See short description and definitions on kidney
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
An acceptable chronic
rat feeding study identified the following effects: seizures,
including seizures resulting in death, decreased body weight gain,
decreased food consumption and food conversion efficiency, decreased
hematology measures, alterations in clinical chemistry (cholesterol,
calcium, and protein), alterations in thyroid hormones, alterations
in urine chemistry, changes on gross necropsy, increase in liver
and thyroid weights, and progressive senile
nephropathy (kidney effects).
The NOEL for systemic toxicity was 0.5 ppm.
Ref: US EPA Pesticide Fact Sheet. May 1996.
http://www.fluoridealert.org/pesticides/fipronil.epa.facts.may.1996.htm
--2 year dietary study
in rats. The carcinogenic potential of fipronil was determined
in a 2-year study carried out in the rat (CD strain). Animals
(50/sex/dose) received dietary administration of fipronil (batch
number PGS, 95.4% purity) at either 0.5, 1.5, 30 or 300 ppm; equivalent
to 0.02, 0.06, 1.3 and 13 mg/kg/d (males) and 0.03, 0.08, 1.6
and 17 mg/kg/d (females). (page 89)
-- At study termination histopathological findings were confined
to a statistically signifiicant increase
in progressive senile nephropathy in males and
thyroid "follicular cysts" (growth anomaly) at ≤30
ppm in females. (page
91)
Ref:
April 204. Evaluation
on : Fipronil (Horticultural Uses).
No. 212.
UK Dept. for Environment, Food and Rural Affairs, Pesticides Safety
Directory.
http://www.fluorideaction.org/pesticides/fipronil.uk.report.apr.2004.pdf
Flazasulfuron
- Herbicide - CAS No. 104040-78-0
• Long term toxicity and carcinogenicity . Target / critical
effect: Liver (centrolobulillar hypertrophy)
in mice and kidney (chronic nephropathy)
in rats. Lowest relevant NOAEL: 1.3mg/kg bw/day: 2-years
rats. No evidence for carcinogenic potential.
Flonicamid
- Insecticide - CAS No. 158062-67-0
-- Reproductive and
developmental toxicity. A developmental toxicity study in rats
resulted in the maternal and developmental no observed adverse
effect levels (NOAELs) of 100 mg/kg/day. The maternal lowest observed
adverse effect level (LOAEL) was 500 mg/kg/day based on the treatment-related
effects observed on the liver
and kidney of the dams in the highest dose group...
-- In the multi-generation rat reproduction study, the NOAEL was
300 ppm for both parental animals (13.5-32.8 and 16.3-67.0 mg/kg/day,
respectively, for males and females) and their offspring. The
effects at the highest dose of 1,800 ppm included the following:
increased kidney weights and gross and histopathological
alterations in the kidney...
-- In a 90-day rat feeding study the NOAEL was established at
200 ppm (12.11 mg/kg/day) for males and 1,000 ppm (72.3 mg/kg/day)
for females. The NOAELs were based on effects on
hematology, triglycerides, and pathology in the liver
and kidney.
-- In a 13-week mouse study, the NOAEL was 100 ppm (15.25 mg/kg/day
in males and 20.1 mg/kg/day in females). The LOAEL is 1,000 ppm
(153.9 mg/kg/day in males and 191.5 mg/kg/day in females) based
on hematology effects and changes in glucose,
creatinine, bilirubin, sodium, chloride and potassium levels,
increased liver and spleen weights and histopathology findings
in the bone marrow, spleen and kidney.
-- In a rat 24-month combined chronic and oncogenicity study,
flonicamid technical was not carcinogenic in rats. The NOAEL was
200 ppm (7.32 mg/kg/day) for males and 1,000 ppm (44.1 mg/kg/day)
for females. The LOAEL was 1,000 ppm for males and 5,000 ppm for
females based on histopathology in the kidney,
hematology effects, hepatic effects
including changes in biochemical parameters, increased organ weights,
and histopathological changes. Atrophy of striated muscle fibers,
cataract and retinal atrophy observed in the high dose females
were considered to be due to acceleration of spontaneous age-related
lesions.
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
-- 90-Day
oral toxicity rodents (rats). 28-day range-finding. NOAEL
is 100 ppm (7.47 mg/kg/day) for males and 1,000 ppm (81.9 mg/kg/day)
for females.
LOAELs were 500 ppm (36.45 mg/kg/day) for males based on changes
in the kidney (hyaline deposition)
and 5,000 ppm for females (372.6mg/kg/day) based on kidney
(hyaline deposition), liver changes
(centrilobularhypertrophy), hematological effects (anemia)
and clinical chemistry (increased cholesterol)
--
90-Day oral toxicity (nonrodents- dogs).
NOAEL is 8 mg/kg/day in males and 20 mg/kg/day for female. LOAEL
is 20 mg/kg/day in males and 50 mg/kg/day in females, based on
acute clinical signs in males and females (vomiting,
first observed on Day 1 and last observed on Day 90), clinical
pathology at 7 weeks (increased total protein
levels in males, lower red blood cells and higher reticulocytes
counts in females), increased adrenal
weights in males, decreased thymus gland weights in males,
and increased kidney tubular vacuolation
in females at study termination
-- Prenatal
developmental toxicity (rats).
Maternal.
NOAEL is 100 mg/kg bw/day. LOAEL is 500 mg/kg bw/day, based on
increased liver weight, and liver
and kidney pathological changes
(hypertrophy of centrilobular hepatocytes in liver and
vacuolation of proximal tubular cell in kidneys)
--
Chronic dietary.
2-Generation Reproduction
rat. Parental LOAEL = 22 mg/kg/day based on increased kidney
weights, kidney hyaline deposition,
increased blood serum LH (F1 females).
Ref:
August 31, 2005. Flonicamid; Pesticide Tolerance. Final Rule.
Federal Register.
http://www.fluoridealert.org/pesticides/flonicamid.fr.aug.31.2005.html
Floransulam
- Herbicide - CAS No. 145701-23-1
-- Short
term toxicity. Target / critical
effect: Anemia, hepatotoxicity , renal
hypertrophy epithelial cells, collecting ducts, adrenal
vacuolation(dog ) Lowest relevant oral NOAEL / NOEL: 1
y & 90 d dog (oral feed) ; 5 mg/kg bw/d;...
-- Long term toxicity and carcinogenicity.
