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 pesticides included in this section are: |
Pesticide
CAS
No. |
Cancer
detail |
Cancer
site |
Activity |
Approved
in the US in or on Food Commodities |
Registered
use:
(includes a very limited nmber of countries) |
Silafluofen
105024-66-6 |
Tumor-promoting |
na |
Insecticide
Termiticide
Wood
preservative |
NO |
India,
Japan, Taiwan, Vietnam
Japan:
Apple, Pear, Persimon, Rice, Tea
Taiwan:
Drupe, Rice, Small berries |
Sodium
fluoride
7681-49-4 |
A
1992 New Jersey Department of Health report: "Between
the years 1970 and 1989, the rate of osteosarcoma (among 10-19
year old males) was found to be 3.5 to 6.3 times greater in
the fluoridated versus unfluoridated areas." |
•
Bladder (Cryolite workers)
•
Lung (Cryolite workers)
•
Osteosarcoma
(Young boys; male rats)
•
Uterine cancer |
Wood
preservative
EPA
List 4B Inert |
YES
US
- Because this is an "Inert", the public is not
allowed to know which crops it is used on. |
Australia,
Canada, New Zealand, US, Vietnam |
Tetraconazole
112281-77-3 |
US
EPA:
Likely
to be carcinogenic to humans |
•
Liver |
Fungicide |
YES
US:
Cattle, Milk, Sugarbeets,
Sugarbeet-related commodities
See
food
tolerances |
Brazil,
Hungary, Japan, Portugal, South Africa, Taiwan, UK, US |
Thiazopyr
117718-60-2 |
US
EPA:
PossibleHuman
Carcinogen |
•
Thyroid |
Herbicide |
YES
US:
Grapefruit,
Orange
See
food
tolerances |
Australia,
US |
Tolylfluanid
731-27-1 |
US
EPA:
Likely
to be carcinogenic to humans |
•
Thyroid |
Fungicide
|
YES
US
approved
tolerances:
On Imported: Apple, Grape, Tomato, Hop
See
food
tolerances |
Australia,
Denmark, Finland, Germany, Hungary, New Zealand, Tanzania,
UK, US |
Trifluralin
1582-09-8
|
US
EPA:
Possible
Human Carcinogen |
•
Urinary bladder tumors in females
•
Renal pelvis carcinomas in male rats
•
Thyroid (males)
•
Non-Hodgkin's Lymphoma
•
Testicular |
Herbicide |
YES
US
- permitted in or on 129 food commodities
See
food
tolerances |
Australia,
Canada, Finland, Germany, Hungary, Japan, India, New Zealand,
Portugal, South Africa, Taiwan, UK, US, Vietnam |
Triflusulfuron-methyl
126535-15-7 |
US
EPA: Possible
Human Carcinogen |
•
Liver
•
Testicular |
Herbicide |
YES
US:
Beet (sugar, roots & tops), Chicory root
See
food
tolerances |
Canada,
Denmark, Finland, Germany, Netherlands, UK, US |
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.
Silafluofen
- Insecticide, Termiticide,
Wood preservative - CAS No. 105024-66-6
Abstract: The tumor-promoting activities
of 5 commercial compounds used in termiticides were measured by
a cell-transformation assay employing Bhas 42 cells. Their initiating
activities were also measured by the microsuspension assay employing
S. typhimurium TA98 and TA100 strains. The results of the transformation
assay confirmed the tumor-promoting activities
of fenitrothion, silafluofen and
bifenthrin. Furthermore, the mutagenicity of S-421 and fenitrothion
were also confirmed. Consideration of 2-stage
carcinogenesis suggests that concurrent use of and long-term exposure
to these compounds that have tumor-promoting and initiator activity,
and compounds exhibiting either type of activity individually
should be avoided as much as possible.
Ref: J
UOEH. 2004 Dec 1;26(4):423-30. Tumor-promoting activity and mutagenicity
of 5 termiticide compounds.Goto S, Asada S, Fushiwaki Y, Mori
Y, Tanaka N, Umeda M, Nakajima D, Takeda K.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15624354
Sodium
fluoride -
Wood
preservative, EPA List 4B Inert - CAS No. 7681-49-4
A New Jersey
Department of Health study found that the
rate of osteosarcoma occurred at higher rates in young males from
fluoridated versus unfluoridated areas. Between the years 1970
and 1989, the rate of osteosarcoma
(among 10-19 year old males) was found to be 3.5 to 6.3 times
greater in the fluoridated versus unfluoridated areas.
