Function: The ovary,
or female gonad, is:
1. an exocrine gland, producing ova
2. an endocrine gland, secreting
a. the female hormones estrogen and progesterone
b. androgens, typically considered male hormones
Ref: http://www.cvm.okstate.edu/instruction/mm_curr/histology/fr/HiFRp03.htm
Estrous:
A reproductive cycle in some female mammals (but not female
humans, who instead have menstrual cycles). The cycle is
characterised by a short period of intense sexual desire
(called estrus or heat) when the animal is fertile, which
often occurs only once or twice a year, and involves correlating
physical changes of the reproductive tract.
|
The Endocrine System:
Illustration by K. Born in Our Stolen Future
(1996)
by Theo Colborn, Dianne Dumanoski and JP Myers
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.
Bifenthrin
- Acaricide, Insecticide - CAS Numbers:
82657-04-3 (Cis); 83322-02-5 (Trans)
REPRODUCTION, RAT.
50429-065 - 50429-070; 42427-42432; "Multigeneration Reproduction
Study with FMC 54800 (Biphenate) Technical in Rats"; 834; FMC
Toxicology Laboratory; 1/31/86; Bifenthrin technical (FMC 54800),
88.35% a.i., 98% cis, 2% trans; 100, 60, 30 and 0 ppm in the feed
for 8 weeks prior to F0 mating through F2b weaning; 25/sex/dose;
no fertility or reproductive effects, other effects include tremors
during lactation, ovary weight reduction
in adults; NOEL = 100 ppm (reproductive/fertility), NOEL
= 60 ppm (tremors), NOEL = 30 ppm (ovary
weight reduction); No Adverse Effects Indicated; Study
Acceptable. (Martz, 1/5/87; Updated 5/8/89, Morgan)
Ref: Summary of toxicology data: Bifenthrin.
California EPA, Department of Pesticide Regulation, Medical Toxicology
Branch. Original date: August 26, 1987 Revised dates: 7/9/90,
9/19/94, 4/4/00.
http://www.cdpr.ca.gov/docs/toxsums/pdfs/2300.pdf
A 13-week feeding study
in dogs (by capsule) of doses at nominal dose levels of 0, 2.5,
5, 10, or 20 milligram/kilogram/day (mg/kg/day) (equivalent to
2.21, 4.42, 8.84, and 17.7 mg/kg/day, based on percent active
ingredient (a.i.)) for 13 weeks. There was no mortality during
the study... A non-statistically significant, but possibly treatment-
related reduction in body weight (bwt) gain was noted in females
at 17.7 mg/kg/day (0.6 kilogram (kg)) relative to the controls
(1.3 kg). None of the females at 8.84 or
17.7 mg/kg/day showed cyclic activity or signs of estrus,
but cyclic activity was observed in 2, 2, and 1 female at 0, 2.21,
and 4.42 mg/kg/day, respectively and \4/5\ showed signs of estrus.
The lowest observed effect level (LOEL) for this 13-week study
is 4.42 mg/kg/day based on the increased incidence of tremors
in both sexes. The NOEL is 2.21 mg/kg/day.
Ref: Federal Register: November 26, 1997.
Bifenthrin; Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/Bifenthrin.FR.Nov.1997.htm
Clodinafop-propargyl
-
Herbicide - CAS No. 105512-06-9
-- Top dose group males
showed a higher incidence of prostate adenoma,
while prostate hyperplasia was reduced. However, the total incidence
of proliferative changes in the prostate remained unchanged
indicating a progression from prostate hyperplasia to adenoma.
Females treated at the same high dose had higher incidences of
ovary tubular adenoma. The
slightly enhanced incidences of these lesions are likely a consequence
of the severe disturbance of the general metabolic balance due
to excessive liver toxicity. In fact, male rats fed 750 ppm exhibited
a marked increase in peroxisomal oxidation, and an increase in
cytochrome P450 4A1/ A3 and 4A2 in their livers. Further, a decrease
in cytochrome P450 isoenzymes including CYP 2A, CYP 3A, and male-specific
CYP 2C11 was observed. The total oxidation rate of
testosterone, aromatase (CYP
19A1) activity plasma estradiol concentration and plasma-- dihydrotestosterone
are altered at this level of treatment. Clodinafop-propargyl is
a potent peroxisome proliferator in the rat liver and this peroxisomal
prolifering activity manifests itself by altering Cytochrome P450-dependent
monooxygenses which are involved in steroid hormone homeostasis.
The NOAEL of 10 ppm was equivalent to a mean daily dose
of 0.32 mg/kg in males and 0.37 mg/kg in females. The EPA HIARC
concluded that based on hepatocellular hypertrophy and kidney
findings, the NOAEL was 1 ppm (0.031 in males and 0.034 in females.
-- Dietary treatment of rats with concentrations over 2 years
resulted in initial inappetence in males and reduced body weight
development in both sexes treated at 750 ppm. The main target
organ of toxicity was the liver. Changes in plasma protein and
lipid levels, strongly enhanced serum activities of liver enzymes,
increased liver weights, and severe liver necroses were observed
at dietary doses of 300 and 750 ppm in males and at 750 ppm in
females. The degenerative lesions provide strong evidence that
these dose levels exceeded a maximum tolerated dose (MTD). Top
dose group males showed a higher incidence
of prostate adenoma, while prostate hyperplasia was reduced.
However, the total incidence of proliferative changes in the prostate
remained unchanged indicating a progression from prostate hyperplasia
to adenoma. Females treated at the same high dose had higher incidences
of ovary tubular adenoma. The slightly
enhanced incidences of these lesions are likely a consequence
of the severe disturbance of the general metabolic balance due
to excessive liver toxicity. In fact, male rats fed 750 ppm exhibited
a marked increase in peroxisomal oxidation, and an increase in
cytochrome P450 4A1/ A3 and 4A2 in their livers. Further, a decrease
in cytochrome P450 isoenzymes including CYP 2A, CYP 3A, and male-specific
CYP 2C11 was observed. The total oxidation rate of testosterone,
aromatase (CYP 19A1) activity plasma estradiol concentration and
plasma-- dihydrotestosterone are altered at this level of treatment.
