See
FAN's summary of all the pesticides with Cancer effects.
Due
to length, the Cancer effects section is now presented in 4 parts.
The most recent United
States Cancer Statistics report was released in November
2003. This is the 2nd annual report prepared by the Centers
for Disease Control and Prevention and the National Cancer
Institute, in collaboration with the North American Association
of Central Cancer Registries.
In 1998 I published the Citizens' Guide
to 667 Chemicals Known to Cause Human Cancer in the newsletter
Waste Not. The four top uses of these chemicals were in
the manufacture of
Plastics
Pharmaceuticals
Pesticides
Dyes
Of the 667 known carcinogenic chemicals,
84 were identified by the US EPA in 1997 as "High Production
Volume Chemicals" - produced in quantities greater
than 1 million pounds a year.
If society wants to prevent cancer, the
first step would be to ban the use, production and release
of known and suspected carcinogens. - EC.
Towards
what ultimate point is society tending by its industrial
progress?
When the progress ceases, in what condition are we to expect
that it will leave mankind?
- John Stuart Mill, 1857 -
|
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
- Acaracide,
Insecticide
- CAS No. 120068-37-3
Group
C -- Possible Human Carcinogen.
Thyroid follicular cell adenomas,
carcinomas & combined adenomas/carcinomas (M); thyroid follicular
cell adenomas and combined adenomas/carcinomas (F); Charles River
CD 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
Group
C--Possible Human Carcinogen.
Reviewed 7/ 18/ 95.
Ref:
List of Chemicals Evaluated for Carcinogenic Potential. Science
Information Management Branch, Health Effects Division, Office
of Pesticide Programs, U. S. Environmental Protection Agency.
March 15, 2002.
http://www.biomuncie.org/chemicals_evaluated_for_carcinog.htm
Cancer.
The EPA's Health Effects Division Carcinogenicity
Peer Review Committee classified fipronil in Group
C - Possible Human Carcinogen, based on thyroid tumors observed
in rats at 300 ppm (HDT). Mechanistic data indicate that these
tumors are related to a disruption in the thyroid-pituitary status
and are specific to the rat. In addition,
there was no apparent concern for mutagenic activity. Thus, it
was recommended that RfD methodology, i.e. non-linear or threshold,
be used for the estimation of human risk.
Ref:
August 24, 2005. Federal Register. Fipronil; Notice of Filing
a Pesticide Petition to Establish a Tolerance for a Certain Pesticide
Chemical in or on Food.
http://www.fluorideaction.org/pesticides/fipronil.fr.aug.24.2005.html
-- Carcinogenic classification
and risk quantification. EPA has classified this chemical as a
Group C--Possible Human Carcinogen, based on increases in
thyroid follicular-cell tumors in both sexes of the rat,
which were statistically significant
by both pair-wise and trend analyses. EPA has used the RfD methodology
to estimate human risk because the thyroid
tumors are due to a disruption in the thyroid-pituitary
status. There was no apparent concern for mutagenicity.
Ref:
Federal Register: July 17, 1998. Fipronil; Pesticide Tolerance.
Final Rule.
http://www.fluoridealert.org/pesticides/fipronil.fr.july.17.1998.htm
Flonicamid
- Insecticide - CAS No. 158062-67-0
Suggestive
Evidence of Carcinogenicity,
but not sufficient to assess human carcinogenic potential. Nasal
lacrimal duct squamous cell carcinomas
possibly
treatment-related in female Wistar rats; Mitogenesis MOA accepted
for lung tumors in CD-1 mice (both
sexes).
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
--
Cancer. Suggestive
evidence of carcinogenic potential.
-- Carcinogenicity (mice).
NOAEL was not established. LOAEL is 250 ppm (equivalent to 29/38mg/kg/
day [M/F]), based on minimal to moderate centrilobular
hepatocellular hypertrophy, minimal
to severe extramedullary hematopoiesis, minimal to moderate
pigment deposition in the sternal bone marrow,
and increased incidence of tissue masses/nodules
in the lungs in the males, and minimal
to moderate decreased cellularity in the femoral bone marrow and
hyperplasia/hypertrophy of the epithelial
cells of the terminal bronchioles of the females At the doses
tested, the carcinogenic potential of IKI-220 (flonicamid) is
positive at 250 ppm in males and females based on the increased
incidence of alveolar/bronchiolar adenomas, carcinomas, and combined
adenomas/carcinomas. Dosing was considered adequate based
on increased incidence of tissue masses/nodules in the lungs and
microscopic findings in the liver, spleen, bone marrow, and lungs.
However, data were provided suggesting this effect is specific
to sensitive strains of mice. Carcinogenic
in mice.
--
Combined Chronic/ carcinogenicity (rats).