Ref: Cohn PD. (1992). A Brief Report On
The Association Of Drinking Water Fluoridation And The Incidence
of Osteosarcoma Among Young Males. New Jersey Department of Health
Environ. Health Service: 1- 17.
Abstract:
The US National Toxicology Program has shown equivocal evidence
of carcinogenic activity of sodium fluoride (NaF) in male F344/N
rats based on the occurrence of five osteosarcomas in treated
animals. In the study the osteosarcomas developed mainly in the
rat vertebrae. To provide a possible mechanistic basis for the
observed tumors, the genotoxic effects of NaF on the possible
target organ of NaF carcinogenesis were examined. Rat vertebral
body-derived (RVBd) cells were established from trabecular bone
of vertebral bodies of a male F344/N rat 6 weeks of age and treated
with NaF. RVBd cells in secondary culture exhibited a high level
of alkaline phosphatase (ALP) activity when the cells at confluence
were assayed by ALP staining. When the histochemical examination
was performed on RVBd cell colonies, most of the colonies were
stained positively for ALP. Confluent RVBd cells were responsive
to 10(-8) M 1 alpha.25-dihydroxyvitamin D3 with a 7.7-fold increase
in osteocalcin production over base line values. The von Kossa
staining demonstrated that in the presence of 2 mM beta-glycerophosphate,
RVBd cells that were allowed to grow past confluence for approximately
2 months formed mineralized nodules. When RVBd cells in tertiary
culture were treated with NaF at 0.5-2.0 mM for 24-72 h, the growth
and/or survival of the treated cells was reduced in a dose-dependent
manner. Significant increases in the frequencies
of chromosome aberrations were induced in a dose- and treatment
time-dependent fashion when NaF was administered to RVBd cells
at 0.5 and 1.0 mM for 24 and 48 h. The results indicate that NaF
is genotoxic to rat vertebrae, providing a possible mechanism
for the vertebrae, as a target organ of NaF carcinogenesis.
Ref: Mutat
Res. 1996 May;368(1):7-13. Clastogenic activity of sodium
fluoride to rat vertebral body-derived cells in culture.
Mihashi M, Tsutsui T.
In a 1990
National Toxicology Program fluoride rat study, a statistically-significant,
dose-dependent trend increase in osteosarcoma among the fluoride-treated,
male rats was reported. According to a review of NTP's
findings by the World Health Organization:
In male F344/N rats receiving 0.2, 0.8, 2.5 or 4.1 mg fluoride/kg
body weight per day, the incidence of osteosarcomas (three tumours
in the vertebra and one in the humerus) was 0/80, 0/51, 1/50
and 3/80, respectively (NTP, 1990). A pairwise comparison of
the incidence in the high-dose group versus controls was not
statistically significant (P = 0.099); if an extraskeletal osteosarcoma,
located in the subcutis of the flank of one high-dose male rat,
was included in the total tumour incidence in this group of
animals, the pairwise comparison with the control group remained
statistically insignificant (P = 0.057). However,
the osteosarcomas occurred with a statistically significant
(P = 0.027, by logistic regression) dose-response trend (NTP,
1990) ...In assessing the evidence for
the carcinogenicity of fluoride derived from studies conducted
with laboratory animals, some significance might be attributed
to the observation of a dose–response trend in the occurrence
of osteosarcomas in male F344/N rats administered sodium fluoride
in drinking-water (NTP, 1990). Such a trend associated
with the occurrence of a rare tumour in the tissue in which
fluoride is known to accumulate cannot be casually dismissed.
Ref:
FLUORIDES. Environmental Health Criteria 227. World Health Organization,
Geneva. 224 page report released August 8, 2002.
http://www.inchem.org/documents/ehc/ehc/ehc227.htm
Excerpt: “We previously reported the cancer morbidity from
1943 through 1987 for 422 male cryolite workers employed for more
than 6 months at the mill from 1924 through 1961. We observed
excess incidences of primary cancer of the lungs and of urinary
bladder tumors (including bladder papilloma)... We have
now extended the follow-up of this cohort by 12 years, at the
end of which the total percentage of cohort members who had died
exceeded 90%. These findings amplify our previous observation
of increased bladder cancer rates among cryolite workers... We
therefore believe that fluoride should be considered a possible
cause of bladder cancer and a contributory cause of primary lung
cancer.”
