A little background... The prostate is a gland of the male reproductive system.
It is located in front of the rectum and just below the
bladder, the organ that stores urine. The main purpose of the prostate is to produce fluid for
semen, which transports sperm during the male orgasm. Ref:
The Endocrine System:
Illustration by K. Born in Our Stolen Future
by Theo Colborn, Dianne Dumanoski and JP Myers
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
Food and Agricultural Organization of the United Nations
This is not an exhaustive list.
When time allows more information will be added.
Herbicide - CAS No. 105512-06-9
Evidence of Carcinogenic Potential.
Prostate gland adenomas in male Tif:RAIf(SPF)
rats at the high dose only cannot be discounted; Peroxisome Proliferator-Activated
Receptor Agonism MOA for liver tumors in mice.
26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the
Office of Pesticide Programs. From: Jess Rowland, Chief Science
Information Management Branch Health Effect Division (7509C) Office
of Pesticide Programs, USEPA.
-- 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.
- Miticide, Ovicide - CAS No.
-- 870.3150 90-Day Feeding Dog NOAEL = 5.33/5.42(M/F) LOAEL =
53.7/55.9 (M/F), based on clinical signs (vomiting foamy fluid
and mucous stool), clinical chemistry, increased
liver weights, and on centrilobular hepatocellular swelling in
the liver and acinar
cell atrophy in the prostate.
Ref: US EPA Pesticide Fact Sheet. August
- Herbicide - CAS No. 79241-46-6
In a 3-generation reproductive study in rats, effects included
reductions in weight gain, fetal weight, ossification,
testicular weight, spleen weight, increased prostate
weight and gestational length. No Effect Level (NEL) was 1 mg/kg/day.
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.
PFOA - Insecticide,
US EPA List 3 Inert
(PFOA) has been found at low levels (10 to 100 parts per billion)
in sera of the general population and at higher levels in occupationally
exposed workers. Although PFOA has been reported to be a promoter
of rodent hepatocarcinogenesis and to alter reproductive hormones
in humans and rodents, there is little information on human health
effects associated with PFOA exposure. The present study examined
the relationship between PFOA and mortality using a retrospective
cohort mortality design. The cohort consisted of 2788 male and
749 female workers employed between 1947 and 1983 at a plant that
produced PFOA. The all-causes standardized mortality ratio was
.75 (95% confidence interval [CI], .56 to .99) for women and .77
(95% CI, .69 to .86) for men. Among men the cardiovascular standardized
mortality rate was .68 (95% CI, .58 to .80) and the all-gastrointestinal
diseases was .57 (95% CI, .29 to .99). There was no significantly
increased cause-specific standardized mortality ratio for either
men or women. Ten years of employment in
exposed jobs was associated with a 3.3-fold increase (95% CI,
1.02 to 10.6) in prostate cancer mortality compared to no employment
in PFOA production. There were only six prostate cancer deaths
overall and four among the exposed workers; thus, the results
must be interpreted cautiously. If prostate cancer mortality
is related to PFOA, PFOA may increase prostate cancer mortality
by altering reproductive hormones in male workers.
1993. J Occup Med Sep;35(9):950-4. Mortality
among employees of a perfluorooctanoic acid production plant;
by Gilliland FD, Mandel JS.
Division of Environmental and Occupational Health, School of Public
Health, University of Minnesota, Minneapolis.
Abstract excerpt: Perfluorooctanoate
(PFOA) and perfluorooctane sulfonate (PFOS) are synthetic surfactants
used in Japan. An epidemiological study
of workers exposed to PFOA revealed a significant increase in
prostate cancer mortality. A cross-sectional
study of PFOA-exposed workers showed that PFOA perturbs sex hormone
homeostasis. We analyzed their concentrations in surface
water samples collected from all over Japan by LC/MS with a solid
phase extraction method... Systematic
searches of Yodo and Kanzaki Rivers revealed two highly contaminated
sites, a public-water-disposal site for PFOA and an airport for
PFOS. The former was estimated to release 18 kg of PFOA/d. PFOA
in drinking water in Osaka city [40
(1.07) ng/L] was significantly higher than in other areas. The
present study confirms that recognizable amounts of PFOA are released
in the Osaka area and that people are exposed to PFOA through
drinking water ingestion.
2004. J Occup Health. Jan;46(1):49-59. Perfluorooctanoate
and perfluorooctane sulfonate concentrations in surface water
in Japan; by Saito N, Harada K, Inoue K, Sasaki K, Yoshinaga
T, Koizumi A.
- CAS No. 122836-35-5
Reproduction and fertility
effects (rat) Nonguideline - [870.3800] Parental/Systemic NOAEL
= 20 mg/kg/day LOAEL = 51 mg/kg/ day (F1 females) based on decrease
in pre-mating body weight gain (10%) Offspring and Reproductive
NOAEL = 16 mg/kg/ day LOAEL = 40 mg/kg/ day based on reduced gestation
day 20 fetal weights; decreased postnatal day 0, 4 and 7 pup weights;
decreased pup survival; delayed vaginal
patency; reduced epididymal, prostate,
and testicular weights Additional information supports the conclusions
reached in the 2- generation reproduction study in rats
Federal Register: September 24, 2003. Sulfentrazone; Pesticide
Tolerances. Final Rule.
- Fungicide - CAS No. 112281-77-3
Chronic & Carcinogenicity Studies.
There were small and flaccid testes with
reduced spermatogenesis, absence of spermatozoa in epididymides,
and small and flaccid prostate and
seminal vesicles with reduced secretion at 800 and 1250
ppm, and interstitial
cell hyperplasia and prominent multinucleate spermatids in the
testes at 1250 ppm. (page
2005 - Evaluation of Tetraconazole in the product Domark 40ME
Fungicide. Australian Pesticides and Veterinary Medicines Authority.