NOAEL is 200
ppm (equivalent to 7.32/8.92mg/ kg/day in males/females). LOAEL
is 1,000 ppm (equivalent to 36.5/44.1mg/ kg/day in males/females)
based on decreased body weights and body
weight gains,and increased incidences of keratitis in males and
striated muscle fiber atrophy in females. At the high dose
there was an incidence (12%)of nasolacrimal
duct* squamous cell carcinomas
slightly outside the historical control
range (0-10%) in male rats. A correlation between the incidence
of inflammation and the fluctuating incidence of nasal tumors
was made across dose groups. EPA did not consider the nasolacrimal
duct tumors to be treatment-related. Female rats had a significant
increasing trend in nasolacrimal duct squamous cell carcinomas
at < 0.05, and at the high dose was slightly above the
historical control mean (0.8%) and range (0-4%). EPA
considered the nasolacrimal duct squamous cell carcinomas to be
possibly treatment related, but that a clear association with
treatment could not be made.
-- Aggregate cancer
risk for U.S. population. In assessing
the carcinogenic potential of flonicamid, EPA took into account
the following weight-of-the-evidence considerations:
i. Flonicamid is not mutagenic.
ii. The treatment-related CD-1 mouse
lung tumors (benign and malignant) which occurred in both sexes
were due to an established mitogenic mode of action that occurred
in a susceptible mouse strain with a high background. A clear
species difference was observed between mice and rats in
the incidence of lung tumors and the BrdU Index studies. (Bromodeoxyuridine
(BrdU) Index studies are used to quantify rates of cell proliferation).
No tumors were seen in the lungs of rats. The flonicamid induced
increase in the BrdU Index appears to be related to the different
sensitivity of strains of mice, with the CD-1 mice being a relatively
sensitive strain.
iii. The only other tumor response
was nasolacrimal duct tumors which occurred in female rats at
the high dose which were considered to be possibly treatment-related,
but a clear association with treatment could not be made. Unlike
male rats, the nasal tumor response in females could not be clearly
associated with spontaneous inflammation related to malocclusion
of incisor teeth, due to the low incidence of both the neoplastic
and non-neoplastic lesions. Given these findings in the cancer
and mutagenicity studies, EPA regards the carcinogenic potential
of flonicamid as very low and concludes that it poses no greater
than a negligible cancer risk to humans.
Ref:
August 31, 2005. Flonicamid; Pesticide Tolerance. Final Rule.
Federal Register.
http://www.fluoridealert.org/pesticides/flonicamid.fr.aug.31.2005.html
-- In the 18-month
mouse study... There were statistically
significant increases in the incidence of alveolar/bronchiolar
adenomas in both sexes of treated groups with hyperplasia/hypertrophy
of epithelial cells in terminal bronchioles. There was
a statistically significant increase
in the incidence of alveolar/bronchiolar carcinomas
in males at 750 ppm and 2,250 ppm and in females at 2,250
ppm only. These effects in the lungs of mice
were not life threatening as most of effects were observed at
the terminal sacrifice and there was no effect of treatment on
mortality in the study. A NOAEL could not be determined from the
dose levels administered. Mechanism-of-action
studies have indicated that the lung effects are unique to the
mouse and are not likely to translate to other species including
the rat. Flonicamid technical
was not carcinogenic in the rat.
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
-- 52964 - 0068, 0069 & 0070 216042, 216043, 216044 “Vol
0068: Dietary Carcinogenicity of IKI-220 Technical in Mice; Vol
0069: Pathology Sub-Report (Supplemental) for Dietary Carcinogenicity
of IKI220 Technical in Mice; Vol 0070: Historical Data for Dietary
Carcinogenicity of IKI-220 Technical in Mice,” (Nagaoka,
T., Nakashima, N.; Shin Nippon Biomedical Laboratories, Ltd.,
Kagoshima, Japan; The Institute of Environmental Toxicology, Ibaraki,
Japan; 1/22/04, 3/30/04, 1/22/04 for volumes 0068, 0069 &
0070, respectively). Flonicamid technical (IKI-220: 98.7% pure)
was fed in diet to Charles River Crj:CD-1®(ICR)BR mice
(50/sex/dose) at 0, 10, 25, 80 and 250 ppm (equivalent
doses: M = 1.20, 3.14, 10, 30.3 mg/kg/day; F = 1.42, 3.67, 11.8,
36.3 mg/kg/day) for 78 weeks. Systemic NOEL = 80 ppm (There was
an increase in lung hyperplasia and hypertrophy (both sexes) and
liver fatty change in centrilobular hepatocytes (F) at 250 ppm.
There was a statistically significant decrease in absolute kidney
weights in females at 250 ppm. There was
a statistically significant increase in lung masses--pulmonary
adenomas and carcinomas in males at 250 ppm.) Not acceptable
(There were numerous deficiencies in this study (see A., above).
