAEL = 3000 mg/kg/day (HDT) LOAEL
= >3000 mg/kg/day
-- there is concern for the severity of the effects observed in
fetuses and young animals when compared to those observed in the
maternal and parental animals (dose- and treatment-related increase
in the incidence of cardiovascular abnormalities,
particularly ventricular septal defect, in the developmental
studies; and decreases in the number of live born pups and pup
body weights in the absence of parental toxicity in the
reproduction study).
Ref: US EPA Pesticide Fact Sheet. April
12, 2001.
http://www.epa.gov/opprd001/factsheets/flumioxazin.pdf
*Pregnant females were
admin 400 mg/kg by gavage on gestation day 11 or 12 or 13 or 14
or 15. Day 12 admin showed: largest incidence of embryonic death,
lowest fetal body weights
& greatest incidence
of ventricular spetal defects.
Ref: US EPA Pesticide Fact Sheet. April
12, 2001.
http://www.epa.gov/opprd001/factsheets/flumioxazin.pdf
Fluometuron
- Herbicide - CAS No. 2164-17-2
--
Organ Toxicity. Toxic injury to the liver,
kidneys, gut and brain is induced when lethal doses of fluometuron
are administered experimentally (10). An increase in spleen weight
and in the incidence of abnormalities in red-blood cells, and
decreased
weight gain in females
were observed in a 90-day study of rats (18).
-- Teratogenic Effects. Pregnant rabbits were given doses of 50,
500 or 1,000 mg/kg/day by gavage during days 6 through 19 of gestation.
An increase in the number of resorbed fetuses was found at all
treatment doses. Reduction in maternal body
weight and food consumption
occurred at doses of 500 and 1,000 mg/kg/day (20).
-- CHRONIC TOXICITY. Rats were fed 7.5, 75, or 750 mg/kg/day for
90 days. At the 750 mg/kg dose, decreased
body weight and congestion in the
spleen, adrenals, liver, and kidneys were evident. The NOAEL for
this study was 7.5 mg/kg/day (100 ppm). When doses of 1.5, 15
or 150 mg/kg/day were fed to puppies for 90 days, congestion of
the liver, kidneys and spleen occurred at the 150 mg/kg
dose. No effects were seen at 15 mg/kg/day (400 ppm) (20).
Ref: Flumeturon. EXTOXNET. Pesticide Information
Profile. March 1994.
http://pmep.cce.cornell.edu/profiles/extoxnet/dienochlor-glyphosate/fluometuron-ext.html
Chronic Study ** 025
068693, "Fluometuron Technical: 1-Year Oral Adminstration to Dogs
(Min 832047)", (CIBA-Geigy Corporation Pharmaceuticals Div., Laboratory
Study No.832047, May 25, 1988). Fluometuron, purity 95.8%, administered
in the feed at concentrations of 0, 20, 400 or 7000 ppm to Beagle
dogs, 5/sex/group for 52 weeks. Three extra/sex dogs in the control
and the high dose groups were continued an additional 4 weeks
without further treatment and served as the recovery group. No
adverse effect. NOEL = 400 ppm (Increased incidence of emesis;
stool irregularities - diarrhea, mucous, soft and bloody stools;
reduced body weight (14-19% less than control
at week 52), body weight gain and feed consumption;
reduced erythrocytic parameters and indices - HGB, RBC,
HCT, MCV and MCHC; and increases in percent Heinz bodies, Howell-Jolly
bodies and reticulocytes; reduced biochemical parameters - SGPT,
glucose and increased cholesterol, bilirubin, potassium and inorganic
phosphorous levels). Reduced HGB, increased platelet count and
WBC for the recovery group. ACCEPTABLE. (JSK & M. Silva, 8/30/89).
Ref: Summary of Toxicology Data. California
Department of Food and Agriculture, Medical Toxicology Branch.
Revised October 29, 1989.
http://www.fluoridealert.org/pesticides/Fluometuron.CA.EPA.Tox.data.pdf
Fluoroacetamide
- Rodenticide - CAS No.
