Adverse Effects
Trifluralin
CAS No. 1582-09-8

 
 

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Abstracts
NTIS Reports

Activity: Herbicide (dinitroaniline)
Structure:


Adverse Effects:
Anemia
Bladder
Blood
Body Weight Decrease
Bone

Cancer:
Possible Human Carcinogen - Urinary bladder, Renal pelvis, Thyroid, Non-Hodgkin's Lymphoma, Testicular
Elevated odds ratio for NON-HODGKIN'S LYMPHOMA among farmers

Dermal
Endocrine:
Suspected Disruptor
Endocrine: Testicular
Endocrine:
Thyroid
Genotoxicity
Heart
Kidney
Liver
Reproductive
Environmental - PBT: Persistent, Bioaccuulative and Toxic

US: As of February 14, 2005, this herbicide is permitted in or on 129 food commodities in the United States - click here to see list


Australia: Trifluralin use in cereals in Western Australia has expanded dramatically from less than 200,000 litres in 1992 to around 3.0 million litres in 1998.
Ref: Progress Report for 1998-1999 Determining MRL’s for New Uses of trifluralin in Cereals. GRDC (Grains Research Development Development Co.) Online as of October 20, 2003.
http://www.agritech.com.au/AgritechOld/1998TrialResults/Progress.Reports/98-99ProgressReport12.htm


UK: In 2000, Trifluralin ranked number 29 for "Most Widely used pesticides in the UK (by Area Treated)"
Rank Formulation Method Area treated (ha) Weight applied (kg ai)
29 Trifluralin Spray 336,747 314,200

Ref: April 29, 2000. UK Department for Environment, Food & Rural Affairs in the online report, "Design of a Tax or Charge Scheme for Pesticides. " Annex C3: Overview of Pesticide Industry


See FAN's compilation of reports (with abstracts) available from
The National Technical Information Service
(NTIS)


A trifluralin (herbicide) releasing device was developed with a theoretical effective lifetime in excess of 100 years. When placed in a layer in soil, the PCD system will prevent root penetration through that layer without harming the overlying vegetation. Equilibrium concentrations of trifluralin in soil can be adjusted (along with the theoretical life of the device) to suit specific needs. The present system was designed specifically to protect the asphalt layer or clay/aggregate barriers on uranium mill tailings piles; PCD devices composed of pellets could also be implanted over burial sites for radioactive and/or toxic materials, preventing translocation of those materials to plant shoots, and thence into the biosphere. (ERA citation 06:013491) ANS waste management conference, Tucson, AZ, USA, 23 Feb 1981.
Ref: 1981 - Application of Controlled Release Technology to Uranium Mill Tailings Stabilization. Authors: Burton FG, Cataldo DA, Cline JF, Skiens WE. Battelle Pacific Northwest Labs. Supporting Agency: Department of Energy, Washington, DC. Report available from The National Technical Information Service. Order No. NTIS/PNL-SA-8872.

Anemia (click on for all fluorinated pesticides)

• Long term toxicity (Annex IIA, point 5.5). Target/critical effect. Body weight reduction, anemia, liver & kidney effects (mouse, rat). (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

Bladder (click on for all fluorinated pesticides)

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

EPA has classified trifluralin as a Group C (possible human) carcinogen. Classification is based on the induction of urinary tract tumors (renal pelvis carcinomas and urinary bladder papillomas) and thyroid tumors (adenomas/carcinomas combined) in one rat study.
Ref: March 2000. Public Health Assessment Cenex Supply and Marketing, Inc. Quincy, Washington. CERCLIS # WAD058619255. Draft for Public Comment.. Prepared by: Washington State Department of Health Under Cooperative Agreement with the Agency for Toxic Substances and Disease Registry. Also available at
http://www.doh.wa.gov/ehp/oehas/Cenex%20PHA%20Draft%20Public%20Review.pdf

Blood (click on for all fluorinated pesticides)

Absorption, distribution, excretion and metabolism in mammals (Annex IIA, point 5.1). Widely distributed; highest concentration in adrenals, fat, kidneys, liver, skin and blood (page 45)
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

High doses of trifluralin are associated with increases in kidney, bladder, and thyroid tumors. Dogs chronically exposed to trifluralin in their diet showed decreased weight gain, changes in hematological parameters, and increased liver weight. Skeletal abnormalities were observed in the offspring of mice exposed via gavage (experimentally introducing trifluralin into the stomach). The RfD for trifluralin is based on increased liver weights and an increase in methemoglobinemia in dogs.
Ref: March 2000. Public Health Assessment Cenex Supply and Marketing, Inc. Quincy, Washington. CERCLIS # WAD058619255. Draft for Public Comment.. Prepared by: Washington State Department of Health Under Cooperative Agreement with the Agency for Toxic Substances and Disease Registry. Also available at
http://www.doh.wa.gov/ehp/oehas/Cenex%20PHA%20Draft%20Public%20Review.pdf

Teratology - rat: Maternal NOEL=100 mg/kg/day; Maternal LEL=500 mg/kg/day (decreased food consumption and increased liver and spleen weights); Developmental NOEL=none; LEL=20 mg/kg/day (reduced skeletal maturity and increased vascular fragility); core grade supplementary (Hoechst Aktiengesellschaft, 1983)
Ref: US EPA IRIS for Trifluralin CASRN: 1582-09-8.

http://www.epa.gov/iris/

Body Weight Decrease (click on for all fluorinated pesticides)