There were no interim kills, nor were all target organs examined
and weighed as recommended by FIFRA Guidelines.), not upgradeable.
Possible adverse effect indicated (There
was a statistically significant increase in pulmonary adenomas
and carcinomas in males at 250 ppm. Silva, 4/29/05
-- Rationale for Regulation by Reference Dose,” (Cohen,
S.M., Hardisty, J.F., McCarty, J.D.; FMC Corporation, Agricultural
Products Group, Princeton, NJ; Document #: flonicamid 04-04, 8/31/04).
This report contains a complete discussion (along with a presentation
of summary data) on the mechanism and potential for oncogenicity
of flonicamid. All studies discussed in this report were presented
for review to DPR. Many of the potential adverse effects, primarily
regarding the incidence of nasal and lung cancer in rats and mice,
respectively, were initially noted in worksheets provided by USEPA.
Upon re-evaluation of the noted effects, the nasal cancers in
rats were found to originate in the nasal-lacrimal duct, which
is more common than the squamous cell carcinomas. The nasolacrimal
duct tumors were determined to be unilateral and not bilateral
which indicated they were spontaneous and not due to treatment.
Based on the low spontaneous incidence of these tumors in humans
versus rats, the potential for their initiation in humans after
flonicamid exposure, were negligible. Lung tumors (observed only
in mice) appeared to be due to mitogenesis, non-linear, non-genotoxic
mode of action for which a threshold dose has been established.
Historical controls were presented for all potential adverse effects.
Included also were complete discussions of all questions raised
by USEPA. This information is supplemental. No worksheet was performed
for this data volume. Silva, 2/2/05.
Reference:
April 28, 2005 - Summary of toxicology data. California EPA, Department
of Pesticide Regulation, Medical Toxicology Branch.
http://www.fluorideaction.org/pesticides/flonicamid.ca.epa.2005.pdf
*
Note: The
nasolacrimal duct carries tears from the
lacrimal sac into the nasal cavity.
Fluazinam
-
Fungicide
- CAS
No. 79622-59-6
Suggestive
Evidence of Carcinogenicity to Humans.
An increase in thyroid gland follicular
cell tumors in male rats, and an increased incidence of
hepatocellular tumors
observed in the male mice was treatment-related.
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
-- Carcinogenicity
mice NOAEL = Males:1.1 mg/kg/day; Females: 1.2 mg/kg/day. LOAEL
= Males: 10.7 mg/kg/day; Females: 11.7 mg/kg/day based on increased
incidences of brown macrophages in the liver
of both sexes, eosinophilic vacuolated hepatocytes in males, and
increased liver weight in females.
Clear evidence of carcinogenicity (hepatocellular tumors) in male
mice, but not in females.
-- Combined chronictoxicity/ NOAEL = Males: 0.38 mg/kg/day; carcinogenicity
rats Females: 0.47 mg/kg/day LOAEL = Males: 3.8 mg/kg/day; Females:
4.9 mg/kg/day based on liver toxicity
in both sexes, pancreatic exocrine atrophy in females and testicular
atrophy in males. Some evidence of carcinogenicity
(thyroid gland follicular cell tumors) in male rats, but not in
females.
-- Carcinogenicity mice NOAEL = Males:<126 mg/kg/day, Females:
<162 mg/kg/day LOAEL = Males: 126 mg/kg/day;
Females: 162 mg/kg/day based on increased liver weights and liver
and brain histopathology in both sexes Equivocal/some
evidence of carcinogenicity (hepatocellular tumors) in male mice,
but not in females,
Ref: Federal Register. September 7, 2001.
Fluazinam; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/fluazinam.fr.sept.7.2001.htm
-- Cancer (oral, dermal, inhalation). `Suggestive evidence of
carcinogenicity, but not sufficient to assess human carcinogenic
potential'' 2 . Quantification of human cancer risk not required.
2 Increases in thyroid gland follicular
cell tumors in male rats; increases in hepatocellular (liver)
tumors in male mice.2 (Ref 2: 2Cancer Assessment Document
- Evaluation of the Carcinogenic Potential of Fluazinam, March
29, 2001, HED Doc. No. 014512.)
-- Cancer. Since fluazinam has been classified as ``Suggestive
evidence of carcinogenicity, but not sufficient to assess human
carcinogenic potential,'' an exposure assessment was not performed.