640-19-7
ANIMALS ACUTELY POISONED
BY ... /FLUOROACETAMIDE/ SHOW LISTLESSNESS, IRRITABILITY, CLONIC
CONVULSIONS, ABASIA, PILOERECTION, & IRREGULAR RESPIRATION. ONE
CHARACTERISTIC USUALLY OBSERVED IN ANIMALS DYING FROM ACUTE POISONING
WITH FLUOROACETAMIDE AS WELL AS WITH SODIUM FLUOROACETATE IS POSTMORTEM
RIGIDITY. DEATH GENERALLY OCCURS IN COMA AFTER CONVULSIONS HAVE
STOPPED. SUBACUTELY POISONED ANIMALS SHOW
ANOREXIA, EMACIATION, ALOPECIA, & ABSCESS FORMATION. [Hayes,
W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology.
Volume 3. Classes of Pesticides. New York, NY: Academic Press,
Inc., 1991. 1278]
Ref:
FLUOROACETAMIDE CASRN: 640-19-7. Hazardous Substances Data Bank.
http://www.fluorideaction.org/pesticides/fluoroacetamide.hsdb.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 gesttion... 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.
Ref:
Evaluation on: Fluoroglycofen-ethyl. May 1992. Issue No. 50. Department
for Environment, Food and Rural Affairs, Pesticides Safety Directorate,
UK.
Fluoxastrobin
- Fungicide - CAS No. 361377-29-9
-- Subchronic toxicity.
A subchronic toxicity feeding study with rats over 90 days demonstrated
a NOAEL of 7.3 and 18.3 mg/kg bwt/day for males and females, respectively,
based on reduced body weights and
alterations in several urinary tract-related
clinical chemistry parameters, at the higher dose levels. In a
subchronic feeding study in mice over 14 weeks, a NOAEL was not
established based on decreased alanine aminotransferase (ALAT)
and increased absolute and relative liver weights at the low dose
level (21.7 and 35.3 mg/kg bwt/day for males and females respectively).
A 14-week feeding study in dogs demonstrated a NOAEL of
3.0 mg/kg bwt/day based on decreased body
weights and food consumption, and
liver effects (enzyme induction, increased liver weights, cytoplasmic
change), and thyroid effects (decreased T3)
-- Chronic toxicity... A 1-year feeding
study with dogs demonstrated a NOAEL of 1.7 and 1.5 mg/kg bwt/day
for males and females, respectively based on decreased
body weights and slight liver effects
(increased alkaline phosphatase (Aph) and liver weights).
Ref: Federal Register: April 23, 2003. Fluoxastrobin;
Notice of Filing a Pesticide Petition to Establish a Tolerance
for a Certain Pesticide Chemical in or on Food.
http://www.fluoridealert.org/pesticides/Fluoxastrobin.FR.Apr23.2003.htm
• Reproduction
and fertility - rats. Offspring
systemic: decreased
body weights, delayed preputial separation, and incomplete
ossification in the F1 and/or F2 males and females. Parental
systemic: decreased
premating body weight gain of the P-generation
males and females and decreased premating absolute body
weight of the F1 males and females.
• Chronic toxicity-dogs. LOAEL
was 8.1 mg/kg/day for males and 7.7 mg/kg/day for females based
on body weight reductions and hepatocytomegaly
and cytoplasmic changes associated with increased serum liver
alkaline phosphatase indicative of cholestasis.
•
90-Day oral toxicity-rats. reduced
body weight gain and food intake, vacuolation
in the zona fasciculate of the adrenal cortex,
calculi in the urethra and kidney, and histological lesions in
kidney, urinary bladder, and urethra;
• 90-Day oral toxicity-dogs.
dose-related
reductions in net body weight gain
and food efficiency in addition to toxicity findings in the liver
in both sexes (cholestasis) and in kidneys (increased relative
weights in females and degeneration of the proximal tubular epithelium
in males).
•
Combined chronic toxicity / carcinogenicity--rats.
decreased body weight,
decreased body weight gain, and decreased
food efficiency in both sexes; decreased
spleen weight in males; and
microscopic lesions in the uterus of females. The apparent increase
in tumors in the uterus and thyroid were addressed and resolved
by an Agency committee, which
concluded that no carcinogenic concern exists for fluoxastrobin.