Target / critical effect: kidney collecting
duct hypertrophy, papillary mineralisation, necrosis and inflammation
(rat and/or mice) Lowest relevant NOAEL: 2 yr rat (oral feed):
10 mg/kg bw/d. no carcinogenic potential. Other toxicological
studies Renal cells affected are
probably Type A intercalated cells, involved in acid-base regulation.
Ref: September 18, 2002 - Review report
for the active substance florasulam. European Commission Health
& Consumer Protection Directorate-General.
http://www.fluoridealert.org/pesticides/florasulam.eu.sept.2002.pdf
-- 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.
-- The subchronic and chronic toxicity of florasulam was investigated
in the mouse, rat and dog. A 28-d repeat dose dermal toxicity
study was also carried out in rats. In the subchronic and chronic
studies, treatment-related findings were observed in the kidney
in all species and in the liver and
adrenal glands in dogs. In the kidney,
hypertrophy of the epithelial cells
of the collecting ducts occurred in all species tested.
-- In subchronic and chronic dietary studies, treatment-related
findings were observed in the kidneys in
mice, rats and dogs and in the liver and
adrenal glands in the dog.
In the kidney,
hypertrophy of the epithelial cells of the collecting duct was
observed in all species tested. In rats, hypertrophy of
the epithelial cells correlated with elevated serum bicarbonate
levels, urinary acidification, decreased urinary specific gravity
and increased kidney weights. In
dogs, treatment-related findings associated with the
liver included increased ALP activity, decreased serum
albumin and protein levels, increased liver
weights and increased incidence or severity of hepatic
vacuolation. Dogs also exhibited slight
vacuolization of the zona reticularis and zona fasciculata in
the adrenal glands; however, in the absence of any associated
inflammation, necrosis or other changes, the toxicological significance
was uncertain. The most appropriate NOAEL for subchronic and chronic
toxicity end points is 5.0 mg/kg bw/d in the 90-d and 1-year dietary
studies in dogs. At the LOAEL, 50 mg/kg bw/d, treatment-related
findings were observed in the kidneys
and liver in the 90-d and 1-year dietary studies and in the adrenal
glands in the 1-year 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 subchronic dietary toxicity
in Wistar rats (20/sex/group) receiving 0, 10, 100 and 2000 ppm
by dietary inclusion for 13 weeks. Mean achieved dosages during
13-week treatment were 0, 0.7, 7.1 and 144.5 mg/kg/day in males
of the respective treatment groups and 0, 0.8, 8.0 and 161.9 mg/kg/day
in females... Upon terminal necropsy, only high-dose males had
evidence of hepatic enlargement or swelling (7/20), although higher
absolute and relative liver weights were significant (p < 0.01,
Student's t-test) in both males and females of the 2000 ppm group.
Also, relative kidney weights were also
significantly elevated in the high-dose males. Histopathology
confirmed a specific liver toxicity in male rats, marked by significant
dose-related hepatocytic hypertrophy with isolated instances of
vesicular nuclei and or periacinal hepatocytic necrosis. Renal
tubular degeneration, 70% and 20% in 2000 and 100 ppm males respectively,
correlated with elevated kidney weights in these groups.
[ICI AMERICAS INC; 13 Week Dietary Toxicity Study with PP009 in
Rats (Final Report); 05/29/80; EPA Doc No. 88-920006943; Fiche
No. OTS0545346]
-- Fluazifop butyl was evaluated for reproductive and developmental
effects in 2 successive generations of Charles River Wistar strain
rats (30/sex/group) exposed continuously to 0, 10, 80 and 250
ppm in the diet. Each respective parent generation had received
treatment for a minimum of 100 days (F0) and 120 days (F1) prior
to mating. F0 and F1 dams weaned their progeny for 25 days postpartum
to time of offspring selection for mating and continued study
(F1) or sacrifice (F1, F2). Thirty days after sacrifice of their
offspring, the surviving F1 females and select F1 males were sacrificed
and with representative F1 and F2 offspring were examined histologically...
F1 parents were found with gross indications of toxicity.
Liver
and kidney
weights were significantly high (250
ppm) relative to controls, while spleen weights were low in both
sexes (80, 250 ppm).Upon necropsy, these F1 progeny were found
with dose-related increased hydronephrosis
[kidney]... Upon
histological investigation, increased incidence geriatric nephropathy
[kidney] (both sexes, 80 and 250 ppm), distension of mesenteric
and/or cervical lymph nodes (250 ppm) and increased severity of
nephrocalcinosis (females, 80 and
250 ppm), .. [ICI AMERS INC; Fluazifop butyl: Effects Upon Reproductive
Performance of Rats Treated Continuously Through 2 Generations
(Final Report); 03/17/81; EPA Doc No. 88-920006849; Fiche No.
OTS05543854]
--- Definition for nephrocalcinosis:
A form of renal stone disease where the kidney tissue is characterised
by foci of calcification in addition to numerous deposits of calcium
phosphate and calcium oxalate.
Ref: TOXNET profile from Hazardous Substances
Data Bank for FLUAZIFOP-BUTYL.
http://www.fluoridealert.org/pesticides/fluazifop-butyl.toxnet.hsdb.htm
Fluazifop-P-butyl
- Herbicide - CAS No. 79241-46-6
... Subchronic and chronic toxicity studies with fluazifop-butyl
or fluazifop-P-butyl show that the rat is more sensitive to toxic
effects than the dog, rabbit or hamster, possibly due to longer
retention time of the major metabolite (fluazifop acid) in the
rat. The kidney and liver
are the target organs and the toxicity is expressed as exacerbation
of age related kidney toxicity and liver toxicity in the presence
of peroxasome proliferation (page 5).