Ref: Federal Register: April 18, 2002. Fluazinam;
Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/fluazinam.fr.apr.18.2002.htm
Flucythrinate
-
Acaricide, Insecticide - CAS No. 70124-77-5
Abstract:
Male Sprague-Dawley rats dosed with N-nitrosodiethylamine
(NDEA) 24 h after two-thirds partial hepatectomy were treated
with the pyrethroid insecticides fenvalerate, flucythrinate
or cypermethrin in the diet for 20 weeks. Altered hepatic foci
were analyzed by quantitative stereology from paraffin-embedded
sections stained for gamma-glutamyltranspeptidase (GGT) or glutathione
S-transferase P (GST-P). The present results demonstrate that
the pyrethroids tested all enhance the development of NDEA-initiated,
GGT-positive foci in rat liver at non-hepatotoxic doses. On the
contrary, the volume fractions of GST-P-positive foci were not
elevated as compared to the control group. The three pyrethroids
tested all inhibited the transfer of Lucifer Yellow CH between
WB-F344 rat liver epithelial cells in culture, supporting the
increase of GGT-positive foci and suggesting
that these substances can act as tumour promoters.
The discrepancy between the results from analyses using
GGT or GST-P as markers emphasizes the importance of understanding
the mechanism underlying the expression of different markers for
preneoplastic lesions and the importance of such effects in tumour
promotion.
Ref: Enhancement of altered hepatic
foci in rat liver and inhibition of intercellular communication
in vitro by the pyrethroid insecticides fenvalerate, flucythrinate
and cypermethrin; by Hemming H, Flodstrom S, Warngard L. Carcinogenesis
1993 Dec;14(12):2531-5
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7903603&dopt=Abstract
Fludioxonil
- Fungicide
- CAS No. 131341-86-1
-- Combined Chronic
Toxicity/ Carcinogenicity in rats: NOAEL = 37 mg/kg/day (M) and
44 mg/kg/day (F) LOAEL = 113 mg/kg/day (M) and 141 mg/kg/day
(F) based on decreased mean body weight gain, slight anemia (F),
and increased incidence and severity of liver lesions (degeneration)
in both sexes. There was no evidence of carcinogenicity in male
rats, but there was a statistically significant increase, both
trend and pairwise, of combined hepatocellular tumors in female
rats. Classified as ``Group D'' by OPP Cancer Peer Review Committee.
Carcinogenicity mice: increased incidence of mice convulsing when
handled (M) and increased absolute liver weight and grossly enlarged
livers (F). Statistically significant trend
for malignant lymphomas in females...
-- 90-Day oral toxicity in NOAEL = 64 mg/kg/day (M) and 70 mg/kg/day
rats (F) LOAEL = 428 mg/kg/day (M) and 462 mg/kg/day (F) based
on decreased weight gain (both sexes), chronic nephropathy (M)
and centrilobular hepatocyte hypertrophy (F).
-- In vivo Rat hepatocyte Male rats were orally dosed 1250, 2500
and micronucleus assay 5,000 mg/kg and hepatocytes were harvested.
Micronucleated hepatocytes were found in Phase II at the low and
mid dose levels but not at the high dose level and not in Phase
I. Positive for mutagenicity in hepatocytes
exposed in vivo.
Ref: Federal Register: December 29, 2000.
Fludioxonil; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/fludioxonil.fr.dec.2000.htm
--
The EPA classified Fludioxonil as a Group D - not classifiable
as to human carcinogenicity. The evidence is inadequate and cannot
be interpreted as showing either the presence or absence of a
carcinogenic effect. In one mouse study, there was a significant
trend for malignant lymphomas in
female mice up to 3,000 ppm. However, in a second study up to
7,000 ppm, the limit dose, there was no evidence of carcinogenicity
for either sex. In rats, fludioxonil produced
a significant trend and pair- wise increase in hepatocellular
tumors, combined, in female rats at doses adequate to assess carcinogenicity.
The EPA determined that based on the increase
in liver tumors in female rats that was statistically significant
for combined adenoma/carcinoma only, the lack of tumorogenic response
in male rats or in either sex of mice, and the need for additional
mutagenicity studies, a Group D classification was appropriate.
However, the Agency has since received the additional mutagenicity
studies and based on the negative preliminary findings of the
studies, the fact that the statistical increase in liver tumors
in female rats occurred only at the highest dose, the lack of
tumorigenic response in male rats and mice, the Agency has concluded
that fludioxonil does not pose a significant
cancer risk.
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
Fluometuron
- Herbicide - CAS No. 2164-17-2
Group
C -- Possible Human Carcinogen.
Statistically significant increases in combined adenomas/carcinomas
of the lung (M); Malignant lymphocytic
lymphomas (F); CD-1 mice.
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
Group C--Possible
Human Carcinogen. Reviewed 8/ 28/ 96.
Ref:
List of Chemicals Evaluated for Carcinogenic Potential. Science
Information Management Branch, Health Effects Division, Office
of Pesticide Programs, U. S. Environmental Protection Agency.