• Long term toxicity (Annex IIA, point 5.5). Target/critical effect. Body weight reduction, anemia, liver & kidney effects (mouse, rat). (page 46).
Reproductive toxicity (Annex IIA, point 5.6). Reproduction target / critical effect. Decreased maternal growth, anaemia, uterine atrophy and decreased offspring growth and survival from 40,750,8 mg/kg bw/day (rat). (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

-- 146 117267, "A Chronic Toxicity Study of Trifluralin (Compound 036352) Administered Orally to Beagle Dogs for 1 Year", (E.R. Adams, N.R. Bernhard & W.H. Jordan, Lilly Research Laboratories, Lab. Project ID D07190, 8/6/92). Trifluralin (purity 99.86%) was administered (once/day) to Beagle dogs (4/sex/dose) in gelatin capsules at 0 (empty gelatin capsule), 0.75, 2.4 or 40 mg/kg for one year. NOEL = 2.4 mg/kg (Body weights were decreased in females at 40 mg/kg. Several effects were observed in hematology and clinical biochemistry parameters in both sexes at 40 mg/kg. Liver weights were increased in both sexes at 40 mg/kg and heart and adrenal weights were decreased in females at 40 mg/kg. Kidney and liver histopathology (pigment deposition) was observed in both sexes at 40 mg/kg.) No adverse effect. ACCEPTABLE. (Kishiyama & Silva, 11/21/95).
-- ** 089 036915 "A Teratology Study (I) of Trifluralin (EL-152, Compound 36352) Administered Orally to Dutch Belted Rabbits." (Lilly Research Labs., 10/31/84, Study B02283 and Study BO1784) Trifluralin (96.7% pure), lot 00554AP2; 0, 100, 225, 500, or 800; oral gavage, days 6 - 18; 20/group; maternal NOEL = 225 mg/kg (maternal death and abortions), developmental toxicity NOEL = 225 mg/kg (decreased fetal weight); Complete and ACCEPTABLE WITH 036916. No adverse developmental toxicity reported. JAP, 11/18/85. EPA one-liner: Maternal NOEL = 225 mg/kg (abortions and anorexia), fetotoxic NOEL = 225 mg/kg (decreased percentage of live fetuses - cardiomegally and wavy ribs at 500 mg/kg/day); Core grade = Supplementary
-- 089 036916 "A Teratology Study (II) of Trifluralin (EL-125, Compound 36352) Administered to Dutch Belted Rabbits." (Lilly Research Lab.s, 12/6/85, Study B01784) Trifluralin (96.7%) given by oral gavage at 0, 100, 225, 500 mg/kg; 25/group; no adverse effects reported; maternal NOEL = 100 mg/kg (death, abortions, decreased body weight gain, food consumption); developmental toxicity NOEL = 225 mg/kg (decreased fetal weight, increased resorptions); complete and ACCEPTABLE WITH 089 036915. JAP, 10/31/85. EPA one-liner: Maternal NOEL = 100 mg/kg/day, fetotoxic NOEL = 225 mg/kg/day; Core grade = Minimum.
-- 089 036914 "A Teratology Study of Trifluralin (EL-152, Compound 36352) Administered Orally to Charles River CD Rats." (Lilly Research Laboratories, 10/22/84, Study RO8484) Trifluralin (96.7% pure), lot 00554AP2; given by oral gavage at 0, 100, 225, 475 or 1000 mg/kg, 25 rats/group; NOEL( maternal toxicity) = 225 mg/kg/day (decreased body weight and food consumption); NOEL (developmental toxicity) = 475 mg/kg/day (decreased fetal weight); ACCEPTABLE. No adverse developmental toxicity reported. JAP, 12/6/85. EPA one-liner: Teratogenic NOEL > 100 mg/kg/day, maternal NOEL = 225 mg/kg/day (decreased body weight and lowered food consumption); fetotoxic NOEL = 475 mg/kg/day (decreased mean fetal weight); Core grade = Minimum.
-- 099, 100, 101 50750, 50751, 50752 "A One-year Two-generation Reproduction Study in CD Rats Maintained on Diets Containing Trifluralin." (Lilly Research Labs, 8/86, R06384 and R13984) Trifluralin technical, 96.45%, lot 554AP2, initial nitrosamine content at 0.33 ppm with 99.43% off contents identified; fed in the diet at 0, 0.02, 0.63 or 0.2% (equivalent to TWA’s of 15, 47 and 148 mg/kg/day); 25/sex/group; 2 litters per generation; parental NOEL = 0.063% (decreased body weight gain), reproductive NOEL > 0.2%; no adverse reproductive effect reported; ACCEPTABLE. JG, 5/14/87.
Ref: SUMMARY OF TOXICOLOGY DATA TRIFLURALIN. California EPA, Department of Pesticides, Medical Toxicology Branch. Revised as of 11/29/95.
http://www.cdpr.ca.gov/docs/toxsums/pdfs/597.pdf

Bone (click on for all fluorinated pesticides)

5.2 RISK TO AQUATIC ORGANISMS.Trifluralin induces vertebral lesions in several fish species, and in some instances this effects is induced after short term exposure (24 hours for brown trout). (page 21-22).
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