Clodinafop- propargyl is a potent peroxisome proliferator in the
rat liver and this peroxisomal prolifering activity manifests
itself by altering Cytochrome P450-dependent monooxygenses which
are involved in steroid hormone homeostasis. The NOAEL of 10 ppm
was equivalent to a mean daily dose of 0.32 mg/kg in males and
0.37 mg/kg in females. The EPA HIARC concluded that based on hepatocellular
hypertrophy and kidney findings, the NOAEL was 1 ppm (0.031 in
males and 0.034 in females...
8. Endocrine disruption. No special studies investigating potential
estrogenic or endocrine effects of clodinafop-propargyl have been
conducted. However, the standard battery of required studies has
been completed. These studies include an evaluation of the potential
effects on reproduction and development and an evaluation of the
pathology of the endocrine organs following repeated or long-term
exposure. Although prostate adenomas and
ovarian adenomas were observed to be statistically increased in
rats at the highest feeding level with clodinafop-propargyl, this
feeding level clearly exceeded the MTD and the livers in these
rats were severely compromised. These findings in the endocrine
organs were considered to be secondary to the severe liver effects.
Ref: Federal Register: April 26, 2000 [Page
24471-24477]. Notice of Filing a Pesticide Petition to Establish
a Tolerance for Certain Pesticide Chemicals in or on Food.
http://www.fluoridealert.org/pesticides/Clodinafop-prop.Apr26.2000.htm
Cyfluthrin
-
Insecticide - CAS No. 68359-37-5
-- Rats Four
groups of 30 male and 24 female Mura:SPRA (SPF 68 Han) rats received
14C radiolabelled cyfluthrin as either oral doses of 0.5 or 10 mg/kg
bw or intravenous or intraduodenal doses of 0.5 mg/kg bw. Another
group received unlabelled cyfluthrin orally once a day for 14 consecutive
days, followed by a single oral dose of 0.5 mg/kg bw 14C-cyfluthrin...
The residues found in the organs and tissues were influenced by
the route of administration, as the mean relative concentration
of cyfluthrin in the bodies of males and females at sacrifice was
lower after oral administration (0.013) than after intravenous injection
(0.06). Female rats had higher plasma concentrations after oral
administration of the single high or low dose; 48 h after administration,
lower concentrations were detected in the bone and muscle of animals
of each sex and in the testes of males rats.
The sciatic nerve showed a similar relative concentration value,
which may explain the toxic effects observed on the peripheral nervous
system. Higher concentrations were detected in the spleen, adrenal
glands, liver, and plasma of both males and females and in
the ovaries. The renal fatty tissue
concentration was about seven times higher after either oral or
intravenous administration, whereas the mean concentration in
brain was significantly lower ( p = 0.0006-0.006) (Klein
et al., 1983).
-- Groups of 28 male and 28 female Sprague-Dawley rats received
diets containing 0, 100, 300, or 1000 mg/kg cyfluthrin (purity,
95%) incorporated into the powdered diet on a 0.4% maximum clay
carrier, daily for three months... The food consumption and body-weight
gains of females and males at the highest dose were significantly
lower than those of the control group. The body-weight gain depression
in females appeared to recover after cessation of treatment, while
that of the males remained significantly low... The absolute weights
of the liver, heart, and lung were decreased in male rats at the
high dose, and females at this dose had depressed liver, kidney,
adrenal, and
ovarian weights. In both males and females at the high dose,
the relative weight of the submaxillary gland was increased...
Ref: Cyfluthrin. Toxicological evaluation
of certain veterinary drug residues in food. WHO FOOD ADDITIVES
SERIES 39 Prepared by: The forty-eighth meeting of the Joint FAO/WHO
Expert Committee on Food Additives (JECFA). World Health Organization,
Geneva 1997. http://www.fluoridealert.org/pesticides/Cyfluthrin.WHO.Tox.Eval.97.htm
Dichlofluanid
- Wood Preservative, Antifoulant, Fungicide, Acaricide -
CAS No. 1085-98-9
-- Two-year Study.
The following study is considered to be flawed due to the lack
of histopathological evaluation and it was not GLP compliant.
Beagles (4/sex/group) received dietary administration of either
0, 100, 300, 1000 or 3000 ppm dichlofluanid (90 % purity); equivalent
to 3.6, 10.5, 34 and 107 mg kg -1 d -1 (males) and 3.4, 11, 34
and 101.4 mg kg -1 d -1 (females) respectively,
for a two year study period... Absolute organ weights in males
of the liver, lung, spleen, kidneys, adrenals, pancreas and heart
were all decreased at 3000 ppm; the greatest being a 35 % decrease
in testes weight. Decreases in relative organ weights were reported
in males in the thyroid, heart, spleen and testes (20 % at 3000
ppm) at the top dose. The relative kidney and liver weights were
elevated at both 1000 (21 and 3.4 %) and 3000 ppm (18 and 10 %).
In females absolute organ weights were reduced : the thyroid in
all treatment groups, by 32-36 %; ovaries 31-55 % from 100 ppm;
and heart by 14-27 % at 1000 and 3000 ppm. The absolute spleen
weights were raised in females at 1000 ppm and above by
18-20 %. In females there was a slight increase in the relative
organ weights of the pancreas above 1000 ppm and spleen weight
was elevated by 25 and 60 % at 1000 and 3000 ppm. A decrease
in ovary weight was reported at all doses (55 % at 3000 ppm).
The changes in organ weight in females preclude the setting of
a NOEL. [Unpublished, 1969]
Ref:
January
2003 - Evaluation
on: Booster biocides in antifouling products. Full review of Dichlofluanid.
No. 206. Evaluation of Fully Approved or Provisionally Approved
Products. Prepared by : The Health and Safety Executive Biocides
& Pesticides Assessment Unit, Magdalen House, Stanley Precinct
Bootle Merseyside L20 3QZ Available from: Department for Environment,
Food and Rural Affairs, Pesticides Safety Directorate, Mallard
House, Kings Pool, 3 Peasholme Green, York YO1 7PX, UK. Also available
at:
http://www.pesticides.gov.uk/citizen/Evaluations/206_dichlofluanid.pdf
PubMed Abstract: Two
types of reactions were observed on the alteration of Drosophila
vitellogenesis [established
biomarker for estrogen action] by the four fungicides
used in this study. Dithane M45 resulted in stimulation associated
with egg retention. However, the other three fungicides (Benlate,
Bouillie bordelaise and Euparene) resulted in inhibition to a
varying degree. Although the inhibition was comparatively limited
due to Benlate it induced an egg retention. The inhibition was
very high due to Bouillie bordelaise and Euparene [dichlofluanid].