Ref: Extended follow-up of cancer incidence
in fluoride-exposed workers. Grandjean P, Olsen JH. J Natl Cancer
Inst. 2004 May 19;96(10):802-3.
Note: See FAN
Science Watch #11 for a discussion of these findings.
Abstract. Age-specific
and age-standardized rates (ASR) of registered cancers for nine
communities in the U.S.A. (21.8 million inhabitants, mainly white)
were obtained from IARC data (1978-82, 1983-87, 1988-92). The
percentage of people supplied with "optimally"
fluoridated drinking water (FD) obtained from the Fluoridation
Census 1985, U.S.A. were used for regression analysis of incidence
rates of cancers at thirty six sites (ICD-WHO, 1957). About two-thirds
of sites of the body (ICD) were associated positively with FD,
but negative associations were noted for lip cancer, melanoma
of the skin, and cancers of the prostate and thyroid gland. In
digestive organs the stomach showed only limited and small intestine
no significant link. However, cancers of
the oral cavity and pharynx, colon and rectum, hepato-biliary
and urinary organs were positively associated with FD.
This was also the case for bone cancers
in male, in line with results of rat experiments. Brain
tumors and T-cell system Hodgkin's disease, Non-Hodgkin lymphoma,
multiple myeloma, melanoma of the skin and monocytic leukaemia
were also correlated with FD. Of the 36 sites, 23 were
positively significant (63.9%), 9 not significant (25.0%) and
4 negatively significant (11.1%). This may indicate a complexity
of mechanisms of action of fluoride in the body, especially in
view of the coexising positive and negative correlations with
the fluoridation index. The likelihood of fluoride acting as a
genetic cause of cancer requires consideration.
Ref:
J Epidemiol 2001 Jul;11(4):170-9. Regression
analysis of cancer incidence rates and water fluoride in the U.S.A.
based on IACR/IARC (WHO) data (1978-1992). International Agency
for Research on Cancer; by Takahashi
K, Akiniwa K, Narita K.
Abstract:
The Okinawa Islands located in the southern-most part of Japan
were under U.S. administration from 1945 to 1972. During that
time, fluoride was added to the drinking water supplies in most
regions. The relationship between fluoride concentration in drinking
water and uterine cancer mortality rate
was studied in 20 municipalities of Okinawa and the data were
analyzed using correlation and multivariate statistics. The main
findings were as follows.
(1) A significant positive correlation was
found between fluoride concentration in drinking water and uterine
cancer mortality in 20 municipalities (r = 0.626, p < 0.005).
(2) Even after adjusting for the potential confounding variables,
such as tap water diffusion rate, primary industry population
ratio, income gap, stillbirth rate, divorce rate, this association
was considerably significant.
(3) Furthermore, the time trends in the uterine cancer mortality
rate appear to be related to changes in water fluoridation practices.
Ref:
J Epidemiol. 1996 Dec;6(4):184-91. Relationship
between fluoride concentration in drinking water and mortality
rate from uterine cancer in Okinawa prefecture, Japan; by
Tohyama E.
Erratum
in: * J Epidemiol 1997 Sep;7(3):184
Tembotrione - Herbicide - CAS No. 335104-84-2
• Long-term dietary administration of tembotrione resulted in an increased incidence of thyroid adenomas and squamous cell carcinomas of the cornea in male rats. Since the incidence of thyroid adenomas was not statistically significant, they were considered unrelated to treatment. The levels of the doses tested were adequate. No tumors were noted in female rats or in male and female mice after long-term dietary administration of tembotrione. The HED CARC (April 11, 2007) classified tembotrione as "Suggestive Evidence of Carcinogenic Potential" by the oral route based on the occurrence of eye tumors in male rats; therefore, the quantification of cancer risk is not required.
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
Likely
to be Carcinogenic to Humans. Hepatocellular
adenomas, carcinomas and combined adenomas/carcinomas in both
sexes; Crl:CD-1 (ICR) 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.
Likely
to be carcinogenic to humans.
Reviewed 1/ 11/ 00.
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 Classification: Tetraconazole
was classified as —likely to be carcinogenic to humans“
based on the occurrence of liver tumors in male and female mice.