Sheepshead minnows, Cyprinodon variegatus Laeepede, exposed to 5 5 to 31 /xg/1 of the herbicide trifluralin, throughout their first 28 days of life, developed a heretofore undescribed vertebral dysplasia. This dysplasia consisted of semisymmetrical hypertrophy of vertebrae (three to 20 times normal), characterized by foci of osteoblast and fibroblasts actively laying down bone and bone precursors. Effects of the abnormal vertebral development were dorsal vertebral growth into the neural canal, ventral compression of renal ducts, and longitudinal fusion of vertebrae. Fish, exposed for 51 days to 16-6 /ng/1 trifluralin and thereafter depurated for 41 days, showed no increase in vertebral dysplasia during depuration; however, residual spinal column damage was evident. Serum calcium concentrations were elevated in adult fish exposed for 4 days to 16-6 /xg/1 trifluralin. Fluorosis or mimicry of hypervitaminosis A are considered possible mechanisms for the osseous effect, but are not considered to be the only possible causes. The highly predictable nature of this disorder in experimental exposures strengthens the probability that young flsh may serve as experimental models for determining effects of chemicals on early vertebrate ontogeny, particularly in regard to skeletal development.
Excerpt: Trifluralin (2, 6 dinitro-N, N-dipropyl-4-(trifluoromethyl) Benzamine) is a fluorine containing, pre-emergent herbicide widely used in the United States (Wiswesser 1976). Continuous laboratory exposure of early life stages of the sheepshead minnow Cyprinodon variegatus Laeepede to relatively low concentrations of trifluralin results in marked vertebral dysplasia...
Ref:
Vertebral dysplasia in young fish exposed to the herbicide trifluralin. By JA COUCH, JT WINSTEAD, DJ HANSEN and LR GOODMAN. Journal of Fish Diseases 1979, 2, 35-42.
Full report at: http://www.fluorideaction.org/pesticides/trifluralin.1979.paper.pdf

High doses of trifluralin are associated with increases in kidney, bladder, and thyroid tumors. Dogs chronically exposed to trifluralin in their diet showed decreased weight gain, changes in hematological parameters, and increased liver weight. Skeletal abnormalities were observed in the offspring of mice exposed via gavage (experimentally introducing trifluralin into the stomach). The RfD for trifluralin is based on increased liver weights and an increase in methemoglobinemia in dogs.
Ref: March 2000. Public Health Assessment Cenex Supply and Marketing, Inc. Quincy, Washington. CERCLIS # WAD058619255. Draft for Public Comment.. Prepared by: Washington State Department of Health Under Cooperative Agreement with the Agency for Toxic Substances and Disease Registry. Also available at
http://www.doh.wa.gov/ehp/oehas/Cenex%20PHA%20Draft%20Public%20Review.pdf

-- ** 089 036915 "A Teratology Study (I) of Trifluralin (EL-152, Compound 36352) Administered Orally to Dutch Belted Rabbits." (Lilly Research Labs., 10/31/84, Study B02283 and Study BO1784) Trifluralin (96.7% pure), lot 00554AP2; 0, 100, 225, 500, or 800; oral gavage, days 6 - 18; 20/group; maternal NOEL = 225 mg/kg (maternal death and abortions), developmental toxicity NOEL = 225 mg/kg (decreased fetal weight); Complete and ACCEPTABLE WITH 036916. No adverse developmental toxicity reported. JAP, 11/18/85. EPA one-liner: Maternal NOEL = 225 mg/kg (abortions and anorexia), fetotoxic NOEL = 225 mg/kg (decreased percentage of live fetuses - cardiomegally and wavy ribs at 500 mg/kg/day); Core grade = Supplementary
Ref: SUMMARY OF TOXICOLOGY DATA TRIFLURALIN. California EPA, Department of Pesticides, Medical Toxicology Branch. Revised as of 11/29/95.
http://www.cdpr.ca.gov/docs/toxsums/pdfs/597.pdf

Teratology - rat: Maternal NOEL=100 mg/kg/day; Maternal LEL=500 mg/kg/day (decreased food consumption and increased liver and spleen weights); Developmental NOEL=none; LEL=20 mg/kg/day (reduced skeletal maturity and increased vascular fragility); core grade supplementary (Hoechst Aktiengesellschaft, 1983)
Ref: US EPA IRIS for Trifluralin CASRN: 1582-09-8.

http://www.epa.gov/iris/

Fish Vertebral Lesion Study: Based on the results from the field monitoring study, the Agency required a fish vertebral lesion study. The study submitted has been classified as invalid because of an inadequate control group, however, additional data are not required. Trifluralin contamination in both the acetone and water controls led to detectable concentrations in the fish at termination. Also, the stock fish that were used as a negative control were three to four weeks older than the test organisms at the time of radiographic exams. The stock fish had high incidence of wavy ribs (27.5%) and vertebral anomalies (23.8%). The Trifluralin Data Development Consortium (TDDC) has submitted a rebuttal to the review that classified this study as invalid. This rebuttal is currently being evaluated by the Agency. The Agency will explore with TDDC the appropriateness of a field monitoring study following the review of the rebuttal submission (MRID 42439601).
Ref: US EPA RED (Reregistration Eligibility Decision) for Trifluralin. EPA 738-R-95-040. April 1996.
http://www.fluorideaction.org/pesticides/trifluralin.red.1996.epa.pdf

Sheepshead minnows, Cyprinodon variegatus Lacepede, exposed to 5-5 to 31 micrograms/l of the herbicide trifluralin, throughout their first 28 days of life, developed a heretofore, undescribed vertebral dysplasia. This dysplasia consisted of semisymmetrical hypertrophy of vertebrae (three to 20 times normal), characterized by foci of osteoblast and fibroblasts actively laying down bone and bone precursors. Effects of the abnormal vertebral development were dorsal vertebral growth into the neural canal, ventral compression of renal ducts, and longitudinal fusion of vertebrae. Fish, exposed for 51 days to 16-6 micrograms/l trifluralin and thereafter depurated for 41 days, showed no increase in vertebral dysplasia during depuration; however, residual spinal column damage was evident. Serum calcium concentrations were elevated in adult fish exposed for 4 days to 16-6 micrograms/l trifluralin. Fluorosis or mimicry of hypervitaminosis A are considered possible mechanisms for the osseous effect, but are [abstract truncated].
Ref: 1981 - Vertebral Dysplasia in Young Fish Exposed to the Herbicide Trifluralin; by Couch J, Winstead JT, Hansen DJ, Goodman LR. Report available from The National Technical Information Service. Order No. NTIS/PB80-17775.