With Bouillie bordelaise an egg retention occured together with
the reduction of vitellogenesis and
caused an increase in the rate of the follicle resorption. The
latter depended on the duration of treatment. With
Euparene [dichlofluanid], no egg retention was observed and the
toxicity was only noticed on vitellogenesis.
Ref: J Environ Sci Health B 1997 May;32(3):411-28.
[Ovarian
activity of Drosophila melanogaster Meigen (Diptera), during a
chronic intoxication with four fungicides: anatomical and cytological
study] [Article in French] by Marchal-Segault D, Lauge G.
Dichlofluanide has
been reported as a hormonal active substance
in the environment in a review of the German Umweltbundesambt
(Schramm et al., 1996). However, a concentration range for which
this "hormonal activity" was found, was not reported
(page 44). [Schramm K.-w., thumm W. * Kettrup A. (1996). Hormonal
active substances in the environment: exposition, impact and detection.
Expert Round. Endocrinically active chemicals in the environment.
UBA Texte 3/96. Umweltbundesamt, Germay.]
Ref: RIVM report 601506005. BIOCIDES (II).
Refined aquatic environmental risk assessment of 28 priority biocides.
B.J.W.G. Mensink. November 2000. RIVM = Rijksinstituut voor Volksgezondheid
en Milieu. National Institute of Public Health and the Environment.
http://www.rivm.nl/bibliotheek/rapporten/601506005.pdf
Dithiopyr
- Herbicide -
CAS No. 97886-45-8
The following results
were presented by a Monsanto scientist.
-- Four-week Feeding Study in Mice.
Dithiopyr was administered via the diet to groups of 6 male and
6 female CD-1 mice for 4 weeks at concentrations of 0, 300, 1000,
3000, 10,000 and 30,000 ppm... [No concentrations
listed for the following effects:]-- Liver enlargement
and discoloration, adrenal enlargement,
and atrophy of the thymus,
spleen, seminal vesicles,
ovaries and uterus
were noted on gross post-mortem examination... (The
Institute of Environmental Toxicology, 1987)
-- Thirteen-week Feeding Study in Mice.
Dithiopyr was administered via the diet to groups of 12 male and
12 female CD-1 mice for 13 weeks at concentrations of 0, 10, 100,
1000 and 5000 ppm... Other findings included [no
concentrations listed]: multiple organ weight effects,
adrenal cortical hypertrophy and
ovarian atrophy. The subchronic NOEL
in mice is considered to be 10 ppm. (The
Institute of Environmental Toxicology, 1989)
Ref: Summary
of Toxicology Studies With Dithiopyr. Dennis P. WARD. Toxicology
Department, The Agricultural Grop, A Unit of Monsanto
Company (Received February 20, 1993). Also available at
http://wwwsoc.nii.ac.jp/pssj2/tec_info/dithiopy.pdf
Epoxiconazole
-
Fungicide - CAS No. 135319-73-2 (formerly
106325-08-0)
Endocrine disruption.
A series of mechanistic studies were performed to elucidate and
define the aromatase enzyme inhibition properties of epoxiconazole.
The following conclusions can be drawn from the in vivo data:
The effects on the ovaries are assessed
to be the result of the following: Decreasing
aromatase enzyme activity which is responsible for converting
both testosterone and adrostendione (male sex-steroids) into female
sex steroids (e.g., estradiol). This action would result
in decreased estradiol (i.e., estrogen) and increased androgen.
As a consequence of reduced estradiol levels, measured LH and
FSH concentrations are slightly altered. The increased incidences
of neoplasms in the ovaries are considered
to be the result of a continuous cell proliferation by these stimulating
[[Page 57342]] hormones of the regulating hormones of the
pituitary-gonadal axis (LH and FSH). The changes adrenals are
assessed to be the result of the following: Decreasing adrenal-cortical
enzyme activity. This action would result in decreased adrenal
hormones such as corticosterone levels. As a consequence of reduced
corticosterone levels, pronounce ACTH concentrations are found.
The increased incidences of neoplasms in the adrenals are considered
to be the result of a continuos cell proliferation by these stimulating
hormones of the pituitary-adrenal axis ACTH.
Ref: Federal Register: September 22, 2000
[Page 57338-57344]. Notice of Filing Pesticide Petitions to Establish
Tolerances for Certain Pesticide Chemicals in or on Food. http://www.fluoridealert.org/pesticides/Epoxiconazole.FR.Sept.2000.htm
"Epoxyconazole
106325-08-0 Banned. Low degradability, toxic to water-living organisms
and endocrine effects. 1997."
Definition: "Banned. A substance which for health or environmental
reasons by an authority decision is either no longer approved
for any area of application, or for which an approval or registration
has been denied from the first instance."
Ref: Euopean Commission. Appendix 5. Substances
which may not be included as active ingredients in approved pesticide
products, Chapter 15, Section 2, subsection one.
http://www.kemi.se/lagar_eng/pdf/app5_8.pdf
Ethalfluralin
- Herbicide - CAS No. 55283-68-6
--
In vitro mammalian chromosome aberration test: In Chinese hamster
ovary cells, ethalfluralin was negative
without S9 activation, but it was clastogenic
with activation.
Ref: Federal Register: January 17, 2002.
Ethalfluralin; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Ethalfluralin.FR.Jan17.2002.htm
Flonicamid
- Insecticide - CAS No. 158062-67-0
-- 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. Findings noted in the top dose females included delayed
vaginal opening and increased liver, kidney and spleen weights
in the F1 generation and reduced
ovary and adrenal weights in the parental generation and
decreased uterine weights in the F1 female weanlings.
There was an increase in the FSH and LH
levels in F1 females tested for these endpoints. These
findings did not affect the reproductive performance or survival
of offspring in the study.