The Carcinogenicity Assessment Review Committee recommended that
a low dose extrapolation model be applied to the experimental
animal tumor data and that quantification of risk be estimated
for male and female mouse liver tumors for Tetraconazole. The
most potent unit risk will be used for the purpose of lifetime
cancer risk assessment by the Agency. In this case, the most potent
unit risk, Q1*, is that for male mouse liver benign and/or malignant
combined tumor rates at 2.30 x 10-2 in human equivalents.
-- The highest estimated cancer risk is
6.7 x 10-4 for mixer/loaders working without gloves, However,
the labeling requires gloves and the estimated cancer risk for
mixer/loaders wearing gloves falls to 7.5 x 10-6. The remaining
risks to agricultural workers applying tetraconazole to sugarbeets
range from 7.5 x 10-6 7.7 x 10-7. Post-application cancer risk
is 5.1 x 10-6 or lower, which does not exceed the Agency‘s
level of concern.
Ref: April 2005. Pesticide Fact Sheet:
Tetraconazole. US EPA.
Ref: April 2005. Pesticide Fact Sheet:
Tetraconazole. US EPA.
http://www.fluorideaction.org/pesticides/tetraconazole.epa.2005.facts.pdf
-- Carcinogenicity.
Tetraconazole has not been classified with respect to carcinogenic
potential by EPA. However, based on the tumorigenic results in
the mouse carcinogenicity study, EPA has made an initial determination
that a Q1* should be determined based on the male mouse benign
liver tumors, excluding the highest dose. The Q1* is 0.037
(mg/kg/day)-1.
-- Aggregate cancer risk for U.S. population. Tetraconazole produced
statistically significant increases in male and female mouse liver
adenomas and carcinomas. Based on a determination of the
Q1* for this tolerance setting action only, the Q1* was determined
to be 3.7 x 10-2 based on benign tumors in males with the exclusion
of the high dose group. The cancer risk for the U.S. population
is, without adjustment, 2.5 x 10-6. Because this is an emergency
exemption use of tetraconazole, it is considered appropriate to
divide the cancer risk by a factor of 14 [5 years for potential
emergency exemption use/70 years lifetime = 1/14]. The adjusted
cancer risk for the U.S. population is 1.8 x 10-7 and this adjusted
cancer risk is below EPA's level of concern.
-- Reproductive toxicity study-- Rats. In the 2-generation reproductive
toxicity study in rats, the maternal (systemic) NOAEL was 0.7
mg/kg/day, based on dystocia, delayed vaginal
opening, and increased liver weight
at the LOAEL of 5.9 mg/kg/day. The developmental (pup) NOAEL was
0.7 mg/kg/day, based on increased time to observation of
balanopreputial skin fold and liver
weight at the LOAEL of 5.9 mg/ kg/day. At the high dose of 35.5
mg/kg/day, there was a decrease in the mean number of live pups
per litter on lactation days 0 and 4 (precull) in the presence
of significant maternal toxicity.
Ref: Federal Register: December 6, 1999.
Tetraconazole; Pesticide Tolerances for Emergency Exemptions.
Final Rule.
http://www.fluoridealert.org/pesticides/tetraconazole.fr.dec.1999.htm
Chronic & Carcinogenicity Studies.
In a carcinogenicity study, mice received 0, 10, 90, 800 or 1250
ppm of tetraconazole in the diet for 80 weeks. ... Benign
and malignant liver cell tumors were increased at 800
and 1250 ppm, and resulted in the high mortality at 1250 ppm.
The NOEL was 10 ppm (1.4 mg/kg bw/day). (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
Thiazopyr
- Herbicide - CAS No. 117718-60-2
Group
C -- Possible Human Carcinogen. Statistically
significant increase in thyroid follicular
cell tumors (M). Increases in renal
tubular adenomas (M & F); however statistically significant
positive trend in F only; Sprague-Dawley 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 5/ 25/ 94.
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 thyroid
tumors were determined in three special
thyroid function studies to be secondary to a
disturbance
of thyroid/pituitary
homeostasis and were attributed to a hormonally-mediated
mechanism for thyroid tumor induction.
The effects were dose-responsive and with the exception of thyroid
weight, all effects
were completely reversible when thiazopyr was removed from the
diet. Based on limited evidence for carcinogenicity,
thiazopyr is classified as Category
C, possible human carcinogen, by the USEPA Health Effects Division
Carcinogenicity Peer Review Committee.