Ref:
December 10, 2004. US
EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance
Reassessment Eligibility Decision (TRED) Document. EPA Docket
number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf
ONCOGENICITY, MOUSE
[OR HAMSTER] 411-125 180756 Rattray, N. J., "Fluazifop-p-butyl:
80 week carcinogenicity study in hamsters," Central Toxicology
Laboratory (CTL), Alderley Park Macclesfield, 2/1/01. Lab Study
ID: Syngenta No.1606-01. Golden Syrian hamsters, 51/sex/group,
were dosed in diet with 0, 0, 200, 750, or 3000 ppm fluazifop-p-butyl
(91.6%) for 81-83 weeks. The dual control groups were treated
identically. An additional 12/sex/group (same doses) were allocated
for 1-yr sacrifice (for hematology only). Estimated achieved doses
were 12.5, 47, and 194 mg/kg/day (M) and 12.1, 46, and 181 mg/kg/day
(F). No NOEL was established. Changes seen at all dose levels
included chronic progressive nephropathy,
factoring both incidence and degree, in kidneys of both sexes;
gall stone formation at all dose levels
in males; testicular tubular degeneration,
factoring both incidence and degree, dose-related in all treated
male groups; and elevated liver weights in all female groups.,,
Ref: May 20, 2002. SUMMARY OF TOXICOLOGY
DATA FLUAZIFOP-P-BUTYL. California EPA. Department of Pesticide
Regulation. Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/fluazifop-p-butyl.caepa.02.pdf
4.2.3.1 Developmental Toxicity Study Conclusions. The LOAEL is
5.0 mg/kg/day based on decreased fetal weight and increased
incidence of hydroureter in fetuses and litters, and delayed
ossification in a 160 litter/group developmental toxicity study
(MRID# 00088858). (page 31).
Ref:
December 10, 2004. US
EPA. Fluazifop-P-butyl: Revised HED Chapter of the Tolerance
Reassessment Eligibility Decision (TRED) Document. EPA Docket
number: OPP-2004-0347-0003
Flucythrinate
-
Acaricide, Insecticide - CAS No. 70124-77-5
-- 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... Absolute and relative kidney
weights were significantly elevated in mid- and high- dose males
while only the relative kidney weight
was elevated in high- dose females.... (Brewer et al., 1981).
-- Groups of 6 male and 6 female Beagle dogs received technical
flucythrinate (87.3% pure) in the diet at 0, 30, 100, or 300 ppm
daily for 24 months... At sacrifice, the relative liver,
kidney, and pituitary weights were increased in both high-dose
males and females, while increases in relative spleen, testis
and lung weights were noted for high-dose males only... ((Spicer
et al., 1984).
Ref: 1985 World Health Organization Review
for Flucythrinate.
http://www.fluoridealert.org/pesticides/flucythrinate.1985.who.htm
Fludioxonil
- Fungicide - CAS No. 131341-86-1
Fludioxonil safety.
a. Ciba has submitted over 25 separate toxicology studies in support
of tolerances for fludioxonil. According to Ciba, fludioxonil
has a low order of acute toxicity by the oral, dermal, and inhalation
exposure routes. The compound is slightly irritating to the eye,
non-irritating to skin, and is not a dermal sensitizer. It is
not a teratogen and does not affect reproduction or fertility.
The kidney and liver have been identified
as target organs in subchronic and chronic toxicity studies.
No mutagenic activity has been seen in vivo.
Ref: Federal Register. February 5, 1997.
[PF-695; FRL-5584-1]
http://www.fluoridealert.org/pesticides/fludioxonil.fr.feb.5.1997.htm
A combined chronic
toxicity/carcinogenicity study in rats fed 0, 10, 30, 100, 1,000
and 3,000 ppm for either 12 or 24 months (males: 0, 0.37, 1.1,
3.7, 37 and 113 mg/kg/day, respectively; females: 0, 0.44, 1.3,
4.4, 44 and 141 mg/kg/day respectively)... At necropsy, [[Page
56078]] males at the 3,000 ppm dose level exhibited an increased
incidence of enlarged livers, and kidneys
with discolored foci or general discoloration and an increased
severity of progressive nephropathy;
kidneys with cysts were reported
at both the 1,000 and 3,000 ppm dose levels. For females in the
1,000 and 3,000 ppm dose levels there was an increase incidence
of general discoloration of the the kidneys.
Ref: Federal Register.October 29, 1997.
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
-- 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
Flufenacet
- Herbicide - CAS No. 142459-58-3
NOEL = 40 ppm [1.29
mg/kg/day in males and 1.14 mg/kg/day in females] LOEL = 800 ppm
[27.75 mg/kg/day in males and 26.82 mg/kg/day in females] based
on increased alkaline phosphatase, kidney,
and liver weight in both sexes, increased cholesterol in males,
decreased T3, T4 and ALT values in both sexes, and increased incidence
of microscopic lesions in the brain [axonal
degeneration], eye [vacuolization of the ciliary body epithelium],
kidney [hyperplasia of the epithelial cells], spinal cord
[axonal degeneration], sciatic nerve [axonal degeneration] and
liver [hepatocytomegaly].
Ref: EPA Pesticide Fact Sheet, April 1998
http://www.epa.gov/opprd001/factsheets/flufenacet.pdf
Flufenoxuron
- Acaricide, Insecticide, Herbicide - CAS No. 101463-69-8
Abstract: Flufenoxuron
(Benzoylphenyl urea derivative) - antimoulting insecticide Ð is
recently used for controlling insect reproduction in cultivated
areas. The study determined the hazardous effects of the applied
dose-treatment during the critical period of rat embryonic development
and the induction of growth retardation. In the present work,
flufenoxuron was intragastrically administered by stomach intubation
to pregnant rats at concentration levels 0 & 20 mg/kg b.wt.
in saline solution every other day on gestation day 7 till parturition.
Experimental and control pregnant rats were sacrificed on days
13 & 16 of gestation and the foetuses were fixed in 10 percent
formol saline. Histological abnormalities
of thyroid, liver and kidneys of mothers as well as of skeletal
axial and appendicular regions of foetuses were investigated.
Foetuses
maternally treated with flufenoxuron exhibited delayed differentiation
of chondrification and ossification of axial and appendicular
regions. The observed defects in foetuses may be attributed to
the histological abnormalities of thyroid, liver and kidneys
of maternal tissues as well as to the direct effect of the parents
as a result of the insecticide or its metabolites on the affected
structures during early morphogenesis and differentiation.
Ref: J. Egypt. Ger. Soc. Zool., Vol. 25(B),
65-81, 1998. PATTERNS
OF DEVELOPMENTAL DEFECTS OF RAT FOETUSES MATERNALLY TREATED WITH
AN ENVIRONMENTAL ANTIMOULTING INSECTICIDE FLUFENOXURON; by Karim,
S.A.
http://www.egsz.org/BiologicalCurrentContent/Zoology/Comparative%20Physiology/TOXICOLOGY.htm
Flufenpyr-ethyl
- Herbicide - CAS No. 188489-07-8
-- The kidney
and liver appear to be the target organs of flufenpyr-ethyl.
EPA has not had the opportunity to review the toxicity studies
on flufenpyr-ethyl and has not established toxic endpoints.