-- Endocrine
disruption. No special studies investigating potential
estrogenic or other endocrine effects of flonicamid have been
conducted. Some suggestions of possible endocrine effects were
reported at the highest dose tested (1,800 ppm) in the multi-generation
reproduction study which showed increased FSH and LH levels, a
delay in the time to vaginal opening in the F1 generation, and
reduced ovary and adrenal weights
in the parental generation. However, there were no effects on
reproductive performance or survival of the offspring in the study.
At levels that are expected to be found in the environment, flonicamid
will not cause any endocrine-related effects.
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
Fluazifop-butyl
- Herbicide - CAS No. 69806-50-4
--
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... Necropsy of
F0 parents revealed no gross pathology and, although testes and
epididymis of F0 males of a 250 ppm exposure were reduced, histological
review identified no treatment-related changes. Conversely, F1 parents
were found with gross indications of toxicity.. . Testis and epididymis
weights in the males (80, 250 ppm), and pituitary gland (80, 250
ppm), uterus (80, 250 ppm), brain (250 ppm) and lung weights (250
ppm) in females were significantly reduced.
Female F1 ovarian weights were
increased relative to controls in association with a 250 ppm dietary
exposure. 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), and an increased slight testicular tubular atrophy
in males (250 ppm) were noted... [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]
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
ONCOGENICITY, MOUSE
[OR HAMSTER] 411-125 180756 Rattray, N. J., ÒFluazifop-p-butyl:
80 week carcinogenicity study in hamsters,Ó 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... Findings at the higher two dose
levels only included decreased testes weights,
reduced spermatozoa counts in epididymides
and increased cataract development in males.
Stromal cell/sex cord hyperplasia was elevated
in high dose females. Benign stromal cell/sex cord tumors
were slightly but significantly elevated in 3000 ppm females (incidences
of 1, 1, 3, 4, and 5 in controls through high dose groups, respectively).
Study is not acceptable, but presumed upgradeable (there is a
need to explain why this species was selected for this study,
and individual data for hamsters should be provided). The ovarian
tumor findings, in addition to the several noted histopathology
findings without NOELÕs, are possible adverse effects. Contemporary
historical control data are needed if the registrant desires to
re-visit DPR conclusions about findings of this study. The DPR
review briefly discusses some ramifications of ovarian and testicular
findings. Aldous, 5/20/02.
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
Target
Organs: Liver, skin, kidney, eye, bone marrow, blood, reproductive
system.
Ref: Material Safety Data Sheet for Fusilade
DX (active indredient Fluazifop-P-Butyl).
Syngenta. January 21, 2002.
http://www.fluoridealert.org/pesticides/Fluazifop-P-Butyl.MSDS.pdf
Fludioxonil
- Fungicide - CAS No. 131341-86-1
-- Gene mutation and
other genotoxic effects were studied using fludioxonil technical:
... iii. Chromosome aberrations assay (in
vitro) in Chinese hamster ovary (CHO) cells with and without S9
activation provided convincing evidence that
[[Page 53823]] fludioxonil is a clastogen and polyploidy
inducer.
Ref: Federal Register. October 7, 1998.
Fludioxonil; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/Fludioxonil.FR.Oct.1998.htm
--
In vitro Chromosome aberration. Chinese hamster
ovary cells were tested with and without metabolic activation
from 1.37 to 700 g/mL. Positive for nondisjunction
of chromosomes both in the presence and absence of activation.
-- Fludioxonil was not mutagenic in the tests for gene mutations.
However, because of the powerful induction
of polyploidy in the in vitro Chinese hamster ovary cell cytogenetic
assay and the suggestive evidence of micronuclei induction
in rat hepatocytes in vivo, additional mutagenicity testing was
performed in an in vivo study specifically designed for aneuploidy
analysis.
Ref: Federal Register: December 29, 2000.
Fludioxonil; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Fludioxonil.FR.Dec.2000.htm
Genotoxicity. Mutagenicity
potential of fludioxonil was tested in several studies.
In the Chinese hamster ovary (CHO) cell assay, some clastogenic
and polyploidogenic effects were seen at or near the precipitating
concentration of the test substance. However, results were
negative in the Ames assay, CHO V79 cell assay, hepatocyte DNA
repair assay, rat hepatocyte micronucleus test, mouse bone marrow
test, and Chinese hamster bone marrow test. A dominant lethal
test conducted in the mouse was also negative.
Ref: Federal Register. March 29, 2000. [Page
16602-16608]. Notice of Filing a Pesticide Petition to Establish
a Tolerance for Certain Pesticide Chemicals in or on Food.
http://www.fluoridealert.org/pesticides/Fludioxonil.FR.March29.2000.htm
Flufenoxuron
- Acaricide, Insecticide, Herbicide - CAS No. 101463-69-8
-- Abstract:
Flufenoxuron (Benzoylphenylurea derivative)-an environmental antimoulting
insecticide-is recently used for controlling insect production in
cultivated areas. In the present work, the insecticide was administered
intragastrically by stomach tube at a dose of 20 mg/kg b.wt. to
the Juvenile female and male albino rats (Rattus norvegicus)
every other day for three weeks. Histological examination of ovaries
revealed that the flufenoxuron induced massive
degeneration of ovarian follicles with much
cellular debris in the antrum and pyknotic granulosa cells.
On
the other hand,
the testis of flufenoxuron-treated animals exhibited marked decrease
of the thickness of tunica albuginea and atrophy of the seminiferous
tubules. There was a marked increase of desquamated spermatogenic
cells within the lumina of seminiferous tubules. Multinucleated
giant cells and vanishing of sperms were observed in the majority
of tubules of flufenoxuron-treated animals in comparison with control.
Epididymides sperm of experimental group exhibited the presence
of increased number of spermatic precursors as well as varieties
of sperm anomalies. The hepatic tissues toxicated with the insecticide
showed nuclear disintegration, massive breakdown of hepatocytes
and internal haemorrhage. The observed gonadal dysfunction may be
attributed to hepatic damage or decline of gonadal hormone
involved in either processes.