A NOEL of 4.4 mg/kg/day and a Margin of Exposure approach were
selected for use in carcinogenicity risk assessment...
-- A two year rat carcinogenicity study at doses of 0, 0.04, 4.4,
44.2 or 136.4 mg/kg/day (Males) 0, 0.06, 0.6, 5.6, 56.3 or 177.1
mg/kg/day (female) with a NOEL of 4.4 mg/kg/day. The effects were
protruding eyes, evidence of
mild anemia, increased GGT and cholesterol,
increased absolute and relative liver, kidney and thyroid weights
and significant increase in microscopic lesions in the liver (hypertrophy
and vacuolar changes), kidney (nephropathy) and thyroid (hypertrophy
and hyperplasia); decreased mean body weight and body weight gain
and food consumption. A statistically
significant increase in thyroid follicular cell adenomas/cystadenomas
were observed in males at 44.2 and 136.4 mg/kg/day. A nonsignificant
increase in renal tubular adenomas in high-dose females was considered
to be equivocal.
-- The EPA Health
Effects Division Carcinogenicity Peer Review Committee classified
thiazopyr as a Group C, possible human carcinogen and recommended
that for the purpose of risk characterization a Margin of Exposure
(M.O.E.) approach should be used in evaluation of the consequences
of human exposure.
-- Special mechanistic studies for mode of toxic action on thyroid
function. The results of three studies on the effects of thiazopyr
on thyroid function and mechanisms involved in the disposition
of T4 in rats were reviewed. These studies are described below:
---- a. Thiazopyr was administered through the diet at 0 and 150
mg/kg/day rats to determine the subchronic effect on hormone level
and other biochemical endpoints. Animals were assayed at 7, 14,
28, 56 or 90 days. Significant decreases in body weight gain were
observed at 90 days. Early in the study the treated rats showed
increases in TSH (ranging from 133 to 200% of controls) and decreases
in T4 (ranging from 43% to 76% of controls). In addition there
were increases in liver and thyroid weights and increases in thyroid
follicular cell hypertrophy/hyperplasia. Reverse T3 was increased
at 28 days, and T3 was either not affected or increased. There
were indications of increases in hepatic UDPGT activity and significant
increases in T4 UDPGT activity. Hepatic 5'-monodeiodinase activity
was either not affected or decreased. The effects observed in
this study were supportive of the theory that thiazopyr may induce
thyroid tumors through a disruption in the thyroid-pituitary hormonal
feedback mechanisms.
---- b. A second study on the effects of thiazopyr on the biochemical
mechanisms of thyroid toxicity in rats at doses of 0, 0.5, 1.5,
5, 15, 50 or 150 mg/kg/day was conducted. Dose response effects
on various biochemical parameters were observed. Two groups of
the rats in the study were observed for reversibility of effects
observed up to 56 and 112 days. Doses at
15, 50 and 150 mg/kg/day significantly increased the liver weights.
Thyroid weights were increased at doses of 50 and 150 mg/kg/day.
There were no significant effect on body weight or body weight
gains during the study. The T4 UDPGT levels
were increased by 117 and 376% above controls at the 50 and 150
mg/kg/day dosages. Effects of 150 mg/kg/day were increases
in T3, TSH and rT3 serum concentrations, and increased incidence
of follicular cell hypertrophy/hyperplasia at the 150 mg/kg/day
dose. A NOEL of 1.5 mg/kg/day was determined based on liver weight
increases. Thyroid weight was the only parameter that did not
return to those similar to the controls.
At the 56 and 112 day recovery periods the thyroid weights were
120 and 123% of control values, respectively.
---- c. A third thyroid function study on the biochemical mechanisms
involved with disposition of T4 in rats fed dosages of 0 and 150
mg/kg/day for 56 days was conducted. Rats feed thiazopyr had
increase T4 UDPGT activity and total deiodinase activity in their
livers. There was also a two-fold increase in mixed function oxidase
enzyme activity.
-- Results of the three studies suggest that increased glucuronidation,
deiodination of T4 and T3, and increased rate of clearance of
T4 from the blood and excretion of the hormone and its metabolites
in the bile could significantly reduce the level of circulating
T4 in the male rat. Results of these studies support the hypothesis
tht thiazopyr may induce thyroid tumors through a disruption of
the thyroid-pituitary hormonal feedback mechanism circulating
T4 in the male rat.