-- Reproduction. In the rat reproduction study, flufenpyr-ethyl
technical was administered in the diet at levels of 0, 200, 2,000,
and 20,000 ppm for 2-generations. Parental toxicity was observed
at all dose levels, although the effects at the low dose were
minimal. Parental toxicity was exhibited by dose-related microscopic
changes in the kidney in high dose F0 animals, in all treated
F1 males, and in high dose F1 females. There were also 2 high
dose F1 males that died possibly as a result of treatment...
-- A second 1-generation reproduction study was performed to establish
a clear NOAEL for adult
kidney lesions using the dose levels of 20, 50 and 100
ppm. The results of the study indicate that the NOAEL for histological
changes in the kidneys of F1 male rats was 100 ppm. No
other treatment related findings were noted at any dose level
indicating 100 ppm as the NOAEL for treatment and reproductive
effects evaluated in the study.
-- A mechanistic study was also conducted to investigate the reproducibility
and reversibility of the kidney lesions
observed in the initial 2-generation reproduction study. In the
first study, the effects observed at 200 ppm in the F1 males,
basophilic tubules and interstitial inflamation, were minimal
but slightly increased in incidence and severity and a slight
increase in interstitial fibrosis of the cortex was also observed.
In this mechanistic study, using dose levels of 0 and 2,000 ppm,
the NOAEL for histological changes in the kidneys of F0 and F1
male rats and reproductive effects was 2,000 ppm. The histological
changes seen in the kidneys in the original study was not reproducible.
-- Subchronic toxicity. Subchronic oral toxicity studies conducted
with flufenpyr-ethyl in the rat, mouse and dog indicate a low
level of toxicity. i. Rats. Pure (99.4%) flufenpyr-ethyl was tested
in rats at dose levels of 0, 600, 2,000, 6,000, and 20,000 ppm
in the diet for 13 weeks. Effects observed included urinary incontinence,
increased food and water consumption, slight hematological and
blood biochemistry changes, decreased spleen weights, an increase
in the incidence and severity of basophilic tubules of the kidneys
and slight to mild diffusely distributed vacuolation in the
liver. Based on these results, the NOAEL was 2,000 ppm
(134.2 mg/kg/day) for the males and 20,000 ppm (1,509.6 mg/kg/day)
for the females.
-- Mice. In a 78-week oncogenicity study with mice, flufenpyr-
ethyl technical was administered at dose levels of 0, 350, 3,500,
and 7,000 ppm. Male animals exhibited slight anemia. Females had
increased liver and kidney weights
(week 53 only). Slight to moderate hepatocellular fatty vacuolation
and necrosis were observed. There were no increases in incidence
of pre-neoplastic or neoplastic lesions. Based on these results,
the NOAEL was 350 ppm for both sexes (39.9 mg/ kg/day for males
and 43.7 mg/kg/day for females).
Ref:
Federal Register: June 25, 2003 (Volume 68, Number 122)] [Notices]
[Page 37813-37820]. Flufenpyr-ethyl; Notice of Filing a Pesticide
Petition to Establish a Tolerance for a Certain Pesticide Chemical
in or on Food.
http://www.fluorideaction.org/pesticides/flufenpyr-ethyl.fr.june.03.htm
Flumetsulam
- Herbicide - CAS No. 98967-40-9
-- 90-Day oral toxicity, Rat - NOAEL (M/F) 250 mg/kg/day. LOAEL
(M/F) 1000 mg/kg/day based on severe bilateral
tubular-interstitial nephritis.
-- -- The
kidney appears to be the primary target organ of rats and dogs
following subchronic to chronic exposures.
Ref: August 31, 2004: Flumetsulam:
HED Risk Assessment for the Tolerance Reassessment Eligibility
Document (TRED).
Chronic toxicity. In
a 1-year dietary study in dogs, the NOEL was 100 mg/kg/day and
the LOEL was 500 mg/kg/day. The animals were administered feed
containing 0, 20, 100, and 500 mg/kg/day. Reduced body weights
and inflammatory and atrophic changes in
the kidneys occurred in the
500 mg/kg/day dose groups. In a combined feeding carcinogenicity/chronic
study in mice there were no treatment-related effects and there
was no evidence of a carcinogenic response. Systemic NOEL was
greater than or equal to 1,000 mg/kg/day (limit dose); a LOEL
was not established. In a combined feeding carcinogenicity/chronic
study in rats, renal pathological alterations
were seen in males. No treatment-related effects were seen
in females at the highest dose (1,000 mg/kg/day) which is the
limit dose. There was no carcinogenic response. The NOELs were
500 mg/kg/day in males and 1,000mg/kg/day in females. The LOEL
was 1,000 mg/kg/day in males; a LOEL was not established in females.
Based on the chronic toxicity data, EPA has established the RfD
for flumetsulam at 1.0 milligram (mg)/kilogram (kg)/day. The RfD
for flumetsulam is based on the 1-year chronic study in dogs with
a NOEL of 100 mg/kg/day and an uncertainty (or safety) factor
of 100. Thus, it would not be necessary to require the application
of an additional uncertainty factor above the 100-fold factor
already applied to the NOEL.
Ref: Federal Register: September 17, 1997
[Notices] [Page 48842-48848]. Notice of Filing of Pesticide Petitions.
http://www.fluoridealert.org/pesticides/flumetsulam.fr.sept.17.1997.htm
Flumiclorac-pentyl
- Herbicide - CAS No. 87546-18-7
In the rat, the kidney is a potential target organ at high dose
levels. Effects included urinary incontinence, increased water
consumption, increased urine volume, and increased kidney weights
in the females, and increased squamous epithelial cells in urinary
sediment and increased kidney weights in the males. Nephropathy
was evident in male rats in a two-generation reproduction study
following administration of high dose levels.
Reference: June 28, 2005. US EPA. Health
Effects Division Chapter of the Tolerance Reassessment Eligibility
Decision Document (TRED).
http://www.fluorideaction.org/pesticides/flumiclorac-p.opp-2005-0229-0003.pdf
-- Chronic Toxicity
(Including Cancer): Studies with Flumiclorac Pentyl Technical
indicate that repeated high exposures produced changes in
liver, kidney, and
red blood cells but did not
produce cancer in test animals.
-- Potentially Aggravated Condition: Individuals with preexisting
diseases of the liver, kidney, or
red blood cells may have increased
susceptibility to the toxicity of excessive exposures.