March 15, 2002.
http://www.biomuncie.org/chemicals_evaluated_for_carcinog.htm
• The
significant cancer risk contributors have been identified as drinking
water (direct and indirect, all sources), and
several rotational crops with wheat
(flour), soybean (oil), and rice (white) having the highest contributions.
(page 7)
• A re-examination and statistical analysis of the rates
of all lymphocytic lymphomas in female mice and all alveolarhronchiolar
hyperplasia, adenomas, and carcinomas in male mice from the carcinogenicity
study in mice (0, 10,500, or 2000 ppm [83-2b]) indicated
that male mice had a significant increasing trend in alveolar/bronchiolar
adenomas andor carcinomas combined at p < 0.05. There
were no significant differences in the pair-wise comparisons of
the dosed groups with the controls. The male alveolarhonchiolar
tumor rates were 15/56, 16/59, 19/56, and 24/58, respectively
(L. Taylor Memorandum 9/13/95, TXR 012742). Female
mice had a significant increasing trend and a significant difference
in pair-wise comparison of the high-dose group (2000 ppm) with
the controls for lymphocytic lymphomas at p < 0.05.
The lymphatic tissue tumor rates were 4/5 1, 10124, 6/17, and
12/53, respectively (L. Taylor Memorandum 9/13/95, TXR 012742).(page
9)
• D. Classification of Carcinogenic Potential. The
Health Effects Division Carcinogenicity Peer Review Committee
(CPRC) met on Oct. 11, 1995 to discuss and evaluate the weight-of-the-evidence
on fluometuron with particular reference to its carcinogenic potential.
The consensus of the CPRC was that fluometuron should be classified
as Group C -possible human carcinogen and
for the purpose of risk characterization, both a low dose extrapolation
model (Q,’) applied to the animal data (lung tumors in male
mice) and the Reference Dose (RfD) approach should be used.
This was based on statistically significant increases in combined
adenomadcarcinomas of the lungs in male mice and malignant lymphocytic
lymphomas in female mice, at a dose which was less than
adequate for fully assessing the carcinogenic potential of fluometuron
( L. Taylor Memorandum 8/28/96, TXR 012049).
A quantitative risk assessment-Q,* was performed for fluometuron
(B. Fisher Memorandum 12/24/96, TXR 012809). The unit risk, QI*(mg/kg/day)-’of
fluometuron, based upon male mouse combined lung (adenomas and/or
carcinomas) tumor rates is 1.80 x lo-*in human equivalents (converted
from animals to humans by use of the 314‘s scaling factor-1994,
Tox Risk, 3.5-K. Crump) (Ref. 1).
The dose levels used from this 2-year study were 0, 10,500, and
2000 ppm of fluometuron. The corresponding tumor rates (from re-read
slide data, 7/92) for the male mice were 15/56, 16/59, 19/56,
and 24/58 respectively.
The
estimate of unit risk, Q1*was based upon lung (adenoma and/or
carcinoma) tumor rates in male mice. Since male mice had
statistically significant increases in mortality with dose increments
of fluometuron, the estimate of the unit risk, Q1*,was
obtained by the application of the time-to-tumor Weibull model
(Tox-Risk program, version 3.5-K. Cnunp). The resulting estimate
of unit risk, Q1*,was converted to human equivalents by the use
of weights of 0.03 kg for the mice and 70 kg for the humans and
the 3/4’s scaling factor for interspecies extrapolation.
It is to be noted that Q,* (mg/kg/day)-’ is an estimate
of the upper bound on risk and that (as stated in the EPA Risk
Assessment Guidelines) “the true value of the risk is unknown,
and may be as low as zero. (page 11-12).
(1). See memo-Deriving Q,*s Using
the Unified Interspecies Scaling Factor, P.A. Fenner-Crisp. Director-HED,
7/1/94.
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
Twelve
of the 26 most widely used pesticides in the U.S. are classified
as possible or probable carcinogens by the EPA
based on studies of laboratory animals, with an annual use that
totals 380 million pounds. (atrazine (C=possible), metolachlor
(C), metarn sodium (B2=probable), dichloropropene (B2), cyanazine
(C), pendimethalin (C), trifluralin (C), acetochlor (B2), chlorothalonil
(likely), mancozeb (B2), fluometuron
(C), and parathion (C). Four frequently used pesticides have been
associated with increased risk of cancer for exposed humans in
epidemiological studies. 190 million pounds of these four pesticides
are used annually in the U.S., including 120 million household
applications every year. (atrazine, 2,4 D, glyphosate, diazinon).
(Journal of Pesticide Reform, Summer 1999, at 5). Last
year, the EPA moved under the Food Quality Protection Act to phase
out residential uses of diazinon, but agricultural uses remain
legal.