•
90-Day Subchronic Oral Toxicology-Dog.
dose-related reductions
in net body weight gain and food efficiency; toxicity findings
in the liver (cholestasis) in both sexes;
and toxicity findings in the kidneys (increased relative weights
in females and degeneration of the proximal tubular epithelium
in males).
Ref: Federal Register. September 16, 2005.
Fluoxastrobin; Pesticide Tolerances. Final Rule.
http://www.fluorideaction.org/pesticides/fluoxastrobin.fr.sept16.05.html
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 2-generation reproductive toxicity
study, fluopicolide was administered to rats at
dietary levels of 0, 100, 500, or 2000 ppm. The NOAEL was 500
ppm (equivalent to 26 and 33 mg/kg/day for males and females respectively)
for developing offspring and for parental/systemic toxicity. The
LOAEL was 2000 ppm based on decreased body
weight and organ weight changes in both F0 anb F1 and F2 pups.
The reproductive NOAEL was 2000 ppm.
Chronic toxicity
(page 4)
i. Lower body weight gain at the
limit dose of 1000 mg/kg/day was the only treatment-related effect
noted in a 52-week dog study performed at 70,
300, and 1000 mg/kg/day by gavage.
iii. The oncogenic potential of fluopicolide was investigated
in C57BL/6 mice at dietary levels of 0, 50, 400,
or 3200 ppm. Significantly lower body weight
gain was seen at 3200 ppm in conjunction with a slight
decrease in food consumption....
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
Flupyrsulfuron-methyl,
sodium salt -
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
-- Oral long-term toxicity
and carcinogenicity. 2-year dietary study in rats. groups of 50
male and 50 female outbred albino Sprague-Dawley CRL :COBS CD(SD)BR
rats were administered fluquinconazole (93.2% purity) in the diet
at concentrations of 0 (control), 1, 20 or 100 ppm. Additionally
20 animals/sex/dose designated for the interim-kill received the
test compound at concentrations of 0, 1, 5, 10 or 100 ppm for
12 months... Mortalities over the 24-month period were 24/50,
28/50, 28/50 and 31/50 in males and in females 33/50, 36/50 and
39/50 at dose levels of 0, 1, 20 and 100 ppm... Post-mortem examinations
showed the most probable cause of deaths in males to be pituitary
tumors followed by chronic progressive nephropathy and urinary
tract infections. In females mammmary tumors followed by pituitary
tumors were considered the most probable cause of morbidity...
Feed consumption was very slightly increased at the 100 ppm dose
level (7% in males and 15% in females over weeks 1-104) compared
to controls. Body weight gain was
during weeks 0-55 reduced in treated females (9-12%) compared
with controls but was significantly reduced
during weeks 55-103 in males (13% at 10 ppm and 68% at 100 ppm)
and in females (40% at 100 ppm dose level)...
--
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...
Reductions in body weight gain occurred
in males only at 100 ppm (17%) and 10 mg/kg bw/day (16%)
ppm compared to controls. The reduction
in body weight gain in the surviving males at the 200 ppm dose
level was 39% compared with that of the control over the
treatment period...
-- 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
Fluridone
- Herbicide - CAS No. 59756-60-4
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
-- Three studies were
conducted concurrently, using Fischer rats fed the same dietary
levels of Fluridone [0, 200, 650, 2000 ppm (0, 8, 25, 81 mg/kg/day)].
The first study was a 1-year feeding study (R-1126) in which 120
animals were divided into four groups of 15 animals/sex/dietary
level. The other two studies were reported to be replicate 2-year
oncogenic assays (Nos. R-1136 and R-1146), in which 240 animals
per assay were divided into four groups of 30 animals/sex/dietary
level. These three studies constitute a 2-year study with 75 animals/sex/dietary
level of which 15 animals/sex/dietary level were sacrificed at
12 months. Effects observed at 650 ppm included glomerulonephritis
[kidney], atrophic testes,
eye keratitis,
decreased body weight and organ weights.
