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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 MRLÕs 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
|
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 TWAÕs 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-HodgkinÕs
lymphoma among farmers exposed to trifluralin, among
other herbicides (OR 12.5, 95% CI 1.6-116.1). However, these
other significant chemical exposures confound the analysis
with respect to trifluralin.
Animal
bioassays
1. Mouse long-term diet studies (treated 78 weeks + additional
12 weeks observation): NCI, 1978. Significant
increases in hepatocellular carcinomas and alveolar and
bronchial adenomas were seen in
female mice receiving 0, 2740 or 5192 ppm in the
diet. A small increase in relatively rare forestomach
carcinomas seen in low-dose female
mice (4/45 versus 0/60 in pooled controls)
was also considered treatment-related. Increased tumor incidences
in male mice were not significant. The
NCI concluded that "technical grade trifluralin is a carcinogen
in female B6C3F1 miceÉ" This
study used technical grade trifluralin, later found to be
contaminated with N-nitroso-n-propylamine (NDPA).
2.
Rat long term diet studies (treated 78 weeks + additional
33 weeks observation): NCI, 1978. No increase in tumors
was observed in male or female rats.
3.
Rat diet studies: Emmerson et al., 1980 (This series of
studies has not been published in the open literature, but
was submitted to and reviewed by CDFA [1990], and is cited
by US EPA, with a summary in IRIS). Technical grade trifluralin
with <0.01 ppm of NDPA was administered to both sexes of
Fischer 344 rats at 0, 813, 3250 or 6500 ppm in diet. Uncommon
transitional cell carcinomas of the renal pelvis epithelium
were increased in all treated groups of males, reaching
significance in the high-dose group. Dose-dependent
increases in tumors of the bladder or renal pelvis transitional
epithelium were observed in both sexes (males: 0/60,
3/59, 4/60, 7/60; females: 0/60, 0/60, 1/60, 5/60). In addition,
thyroid follicular adenomas and carcinomas
were significantly increased in high-dose male rats.
4.
Mouse long-term diet studies (2 years): Francis et al.,
1991. Technical grade trifluralin with < 0.01 NDPA was administered
at 0, 563, 2250, or 4450 in diet to males and female B6C3F1
mice. No evidence of oncogenicity was observed, although
the high dose resulted in significantly
decreased body weight gains.
5.
Rat long-term diet studies (2 years): Eli Lilly, 1966, as
reported in US EPA 1986 Peer Review of Trifluralin. In groups
of 25 of each sex, Sprague-Dawley rats were administered
0, 200, 1000, or 2000 ppm trifluralin in the diet. "The
CAG concluded that this study showed no evidence of carcinogenicity
and that the study was an adequate basis for safety evaluation."
IARC
(1991) reviewed the published data on trifluralin and concluded
that there was limited evidence of
carcinogenicity in animals (group 3). However, since
they do not, as a matter of policy, review studies which
have only been submitted for product registration purposes
and not otherwise published, their review included only
the NCI (1978) rat and mouse studies and the mouse studies
by Francis et al. (1991). Neither the positive study by
Emmerson et al. (1980), nor the non-positive result obtained
by Eli Lilly (1966) was considered. US EPA currently classifies
trifluralin as a Class C - possible human carcinogen.
Other
relevant data
Trifluralin was negative in the dominant lethal test in
rats and in assays for SCEs and induction of reverse mutations
in Salmonella (CDFA, 1990), however,
it induced aneuploidy in Neurospora crassa, and yielded
mixed results in aneuploidy tests in Drosophila (IARC, 1991).
Trifluralin is structurally related
to ethalfluralin, which produces mammary gland fibroadenomas
in female rats (IRIS).
Preliminary
evaluation of carcinogenicity and exposure data:
There
is a MEDIUM level of carcinogenicity concern over trifluralin.
Concern is due to dose-dependent increases in the incidences
of tumors of the transitional epithelium
of the bladder and renal pelvis in male and female
F344 rats, and significant increases
in thyroid follicular tumors in males. Similar observations
were not made in studies in other strains of rats. It is
noteworthy that in the positive study, the number of animals
observed with renal calculi increased
substantially with increasing dose; they were found in the
majority of high-dose animals. There was a positive bioassay
in female mice at three tumor sites, but the study is compromised
by contamination with N-nitroso-n-propylamine and was considered
unacceptable by CDFA (1990). A follow-up study with a sample
of greater purity did not find an effect under similar circumstances.
The level of concern is reinforced
by the possible (but unproven) association with lymphoma
among exposed farmers and the structural similarity to the
animal tumorigen ethalfluralin. The single positive
observation of genotoxicity in short-term tests neither
adds nor detracts from the level of concern.
There
is a HIGH level of concern over the extent of exposure to
trifluralin.
It is used on a large number of California crops; 1,404,088
lbs were applied in 1993 (DPR, 1995). Most usage is on cotton
and alfalfa, indicating that, like other agricultural chemicals,
occupational exposures are possible. The general public
may consume food crops treated with trifluralin, especially
tomatoes, carrots and grapes, and could be additionally
exposed by dermal and inhalation routes from lawn products
(HSDB). Trifluralin may also bioaccumulate
in fish (HSDB).
References
California
Department of Pesticide Regulation (DPR, 1995). Pesticide
Use Report, Annual 1993. DPR, Information Systems Branch,
Cal/EPA, Sacramento, CA.
California
Department of Food and Agriculture (1990). Summary of toxicology
data, trifluralin. CDFA, Medical Toxicology Branch, Sacramento,
CA.
Emmerson
JL, Pierce EC, McGrath JP et al. (1980). The chronic toxicity
of compound 36352 (trifluralin) given as a component of
the diet to Fischer 344 rats for two years. Studies R-87
and R97, submitted by Elanco Products Co., division of Eli
Lilly Co.) as cited in IRIS and discussed in Peer Review
of Trifluralin by the Toxicology Branch Peer Review Committee
(April 11, 1986 memorandum from R. Bruce Jaeger).
Francis
PC, Emmerson JL, Adams ER, Owen NV (1991). Oncogenicity
study of trifluralin in B6C3F1 mice. Food Chemical Tox 29(8):549-555.
Hazardous
Substances Data Bank (HSDB, 1995). National Library of Medicine.
Hoar
SK, Blair A, Holmes FF, Boysen CD, Robel RJ, Hoover R, Faumeni
JF (1986). Agricultural herbicide use and risk of lymphoma
and soft-tissue sarcoma. JAMA 256(9):1141-1147.
Integrated
Risk Information System (IRIS). US EPA.
International
Agency for Research on Cancer (IARC, 1991). IARC monographs
on the evaluation of carcinogenic risks to humans, Volume
53. Occupational exposures in insecticide application, and
some pesticides. IARC, Lyon.
National
Cancer Institute (NCI) (1978). Bioassay of trifluralin for
possible carcinogenicity. CAS No. 1582-09-8. NCI Technical
Report Series No. 34. DHEW Publication No. (NIH) 78-834,
Bethesda, MD.
USEPA,
Federal Register. 55 FR 17560, April 25 1990: other notices
1988-1992. |
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 #Õs 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 |
|
|