Ref: US EPA. Pesticide Fact Sheet.
Thiazopyr. Reason for Issuance: Registration of a New Chemical
Date Issued: February 20, l997.
http://www.epa.gov/opprd001/factsheets/thiazopyr.pdf
Tolylfluanid
- Fungicide - CAS No. 731-27-1
Likely
to be Carcinogenic to Humans. Thyroid tumors
in male and female Wistar rats. Linear low-dose extrapolation
approach recommended.
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 Classification: ``Likely to be carcinogenic to humans''
by the oral route, based
on thyroid tumors in high-dose male and female rats. The
FQPA SF Committee further recommended a linear low-dose extrapolation
approach for the quantification of human cancer risk based on
the thyroid tumors in rats. Q1* = 1.59 x 10-\3\ based upon male
rat thyroid adenomas and/or carcinomas combined... Cancer. A partially
refined, cancer dietary exposure assessment was conducted for
the general U.S. population using the same assumptions as were
used in the chronic risk assessment (listed in the preceding section).
Import share data generated within the Agency were used in the
assessment to estimate what proportion of the grape, apple, hop,
and tomato consumed in the United States are imported. Modified
DEEM\TM\ processing factors based on the results of processing
studies were used for raisins and apple and grape juice/juice
concentrates. Default DEEM\TM\ processing factors were used for
all other processed commodities The cancer risk estimate is 1.2
x 10-\6\ for the general U.S. population.
Ref: Federal Register: September 25, 2002.
Tolylfluanid; Pesticide Tolerance. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/tolylfluanid.fr.sept25.2002.htm
Trifluralin
- Herbicide - CAS No. 1582-09-8
Group
C -- Possible Human Carcinogen. Thyroid
(follicular celladenomas & carcinomas); Neoplasms of the
renal pelvis (M); Benign urinary
bladder tumors (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
Long term toxicity and carcinogenicity (Annex IIA, point 5.5).
Carcinogenicity. Evidence
of carcinogenic potential in Fischer 344 rat, (tumour formation
in various tissues, i.e. kidney, urinary bladder, thyroid, Leydig
cell). The mechanism of tumour formation is not identified.
R40. (page 46)
Ref: March 14, 2005. European
Food Safety Authority: Conclusion regarding the
peer review of the pesticide risk assessment of the active substance
trifluralin. EFSA Scientific Report (2005) 28, 1-77.
http://www.fluoridealert.org/pesticides/trifluralin.eu.long.2005.pdf
Group
C--Possible Human Carcinogen.
Reviewed 11/ 29/ 89.
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 Classification
The OPP Carcinogenicity Peer Review Committee evaluated all the
available carcinogenicity data on trifluralin (April 4, 1986),
and it concluded that there is limited evidence of carcinogenicity
in male and female rats based upon an increase in combined malignant
and benign urinary bladder tumors in females,
renal pelvis carcinomas in male rats, and thyroid gland follicular
cell tumors (adenomas plus carcinomas combined) in males. Trifluralin
has been classified as a Group "C" possible
human carcinogen with a Q of 0.0077 (mg/kg/day) . The upper
bound 1 * -1 dietary cancer risk is is approximately 1.0 x 10
. -6
Ref: Reregistration Eligibility Decision
(RED) Trifluralin. US EPA, Office of Prevention, Pesticides and
Toxic Substances. EPA 738-R-95-040. April 1996.
http://www.fluoridealert.org/pesticides/Trifluralin.RED.1996.EPA.pdf
The
following is from (page 43-45):
PRIORITIZED
CANDIDATE CHEMICALS UNDER CONSIDERATION FOR CARCINOGENICITY
EVALUATION: BATCH #1.
Office of Environmental Health Hazard Assessment, California
Environmental Protection Agency May 1997.http://www.oehha.ca.gov/prop65/pdf/batch1.pdf
CARCINOGENICITY
DATA SUMMARY: TRIFLURALIN
Trifluralin
(CAS No. 1582-09-8) is an herbicide for grasses and broadleaf
weeds. Trifluralin was reviewed by IARC in 1991. IARC concluded
that the evidence of carcinogenicity was inadequate in humans
and limited in animals (group 3 carcinogen). However, their
review included only the NCI (1978) rat and mouse studies
and the mouse studies by Francis et al. (1991). The studies
by Emmerson et al. (1980) and Eli Lilly (1966) were not
considered. US EPA has posted a series of reviews and actions
relating to trifluralin (USEPA, Federal Register) and IRIS
currently lists trifluralin as a Class C - possible human
carcinogen.