Ref: J. Egypt. Ger. Soc. Zool., Vol. 25(B),
45-64, 1998. EFFECTS
OF FLUFENOXURON-AN ENVIRONMENTAL ANTIMOULTING INSECTICIDE ON GONAD
FUNCTION OF ALBINO RATS; by EL-Sayyad, H.I. and Karim, S.A. http://www.egsz.org/BiologicalCurrentContent/Zoology/Comparative%20Physiology/TOXICOLOGY.htm
Fluorouracil
- Former
insect Chemosterilant; now used as a pharmaceutical - CAS
No. 51-21-8
Fluorouracil has not
been adequately studied in animals to determine its effects on
fertility and general reproductive performance. Following intraperitoneal
administration of 125 or 250 mg/kg in rats,
chromosomal aberrations and changes in chromosomal organization
of spermatogonia were induced; spermatogonial
differentiation was also inhibited, resulting in transient infertility.
In a strain of mouse that is sensitive to the induction
of sperm head abnormalities after
exposure to a number of chemical mutagens and carcinogens, no
abnormalities were produced at oral dosages of up to 80 mg/kg
daily. Following intraperitoneal administration at weekly doses
of 25 or 50 mg/kg weekly for 3 weeks during the preovulatory phases
of oogenesis in female rat, the incidence
of fertile matings was substantially reduced,
development of preimplantation and postimplantation embryos was
delayed, and the incidence of preimplantation lethality and chromosomal
anomalies in the embryos was increased. In a limited study in
rabbits, a single 25 mg/kg dose or daily doses of 5 mg/kg for
5 days had no effect on ovulation, appeared not to affect implantation,
and had only a limited effect in producing zygote
destruction. Drugs that inhibit DNA, RNA, and protein synthesis
like fluorouracil might be expected to have adverse effects on
gametogenesis. [McEvoy, G.K. (ed.).
American Hospital Formulary Service - Drug Information 93. Bethesda,
MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus
Supplements, 1993). 576]
Ref: TOXNET profile from Hazardous Substances
Data Base for FLUOROURACIL.
http://www.fluoridealert.org/pesticides/Fluorouracil.TOXNET.HSDB.htm
•
Definition
• Gametogenesis:
The meiotic process by which mature gametes (ova and sperm) are
formed.
• Oogenesis
refers specifically to the production of ova and spermatogenesis
to the production of sperm. [Definition from: GeneTests from the
University of Washington and Children's Health System, Seattle]
Flurprimidol
- Plant Growth Regulator - CAS No. 56425-91-3
-- Subchronic Studies.
A 90-day feeding study in rats treated to 0, 1.68, 6.04, 20.39,
68.34 mg/kg/day (males) and 0, 1.98, 7.13, 24.37, 78.47 mg/kg/day
(females) of flurprimidol. The systemic No-Observable- Effect-Level
(NOEL) was 1.68 mg/kg/day and the Lowest-Effect- Level (LEL) was
6.04 mg/kg/day based on increased hepatic
enzyme induction in males (significant and dose increases
in p- nitroanisol O-demthylase activity). At 24.37 mg/kg/day there
was increased relative and absolute ovarian
(female) and relative liver (male) weight.
At 68.34 mg/kg/day, there was increased absolute liver weight
(males).
Ref: EPA Pesticide Fact Sheet for Flurprimidol.
Reason for Issuance: New Chemical Registration. Date Issued: FEB
22 1989. Fact Sheet Number: 202.
http://www.fluoridealert.org/pesticides/Flurprimidol.EPA.Facts.1989.htm
-- 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: EPA Pesticide Fact Sheet for Flurprimidol.
Reason for Issuance: New Chemical Registration. Date Issued: FEB
22 1989. Fact Sheet Number: 202.
http://www.fluoridealert.org/pesticides/Flurprimidol.EPA.Facts.1989.htm
Lactofen
- Herbicide - CAS No. 77501-63-4
-- Subchronic feeding--
Mice-- 3-month. Groups of Male and female mice were fed diets
containing Lactofen Technical at concentrations of 0, 40, 200,
1,000, 5,000, and 10,000 for 13-weeks. At week 5, the dosage of
the 40 ppm groups was increased to 2,000 ppm. Treatment related
mortality occurred at dosages above 1,000 ppm. The LOEL was 200
ppm based on: increased WBC; decreased hematocrit, hemoglobin
and RBC; increased alkaline phosphatase, SGOT, SGPT, cholesterol
and total serum protein levels; increased weights or enlargement
of the spleen, liver, adrenals, heart and
kidney; histopathological changes of the liver, kidney, thymus,
spleen, ovaries and testes.
In general, effects were slight in the 200 ppm groups, and moderate
to severe in the 1,000 ppm groups.
Ref: Federal Register: February 25,
1998 [Page 9532-9540]. Notice of Filing of Pesticide Petition.
http://www.fluoridealert.org/pesticides/Lactofen.FR.Feb.1998.htm
Norflurazon
- Herbicide - CAS No. 27314-13-2
-- A two-year carcinogenicity
study was conducted in male and female CD-1 HaM/ICR Swiss mice
in which 125 mice/sex/dose were administered technical norflurazon
in the diet at dose levels of 0, 85, 340, or 1360 ppm (0, 12.8,
58.7, or 218.8 mg/kg/day) for 100-104 weeks...
Increased incidences of enlarged spleen, nephritis, swollen/enlarged
liver, and nodular enlargement of the liver were observed in high
dose male mice, while increased incidences of pyelonephritis,
enlarged liver, and
cystic ovaries were observed in high dose female mice.
Carcinogenic potential was evidenced by an increased incidence
of hepatic adenoma and combined adenoma/carcinoma
in high dose male mice. The systemic NOEL was determined
to be 12.8 mg/kg/day (85 ppm) for male mice, and 58.7 mg/kg/day
(340 ppm) for female mice. The systemic LEL was determined to
be 58.7 mg/kg/day (340 ppm) for male mice, based on the increased
incidence of enlarged spleen, increased
absolute and relative liver weight, and increased incidence of
nephritis. The systemic LEL was determined to be 218.8
mg/kg/day (1360 ppm) for female mice, based on the increased incidence
of enlarged liver and cystic
ovaries, the
increased absolute and relative liver weight,
and the increased incidence of pyelonephritis (guideline ¤83-2;
MRID 00111649).