Pituitary glands of sheepshead minnows, Cyprinodon variegatus, exposed for 19 months to 1-5 micrograms/l trifluralin were significantly enlarged and possessed histopathologic characteristics (when compared to glands of controls) such as pseudocysts, congestion of blood vessels and edema. Most of the fish with enlarged pituitaries also had diffuse vertebral hyperostosis and other dysplastic vertebral changes. Several speculative mechanistic paths are suggested for the mode of the effect of trifluralin on the vertebral and pituitary tissues. Study of the form and function of pituitary glands of teleosts from natural populations might provide indications of chronic physiological stress, particularly in relation to chemical pollutant stress. Journal article, Pub. in the Jnl. of Fish Diseases, v7 p157-163, 1984.
Ref: 1984 - Histopathology and Enlargement of the Pituitary of a Teleost Exposed to the Herbicide Trifluralin; by Couch JA. Report available from The National Technical Information Service. Order No. NTIS/PB88-162375.

SKELETAL VARIANT ASSAY SYSTEM(SVAS) FOR DETECTION OF BIOLOGICAL EFFECTS OF ENVIRONMENTAL CONTAMINANTS
Author: BECK SL
Source: TOXICOL APPL PHARMACOL 37:149,1976

Name of Agent: 2,4,5-T ( 93-76-5 ) TRIFLURALIN ( 1582-09-8 ) CORN OIL ( 8001-30-7 )
No Abstract

POSTNATAL DETECTION OF PRENATAL EXPOSURE TO HERBICIDES IN MICE,USING NORMALLY OCCURRING VARIATIONS IN SKELETAL DEVELOPMENT
Author: BECK SL
Source: TERATOLOGY 15:15A,1977
Name of Agent (CAS RN): TRIFLURALIN ( 1582-09-8 ) 2,4,5-T ( 93-76-5 ) CORN OIL ( 8001-30-7 )

No Abstract

ASSESSMENT OF ADULT SKELETONS TO DETECT PRENATAL EXPOSURE TO 2,4,5-T OR TRIFLURALIN IN MICE
Author: BECK SL
Source: TERATOLOGY 23:33-55,1981
No Abstract

THE SKELETAL VARIANT ASSAY SYSTEM (SVAS): A POSTNATAL SCREEN FOR DETECTION OF PRENATAL INSULT
Author: BECK SL
Source: TERATOLOGY 29(2):17A-18A,1984 T
Test Object: MAMMAL, MOUSE Sex Treated: FEMALE
Name of Agent (CAS RN): 2,4,5-T ( 93-76-5 ) TRIFLURALIN ( 1582-09-8 ) CAPTAN ( 133-06-2 ) THALIDOMIDE ( 50-35-1 ) DIPHENYLHYDANTOIN ( 57-41-0 ) CORTISONE ( 53-06-5 ) DECAMETHRIN ( 52918-63-5 ) ACETAZOLAMIDE ( 59-66-5 ) TRYPAN BLUE ( 72-57-1 ) BROMODEOXYURIDINE ( 59-14-3 )
No Abstract

A COMPARISON OF THE SKELETAL VARIANT ASSAY SYSTEM (SVAS) ACROSS EXPERIMENTS: FREQUENT RESPONSES, HIGH MAGNITUDE EFFECTS, CLUSTERS, AND UNIQUE EFFECTS
Author: BECK SL
Source: TERATOLOGY 35(2):54A-55A,1987
Test Object: MAMMAL, MOUSE Sex Treated: FEMALE
Name of Agent (CAS RN): 2,4,5-T ( 93-76-5 ) TRIFLURALIN ( 1582-09-8 ) ACETAZOLAMIDE ( 59-66-5 ) TRYPAN BLUE ( 72-57-1 ) BUDR ( 59-14-3 )

Cancer: Possible Human Carcinogen - BLADDER, RENAL PELVIS, THYROID (click on for all fluorinated pesticides)

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 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).

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.

Dermal (click on for all fluorinated pesticides)

Absorption, distribution, excretion and metabolism in mammals (Annex IIA, point 5.1). Widely distributed; highest concentration in adrenals, fat, kidneys, liver, skin and blood (page 45)
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

Abstract: A case report was presented of a 61 year old male laboratory supervisor in a pesticide company with no reported history of hay fever, asthma or childhood eczema who experienced allergic contact dermatitis as a result of exposure to trifluralin (1582-09-8) and benefin (1861-40-1). He had been employed in the testing of pesticides since 1951. He presented with erythematous and pruritic dermatitis involving the exposed areas of skin on the face, neck, chest and arms. Although he was exposed to multiple pesticides, he was able to temporally link his reaction to exposure to several pesticides, including benefin and trifluralin. The patient was patch tested with a standard series, a pesticide series and the pesticides to which he was exposed. At 2 and 4 days, the tests elicited 2+ reactions to trifluralin and benefin. Patch tests in 12 control subjects with trifluralin and benefin showed no positive reactions. The authors note that although trifluralin and benefin have previously been reported to cause skin and eye irritation, no previous reports of allergic contact dermatitis have been made.
Ref: Pentel MT et al. (1994). Allergic Contact Dermatitis from the Herbicides Trifluralin and Benefin. Journal of the American Academy of Dermatology, Vol. 31, No. 6, pages 1057-1058.

