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
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Note:
This is not an exhaustive list.
When time allows more information will be added.
Cyhalothrin,
lambda -
Insecticide - CAS No. 91465-08-6
A carcinogenicity study
in mice fed dose levels of 0, 20, 100, or 500 ppm (0, 3, 15, or
75 mg/kg/day) in the diet for 2 years. A systemic NOEL was established
at 100 ppm and systemic LOEL at 500 ppm based on decreased body
weight gain in males throughout the study at 500 ppm. The Agency
has determined that the chemical was not tested at a sufficiently
high dose level for carcinogenicity testing in female mice. In
addition, due to an equivocal finding
for mammary tumors in females (1/52,
0/52, 7/52, 6/52), the Agency classified the chemical as a Group
D carcinogen.
Ref: Federal Register. March 27, 1995. Lambda-Cyhalothrin;
Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/Lambda-Cyhal.FR.Mar.27.1995.htm
Ethalfluralin
- Herbicide - CAS No. 55283-68-6
Group C --
Possible Human Carcinogen. Mammary tumors
(F); Suggestion of bladder tumors (F) and
kidney tumors (M & F); Fischer 344 rats.
Ref: April
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.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf
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... At autopsy, high-dose females exhibited an increased
incidence of cystic uterus... The uterine
cysts found at autopsy in the high-dose females were characterized
as endometrial cysts. In the high-dose females, further slight
increases in uterine pathology were described histologically,
namely etritis/endometritis, cystic endometrial hyperplasia and
uterine fibrovascular polyps. Mammary
fibroadenomas occurred at similar incidences in all female
groups. The incidence of mammary adenomas
in treated females exceeded that of controls, but not in a dose-related
manner. Mammary adenocarcinomas occurred
at higher incidence at 60 and 120 ppm, but not in a dose-related
manner. The latter incidences remained within the range of historical
control data. The variable incidences and lack of dose-response
relationships contraindicate a neoplastic response, but in view
of the observed weight losses, especially in high-dose groups,
these findings cannot be discounted entirely...
Ref: 1985 World Health Organization Review
for Flucythrinate.
http://www.fluoridealert.org/pesticides/Flucythrinate.1985.WHO.htm
Fluquinconazole
- Fungicide
- CAS No. 136426-54-5
-- Oral long-term toxicity
and carcinogenicity. 2-year dietary study in rats. groups of 50
male and 50 female outbred albino Sprague-Dawley CRL :COBS CD(SD)BR
rats were administered fluquinconazole (93.2% purity) in the diet
at concentrations of 0 (control), 1, 20 or 100 ppm. Additionally
20 animals/sex/dose designated for the interim-kill received the
test compound at concentrations of 0, 1, 5, 10 or 100 ppm for
12 months... Mortalities over the 24-month period were 24/50,
28/50, 28/50 and 31/50 in males and in females 33/50, 36/50 and
39/50 at dose levels of 0, 1, 20 and 100 ppm... Post-mortem examinations
showed the most probable cause of deaths in males to
be pituitary tumors followed by chronic
progressive nephropathy and
urinary tract infections. In females mammmary
tumors followed by pituitary tumors
were considered the most probable cause of morbidity... In the
thyroid gland a significantly higher incidence in follicular cell
tumors were noted in the 100 ppm dose level in both sexes. Historical
tumor incidences provided showed that the slight statistically
non-significant increase in thyroid follicular cell tumors at
the lowest and intermediate dose levels were at the upper limit
of the historical control range and therefore in the absence
of a dose response they were considered to be not of toxicological
significance...
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
PFOS - Insecticide,
US EPA List 3 Inert
3.5 Carcinogenicity.
The chronic toxicity and carcinogenicity of perfluorooctane
sulfonic acid potassium salt (PFOS; T-6295) have been studied
in rats (3M, 2002). The results of the study show that PFOS
is hepatotoxic and carcinogenic, inducing tumors of the liver,
and of the thyroid and mammary glands. Based on the liver toxicity,
the no-observed-adverse-effect level (NOAEL) for PFOS is considered
to be 0.5 ppm in male rats and 2 ppm in female rats; the low
observed-adverse-effect level (LOAEL) is 2 ppm in male rats
and 5 ppm in female rats. In this study, groups of 40-70 male
and female Crl:CD (SD)IGS BR rats were given PFOS in the diets
at concentrations of 0.5, 2, 5, or 20 ppm for 104 weeks. A control
group was given diets containing acetone, the vehicle. A recovery
group was given the test material at 20 ppm for 52 weeks and
was observed till death...
Table
3. Summary of carcinogenicity
data of PFOS in rats (page 37) |
Tumor:
Mammary |
Tumor
incidence (%) - Females |
0 |
0.5
ppm |
2 ppm |
5 ppm |
20
ppm^^ |
20
ppm^^
recovery# |
Fibroadenoma/adenoma |
38.3
(23/60) |
60.0**
(30/50) |
45.8
(22/48) |
52.04
(26/50) |
25
(15/60) |
Carcinoma |
18.3
(11/60) |
24.0
(12/50) |
31.2
(15/48) |
22.0
(11/50) |
23.3
(14/60 |
Combined |
48.3
(29/60) |
72.0**
(36/50) |
64.6**
(31/48) |
58,0
(29/50) |
40.0
(24/60) |
*Significant
positive trend (P < 0.03).
** Significantly increased over the
control (P < 0.05).