Carcinogenicity
data available:
Epidemiological
studies
1. Population-based case-control study: Hoar, 1986. This
study of white males in an agricultural setting found an
elevated odds ratio for non-Hodgkin's
lymphoma among farmers exposed to trifluralin, among
other herbicides (OR 12.5, 95% CI 1.6-116.1). However, these
other significant chemical exposures confound the analysis
with respect to trifluralin.
Animal
bioassays
1. Mouse long-term diet studies (treated 78 weeks + additional
12 weeks observation): NCI, 1978. Significant
increases in hepatocellular carcinomas and alveolar and
bronchial adenomas were seen in
female mice receiving 0, 2740 or 5192 ppm in the
diet. A small increase in relatively rare forestomach
carcinomas seen in low-dose female
mice (4/45 versus 0/60 in pooled controls)
was also considered treatment-related. Increased tumor incidences
in male mice were not significant. The
NCI concluded that "technical grade trifluralin is a carcinogen
in female B6C3F1 miceÉ" This
study used technical grade trifluralin, later found to be
contaminated with N-nitroso-n-propylamine (NDPA).
2.
Rat long term diet studies (treated 78 weeks + additional
33 weeks observation): NCI, 1978. No increase in tumors
was observed in male or female rats.
3.
Rat diet studies: Emmerson et al., 1980 (This series of
studies has not been published in the open literature, but
was submitted to and reviewed by CDFA [1990], and is cited
by US EPA, with a summary in IRIS). Technical grade trifluralin
with <0.01 ppm of NDPA was administered to both sexes of
Fischer 344 rats at 0, 813, 3250 or 6500 ppm in diet. Uncommon
transitional cell carcinomas of the renal pelvis epithelium
were increased in all treated groups of males, reaching
significance in the high-dose group. Dose-dependent
increases in tumors of the bladder or renal pelvis transitional
epithelium were observed in both sexes (males: 0/60,
3/59, 4/60, 7/60; females: 0/60, 0/60, 1/60, 5/60). In addition,
thyroid follicular adenomas and carcinomas
were significantly increased in high-dose male rats.
4.
Mouse long-term diet studies (2 years): Francis et al.,
1991. Technical grade trifluralin with < 0.01 NDPA was administered
at 0, 563, 2250, or 4450 in diet to males and female B6C3F1
mice. No evidence of oncogenicity was observed, although
the high dose resulted in significantly
decreased body weight gains.
5.
Rat long-term diet studies (2 years): Eli Lilly, 1966, as
reported in US EPA 1986 Peer Review of Trifluralin. In groups
of 25 of each sex, Sprague-Dawley rats were administered
0, 200, 1000, or 2000 ppm trifluralin in the diet. "The
CAG concluded that this study showed no evidence of carcinogenicity
and that the study was an adequate basis for safety evaluation."
IARC
(1991) reviewed the published data on trifluralin and concluded
that there was limited evidence of
carcinogenicity in animals (group 3). However, since
they do not, as a matter of policy, review studies which
have only been submitted for product registration purposes
and not otherwise published, their review included only
the NCI (1978) rat and mouse studies and the mouse studies
by Francis et al. (1991). Neither the positive study by
Emmerson et al. (1980), nor the non-positive result obtained
by Eli Lilly (1966) was considered. US EPA currently classifies
trifluralin as a Class C - possible human carcinogen.
Other
relevant data
Trifluralin was negative in the dominant lethal test in
rats and in assays for SCEs and induction of reverse mutations
in Salmonella (CDFA, 1990), however,
it induced aneuploidy in Neurospora crassa, and yielded
mixed results in aneuploidy tests in Drosophila (IARC, 1991).
Trifluralin is structurally related
to ethalfluralin, which produces mammary gland fibroadenomas
in female rats (IRIS).
Preliminary
evaluation of carcinogenicity and exposure data:
There
is a MEDIUM level of carcinogenicity concern over trifluralin.