Endocrine: Suspected Disruptor (click on for all fluorinated pesticides)

REPRODUCTIVE TOXICITY. Four studies were submitted in the dossier on rat and one in the dog in order to determine the reproductive effects of trifluralin (one-, two- and four-generation studies). Two studies were not acceptable according to the rapporteur Member State, these (four generation in the rat and the dog study) were of very old date (1966) and thus there were many deficiencies and deviations according to test guideline. A summary of the two-generation rat study is also presented in the Addendum. There were no direct effects on reproductive performance or fertility observed. Whether trifluralin was a possible endocrine disrupter was discussed at the expert meeting (May 2004). The meeting agreed that there were no clear evidence only limited evidence for endocrine effects, recorded at high dose levels and being hard to distinguish from systemic toxicity (page 11).
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

Suspected Endocrine Disruptor
Ref: PAN Pesticides Database

Suspected Endocrine Disruptor
Ref: June 14, 2001 - Implementation of the Community Strategy for Endocrine Disruptors - a range of substances suspected of interfering with the hormone systems of humans and wildlife. Communication from the Commission to the Council and the European Parliament. Commission of the European Communities, Brussels COM (2001) 262 final.

http://www.fluoridealert.org/pesticides/Endocrine.Disruptors.EC2001.pdf
- More information available at:
http://europa.eu.int/eur-lex/en/com/cnc/2001/com2001_0262en01.pdf

Endocrine: Testicular (click on for all fluorinated pesticides)

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

Endocrine: Thyroid (click on for all fluorinated pesticides)

-- EPA has classified trifluralin as a Group C (possible human) carcinogen. Classification is based on the induction of urinary tract tumors (renal pelvis carcinomas and urinary bladder papillomas) and thyroid tumors (adenomas/carcinomas combined) in one rat study.
Ref: March 2000. Public Health Assessment Cenex Supply and Marketing, Inc. Quincy, Washington. CERCLIS # WAD058619255. Draft for Public Comment.. Prepared by: Washington State Department of Health Under Cooperative Agreement with the Agency for Toxic Substances and Disease Registry. Also available at

http://www.doh.wa.gov/ehp/oehas/Cenex%20PHA%20Draft%20Public%20Review.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

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

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.
Ref:
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

Genotoxicity (click on for all fluorinated pesticides)

Abstract: The genotoxicity of trifluralin (1582098) was examined in human lymphocytes. Lymphocyte cultures were established from blood samples drawn from two healthy young male donors. These were treated with 0 to 200 micrograms per milliliter (microg/ml) trifluralin with or without metabolic activation from S9 mix for up to 72 hours (hr). Induction of sister chromatid exchanges (SCEs) was assessed after 2 or 48hr of incubation with trifluralin. Micronuclei induction was evaluated after 72hr of trifluralin treatment. Induction of chromosome aberrations was assessed after 30hr of incubation with trifluralin. Cytotoxicity was assessed by measuring changes in the proliferative rate index (PRI), determined by examination of the first three metaphases, and the cytokinesis block proliferative index (CBPI). Trifluralin treatment for 48hr in the absence of S9 mix caused a slight, but statistically significant increase in SCE frequency in lymphocytes from both donors at 50microg/ml, the highest concentration tested. Treatment with 25microg/ml trifluralin in the absence of S9 mix also caused a significant increase in SCE frequency in lymphocytes from one donor. Treatment with 200microg/ml trifluralin for 2hr in the presence of S9 mix caused a significant increase in SCE frequency in lymphocytes from both donors. These effects were accompanied by slight decreases in the PRI and CBPI. Trifluralin did not increase the frequency of chromosome aberrations or micronuclei above the background level. The authors conclude that trifluralin is able to exert weak cytotoxic and genotoxic effects in cultured human lymphocytes. The SCE assay seems to be more sensitive for detecting these types of effects than the chromosome aberration or micronucleus assays.
Ref: Ribas G et al. (1996). Genotoxic Evaluation of the Herbicide Trifluralin on Human Lymphocytes Exposed In Vitro. Mutation Research, Vol. 371, Nos. 1/2, pages 15-21, 30 references, 1996.

Abstract: In the present study, the herbicides bentazone, molinate, thiobencarb and trifluralin were evaluated for mutagenic and recombinagenic effects using the wing spot test of Drosophila melanogaster (somatic mutation and recombination test, SMART). Both standard (ST) and high-bioactivation (HB) fly crosses were used, the latter cross is characterised by a high sensitivity to promutagens and procarcinogens. Three-day-old larvae, transheterozygous for the multiple wing hairs (mwh, 3-0.3) and flare-3 (flr(3), 3-38.8) genes, were chronically fed with six different concentrations of each herbicide. Feeding ended with pupation of the surviving larvae and the genetic changes induced in somatic cells of the wing's imaginal discs lead to the formation of mutant clones on the wing blade. Point mutation, chromosome breakage and mitotic recombination produce single spots; while twin spots are produced only by mitotic recombination. Bentazone, usually considered as a non-mutagen, gave positive results in the wing spot test with the high-bioactivation cross. Molinate, about which information on mutagenic effects is inconclusive, gave positive responses in both the standard and the high-bioactivation crosses, while the other thiocarbamate, thiobencarb, gave positive results only in the standard cross and at the highest concentration tested (10 mM). Finally, trifluralin, one of the most widely studied herbicides for genotoxic effects, gave positive results in the wing spot test with both crosses. Apart from the interest of the results found in the genotoxic evaluation of the four selected herbicides, our results also contribute to extend the existing database on the Drosophila wing spot test, and corroborate the utility of the use of high-bioactivation strains for the genotoxic evaluation of xenobiotics.
Ref: Evaluation of the genotoxicity of four herbicides in the wing spot test of Drosophila melanogaster using two different strains; by Kaya B, Marcos R, Yanikoglu A, Creus A. Mutat Res. 2004 Jan 10;557(1):53-62.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14706518

