Fluorinated and Fluoride Pesticides
Pesticides beginning with A-E F G-R S-Z


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:



Cancer detail

Cancer site


Approved in the US in or on Food Commodities Registered use:
(includes a very limited nmber of countries)







Wood preservative


India, Japan, Taiwan, Vietnam

Japan: Apple, Pear, Persimon, Rice, Tea

Taiwan: Drupe, Rice, Small berries

Sodium fluoride


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


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 



US EPA: Likely to be carcinogenic to humans

• Liver



US: Cattle, Milk, Sugarbeets,
Sugarbeet-related commodities 

See food tolerances


Brazil, Hungary, Japan, Portugal, South Africa, Taiwan, UK, US 



US EPA: PossibleHuman Carcinogen

• Thyroid



US: Grapefruit, Orange

See food tolerances

Australia, US



US EPA: Likely to be carcinogenic to humans

• Thyroid



US approved tolerances:
On Imported: Apple, Grape, Tomato, Hop

See food tolerances

Australia, Denmark, Finland, Germany, Hungary, New Zealand, Tanzania, UK, US  



US EPA: Possible Human Carcinogen

• Urinary bladder tumors in females

• Renal pelvis carcinomas in male rats

• Thyroid (males)

• Non-Hodgkin's Lymphoma

• Testicular



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



US EPA: Possible Human Carcinogen

• Liver

• Testicular



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


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.
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.

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.

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.
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.

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.

-- 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.

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.

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.
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.

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.

-- 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.

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.
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.

-- 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.

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.
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.

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.

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.

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.

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.


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 mice…" 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).


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).
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.

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.

-- 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.

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