-- SUBCHRONIC: Compound-related effects noted at very high dose
levels of Flumiclorac Pentyl Technical in rodents and/or dogs
included: increased liver and kidney
weights; histological changes in the kidney and
liver; slight changes in blood biochemistry parameters; decreased
red blood cell count, hemoglobin, and hematocrit;
and slight decreases in body weight. The NOEL in rats and
mice was 1000 ppm.
-- CHRONIC/CARCINOGENICITY: Effects of long-term high dose exposures
to Flumiclorac Pentyl Technical in rodents and/or dogs consisted
primarily of increases in kidney
and liver weights, slight changes
in blood biochemistry, and histological changes in the liver.
The lowest NOEL was 300 ppm in the mouse study. Flumiclorac Pentyl
Technical was not carcinogenic in either rats or mice.
Ref: Material
Safety Data Sheet for RESOURCE TM Herbicide.
http://www.fluoridealert.org/pesticides/flumiclorac-pentyl.msds.htm
Flumioxazin
- Herbicide - CAS No. 103361-09-7
-- Combined chronic
carcinogenicity - rat: NOAEL = mg/kg/day: males = 1.8, females
= 2.2 LOAEL = mg/kg/day: males = 18.0, females = 21.8 based on
increased chronic nephropathy [kidney] in
males and decreased hematological parameters in females
(Hgb, MCV, MCH and MCHC) No evidence of carcinogenicity
Ref: Federal Register: April 18, 2001. Flumioxazin;
Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/flumioxazin.fr.apr.18.2001.htm
-- Rats. A 90-day
subchronic toxicity study was conducted in rats, with dietary
intake levels of 0, 30, 300, 1,000 and 3,000 ppm flumioxazin technical
(98.4% purity). The NOAEL of 300 ppm was based on decreased bwts;
anemia; increases in absolute and/or relative liver, kidney,
brain, heart, and thyroid weights, and histological changes in
the spleen, liver, and bone marrow related to the anemia.
-- A second 90-day subchronic toxicity study was conducted with
a sample of flumioxazin technical of typical purity (94.8%) at
dietary concentrations of 0, 30, 300, 1,000, and 3,000 ppm. The
NOAEL was 30 ppm based on anemia and related hematological changes;
increases in liver, heart, kidney,
and thyroid weights; and histological changes in the spleen, liver,
and bone marrow related to the anemia.
Ref: Federal Register: February 14, 2001
[Notices] [Page 10292-10301]. Notice of Filing a Pesticide Petition
to Establish a Tolerance for a Certain Pesticide Chemical in or
on Food.
http://www.fluoridealert.org/pesticides/flumioxazin.fr.feb.14.2001.htm
Fluometuron
- Herbicide - CAS No. 2164-17-2
• The spleen, kidney,
and liver appear to be the organs consistently
affected following exposure to moderate doses of fluometuron
in rats and dogs in subchronic, chronic, developmental, and reproductive
studies. (page 8)
• 3. Dermal Exposure. Short-Term (1-30 days) However, the
developmental rat study (MRID 00163710) can be used for the short-term
dermal exposure based on the developmental NOAEL of 10 mg/kg/day
and LOAEL of 100 mg/kg/day, based on delayed
urinary system development (shortened renal papillae).
This effect can be assumed to have occurred during the dosing
period but delayed until later in development. This provides a
conservative endpoint for short-term exposure.
• 4. Inhalation Exposure (All Durations). A. Short -Term
(1-30 Days) The developmental rat study (MRID 00 163710) encompasses
the appropriate exposure duration (gestation days 6-15) with developmental
NOAEL of 10 mg/kg/day and LOAEL of 100 mg/kg/day, based
on delayed urinary system development
(shortened renal papillae). This study is also supported
by the developmental rabbit study (MRID 00147554) in which the
maternal NOAEL was also 10 mg/kg/day and LOAEL 100 mg/kg/day,
based on increased incidence of stool variations, increased incidence
of abortions, reduced food consumption and decreased maternal
body weight gain.
• Developmental Toxicity, Rat (83-3a) MRID: 00163710,42397601
CITATION: T. Arthur. 1986. A teratoiogy study of fluometuron technical
in the albino rat. Study Number MI# 832125; Tox and Path. Report
No. 199-84. Reproductive and Genetic Toxicology Subdivision Ciba
Geigy Corporation, Summit, NJ 07901. In a developmental study
(MRID 00163710,32397601) fluometuron (95.2% ai, batch # FL 821838)
was administered to 27 female Cr1:COB CD BR rats/dose by gavage
at dose levels of 0, 10, 100, or 1000 mg/kg/day (dosage volume
10 ml/kg/day was adjusted daily for each rats body weight) from
gestation days 6 through 15, inclusive. A dose-related decrease
in fetal weights were observed only in the high-dose group (58%
M, 57% F). No gross observable malformations were observed in
any of the 857 fetuses examined. The fetal M/F sex ratios were
comparable among the groups. A significant
increase in the incidence of shortened or absent renal papillae
was observed in the mid-dose (shortened: 9/82 control, 23/83 high;
absent: 3/82 control, 2/83 high) compared to control.
It should be noted that a statistical analysis was not performed
on the high-dose-due to growth retardations, and reduced fetal
weights. Significant fetal skeletal
variations were observed only in the high-dose group and included
incomplete ossification and widened sutures of the skull, wavy
ribs, and bipartite and fused sternebrae, unossified teeth, vertebral
centra, ischium/Os pubis, metatarsal and the distal phalanges
of the fore-and hind-paws. (pages 51-52).
Ref.
February 1, 2005. US EPA: Fluometuron: Revised HED Risk Assessment
for Phase III of the Reregistration Eligibility Decision. Docket
Identification Number: OPP-2004-0372-0008.
http://www.fluorideaction.org/pesticides/fluometuron.opp-2004-0372-0008.pdf
-- Organ Toxicity.
Toxic injury to the liver,
kidneys, gut and brain
is induced when lethal doses of fluometuron are administered experimentally
(10). An increase in spleen weight and in the incidence of abnormalities
in red-blood cells, and decreased weight gain in females were
observed in a 90-day study of rats (18).
-- CHRONIC TOXICITY. Rats were fed 7.5, 75, or 750 mg/kg/day for
90 days. At the 750 mg/kg dose, decreased
body weight and congestion in the spleen, adrenals, liver, and
kidneys were
evident. The NOAEL for this study was 7.5 mg/kg/day (100 ppm).