2.4 GENOTOXICITY. In the DAR, 11 in vitro studies and five in vivo studies have been evaluated and presented. There was evidence of aneuploidy induction from an in vitro chromosome aberration study, positive effects in a comet tail test, as well as weak positive effects in an in vivo micronucleus study. In order to clarify these effects, the need of performing of a new micronucleus study was requested by the rapporteur Member State. This was stated as a data requirement in level 4 of the DAR “An in vivo bone marrow micronucleus assay in mice with kinetochore or centromeric staining in order to ascertain the nature of the micronuclei induced”. The new study was performed and submitted by the notifier and the rapporteur Member State has evaluated and presented it in the Addendum. No increase in the incidence of micronuclei formation or the aneuploidy was recorded, when it was administered as a single dose to male and female mice. Hence, trifluralin is considered negative for clastogenic and aneugenic potential in the present study (page 10)
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

Heart (click on for all fluorinated pesticides)

-- ** 089 036915 "A Teratology Study (I) of Trifluralin (EL-152, Compound 36352) Administered Orally to Dutch Belted Rabbits." (Lilly Research Labs., 10/31/84, Study B02283 and Study BO1784) Trifluralin (96.7% pure), lot 00554AP2; 0, 100, 225, 500, or 800; oral gavage, days 6 - 18; 20/group; maternal NOEL = 225 mg/kg (maternal death and abortions), developmental toxicity NOEL = 225 mg/kg (decreased fetal weight); Complete and ACCEPTABLE WITH 036916. No adverse developmental toxicity reported. JAP, 11/18/85. EPA one-liner: Maternal NOEL = 225 mg/kg (abortions and anorexia), fetotoxic NOEL = 225 mg/kg (decreased percentage of live fetuses - cardiomegally and wavy ribs at 500 mg/kg/day); Core grade = Supplementary
Ref: SUMMARY OF TOXICOLOGY DATA TRIFLURALIN. California EPA, Department of Pesticides, Medical Toxicology Branch. Revised as of 11/29/95.
http://www.cdpr.ca.gov/docs/toxsums/pdfs/597.pdf

• Note: "Cardiomegaly" - an abnormal enlargement of the heart.

Kidney (click on for all fluorinated pesticides)

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)
Absorption, distribution, excretion and metabolism in mammals (Annex IIA, point 5.1). Widely distributed; highest concentration in adrenals, fat, kidneys, liver, skin and blood (page 45)
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

High doses of trifluralin are associated with increases in kidney, bladder, and thyroid tumors.
Ref: March 2000. CERCLIS # WAD058619255. Draft for Public Comment.. Prepared by: Washington State Department of Health Under Cooperative Agreement with the Agency for Toxic Substances and Disease Registry.

Public Health Assessment Cenex Supply and Marketing, Inc. Quincy, Washington
.
Also available at http://www.doh.wa.gov/ehp/oehas/Cenex%20PHA%20Draft%20Public%20Review.pdf

-- 002, 003 952930, 952931 "The chronic toxicity of compound 36352 (trifluralin) given as a component of the diet to Fischer 344 rats for two years." (Lilly research, 9/16/80, R-87 and R-97) Trifluralin, 100%, no nitrosamine, lots P-65469 and 326EF8; 60 Fischer 344 Rats/sex/group, 30 in each of two replicate studies; fed at 0, 813, 3250 or 6500 ppm in the diet - dose selection based on NCI study (Record no. 027205); diet analyses at 11 intervals; adverse effects: microcytic anemia (both sexes) at 3250 and 6500 ppm, transitional cell carcinoma of renal pelvis epithelium and bladder (both sexes) and thyroid follicular adenoma and carcinoma (males only); sys NOEL = 813 ppm (decreased body weight gain), chronic NOEL < 813 ppm (progressive glomerulonephroses, renal calculi); Complete; ACCEPTABLE. (JPC, 5/21/85 and JG, 5/18/87). No EPA one-liner available. [In the Guidance for the Reregistration of Pesticide Products Containing Trifluralin as the Active Ingredient, August 1986, CDFA Record #51346, Document 207-097, this study is discussed with the footnote that additional data in the Fischer 344 rat is required to resolve the adverse kidney effects "since a NOEL for non-oncogenic kidney effects was not demonstrated...." The EPA states at least one dose should be lower than 813 ppm. JG, 5/14/87.]
-- 109 062079, 062080, "A Special Urinalysis Study in Fischer 344 Rats Maintained on Diets Containing Trifluralin (Compound 36352) for Three Months", (Lilly Research Laboratories, study # R04785, August 1985 and 1986), trifluralin, 96.45% purity, administered in the diet for 3 months to males only with 60/group at 0 and 2.6 mg/kg/day, and with 40/group at 10.7, 42.2, 170.2, and 342.1 mg/kg/day time-weighted average. NOEL for non-oncogenic kidney effects in male Fischer 344 rats = 2.6 mg/kg/day (approx. 50 ppm) (increased urinary K, Ca, AST, LDH, and Alpha 1, Alpha 2 and Beta globulins; increased renal tubular epithelial hyaline droplets). Some were continued on the diets for 4 months followed by 6 weeks on control diet. Treatment effects were reversible in all but the highest dose group. Note: this study was conducted to determine a NOEL for the non-oncogenic kidney effects of trifluralin in the Fischer 344 rat. This question surfaced in the combined rat feeding study record #’s 952930, 952927, and 952931 previously reviewed (JPC, 5/21/85 and JG, 5/18/87, 10/9/88).
Ref: SUMMARY OF TOXICOLOGY DATA TRIFLURALIN. California EPA, Department of Pesticides, Medical Toxicology Branch. Revised as of 11/29/95.
http://www.cdpr.ca.gov/docs/toxsums/pdfs/597.pdf