[Elanco Products Company, Division of Eli
Lilly and Company. 1980a. MRID No. 00103251, 00103305.
Available from EPA. Write to FOI, EPA, Washington, DC 20460.]
Ref: US EPA IRIS for Fluridone. 1990.
http://www.fluoridealert.org/pesticides/Fluridone.EPA.IRIS.1990.htm
Fluroxypyr
- Herbicide - CAS No. 69377-81-7
-- In a range finding
feeding study in dogs, dogs at 500 mg/kg/day exhibited ataxia
and hind limb weakness as well as decreases
in body weight and food consumption.
Histopathology showed moderate acute tubular
nephrosis and a slight to moderate acute gastroenteritis. Some
early signs of acute tubular nephrosis were also seen in both
sexes of dogs at 150 mg/kg/day. The NOEL for the study was 50
mg/kg/day, the LOAEL was 150 mg/kg/day based on histopathological
lesions in the kidneys, decreased testes weights, and increased
adrenal weights in both sexes.
-- In a developmental toxicity study in rats, fluroxypyr administration
resulted in 8 deaths at the high-dose level, and decreased
body-weight gain and food consumption
during the dosing period at this dose level also. Clinical
signs observed in those dying on test included staining of the
skin/fur in the ano-genital area, lethargy, hypothermia, labored
breathing, irregular gait, pale appearance. There were no treatment-related
effects on gross pathologic alterations or absolute and relative
liver and kidney weights at any dose level. The maternal NOEL
is 300 mg/kg/day, the LOAEL is 600 mg/kg/day, based on deaths
and decreased body-weight gain and
food consumption. The
developmental toxicity NOEL is 300 mg/kg/day, and the LOAEL is
600 mg/kg/day, based on an increase in two ossification variations
(incompletely ossified cervical vertebral transverse processes
and pubes).
Ref: US
EPA. Pesticide Fact Sheet. Fluroxypyr. Reason for Issuance: Conditional
Registration Date Issued: September 30, 1998.
http://www.epa.gov/opprd001/factsheets/fluroxypyr.pdf
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.
-- Reproduction Study A 2 generation reproduction study in the
rat treated with (time weighted average) 0, 1.8, 7.3, and 74 mg/kg/day
of flurprimidol had a Parental Systemic Toxicity NOEL of 1.8 mg/kg/day
and a LEL of 7.3 mg/kg/day based on increased incidence of non-neoplastic
hepatocellular alterations including fatty change and vacuolation
(males) and increased susceptibility to stress factors. The Reproductive
NOEL was 7.3 mg/kg/ and the LEL was 74 mg/kg/day based on decreased
mating, fertility, fetal survival (stillbirths), neonatal survival
and neonatal body weight in both sexes and
in both generations. There was an increased incidence of
persistent vaginal estrous and no corpora lutea. Additional parental
signs of toxicity at 74 mg/kg/day included increased susceptibility
to stress (pregnant females) resulting in death, increased relative
liver weight (males and females), depressed
body weight, weight gain and food consumption (males and
females).
Ref: US EPA Pesticide Fact Sheet for
Flurprimidol. 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... Small but statistically
significant decreases in mean maternal body weight were
observed in the 250 and 1000 mg/kg bw/day groups on gestation
days 9-20. When the body weights of the two abnormal dams were
excluded from the analysis, mean maternal
body weights were significantly lower in the 250 and 1000
mg/kg bw/day groups on gestation days 9-20, and they were also
significantly lower in the 5 and 50 mg/kg bw/day groups on gestation
days 18-20. Small but statistically significant
decreases in mean body weight gain were observed in all treatment
groups (including and excluding the abnormal dams) during
dosing and between gestation days 6 and 20. During the post-dosing
period, mean body weight gain was significantly
increased in the 1000 mg/kg/day group only [pages 109-110]...
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...
Significant reductions in mean maternal
body weight gain were observed during the dosing period
at 200 and 600 mg/kg bw/day... 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 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].