Ref: Testimony of the Maine Organic Farmers
and Gardeners Association In support of L.D. 1540. March 29, 2001.
http://www.mofga.org/ge_pesticide_test.html
1980 Abstract:
... A bioassay of the phenylurea herbicide fluometuron for possible
carcinogenicity was conducted by administering the test chemical
in feed to F344 rats and B6C3F1 mice. Groups of 50 rats of each
sex were fed diets containing 125 or 250 ppm of fluometuron for
103 weeks, and groups of 50 mice of each sex were fed diets containing
500 or 1,000 ppm of fluometuron for 103 weeks. Matched controls
consisted of groups of 50 untreated rats and 25 untreated mice
of each sex. All surviving animals were killed at 103 to 105 weeks.
Splenomegaly observed in rats in the subchronic
studies influenced selection of the doses for the chronic study;
however, no splenic effects were observed in the chronic
study. Mean body weights of the dosed groups of male and female
rats and mice were essentially the same as those of the corresponding
control groups. Survival of dosed groups of rats and mice was
similar to that of the corresponding control groups. Similarities
between mean body weights and survival between dosed and control
animals in the chronic study suggest that these animals could
have tolerated higher doses. The only possible
carcinogenic effects from compound administration were in male
mice. Incidences of hepatocellular carcinomas or adenomas in male
mice were dose related, and the incidence in the high-dose group
was marginally higher than that in the corresponding matched controls
or pooled controls from concurrent studies. Under the conditions
of this bioassay, fluometuron was not carcinogenic for F344 rats
or for female B6C3F1 mice. Equivocal results
were obtained for male B6C3F1 mice which may have had an increased
incidence of hepatocellular tumors. Because of the equivocal
findings and because both rats and mice may have been able to
tolerate higher doses, it is concluded that additional testing
of fluometuron for carcinogenicity is warranted. Levels of Evidence
of Carcinogenicity: Male Rats: Negative Female Rats: Negative
Male Mice: Equivocal Female Mice: Negative Synonym: 1,1-dimethyl-3-(a,a,a-trifluoro-m-tolyl)
urea
Ref: Bioassay
of Fluometuron for Possible Carcinogenicity (CAS No. 2164-17-2).
National Toxicology Program. Natl Toxicol Program Tech Rep Ser.
1980 Aug;195:1-99.
Fluorine
THE
HIGH INCIDENCE OF CANCER AMONG HOSPITAL PERSONNEL REPEATEDLY
EXPOSED TO FLUORINE-CONTAINING GENERAL ANESTHETICS RAISES
A FUNDAMENTAL NEED TO EXAMINE OTHER FLUOROCARBON-EXPOSED
WORKERS FOR SIMILAR EFFECTS. /FLUOROCARBONS/ [Clayton,
G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and
Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology.
4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994.
1209]
Ref: TOXNET profile from Hazardous
Substances Data Bank for 1-Chloro-1,1-Difluoroethane.
http://www.fluoridealert.org/pesticides/1-chloro-1,1,-difluo.toxnet.htm
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Fluthiacet-methyl
- Herbicide - CAS No. 117337-19-6
Likely
to be carcinogenic to humans.
Reviewed 12/ 8/ 98.
Ref:
List of Chemicals Evaluated for Carcinogenic Potential. Science
Information Management Branch, Health Effects Division, Office
of Pesticide Programs, U. S. Environmental Protection Agency.
March 15, 2002.
http://www.biomuncie.org/chemicals_evaluated_for_carcinog.htm
-- Fluthiacet-methyl
is classified as a "likely to be a human
carcinogen" based on the presence of pancreatic
tumors (exocrine adenomas, islet cell adenomas and combined islet
cell adenomas + carcinomas) in male rats and liver
tumors (adenomas and combined adenomas + carcinomas) in male and
female mice.
Ref: US EPA. Pesticide Fact Sheet. Fluthiacet-methyl
Reason for Issuance: Conditional Registration Date Issued: April
1999.
http://www.epa.gov/opprd001/factsheets/fluthiacet.pdf
-- Carcinogenicity
rats. NOAEL in males = 2.1 mg/kg/day LOAEL in males = 130 mg/kg/day
NOAEL in females = 2.5 mg/kg/day LOAEL in females = 154 mg/kg/dayIn
males there were decreased body weight,
liver
toxicity, pancreatic
toxicity and microcytic anemia.
In females there were liver toxicity, uterine
toxicity and slight microcytic anemia. In males only at
130 and 219 mg/kg/day there was respectively, an increase in the
trend toward pancreatic exocrine adenomas
and pancreatic islet cell adenomas.
-- Carcinogenicity mice. NOAEL in males and females = 0.1 mg/
kg/day LOAEL in males and females = 0.1 and 1.2 mg/kg/day, respectively,
based on non- neoplastic liver findings.