Ref: US EPA REREGISTRATION ELIGIBILITY DECISION
NORFLURAZON. LIST A. CASE 0229.
http://www.fluoridealert.org/PESTICIDES/Norflurazon.RED.EPA.pdf
-- A nine-month oral
toxicity study (MRID 00091056) was conducted using the F generation
of rats from a two-year carcinogenicity study (MRID 00082019).
In this study, rats were given technical norflurazon in the diet
at dose levels of 0, 125, 250, or 500 ppm (0, 6.25, 12.5, and
25 mg/kg/day) for 39 weeks... At 500 ppm...
Thyroid weight was decreased in males by approximately 30% vs
control,
while thyroid weight was increased in females between 11-47% vs
control. Gonadal
weight (left gonad) was increased in female rats by 30%.
At 250
ppm, thyroid weight was decreased by 30% in male rats, but was
increased by 11-29% in female rats. However, there were no reported
microscopic alterations in this organ at any dose level tested. Gonadal
weight in female rats was increased by 17% vs. control.
The systemic NOEL was determined to be 250 ppm (12.5 mg/kg/day)
in both sexes. The systemic LEL was determined to be 500 ppm (25
mg/kg/day) in both sexes, based on the dose-related increase in
liver weight in male and female rats
at 39 weeks, the increase in gonad weight
of females, and the microscopic changes observed in
kidneys of
both sexes. Although
dramatic effects on thyroid weight were
observed at 250 ppm in both sexes, there were no data indicating
any alteration in histology of this organ. Thus, the weight change,
while indicative of an effect of norflurazon, is not supported
as a toxic effect based on available data (guideline: non-guideline
study; classified as core supplementary; MRID 00091056).
Ref:
US EPA REREGISTRATION ELIGIBILITY DECISION NORFLURAZON. LIST A.
CASE 0229.
http://www.fluoridealert.org/PESTICIDES/Norflurazon.RED.EPA.pdf
PFOA - Insecticide,
US EPA List 3 Inert
Perfluorooctane sulfonate
(PFOS) is a degradation product of sulfonyl-based fluorochemicals
that are used extensively in industrial and household applications.
Humans and wildlife are exposed to this class of compounds from
several sources. Toxicity tests in rodents have raised concerns
about potential developmental, reproductive, and systemic effects
of PFOS. However, the effect of PFOS on the neuroendocrine system
has not been investigated thus far. In this study, adult female
rats were injected intraperitoneally with 0, 1, or 10 mg PFOS/kg
body weight (BW) for 2 weeks. Food and water intake, BW, and estrous
cycles were monitored daily. At the end of treatment, PFOS levels
in tissues were measured by high-performance liquid chromatography
(HPLC) interfaced with electrospray mass spectrometry. Changes
in brain monoamines were measured by HPLC with electrochemical
detection, and serum corticosterone and leptin were monitored
using radioimmunoassay. Treatment with PFOS
produced a dose-dependent accumulation of this chemical in various
body tissues, including the brain. PFOS exposure decreased food
intake and BW in a dose-dependent manner. Treatment with
PFOS affected estrous cyclicity and
increased serum corticosterone levels while decreasing serum leptin
concentrations.
PFOS treatment also increased norepinephrine concentrations in
the paraventricular nucleus of the hypothalamus. These results
indicate that exposure to PFOS can affect the neuroendocrine system
in rats.
Ref: Environ Health Perspect. 2003 Sep;111(12):1485-9.
Neuroendocrine
effects of perfluorooctane sulfonate in rats; by Austin ME,
Kasturi BS, Barber M, Kannan K, MohanKumar PS, MohanKumar SM.
Pyridalyl
- Insecticide - CAS No. 179101-81-6
Subchronic toxicity.
-- Pyridalyl technical was tested in rats
in a 3-month feeding study. Effects included decreased body weight
gain, altered blood biochemistry, increased relative liver weight
and histopathological changes in
the liver, ovary, adrenal and lung.
The NOAEL is 100 ppm (5.56 mg/kg/day in males and 6.45 mg/kg/day
in females).
-- A 13-week
feeding study in mice was
conducted. Effects included decreased
body weight gain, hematological and blood biochemical effects,increased
liver weight, decreased kidney and ovary weights and histopathological
changes in liver, kidney, ovary and
adrenal. The NOAEL is 70
ppm in males (8.169 mg/kg/day) and 700 ppm in females (86.78
mg/kg/day)
Ref: Federal Register: December 5,
2003. Pyridalyl; Notice of Filing a Pesticide Petition.
http://www.fluorideaction.org/pesticides/pyridalyl.fr.dec.5.2003.htm
Tembotrione - Herbicide - CAS No. 335104-84-2
• 90-day Oral Yoxicity - Mouse study: NOAEL =M/F: 64/75.6 mg/kg/day. LOAEL =M/F: 631/783 mg/kg/day based on decreased uterine weights and increased corpora lutea in the ovary in females... (page 47)
• 90-Day Oral Toxicity - Rat study : In females, the following microscopic changes were observed at an increased incidence: multifocal corticotubular basal vacuolation (slight) in the kidneys occurred in a dose-dependent manner 1-6/10 in all treated groups compared to 0/10 in controls; diffuse hypertrophy of the interstitial gland in the ovaries was observed in the 1500 ppm and 7000 ppm groups (3/10) compared to 0/10 in controls. These effects were considered treatment-related. (page 56)
• Certain changes in multiple organs seen in the subchronic, chronic, dermal, and reproduction studies (e.g., microscopic changes in the thyroid gland, adrenal gland, and pancreas; increased number of corpora lutea in the ovary, and delayed preputial separation) may be due to various mechanisms including possible liver-pituitary-thyroid homeostatic disruption or inhibition of steroid synthesis (Page 6)... When additional appropriate screening and/or testing protocols being considered under the Agency’s EDSP have been developed, tembotrione may be subjected to further screening and/or testing to better characterize effects related to endocrine disruption (page 29).
Reference: Tembotrione. Human-Health Risk Assessment for Proposed Uses on Field Corn, Sweet Corn and Popcorn. USEPA. September 7, 2007.