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
Flusilazole
- Fungicide -
CAS No. 85509-19-9
-- 2-Generation Reproduction
- rat: Parental NOEL=3.5 mg/kg/day;
Parental LEL=19 mg/kg/day (decreased body
weight and body weight gain in F1 males during the 90 day
feeding study); Reproductive NOEL and LEL could not be determined;
Developmental NOEL=0.85 mg/kg/day (hydronephrosis
noted at weaning of F2b pups - only trial examined); core grade
supplementary (E.I. du Pont de Nemours & Co., Inc., 1986b)
-- Teratology - rat: Maternal NOEL=10
mg/kg/day; Maternal LEL=100 mg/kg/day (increased mortality after
day 23 of gestation, prolonged gestation, decreased
food consumption and weight gain,
increased relative and absolute liver weight);
Developmental NOEL (pre and post natal)=2
mg/kg/day; Developmental LEL=10 mg/kg/day (increased incidence
of small renal papilla, distended ureter, dilated renal pelvis,
decreased pup survival); core grade minimum (E.I. du Pont de Nemours
& Co., Inc., 1985b)
-- Teratology - rabbit: Maternal
NOEL=12 mg/kg/day; Maternal LEL=35 mg/kg/day (decreased food consumption
and final body weight were observed at one dose only); Developmental
NOEL=12 mg/kg/day; Developmental LEL=35 mg/kg/day (increased resorptions
and abortions, and decreased fetal weight);
core grade minimum (E.I. du Pont de Nemours & Co., Inc., 1985c)
Ref: US EPA IRIS. NuStar CASRN: 85509-19-9.
Available October 6, 2003 at Toxnet.
Fluthiacet-methyl
- Herbicide - CAS No. 117337-19-6
-- 90-day oral Toxicity,
rats and mice. Rats: NOAEL = 6.19 milligrams/ kilograms day (mg/
kg/day) in males 6.80 mg/ kg/day in females LOAEL = 216 mg/ kg/day
in males 249 mg/ kg/day in females Mice: NOAEL = 1.3 mg/kg/ day
in males 1.6 mg/ kg/day in females LOAEL = 66 mg/kg/ day in males
83 mg/kg/ day in females. Based on decreased
body weight gains as well as effects
on hematology, clinical
chemistry, urinalysis
parameters, liver weights and microscopic pathology in rats; and
on effects on the erythropoietic system and liver in mice.
-- 6-week oral toxicity in dogs. NOAEL = 236 mg/kg/ day in males
77.7 mg/ kg/day in females LOAEL = 709 mg/kg/ day in males 232
mg/ kg/day in females based on decreased
body weight gain.
-- 2-generation Reproduction and fertility effects. Parental/systemic
NOAEL = 1.59 mg/kg/ day in males LOAEL = 31.8 mg/kg/ day in males
NOAEL = 1.73 mg/kg/ day in females LOAEL = 35.2 mg/kg/ day in
females based on reduction in male body
weights/ gains and hepatic pathology Reproductive in males:
NOAEL = 31.8 mg/kg/ day LOAEL =313 mg/kg/ day Reproductive in
females: NOAEL = 37.1 mg/kg/ day LOAEL = 388 mg/kg/ day based
on decreases in mean litter body weights.
-- Carcinogenicity rats. NOAEL in males = 2.1 mg/kg/day LOAEL
in males = 130 mg/kg/day NOAEL in females = 2.5 mg/kg/day LOAEL
in females = 154 mg/kg/dayIn males there were decreased
body weight, liver toxicity, pancreatic toxicity and
microcytic anemia. In females there were liver toxicity,
uterine toxicity and slight microcytic anemia.
In males only at 130 and 219 mg/kg/day there was respectively,
an increase in the trend toward pancreatic exocrine adenomas and
pancreatic islet cell adenomas.