When doses of 1.5, 15 or 150 mg/kg/day were fed to puppies for
90 days, congestion of the liver, kidneys
and spleen
occurred at the 150 mg/kg dose. No effects were seen at 15 mg/kg/day
(400 ppm) (20).
Ref: Flumeturon. EXTOXNET. Pesticide Information
Profile. March 1994.
http://pmep.cce.cornell.edu/profiles/extoxnet/dienochlor-glyphosate/fluometuron-ext.html
-- PubMed abstract:
Twelve of fifteen 6-9-mo-old clinically healthy Desert sheep were
given single or repeated daily doses of 25 to 4000 mg cotoran/kg
by drench. Cotoran poisoning was characterized by
grinding of the teeth, ruminal tympany, mydriasis, dyspnea, staggering,
paresis of the hind and forelimbs, and recumbency. Lesions were
widespread congestion and hemorrhage, hepatic fatty change, catarrhal
enteritis and degeneration of the
epithelial cells of the renal proximal convoluted tubules. These
were accompanied by significant increases in the activities of
GOT, LDH and GGT and decreases in serum total protein and calcium.
Ref: Vet Hum Toxicol 1995 Jun;37(3):214-6. Toxicity
of cotoran (fluometuron) in Desert sheep; by Mohamed OS, Ahmed
KE, Adam SE, Idris OF.
Fluopicolide
- Fungicide - CAS
No. 239110-15-7
Chronic
toxicity (page 4)
ii. Chronic toxicity/carcinogenicity was assessed in rats
at dietary levels of 50, 200, 750 and 2500 ppm. The NOAEL was
200 ppm (8.4 mg/kg/day in males and 10.8 mg/kg/day in females)
based on microscopic changes in the liver
and kidneys similar to those observed in the 90-day rat study.
No evidence of carcinogenicity was observed in rats up to 2500
ppm.
Subchronic
toxicity (pages 3-4)
Ninety-day feeding studies were conducted
in dogs, mice and rats.
iii. In a 90-day rat study with dietary
levels of 100, 1400 and 20,000 ppm, the maximum tolerated dose
(MTD) was exceeded at 20,000 ppm based on body weight gain of
30 to 40% below control. The target
organs identified in rats were the liver
(centrilobular hypertrophy) in both sexes and the kidneys
in males (accumulation of hyaline droplets, single cell death
at the proximal tubule epithelium, slight foci of basophilic tubules
and granular casts)
at 1400 ppm and 20,000 ppm. The NOAEL
was 100 ppm, equivalent to 7.4 and 8.4 mg/kg/day, in males and
females, respectively.
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
Fluoroacetamine
- Rodenticide,
Insecticide - CAS
No.
640-19-7
(also
known as Fluoroacetamide or Compound 1081)
Sodium fluoroacetate
and fluoroacetamide are readily absorbed by the gut, but only
to a limited extent across skin. The toxic mechanism is distinct
from that of fluoride salts. Three molecules of fluoroacetate
or fluoroacetamide are combined in the liver to form a molecule
of fluorocitrate, which poisons critical enzymes of the tricarboxylic
acid (Krebs) cycle, blocking cellular respiration. The heart,
brain, and kidneys are the organs
most prominently affected... Crimidine and sodium fluoroacetate
are no longer registered for use as pesticides.
Ref: US EPA.
http://www.epa.gov/oppfead1/safety/healthcare/handbook/Chap17.pdf
Fluoroacetic
Acid - Rodenticide - CAS No.
144-49-0
IN
RATS, MITOCHONDRIA FROM KIDNEY CORTEX ACTIVELY PRODUCED FLUOROCITRATE
MORE THAN 700% ABOVE CONTROL.
2 PATHWAYS OF FLUOROCITRATE ACTIVATION IDENTIFIED. 1 ASSOC WITH
PYRUVATE METAB & NOT DEPENDENT ON OXIDATIVE PHOSPHORYLATION ENERGY;
2ND ASSOC WITH ACETATE METAB & IS ATP DEPENDENT.
[BUFFA P ET AL; FLUORIDE 12 (3): 114 (1979)]
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 mouse 1 and 3 month study, the rat 1 month study and the dog
52 week study, reductions in haemoglobin levels, red blood cell
numbers and packed cell volume were variously seen, predominantly
at the top doses. Nucleated and polychromatic red blood cell numbers
were raised in
the rat study only. These effects appeared reversible, in both
the 1 month rat and mouse studies. It would appear that any potential
haemolytic effects, possibly from aniline-derivatives, are of
secondary importance to other subchronic effects. In dogs there
were initial decreases in body weight and food consumption, which
returned to normal with time, and increased liver and kidney weights.
There was a brown pigment of unknown aetiology
in the renal cortical tubule epithelial cells, which was
PAS and iron-negative.
-- The chronic toxicity and oncongenicity of fluoroglycofen-ethyl
was investigated in mice (2 studies) and rats. In both species,
the systemic toxicity was much the same as had been seen in the
sub-acute studies, the main effects being on the
liver and kidneys... In the
rat study, brown pigment was observed in
the renal tubular cells from week 14 to termination in
the high dose group. A decrease in packed
cell volume, haemoglobin and red cell counts were also seen at
the top dose.
--
A satellite group which was treated for 14 weeks and then given
a 13 week recovery
period showed that the compound related effects were at least
partially reversible. The NOEL for chronic oral exposure to fluoroglycofen-ethyl
was 0.95 mg/kg bw/da (20 ppm) based on the hepatic
and renal effects at 100 ppm.
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
Fluoxastrobin
- Fungicide - CAS No. 361377-29-9
•
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).
•
90-Day oral toxicity-mice. There was a dose
related increase in liver weight in both sexes and in kidney
weight in females, in addition to other effects whose toxicological
relevance was considered uncertain. Among
these effects were increased hepatocellular hypertrophy with cytoplasmic
changes in the high-dose males and minimal to moderate kidney
tubular hypertrophy in mid- and high-dose
females.
•
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
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... At the interim-kill, organ weights showed moderate
significant treatment-realted increase in the absolute liver and
kidney weights in males and females at the 100 ppm dose
level compared with controls. The relative
liver and kidney weights were significantly
increased in males at the 100 ppm dose level and in females at
³ 10 ppm. A significant increase in the incidence of hyaline droplet
deposition in the proximal tubular epithelium occurred in the
kidneys of males (15/20 compared with 6/20 controls) at
the 100 ppm dose level. Minimal to moderate hypertrophy of centrilobular
hepatocytes was observed in the liver of all top dose animals
and at the 10 ppm dose level (10/20 males and 3/20 females). In
the thyroid, an increase in the follicular epithelial height in
both sexes was noted at the 100 ppm dose level. At the terminal-kill,
the absoloute and relative liver and kidney
weights of males and females were slightly to moderately
increased at 100 ppm dose level...