In males, and possibly females, at 10 mg/kg/day for males and
12 mg/kg/day for females; and at 32 gm/kg/day for males and 37
mg/ kg/day for females, there was an increase in the number of
mice with hepatocellular adenomas, carcinomos
and or adenomas/ carcinomas.
-- Chronic Dietary General population. 18-month carcinogenicity
in the mouse. NOAEL = 0.1 mg/kg/day Non-neoplastic liver findings
(increase in absolute and relative liver
weights,
fatty changes, chronic inflammation, karyomegaly, single cell
necrosis and ceroid/lipofuscin pigmentation).
-- Cancer. Fluthiacet-methyl has been classified as ``likely
to be a human carcinogen'' by EPA. The Office of Pesticide
Programs, Heath Effects Division, Cancer Assessment Review Committee
recommended a linear low-dose approach (Q1*) for human risk assessment.
The Q1* is 0.207 (mg/kg/day)-1 in human equivalents and is based
upon the combined hepatocellular tumors (adenomas and carcinomas)
in male mice. EPA conducted a cancer assessment analysis
(food) using DEEM software and Tier 2 chronic dietary exposure
assumptions. The assumptions of this Tier 2 chronic dietary analysis
are as specified above. The cancer risk estimate (food only) for
the U.S. population (total) is 3.93 x 10-8. This risk estimate
translates to a dietary exposure of 1.90 x 10-7 mg/kg/day. This
dietary exposure value was back-calculated based upon the cancer
risk estimate and the Q1*. As cancer risk = Exposure x Q1 * Thus,
Exposure = cancer risk estimate/ Q1 * or Exposure = 3.93 x 10-8/0.207.
Ref: Federal Register: December 21, 2001.
Fluthiacet-methyl; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/fluthiacet.m.fr.dec.21.2001.htm
Fomesafen
- Herbicide - CAS No. 72178-02-0
Group
C--Possible Human Carcinogen.
Reviewed 8/ 27/ 86.
Ref:
List of Chemicals Evaluated for Carcinogenic Potential. Science
Information Management Branch, Health Effects Division, Office
of Pesticide Programs, U. S. Environmental Protection Agency.
March 15, 2002.
http://www.biomuncie.org/chemicals_evaluated_for_carcinog.htm
-- Decreased plasma
cholesterol and triglycerides and increased
liver weights (reversible at 7 days post-treatment) were
observed at 50 mg/kg/day (only dose tested) when administered
in the diet of rats for 4 weeks. In a 90-day rat study, dietary
administration of 5 mg/kg/day (LOEL) produced alterations in lipid
metabolism and increases in liver weight. The NOEL was 0.25 mg/kg/day.
In a 26-week dog study, dietary administration of 25 mg/kg/day
(LOEL) produced alterations in lipid metabolism and liver
changes (changes not defined). The NOEL was 1 mg/ kg/day.
Liver toxicity (increased liver masses,
discolored hepatocytes, and pigmented Kupffer cells) was
observed in a 2-year rat feeding study at 50 mg/kg/day (LOEL).
The NOEL was 5 mg/kg/day. Metabolism studies have shown that fomesafen
accumulates in the liver. EPA believes that there is sufficient
evidence for listing fomesafen on EPCRA section 313 pursuant to
EPCRA section 313(d)(2)(B) based on the available hepatic
toxicity data for this chemical.
Ref:
USEPA/OPP. Support Document for the Addition of Chemicals from
Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) Active
Ingredients to EPCRA Section 313. U. S. Environmental Protection
Agency, Washington, DC (1993). As cited by US EPA in: Federal
Register: January 12, 1994. Part IV. 40 CFR Part 372. Addition
of Certain Chemicals; Toxic Chemical Release Reporting; Community
Right-to-Know; Proposed Rule.
-- 4. Carcinogenicity. Fomesafen is classified as a Group
C carcinogen with a Q* of 1.9 x 10-1
(mg/kg/ day)-1. This classification was based on: (i)
Increases in both adenomas and carcinomas
at several dose levels in both sexes of mice; (ii) some
evidence of reduced latency for the time of tumor appearance;
(iii) limited evidence of mutagenic effects; and, (iv) the structural
similarity of fomesafen to other biphenyl ether herbicides which
have been shown to be carcinogenic.
-- iii. Cancer risk. Based on exposure levels for drinking water,
as given above, the estimate of cancer risk is 2.7 x 10-6.