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
-- 7.2 Subacute toxicity.
a) In a 90-day feeding study, rats were fed diet containing 0,
20, 200 or 2,000 ppm flutriafol. At the highest does,
reduced body weight and food intake, haemotological and
biochemical changes, increased liver weight,
centrilobular hypertrophy,
proliferation of SER, elevated hepatic aminopyrine-N-demethylase
(APDM) activity were noted. In females fed 200 ppm, only adaptive
responses (liver enlargement and elevated APDM) were seen,
whereas minimal fatty change was evident in some males. A NEL
of 20 ppm (approx. 1 mg/kg bw/day) was established by the SSC
(April 1983).
--b) In a 90-day study, dogs were administered oral doses (capsules)
of 0, 1, 5 or 15 mg flutriafol/kg bw/day. Reduced
body weight gain, increased
liver weight, elevated hepatic APDM and plasma ALP activity,
were observed in the 15 mg/kg bw/ dosage group. At the 5 mg/kg
dosage level, APDM activity was elevated in both sexes. Slight
increases in liver weight were seen in females at the low
and intermediate dosage levels. A NEL of 5 mg/kg bw/day was established
by the SSC [Scientific Subcommittee on Pesticides] (April 1983).
-- 7.5 Two year feeding study in the rat (1982-84). Wistar derived
Alpk: AP rats (52/sex/dose) were fed diet containing flutriafol
(purity 93%) at a concentration of 9, 20, 200 or 2,000 for at
least 104 weeks. Additional animals (12/sex/dose) were given identical
treatment and sacrified at 52-54 weeks... Apart from non-specific
clinical observations, the only treatment-related clinical findings
were an increased number of thin rats
and reduction in the number with distended abdomens in the dop
dosage group. A significant reduction in
bodyweight gain was observed in the top dosage group throughout
the study. On termination, the mean bodyweight
of males in the high dosage group was reduced by about 10% compared
to controls, in females the reduction was about 20%.
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/evallist_alphabet.htm
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... An increase in plantar
ulcers was observed in rats fed 2.5 mg/kg/day (LOEL) for 2 years.
The NOEL was 1 mg/kg/day. Decreases in body
weight gain were also observed in this study. Based on
the NOEL of the study, an oral RfD of 0.01 mg/kg/day was derived.
In a 2- generation rat reproduction study, dietary administration
of 5 mg/kg/ day produced decreased body
weight gain and skin lesions in parents and offspring.
Dietary administration of 2.5 mg/kg/day to rats for 13 weeks produced
anemia in blood parameters (decreased hematocrit, hemaglobin,
and red blood cells). The NOEL was 1.0 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
-- 3. Chronic toxicity.
EPA has not established the RfD for fomesafen. For the purposes
of this tolerance, based upon available chronic toxicity data,
the RfD of 0.0025 mg/kg/day was used. This RfD is based on the
NOEL of 0.25 mg/kg/day from the rat carcinogenicity study. A 100-fold
uncertainty factor was used to calculate this RfD. At the LOEL
of 5.0 mg/kg/day there was liver
toxicity and decreased
body weight.
-- iii. Reproductive toxicity study. In the 2-generation reproductive
toxicity study in rats, the parental (systemic) NOEL was 12.5
mg/kg/ day, based on decreased body weight
and liver necrosis at the LOEL of
50 mg/kg/day. The reproductive and developmental (pup) NOELs were
2.5 mg/kg/day, based on decreased pup body
weight and reduced litter size at the LOEL of 12.5 mg/kg/day.
-- v. Conclusion. Based on the rat reproductive toxicity study
discussed above, the pup LOEL (decreased
body weight and reduced litter size) occurred at levels
below the maternal NOEL and demonstrates post- natal pup toxicity
unrelated to maternal effects. These results are suggestive of
a special sensitivity for infants and children following post-natal
exposure. Therefore, EPA recommends applying an extra 10- fold
uncertainty (safety) factor in the chronic risk analysis. The
low percentage of the RfD occupied by the most highly exposed
child subgroup (4.8% of the RfD; 48% using the extra 10-fold factor)
demonstrates that post-natal risks to infants and children are
low.
Ref: Federal Register. November 19, 1997.
Fomesafen; Pesticide Tolerances for Emergency Exemptions. Final
Rule.
http://www.fluoridealert.org/pesticides/Fomesafen.FR.Nov.19.1997.htm
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