Tetraconazole
-Fungicide - CAS No. 112281-77-3
-- The
class of compounds (triazoles) to which tetraconazole belongs
is known to induce liver microsomal enzymes. The follicular cell
hypertrophy and cystic follicular hyperplasia of the thyroid seen
in male rats at 1,280 ppm are also likely to be linked to the
hepatic changes. Compounds such as phenobarbital are also known
to induce thyroid changes in rats due to increased hepatic clearance
of thyroxin, mediated by hepatic enzyme induction.
-- A chronic feeding/carcinogenicity study was conducted with
tetraconazole in Crl:CD-l (ICR)BR mice at dietary levels of 10,
90, 800, and 1,250 ppm for 80 weeks. Treatment-related non-neoplastic
changes were also seen at 1,250 ppm in the lungs, kidneys,
testes, epididymides,
ovaries and bone, particularly the cranium;
a compression of the brain was noted in a number of mice reflecting
the extent of cranial bone changes and an increased
thymic involution was seen in male mice
that died on test.
The 1,250 ppm dietary level for tetraconazole, because of the
substantial bwt gain changes and increased mortality (more in
males), appeared to be above the maximum tolerated dose (MTD).
At 800 ppm, there were increases in non neoplastic changes in
lungs, kidneys, testes, epididymides,
ovaries and bone.
In addition,
there was substantial reduction in weight gain as compared with
zero-dose control animals, but the mortality rate was unaffected.
Eight hundred ppm appeared to be a reasonable estimate of the
MTD for mouse.
Ref: Federal Register: October 14, 1999.
Notice of Filing Pesticide Petitions to Establish a Tolerance
for Certain Pesticide Chemicals in or on Food. PP 9F5066, 9F6023,
and 7E4830.
http://www.fluoridealert.org/pesticides/Tetraconazole.FR.Oct14.1999.htm
Sodium
fluoride -
Wood
preservative, EPA List 4B Inert - CAS No. 7681-49-4
Abstract: SUMMARY: Sodium fluoride (5 mg/kg body weight) was
effective from the 45th day of treatment in causing a significant
decline in DNA and RNA levels of mice ovary and uterus,
indicating alterations in nucleic acid and protein metabolism
in these organs. The oestrus cycle was irregular
with prolonged duration of the diestrus stage which in turn severely
affected the fertility rate in treated mice. The administration
of amino acids glycine and glutamine, individually and in combination
along with NaF, helped in maintaining the status quo of all parameters
as compared to control, thus elucidating their ameliorative role.
Ref: Fluoride 1998; 31(3):143-148. Ameliorative role of amino
acids on fluoride-induced alterations in mice (Part II): ovarian
and uterine nucleic acid metabolism; by D Patel and NJ Chinoy.
This study is Part II of the earlier experiment reported in Fluoride
1996; 29(4):217-226. Full report at
http://www.fluoride-journal.com/98-31-3/313-143.htm
Abstract: Summary.
Forty-eight albino rabbits were administered fluorde as sodium
fluoride subcutaneously in daily doses of 5, 10, 20, and 50 mg/kg
body weight for three and a half months. Twelve controls received
1 cc distilled water/kg body weight/day for the same period. Ovaries
from the control and fluoridated animals were analysed for DNA
and RNA content. The experimental animals
showed significant depletion (P < 0.001) of ovarian DNA and
RNA compared to the controls. The data indicate that fluoride
inhibits nucleic acid synthesis in the ovary. The findings also
suggest that fluoride acts directly on DNA to produce structural
changes in ovarian tissue which were subsequently confirmed by
histopathological examination of control and treated animals.
Further studies are desirable to define the possible role of fluoride
in causing deleterious effects on reproduction such as delayed
oestrus, repeated failure to conceive, and lowered viability detected
earlier in experimental animals.
Ref:
Fluoride
1994; 27(2):76-80. Preliminary observations on alterations
in rabbit ovary DNA and RNA content in experimental fluorosis;
by A
Shashi
Abstract: Summary. A study was made of the effects on ovary and
uterus of adminis-tering sodium fluoride (10 mg/kg body weight)
or aluminium chloride (200 mg/kg body weight) alone and in combination
to female albino mice (Mus musculus) for 30 days. The reversibility
of the induced effects by withdrawal of NaF + AlCl3 treatment
and by administering ascorbic acid (AA), calcium (Ca), or vitamin
E alone and in combination were also investigated. All
treat-ments (NaF, AlCl3, and NaF + AlCl3) resulted in a significant
decline of ovarian protein and 3 ¥ - and 17 ¥ -hydroxysteroid
dehydrogenase activities which could be related to increased cholesterol
levels in the ovary suggesting altered steroidogenesis.
The treatment also caused a hypercholesterolemic
effect in serum. Accumulation of glycogen in uterus could
be related to inhibition of phosphorylase activity affecting carbohydrate
metabolism. The withdrawal of combined treatment for 30 days brought
about an incomplete recovery. However, AA, Ca, or vitamin E supplementation
alone and in combination produced an additive effect for recovery
of most of the parameters almost to control levels. Hence
the effects of NaF and/or AlCl3 are transient and reversible.
Ref: Fluoride 2001; 34(1):9-20. Effects
of sodium fluoride and aluminum chloride on ovary and uterus of
mice and their reversal by some antidotes; by NJ Chinoy and TN
Patel. Full
report available at
http://www.fluoride-journal.com/01-34-1/341-9.pdf
Tembotrione - Herbicide - CAS No. 335104-84-2
• 90-day Oral Yoxicity - Mouse study: NOAEL =M/F: 64/75.6 mg/kg/day. LOAEL =M/F: 631/783 mg/kg/day based on decreased uterine weights and increased corpora lutea in the ovary in females... (page 47)
• 90-Day Oral Toxicity - Rat study : In females, the following microscopic changes were observed at an increased incidence: multifocal corticotubular basal vacuolation (slight) in the kidneys occurred in a dose-dependent manner 1-6/10 in all treated groups compared to 0/10 in controls; diffuse hypertrophy of the interstitial gland in the ovaries was observed in the 1500 ppm and 7000 ppm groups (3/10) compared to 0/10 in controls. These effects were considered treatment-related. (page 56)
• Certain changes in multiple organs seen in the subchronic, chronic, dermal, and reproduction studies (e.g., microscopic changes in the thyroid gland, adrenal gland, and pancreas; increased number of corpora lutea in the ovary, and delayed preputial separation) may be due to various mechanisms including possible liver-pituitary-thyroid homeostatic disruption or inhibition of steroid synthesis (Page 6)... When additional appropriate screening and/or testing protocols being considered under the Agency’s EDSP have been developed, tembotrione may be subjected to further screening and/or testing to better characterize effects related to endocrine disruption (page 29).