This figure is an overestimate, as it was arrived at based on
several very conservative assumptions. Estimates used were calculated
based on data from only one small scale study conducted in NC,
for use of fomesafen on soybeans at a vulnerable site. This represents
a worst case scenario, so is not representative of the ``average''
conditions of use. Additionally, there is language on the product
label warning of the potential of fomesafen
to leach to ground water in vulnerable areas. Vulnerable
areas in this case refers to areas where soils are permeable (sand
and silt loams) and the water table is shallow. The majority of
areas of soybean production, and potential use of fomesafen, will
not likely be vulnerable sites, thus the data used from the one
small scale study greatly overestimates levels which could actually
occur. Further, it is assumed that this exaggerated level will
occur in all drinking water throughout the US, and that each individual
consumes 2 liters of drinking water per day.
-- When considering structural similarities with other chemicals,
fomesafen falls into the class of ``biphenyl ether'' chemical
compounds; this means that this group of chemicals have structural
similarities, including a biphenyl ether group, in common. This
is used as a piece of supporting evidence for the classification
of fomesafen as a Group C carcinogen, since other chemicals of
this group (with similar structure) have been found to be carcinogens.
However, other indications of the carcinogenicity of fomesafen
(i.e., increases of adenomas and carcinomas in a mouse study,
limited evidence of mutagenic effects) were also used in deciding
this cancer classification. At this time, the Agency does not
have sufficient understanding of the structural relationship to
the mechanism of toxicity of these chemicals to conclude that
they may be combined for the purposes of conducting a risk assessment.
Although fomesafen contains some chemical structures in common
with other chemicals that have been found to be carcinogens, EPA
does not yet fully understand the implications of such a relationship,
nor how, or if, these structures relate to the toxicological activity
of the chemical. For the purposes of this tolerance action, therefore,
EPA has not assumed that fomesafen has a common mechanism of toxicity
with other substances.
Ref: Federal Register. November 19, 1997.
Fomesafen; Pesticide Tolerances for Emergency Exemptions. Final
Rule.
http://www.fluoridealert.org/pesticides/fomesafen.fr.nov.19.1997.htm
-- Classification -- C; possible human carcinogen.
-- Animal Carcinogenicity Data. Limited. Sixty-four Charles River
CD-1 mice/sex/dose group were dosed for 2 years with fomesafen
at 0, 1, 5, 100 and 1000 ppm by dietary incorporation. A double-size
control group was used. At 12 months, 24 mice/sex from the controls
and 12 mice/sex from the treated groups were killed. In
male mice at termination, the incidence of liver adenomas was
significantly increased at 1, 100 and 1000 ppm when compared with
controls. The incidences of liver carcinomas and a combination
of liver adenomas and carcinomas were significantly increased
at 1000 ppm. In the females, the incidence of adenomas was increased
at 100 and 1000 ppm and carcinomas were increased at 1000 ppm
when compared with controls. The incidence
of adenomas and carcinomas combined was significantly increased
at 100 and 1000 ppm. Both sexes, therefore, showed a progression
from benign to malignant tumors with increased dose. Some liver
tumors (adenomas and carcinomas) were apparent at the 52-week
interval kill. There was increased mortality
in the males at 100 and 1000 ppm and in the females at 1000 ppm,
due to liver toxicity forcing termination of the study. The
1000 ppm animals were killed at 79 weeks (males) or 89 weeks (females).
The MTD appeared to be exceeded at 100 ppm in the males and 1000
ppm in the females. The tumor increases occurred at dose levels
of fomesafen that were both below and above the MTD (Huntingdon,
1985).
Ref: US EPA. Fomesafen
(CASRN 72178-02-0). IRIS (Integrated Risk Information System).
Fomesafen
sodium -
Herbicide - CAS No. 108731-70-0
There are eight diphenyl ethers that are structurally similar
to diclofop-methyl. Of the chemicals, fomesafen
sodium, haloxyfop-methyl (Verdict), oxyfluorfen, acifluorfen
sodium, nitrofen, and lactofen were reviewed in the initial CPRC
report. All of these chemicals induced liver
adenomas and carcinomas in rats and/or mice. Except for
haloxyfop-methyl, all of the other chemicals
produced positive results in at least one of the mutagenicity
assays... For fomesafen (P.C.Code 123802)
the data included, a 4-week feeding study in the mouse (MRID 40786709),
a 28-day feeding study in the hamster (MRID 40910801) and an in
vitro study (MRID 40910802, Elcombe et al., Annals NY Acad Sci.
804: 628-635 [1996]) with rat, mouse, guinea pig and human hepatocytes...
May
24, 2000 - Cancer
Assessment Document. Evaluation of the
Carcinogenic Potential of Diclofop-Methyl. (Second Review). Final
Report. Cancer Assessment Review Committee, Health Effects Division,
US EPA Office of Pesticide Programs.
Note:
Except for Nitrofen, all the pesticides cited above are fluorinated.
Possible
Carcinogen [Liver - see Fomesafen above]
Ref:
PAN Pesticides Database.
http://www.pesticideinfo.org/Detail_Chemical.jsp?Rec_Id=PC35964
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