Liver (click on for all fluorinated pesticides)

• Long term toxicity (Annex IIA, point 5.5). Target/critical effect ‡ Body weight reduction, anemia, liver & kidney effects (mouse, rat). (page 46).
Absorption, distribution, excretion and metabolism in mammals (Annex IIA, point 5.1). Widely distributed; highest concentration in adrenals, fat, kidneys, liver, skin and blood (page 45)
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

Reproductive (click on for all fluorinated pesticides)

REPRODUCTIVE TOXICITY... The relevant NOAEL for reproduction was set to 4.5-5.8 mg/kg bw/day in the rat based on haematological changes, decreased maternal body weight during gestation and decreased offspring growth and survival, respectively at 40.7-50.8 mg/kg bw/day (Rubin et al., 1987). (page 11).... In order to examine teratogenic or developmental effects of trifluralin four studies in rat and rabbit were submitted in the dossier and two (one rat and one rabbit) were not accepted according to the rapporteur Member State, since it was of very old date (1966) and thus there were many deficiencies and deviation according to test guideline. One dog study was submitted in the dossier but was not considered acceptable according to same statement as above. From these studies it is concluded that trifluralin did not induce teratogenic or fetotoxic effects at non-maternally toxic doses. .(page 11-12)
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

Environmental (click on for all fluorinated pesticides)

Sheepshead minnows, Cyprinodon variegatus Laeepede, exposed to 5 5 to 31 /xg/1 of the herbicide trifluralin, throughout their first 28 days of life, developed a heretofore undescribed vertebral dysplasia. This dysplasia consisted of semisymmetrical hypertrophy of vertebrae (three to 20 times normal), characterized by foci of osteoblast and fibroblasts actively laying down bone and bone precursors. Effects of the abnormal vertebral development were dorsal vertebral growth into the neural canal, ventral compression of renal ducts, and longitudinal fusion of vertebrae. Fish, exposed for 51 days to 16-6 /ng/1 trifluralin and thereafter depurated for 41 days, showed no increase in vertebral dysplasia during depuration; however, residual spinal column damage was evident. Serum calcium concentrations were elevated in adult fish exposed for 4 days to 16-6 /xg/1 trifluralin. Fluorosis or mimicry of hypervitaminosis A are considered possible mechanisms for the osseous effect, but are not considered to be the only possible causes. The highly predictable nature of this disorder in experimental exposures strengthens the probability that young flsh may serve as experimental models for determining effects of chemicals on early vertebrate ontogeny, particularly in regard to skeletal development.
Excerpt: Trifluralin (2, 6 dinitro-N, N-dipropyl-4-(trifluoromethyl) Benzamine) is a fluorine containing, pre-emergent herbicide widely used in the United States (Wiswesser 1976). Continuous laboratory exposure of early life stages of the sheepshead minnow Cyprinodon variegatus Laeepede to relatively low concentrations of trifluralin results in marked vertebral dysplasia...
Ref:
Vertebral dysplasia in young fish exposed to the herbicide trifluralin. By JA COUCH, JT WINSTEAD, DJ HANSEN and LR GOODMAN. Journal of Fish Diseases 1979, 2, 35-42.
Full report at: http://www.fluorideaction.org/pesticides/trifluralin.1979.paper.pdf


Note: Still in use in the EU as of October 2003; however the EU is currently reconsidering its use.
"Trifluralin 1582-09-8 Banned. Low degradability, bioaccumulative and toxic to water-living organisms. 1990."
Definition: "Banned. A substance which for health or environmental reasons by an authority decision is either no longer approved for any area of application, or for which an approval or registration has been denied from the first instance."

Ref: Euopean Commission. Appendix 5. Substances which may not be included as active ingredients in approved pesticide products, Chapter 15, Section 2, subsection one.
http://www.kemi.se/lagar_eng/pdf/app5_8.pdf