Concern is due to dose-dependent increases in the incidences
of tumors of the transitional epithelium
of the bladder and renal pelvis in male and female
F344 rats, and significant increases
in thyroid follicular tumors in males. Similar observations
were not made in studies in other strains of rats. It is
noteworthy that in the positive study, the number of animals
observed with renal calculi increased
substantially with increasing dose; they were found in the
majority of high-dose animals. There was a positive bioassay
in female mice at three tumor sites, but the study is compromised
by contamination with N-nitroso-n-propylamine and was considered
unacceptable by CDFA (1990). A follow-up study with a sample
of greater purity did not find an effect under similar circumstances.
The level of concern is reinforced
by the possible (but unproven) association with lymphoma
among exposed farmers and the structural similarity to the
animal tumorigen ethalfluralin. The single positive
observation of genotoxicity in short-term tests neither
adds nor detracts from the level of concern.
There
is a HIGH level of concern over the extent of exposure to
trifluralin.
It is used on a large number of California crops; 1,404,088
lbs were applied in 1993 (DPR, 1995). Most usage is on cotton
and alfalfa, indicating that, like other agricultural chemicals,
occupational exposures are possible. The general public
may consume food crops treated with trifluralin, especially
tomatoes, carrots and grapes, and could be additionally
exposed by dermal and inhalation routes from lawn products
(HSDB). Trifluralin may also bioaccumulate
in fish (HSDB).
References
California
Department of Pesticide Regulation (DPR, 1995). Pesticide
Use Report, Annual 1993. DPR, Information Systems Branch,
Cal/EPA, Sacramento, CA.
California
Department of Food and Agriculture (1990). Summary of
toxicology data, trifluralin. CDFA, Medical Toxicology
Branch, Sacramento, CA.
Emmerson
JL, Pierce EC, McGrath JP et al. (1980). The chronic toxicity
of compound 36352 (trifluralin) given as a component of
the diet to Fischer 344 rats for two years. Studies R-87
and R97, submitted by Elanco Products Co., division of
Eli Lilly Co.) as cited in IRIS and discussed in Peer
Review of Trifluralin by the Toxicology Branch Peer Review
Committee (April 11, 1986 memorandum from R. Bruce Jaeger).
Francis
PC, Emmerson JL, Adams ER, Owen NV (1991). Oncogenicity
study of trifluralin in B6C3F1 mice. Food Chemical Tox
29(8):549-555.
Hazardous
Substances Data Bank (HSDB, 1995). National Library of
Medicine.
Hoar
SK, Blair A, Holmes FF, Boysen CD, Robel RJ, Hoover R,
Faumeni JF (1986). Agricultural herbicide use and risk
of lymphoma and soft-tissue sarcoma. JAMA 256(9):1141-1147.
Integrated
Risk Information System (IRIS). US EPA.
International
Agency for Research on Cancer (IARC, 1991). IARC monographs
on the evaluation of carcinogenic risks to humans, Volume
53. Occupational exposures in insecticide application,
and some pesticides. IARC, Lyon.
National
Cancer Institute (NCI) (1978). Bioassay of trifluralin
for possible carcinogenicity. CAS No. 1582-09-8. NCI Technical
Report Series No. 34. DHEW Publication No. (NIH) 78-834,
Bethesda, MD.
USEPA,
Federal Register. 55 FR 17560, April 25 1990: other notices
1988-1992.
|
Triflusulfuron-methyl
- Herbicide - CAS No. 126535-15-7
Group
C -- Possible Human Carcinogen. Testicular
interstitial cell adenomas; CD-1 rat (M).
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 5/ 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
-- Carcinogenicity
rats NOAEL = 2.44 mg/kg/day LOAEL = 30.6 mg/kg/day based on decreased
body weight and body weight gain, alteration in hematology
(mainly males) and increased incidences of
interstitial cell hyperplasia in the testes. (Possible)
evidence of carcinogenicity
-- Carcinogenicity mice NOAEL = 14.6 mg/kg/day LOAEL = 349 mg/kg/day
based on increased liver weight and increased hepatic
cell tumors (adenomas and/or carcinomas combined.
(Possible) evidence of carcinogenicity
Ref: Federal Register. June 12, 2002. Triflusulfuron
Methyl; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/triflusulfuron.m.fr.june.02.htm
|