-- Kidney effects were observed in
the rat and mouse and consisted of increases in organ weight and
histopathological changes including hyaline droplet nephropathy,
focal tubular hyperplasia, increases in the incidence of small
and large eosinophilic inclusions, and increase in the incidence
and severity of chronic progressive nephropathy. There is no conclusive
mechanism for the observed kidney effects.
-- 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... Organ weights showed a dose-related increase in
the relative liver weight at dose levels of ³ 20 ppm in males
(15-44%) and at 100 ppm and 10 mg/kg bw/day dose levels (25-27%).
The relative kidney weight was increased
in males only (11-21%) compared with controls at dose levels
of ³ 20 ppm. Gross examination at necropsy revealed accentuation
of the lobular pattern of the liver at dose levels of ³ 5 ppm
in females and at ³ 20 ppm in males. Pale
kidneys were observed in males at dose levels of ² 5 ppm...
Histopathology showed significant treatment-related centrilobular
hepatocyte hypertrophy in males and females at dose levels of
³ 100 ppm. In the kidney, slight to moderate
hyaline droplet mephropathy was observed in males at ³ 20 ppm...
The liver, thyroid and kidneys were noted
to be the target organs of the test compound and significant
changes in these organs indicative of significant hepatic enzyme
induction were considered to be relevant for risk assessment.
-- 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... Haematology, clinical chemistry
and urinalysis parameters showed incidences of statistically significant
changes which were considred to be of limited toxicological significance
because they were either not dose-related or were reported to
be withing the range of historical data. There was an increase
in the absolute liver (35%) and adrenal (36.4%) weights in females
at the 100 ppm dose level. The relative
kidney (14%) and liver (21%) weights in males and the
relative kidney (6.9%) and adrenal (30%) weights in females
were significantly increased at the
100 ppm dose level. In females, the relative liver weight was
increased at dose levels of 15 ppm (14%) and 100 ppm (32%). At
the end of the withdrawal period, the relative
kidney weight in males and the relative liver weight in females
were still siginficantly elevated compared with controls...
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
- Aquatic Herbicide - CAS No. 59756-60-4
CHRONIC EXPOSURE (Fluridone
Technical). The following effects were reported in chronic, teratogenic,
and reproductive toxicity studies in laboratory animals where
experimental dosage levels and durations of
exposure were far in excess of those likely to occur in humans.
-- Chronic Toxicity - Decreased survival in lifetime feeding study.
Increased liver enzyme activity, liver weight, liver cell size,
and microscopic liver cell changes. Increased kidney
weights, and microscopic kidney cell
changes. Increased serum enzyme levels...
Ref: Material Safety Data Sheet for Sonar
SRP Herbicide. SePro Corporation.
http://www.fluoridealert.org/pesticides/fluridone.msds.sepro.1994.PDF
-- 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,
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
-- Chronic toxicity.
EPA has established the RfD for fluroxypyr at 0.5 mg/kg/day. This
RfD is based on histopathological lesions in the kidneys,
decreased testes weights, and increased
adrenal weights in both sexes observed in a 4-week range-finding
feeding study in the dog with a NOAEL of 50 mg/kg/day. An uncertainty
factor of 100 was used in calculating the RfD to account for both
inter- and intra-species variations.
Ref: Federal Register: September 30, 1998.
Fluroxypyr; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/fluroxypyr.fr.sept.30.1998.htm
-- 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 the carcinogenicity study in mice, there were no adverse
effects on survival or clinical signs in either sex. There was
no apparent treatment-related increase in the incidence of any
tumor type in either sex. The LOAEL is 1000 mg/kg/day, based on
decreased body weight/gain in males and an increased
incidence of kidney lesions in females. The NOEL is 300
mg/kg/day.
-- 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
870.4300 Carcinogenicity--Rats
NOAEL = 100 mg/kg/day. LOAEL = 500 mg/kg/day based on chronic
progressive kidney glomerulonephropathy (M&F).(no)
evidence of carcinogenicity.
Ref:
Federal Register. December 31, 2003. Fluroxypyr; Pesticide Tolerance.
Final Rule.
http://www.epa.gov/fedrgstr/EPA-PEST/2003/December/Day-31/p32007.htm
Fluroxypyr
1-methylheptyl ester
-
Herbicide - CAS No. 81406-37-3
Reproductive toxicity
study. In the 2-generation reproductive toxicity study in rats,
the maternal (systemic)
NOAEL was 100 mg/kg/ day, based on increased
kidney weights and kidney histopathology at the LOAEL of
500 mg/kg/day. The developmental (pup) NOAEL was 500 mg/kg/ day,
based on decreased body weight at the LOAEL of 1,000 mg/kg/day.
The reproductive NOAEL was 1,000 mg/kg/day (HDT).... Chronic dietary
all populations: 28-day dog range- finding feeding study LOAEL
= 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 17, 2001.
Fluroxypyr 1-Methylheptyl Ester; Pesticide Tolerances for Emergency
Exemptions. Final Rule.
http://www.fluoridealert.org/pesticides/fluroxypyr.fr.sept.17.2001.htm
Metabolite toxicology.
Administration of fluroxypyr, as the acid or methylheptyl ester
in a variety of toxicological studies, has produced similar effects.
The principal response to sufficiently high dosages, whether administered
over the short-term or, in some cases, over a lifetime, was nephrosis.
Ref:
Federal Register: May 14, 2003 (Volume 68, Number 93)] [Notices]
[Page 25883-25888]. Fluroxypyr; Notice of Filing a Pesticide Petition
to Establish a Tolerance for a Certain Pesticide Chemical in or
on Food
http://www.fluorideaction.org/pesticides/fluroxypyr.fr.may.14.2003.htm
870.4300 Carcinogenicity--Rats
NOAEL = 100 mg/kg/day. LOAEL = 500 mg/kg/day based on chronic
progressive kidney glomerulonephropathy (M&F).(no)
evidence of carcinogenicity.
Ref:
Federal Register. December 31, 2003. Fluroxypyr; Pesticide Tolerance.