# Recovery group; after 52 weeks of treatment.
^^ Note from FAN: The last column is presented as it is
in the Table. No explanation if offered to clarify. |
Ref:
November 21, 2002 report: Hazard Assessment of Perfluorooctane
sulfonate (PFOS) and its salts. Organisation for Economic
Co-operation and Development. ENV/JM/RD(2002)17/FINAL.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf
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Prosulfuron
- Herbicide - CAS No. 94125-34-5
-- Long term toxicity
and carcinogenicity Target / critical effect:
Liver (hepatocellular hypertrophy in mice), indication
of hormonal disruption (uterus and
mammalian gland in rats) at high dose levels. Lowest relevant
NOAEL: NOAEL = 1,7 mg/kg bw/day (18-month, mouse) Carcinogenicity:
No carcinogenic potential
Ref: July 2, 2002 - Review
report for the active substance prosulfuron. European Commission
Health & Consumer Protection Directorate-General.
-- A 2-year chronic feeding/carcinogenicity study in rats fed
dosages of 0, 0.4, 7.9, 79.9 or 160.9 (males), and 0, 0.5, 9.2,
95.7 or 205.8 mg/kg/day (females) was conducted. There was uncertain
evidence of carcinogenicity with slight increases in the incidence
of mammary gland adenocarcinomas in
females at 95.7 and 205.8 mg/kg/day, slight increase in incidence
of benign testicular interstitial cell tumors
at 79.9 and 160.9 mg/kg/day (significant trend only). A systemic
NOAEL of 7.9 mg/kg/day was based on decreased body weight and
body weight gain, hematopoietic effects (males), and possibly
increased serum GGT and decreased liver, kidney and adrenal weights
(females) at 79.9 mg/kg/ day.
-- Carcinogenicity. The HED RfD/Peer Review Committee (PRC) classified
this chemical as a Class D oncogen based on the conclusion that
there was uncertain evidence of carcinogenicity. No relevant treatment-related
oncogenic potential was observed in rats and mice. The slightly
increased incidence of testicular interstitial
cell tumors in male rats at 79.9 mg/kg/day and the
slightly increased incidence of mammary
gland adenocarcinoma in females at 95.7 mg/kg/day
was not significant when the increased survival in these groups
was considered. Furthermore, the overall incidence of mammary
tumors was essentially identical in all groups including the control.
There was no evidence of carcinogenicity in mice and dosages in
both studies were sufficient for identifying a cancer risk. In
the absence of carcinogenicity, it is appropriate that a RfD approach
be used for quantitation of human risks.
Ref: Federal Register: August 25, 1999.
[PF-882; FRL-6093-7]. Notice of Filing a Pesticide Petition to
Establish a Tolerance for Certain Pesticide Chemicals in or on
Food.
http://www.fluorideaction.org/pesticides/prosulfuron.fr.aug.25.1999.htm
Sodium
fluoride - Insecticide,
Wood preservative, US EPA List 4B Inert - CAS No. 7681-49-4
• Note from EC: I include this simply
because of the unexpected results presented.
GROUPS OF 94 C3H & 46 DBA FEMALE MICE, 4-12 MO OF AGE, WERE GIVEN
0.4, 1.0 OR 4.0 MG/L SODIUM FLUORIDE IN DISTILLED DRINKING-WATER
FOR 7-12 MONTHS. GROUPS OF 96 C3H & 45 DBA FEMALES ... AS MATCHED
CONTROLS ... ALSO FED DIET CONTAINING 20-38 MG/KG FLUORINE. /OTHER
GROUPS OF/ 65 & 36 C3H MICE AND 66 & 66 DBA MICE, 2-9 MONTHS OF
AGE, RECEIVED 1.0 & 10.0 MG/L, RESPECTIVELY, SODIUM FLUORIDE IN
DISTILLED WATER FOR 10-17 MONTHS. ALL ... FED MIXED GRAIN DIET
CONTAINING NEGLIGIBLE AMT OF FLUORINE. ... AMONG
MICE THAT RECEIVED 10.0 MG/L FLUORIDE, 63% DIED OF MAMMARY GLAND
CARCINOMAS, COMPARED WITH 50% OF CONTROLS (TAYLOR, 1954).
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of
Chemicals to Man. Geneva: World Health Organization, International
Agency for Research on Cancer, 1972-PRESENT. (Multivolume work).p.
V27 271
(1985)]
Ref: Hazardous Substances Data Bank for
SODIUM FLUORIDE CASRN: 7681-49-4 (online October 2003). Available
at Toxnet
tau-Fluvalinate
- Acaricide, Insecticide - CAS No. 102851-06-9
--
A 2-year study in mice showed no tumorigenic effects of dietary
tau fluvalinate. An increase of mammary
fibroadenomas in female rats in a 2-year gavage study is
judged to be a chance effect.
Ref: Revised
Summary Report. EMEA/MRL/021-REV1/95. Committee for Veterinary
Medicinal Products. The European Agency for the Evaluation of
Medicinal Products.
http://www.fluorideaction.org/pesticides/tau.fluvalinate.1995.review.pdf
Trichlorofluoromethane
-Insecticide, Fungicide, Propellant, EPA List 2 Inert - CAS
No. 75-69-4
/was/ tested by inhalation
on Sprague-Dawley rats and Swiss mice. The animals were exposed
for 4 hr a day, 5 days a week; rats were exposed for 104 weeks,
and mice were exposed for 78 weeks. Animals were observed until
spontaneous death. Trichlorofluoromethane exposure to rats caused
no carcinogenic effects. Trichlorofluoromethane exposure to mice
caused increased numbers of total tumors in females which was
dose related, mammary tumors in females
at 5000 ppm, lung adenomas and leukemias in females, both dose
related.
Ref: Maltoni C et al; Annals of the New
York Academy of Sciences 534: 261-82 (1988)
Website: Hazardous Substances Data Base
for TRICHLOROFLUOROMETHANE.
http://www.fluoridealert.org/pesticides/Trichlorofluorometha.TOXNET.htm
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