Reference: Tembotrione. Human-Health Risk Assessment for Proposed Uses on Field Corn, Sweet Corn and Popcorn. USEPA. September 7, 2007.
Tetraconazole
-Fungicide - CAS No. 112281-77-3
A
chronic feeding/carcinogenicity study was conducted with tetraconazole
in Crl:CD-l (ICR)BR mice at dietary levels of 10, 90, 800, and
1,250 ppm for 80 weeks. Treatment-related non-neoplastic changes
were also seen at 1,250 ppm in the lungs, kidneys,
testes, epididymides,
ovaries and bone, particularly the cranium;
a compression of the brain was noted in a number of mice reflecting
the extent of cranial bone changes and an increased
thymic involution was seen in male mice
that died on test.
The 1,250 ppm dietary level for tetraconazole, because of the
substantial bwt gain changes and increased mortality (more in
males), appeared to be above the maximum tolerated dose (MTD).
At 800 ppm, there were increases in non neoplastic changes in
lungs, kidneys, testes, epididymides,
ovaries and bone.
In addition,
there was substantial reduction in weight gain as compared with
zero-dose control animals, but the mortality rate was unaffected.
Eight hundred ppm appeared to be a reasonable estimate of the
MTD for mouse.
Ref: Federal Register: October 14, 1999.
Notice of Filing Pesticide Petitions to Establish a Tolerance
for Certain Pesticide Chemicals in or on Food. PP 9F5066, 9F6023,
and 7E4830.
http://www.fluoridealert.org/pesticides/Tetraconazole.FR.Oct14.1999.htm
• Metbolism nd Toxicokinetics. Tetraconazole
was broadly distributed to all organs and tissues tested, with
the highest level detected in the liver, followed by kidneys,
gonads, brain and bones.
Low residual levels were still detected in the liver and gastrointestinal
tract (sometimes bones) at 72 hr.
• Chronic & Carcinogenicity Studies.
An absence of corpora lutea in ovaries
and thin uterus in females were seen at 800 and 1250 ppm. ...
Rats received 0, 10, 80, 640 or 1280 ppm (the last dose to males
only) of tetraconazole in the diet for 2 years... At interim sacrifice,
female rats showed an absence of corpora lutea in the ovaries
and a decrease in the incidence of epithelial mucification in
cervix and vagina in all treated groups, and squamous metaplasia
in the endometrial glands of the uterus at 80 and 640 ppm. At
the end of the study, females showed thickened uterus at 640 ppm
and males showed a higher incidence of enlarged cervical lymph
nodes at 640 and 1280 ppm, along with cystic sinuses at 1280 ppm.
(page 5)
Ref: August
2005 - Evaluation of Tetraconazole in the product Domark 40ME
Fungicide. Australian Pesticides and Veterinary Medicines Authority.
http://www.fluorideaction.org/pesticides/tetraconazole.2005.report.australia.pdf
Triflumizole
- Fungicide - CAS No. 68694-11-1
-- Chronic feeding/oncogenicity
studies were conducted in both the rat and mouse. The chronic
feeding study in the rat suggests that the
liver is the main target organ with the
ovary and kidney
as secondary target organs. Although there was an accompanying
increase in organ weights, no carcinogenic effects were seen...
-- A 2-year feeding/oncogenicity study with Sprague-Dawley rats
was conducted. Rats were fed 0, 5, 20 or 80 mg/kg/day doses of
triflumizole equivalent to 0, 100, 400 and 1600 ppm triflumizole
for 104 weeks with an interim sacrifice at 52 weeks. Numerous
organ weights, clinical chemistry and hematology parameters and
microscopic changes indicate the main target organ is
the liver, with fatty vacuolization and periacinar hepatic
hypertrophy seen at all dose levels tested. Ovarian
organ weights as well as well-developed follicles indicate the
ovary as a target...
-- In a 3-generation rat reproduction study, dose levels of 0,
70, 170 and 420 ppm in feed resulted in a NOEL greater than 70
ppm (LDT) based on increased gestation length.
At 170 ppm there was pup mortality. At 420 ppm, there was reduced
body weight gain, increased length of estrous
cycles, reduced vaginal cornification,
extended gestation length and high pup mortality.
Ref: EPA Pesticide Fact Sheet September
1991. Triflumizole (Terraguard, Procure).
http://pmep.cce.cornell.edu/profiles/fung-nemat/tcmtb-ziram/triflumizole/fung-prof-triflumizole.html
-- Endocrine disruption.
In the rat reproduction study there was an increase in placental
weight in females at the high dose level of 170 ppm. There was
also a biologically significant increase
in gestation length in high dose F0 and F2 females (F1a
and F3a intervals). The NOAEL for endocrine effects is 70 ppm
(3.5 mg/kg/day).
Ref: [Federal Register: July 6, 2001 [Notices]
[Page 35623-35628]. Notice of Filing a Pesticide Petition to Establish
a Tolerance for a Certain Pesticide Chemical in or on Food. http://www.fluoridealert.org/pesticides/Triflumizole.FR.July6.2001.htm
-- Two three-generation reproduction studies in rats (when
considered together) with a reproductive toxicity NOEL of 30 ppm
(1.5 mg/kg/day) and a reproductive toxicity LEL of 70 ppm (3.5
mg/kg/day). Triflumizole is considered a
reproductive toxicant.
Ref: Federal Register: November 16, 1994.
Pesticide Tolerances and Feed Additive Regulations for Triflumizole.
Final Rule.
http://www.fluoridealert.org/pesticides/Triflumizole.FR.Nov.16.1994.htm
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