Final Rule.
http://www.epa.gov/fedrgstr/EPA-PEST/2003/December/Day-31/p32007.htm
Flurprimidol
- Plant Growth Regulator - CAS No. 56425-91-3
A rat teratology study
using doses of 0, 2.5, 10, 45 or 200 mg/kg/day of flurprimidol
had a maternal toxicity NOEL of 10 mg/kg/day and a LEL of 45 mg/kg/day
based on decreased body weight gain and
food consumption. The developmental NOEL was 10 mg/kg/day and
the LEL was 45 mg/kg/day based on decreased fetal weight, increased
incidence of hydronephrosis,
hydroureter and numerous
developmental skeletal anomalies.
Ref: US EPA Pesticide Fact Sheet. February
22, 1989.
http://www.fluoridealert.org/pesticides/flurprimidol.epa.facts.1989.htm
•
Hydronephrosis:
Pathological
chronic enlargement of the collecting channels of a kidney, leading
to compression and eventual destruction of kidney tissue, and
diminishing kidney functionning.
http://www.hyperdictionary.com/medical/hydronephrosis
Flurtamone
- Herbicide - CAS No. 96525-23-4
-- Long
term toxicity and carcinogenicity. Target
/ critical effect: Liver: hypertrophy, centrilobular
hypertrophy.
Kidney: increased amyloidosis
in mice. Lowest relevant NOAEL: 2.8 mg/kg bw (2 year rat
study) Carcinogenicity: No carcinogenic potential
Ref:
July3, 2003. Flurtamone. Sanco/10162/2003-Final. Review report
for the active substance flurtamone. Finalised in the [EU] Standing
Committee on the Food Chain and Animal Health at its meeting on
4 July 2003 in view of the inclusion of flurtamone in Annex I
of Directive 91/414/EEC.
http://www.fluorideaction.org/pesticides/flurtamone.eu.july.2003.pdf
Flurtamone:
Table 5.27 The incidence and severity of renal
amyloidosis in unscheduled deaths [page 104] |
Dose |
Males |
Females |
(ppm) |
Incidence |
Mean
grade |
Incidence |
Mean
grade |
0 |
1/10
(10%) |
0.6 |
2/7
(29%) |
0.9 |
30 |
3/5
(60%) |
2.4 |
1/8
(14%) |
0.9 |
300 |
3/11
(30%) |
1.2 |
7/13
(54%) |
2.0 |
3500 |
10/13
(77%) |
2.9 |
7/12
(64%) |
2.8 |
7000 |
10/13
(77%) |
2.8 |
9/19
(47%) |
2.1 |
-- Two-year dietary
study in mice. In a carcinogenicity study, groups CD-1 mice (60/sex/dose)
were fed diets containing 0, 30, 300, 3500 and 7000 ppm flurtamone
(91.9% purity) for at least 78 weeks... The mean intake of flurtamone
for males and females was estimated to be 4.5, 45, 525 and 1050
mg/kg bwday at 30, 300, 3500 and 7000 ppm, respectively. After
78 weeks of treatment, the mortality rate for the 7000 ppm female
mice was significantly higher than controls and a significant
negative survival trend was found in both sexes. The test laboratory
pathologist considered systemic amyloidosis to be the major cause
of death (Table 5.34) [page 102]. Gross necropsy revealed an increased
incidence of enlarged livers and liver masses at dose levels ³3500
and of irregular shaped kidneys at
7000 ppm. Significant increases in mean liver weight (absolute
and relative) were observed in 3500 and 7000 ppm animals (not
statistically significant in 3500 ppm males) at both the interim
and terminal sacrifices (Table 5.26). Significant
decreases in mean absolute kidney weights were observed
in males at 7000 ppm at the interim and terminal sacrifices [page
103]. Microscopic examinations revealed an increased incidence
of systemic amyloidosis (most severe in
the kidneys) in the 3500 and 7000 ppm animals and the 300
ppm females that died or were sacrificed in extremis. The
incidence and severity of renal amyloidosis
is given in Table 5.27. An increase in the incidence of centrilobular
hypertrophy was observed in both sexes at dose levels ³ 3500 ppm.
The incidence of hepatic pigment (primarily in the reticuloendothelial
cells) was increased in males at dose levels ³3500 ppm and in
females at 7000 ppm. There was an increase in the incidence of
degeneration/inflammation/regeneration in the dorsal nasal turbinates
of both sexes at 7000 ppm and in males at 3500 ppm. The severity
and incidence of extramedullary haematopoiesis was increased in
the spleens of the 7000 ppm males and females [page 104] Based
on the incidence and severity of renal amyloidosis
associated with early death in females at 300 ppm, the test laboratory
proposed a NOEL for non-neoplastic lesions of 30 ppm (equivalent
to approximately 4 mg/kg/day) for this study. The NOEL for neoplastic
lesions in mice was determined to be 300 ppm (equivalent to approximately
45 mg/kg/day). In the opinion of the applicant [Rhone-Poulenc
Agriculture Ltd], the observed amyloidosis in the above study
was not a treatment-related effect of flurtamone administration.
The incidences of amyloidosis in this study were re-analysed by
an independent pathologist but the histopathological slides were
not re-examined. It should be noted that systemic amyloidosis
is a common age-related condition in CD-1 mice with a tendency
to be more frequent as a cause of death in females than in males
and the incidence varies widely within laboratories and between
laboratories [page 105]... [page 108]
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
Flusilazol
/ 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)
Ref:
US EPA IRIS. NuStar CASRN: 85509-19-9. Available October 6, 2003,
at Toxnet.
• Definitions:
-- Hydronephrosis: Pathological
chronic enlargement of the collecting channels of a kidney, leading
to compression and eventual destruction of kidney tissue, and
diminishing kidney functionning.
-- Renal papilla
- Renal
Papillary Necrosis Alternate Names : Necrosis - Renal Papillae,
Renal Medullary Necrosis Definition A disorder of the kidney involving
death of some or all of the renal papillae.
Fluxofenim
- Herbicide safener - CAS No. 88485-37-4
-- Chronic/Subchronic
Toxicity Studies. Fluxofenim: Liver
and kidney effects; Thyroid
effects at high doses (dogs).
-- Target Organs Active Ingredients
Fluxofenim: Liver, kidney, and thyroid.
Ref: Ciba-Geigy Material Safety Data Sheet
for Concep-III.
http://www.fluoridealert.org/pesticides/fluxofenim.msds.ciba.1996.htm
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