• trifluralin has been added to the OSPAR (Convention for the Protection of the Marine Environment of the North-East Atlantic) List of Chemicals for Priority action in 2002 because it is considered to be a PBT substance fulfilling the criteria for Persistence, Bioaccumulation and Toxicity (page 3).
• 5.2 RISK TO AQUATIC ORGANISMS. Selenastrum capricornutum is the most sensitive aquatic organism on an acute time-scale and fathead minnow is the most sensitive species on a chronic time-scale when tested with trifluralin and the lead formulation. Due to the difference in Annex VI trigger value, the risk assessment is driven by the endpoints for fish both on an acute as long term time-scale. The resulting acute TER-value at 1 m from a field (7.9) is below and hence breaches the Annex VI trigger value of 100 so the risk should be considered as high. The rapporteur Member State calculated the risk taking into account buffer zones. This resulted in a TER-value of 110 indicating a low acute risk to fish if a bufferzone of 15 meters is taken into account. The choice of a relevant endpoint for the long-term risk to fish was extensively discussed during the EPCO expert meeting (section ecotoxicology, June 2004). Trifluralin induces vertebral lesions in several fish species, and in some instances this effects is induced after short term exposure (24 hours for brown trout). The meeting agreed that the risk assessment should be based in initial PEC and on the NOEC of 0.3 ?g/L (based on the observed vertebral lesions in the study with fathead minnow) together with an uncertainty factor of 10 to conduct the risk assessment. This would lead to a TER value of 0.38 when a buffer zone of 15 m is taken into account (without detailed calculations, a bufferzone of 50 m should lead to a TER-value of approximately 1). Consequently the risk for aquatic organisms should be regarded as high. Therefore the risk should be further refined either by higher tier studies or by a refinement of the exposure assessment. Therefore, the expert meeting set the following data requirement: notifier to submit exposure studies with different exposure times using the fathead minnow as the most sensitive fish species. As an alternative microcosm tests with a more realistic exposure regime may be run (page 21-22).
..... Trifluralin and the metabolites TR-4, TR-7 and TR-14 can be found in concentrations above 10% of the AR in the sediment. Therefore the risk to sediment dwelling organisms needs to be addressed. This risk assessment is available in the addendum 3 of June 2004... (page 22).
..... Studies on bio-accumulation in fish are available as the logPow exceeds 3 and the DT50 in water exceeds 10. The steady state bioconcentration factor is found to be 5674 which exceeds the Annex VI trigger value of 100 for not readily biodegradable product ... This BCF-value and the fact that the depuration is less than 95% after 14 days triggers a fish full life cycle study which is available with the sheephead minnow. The resulting NOEC from this study is 1.3 µg/L (based on fecundity, no vertebral lesions observed) which is higher than the NOEC which is chosen for the long term risk assessment. As mentioned above a high long term risk to aquatic organisms was identified for which a data requirement is still open. Therefore, EFSA proposes that Member States may reconsider the risk for bioaccumulation when this long term assessment is revised, on receipt of the above mentioned data requirement. Residues in fish were found during the available field monitoring study (page 22-23).
High risks were identified for aquatic organisms, in particular the chronic risk to fish, which require consideration of appropriate risk mitigation measures. Using the initial predicted environmental concentrations (PEC’s) together with the no observed effect level (NOEC) of 0.3 ?g/L leads to a toxicity exposure ratio (TER)-value of 0.38 when a bufferzone of 15 metres is taken into account which is below the Annex VI trigger value of 10 (without detailed calculations, a bufferzone of 50 m should lead to a TER-value of approximately 1). Further data to address this risk is needed and the risk assessment can only be concluded when the outstanding data is evaluated (page 3)
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

Ref: PAN Pesticides Database - Chemical Toxicity Studies on Aquatic Organisms. Acute Aquatic Ecotoxicity Summaries for Trifluralin.
http://www.pesticideinfo.org/List_AquireAcuteSum.jsp?Rec_Id=PC35146
Common Name Scientific Name Avg Species LC50 (ug/L) LC50 Std Dev Number of Studies Studies Avg Species Rating
Amphibians
Toad Bufo bufo japonicus 14,000 - 1 Slightly Toxic
Fowler's toad Bufo woodhousei fowleri 150.7 37.8 7 Highly Toxic
Fish
Porgy Acanthopagrus schlegeli 56.0 - 1 Very Highly Toxic
Bunni fish Barbus sharpeyi 250.0 - 1 Highly Toxic
Goldfish Carassius auratus 397.0 312.3 5 Highly Toxic
Agohaze, goby Chasmichthys dolichognathus 120.0 - 1 Highly Toxic
Pacific herring Clupea pallasi 5.00 - 1 Very Highly Toxic
Sheepshead minnow Cyprinodon variegatus 190.0 - 1 Highly Toxic
Common, mirror, colored, carp Cyprinus carpio 391.2 377.1 5 Highly Toxic
Western mosquitofish Gambusia affinis 9,630 9,893 5 Moderately Toxic
Green fish Girella punctata 110.0 - 1 Highly Toxic
Channel catfish Ictalurus punctatus 800.7 711.2 10 Highly Toxic
Bluegill Lepomis macrochirus 197.4 233.1 40 Highly Toxic
Largemouth bass Micropterus salmoides 86.2 19.5 4 Very Highly Toxic
Oriental weatherfish Misgurnus anguillicaudatus 350.0 - 1 Highly Toxic
Striped mullet Mugil cephalus 32.0 - 1 Very Highly Toxic
Rainbow trout,donaldson trout Oncorhynchus mykiss 188.1 326.7 58 Highly Toxic
Medaka, high-eyes Oryzias latipes 430.0 - 1 Highly Toxic
Red Sea Bream Pagrus major 23.0 2.16 3 Very Highly Toxic
Hirame, flounder Paralichthys olivaceus 56.0 - 1 Very Highly Toxic
Grunt Parapristipoma trilineatum 33.0 - 1 Very Highly Toxic
Fathead minnow Pimephales promelas 133.4 33.3 8 Highly Toxic
Harlequinfish, red rasbora Rasbora heteromorpha 733.3 188.6 3 Highly Toxic
Jacopever Sebastes schlegeli 74.0 - 1 Very Highly Toxic
Yellowtail Seriola quinqueradiata 5.00 - 1 Very Highly Toxic
Walleye Stizostedion vitreum vitreum 180.0 - 1 Highly Toxic
 
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