820K90001
TRIFLURALIN
Health Advisory
Office of Drinking Water
U.S. Environmental Protection Agency
I. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Drinking
Water (ODW), provides information on the health effects, analytical method-
ology and treatment technology that would be useful in dealing with the
contamination of drinking water. Health Advisories describe nonregulatory
concentrations of drinking water contaminants at which adverse health effects
would not be anticipated to occur over specific exposure durations. Health
Advisories contain a margin of safety to protect sensitive members of the
population.
Health Advisories serve as informal technical-guidance to assist Federal,
State and local officials responsible for protecting public health when
emergency spills or contamination situations occur. They are not to be
construed as legally enforceable Federal standards. The HAs are subject to
change as new information becomes available.
Health Advisories are developed for one-day, ten-day, longer-term
(approximately 7 years, or 10% of an individual's lifetime) and lifetime
exposures based on data describing noncarcinogenic end points of toxicity.
Health Advisories do not quantitatively incorporate any potential carcinogenic
risk from such exposure. For those substances that are known or probable
human carcinogens, according to the Agency classification scheme (Group A or
B), Lifetime HAs are not recommended. The chemical concentration values for
Group A or B carcinogens are correlated with carcinogenic risk estimates by
employing a cancer potency (unit risk) value together with assumptions for
lifetime exposure and the consumption of drinking water. The cancer unit
risk is usually derived from the linear multistage model with 95% upper
confidence limits. This provides a low-dose estimate of cancer risk to
humans that is considered unlikely to pose a carcinogenic risk in excess
of the stated values. Excess cancer risk estimates may also be calculated
using the One-hit, Weibull, Logit or Probit models. There is no current
understanding of the biological mechanisms involved in cancer to suggest that
any one of these models is able to predict risk more accurately than another.
Because each model is based on differing assumptions, the estimates that are
derived can differ by several orders of magnitude.
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Trifli^ralin
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II. GENERAL INFORMATION AND PROPERTIES
CAS No. 1582-09-8
Structural Formula
N(CH2CH2CH,)2
alpha, alpha, alpha-Trifluro-2,6-dinitro-N,N-dipropyl-p-toluidine
Synonyms
0 2,6-Dinitro-N, N-dipropyl-4-trifluoromethylaniline; Agreflan; Crisalin;
Treflan; L-36352 Trifluralin (U.S. EPA, 1985a,b).
Uses
0 A selective herbicide (preemergent) for control of annual grasses and
broad-leafed weeds. Applied to soybean, cotton and vegetable crops;
fruit and nut trees, shrubs; and roses and other flowers. Also used
on golf courses, rights-of-way, and domestic outdoor and industrial
sites (U.S. EPA, 1985b).
Properties
Chemical Formula
Molecular Weight
Physical State (25°C)
Boiling Point
Melting Point
Density
Vapor Pressure (25°C)
Specific Gravity
Water Solubility (25°C)
Log Octanol/Water Partition
Coefficient
Taste Threshold
Odor Threshold
Conversion Factor
C13H16F3N3°4
335.2
Orange, crystalline solid
139 to 140°C
46 to 49°C
1.1x10~4 mm Hg
0.3 mg/L
4.69
Occurrence
0 Trifluralin is not a potential ground water contaminant due to its
strong adsorption to soil and negligible leaching (U.S. EPA, 1985b).
0 Trifluralin has been detected in finished drinking water supplies
(NAS, 1977).
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Trifluralin August, 1987
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0 Trifluralin has been found in 318 of 377 surface water samples
analyzed and in 13 of 283 ground water samples (STORET, 1987).
Samples were collected at 194 surface water locations and 251 ground
water locations, and trifluralin was found in 9 states. The 85th
percentile of all nonzero samples was 0.10 ug/L in surface water and
.54 ug/L in ground water sources. The maximum concentration found was
16 ug/L in surface water and 0.54 ug/L in ground water.
Environmental Fate
0 Trifluralin at 5 ppm degraded with 15% of the applied trifluralin
lost after 20 days in a silt loam soil (aerobic metabolism) study
(Parr and Smith, 1973). The samples were incubated in the dark at
25°C and 0.33 bar moisture.
0 Trifluralin, applied alone or in combination with chlorpropham or
chlorpropham plus PPG-124, dissipated with a half-life of 42 to 84
days in sandy loam or silt loam soil incubated at 72 to 75°F and 18%
moisture content under laboratory conditions (Maliani, 1976).
0 In an anaerobic soil metabolism study, trifluralin at 5 ppm degraded
in nonsterile silt loam soil, with less than 1% of applied trifluralin
detected after 20 days of incubation (0.33 bar moisture in the dark
at 25°E; anaerobicity was maintained with nitrogen gas). Autoclaving
and flooding the soil decreased the degradation rate of the compound
(Parr and Smith, 1973).
0 l4C-Trifluralin at 1.1 kg/ha was relatively immobile in sand, sandy
loam, silt, loam and clay loam soil columns (30-cm height) eluted
with 60 cm of water, with more than 90% of the applied radioactivity
remaining in the top 0- to 10-cm segment (Gray et al., 1982).
0 Trifluralin concentrations in runoff (water/sediment suspensions)
were less than 0.04% of the applied amount for 3 consecutive years
following treatment at 1.4 kg/ha and 13 to 27 cm of rainfall (Willis
et al., 1975). The field plots (silty clay loam soil, 0.2% slope)
were planted with cotton or soybeans.
0 In the field, 14c-trifluralin (99% pure) at 0.84 to 6.72 kg/ha dissipated
in the top 0- to 0.5 cm layer of a silt loam soil, with 14, 4, and 1.5%
of the applied amount remaining 1, 2 and 3 years, respectively, after
application (Golab et al., 1978). Approximately 30 minor degradates
were identified and quantified; none represented more than 2.8% of
the applied amount. Trifluralin (4 Ib/gal EC) at 0.75 and 1.5 Ib/A
dissipated in a medium loam soil, with 20 and 32%, respectively, of
the applied remaining 120 days after treatment (Helmer et al., 1969;
Johnson, 1977).
0 Trifluralin (4 Ib/gal EC) dissipated from a sandy loam soil treated
at 1.0 Ib ai/A, with a half-life of 2 to 4 months (Miller, 1973).
0 Trifluralin was detected in 107 soil samples taken nationwide at less
than 0.01 to 0.98 ppm in fields treated with trifluralin at various
rates for 1, 2, 3 or 4 consecutive years (Parka and Tepe, 1969).
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Trifluralin August, 1987
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0 Trifluralin was detected in 12% of the soil samples taken from 80
sites in 15 states in areas considered to be regular pesticide-use
areas based on available pesticide-use records (Stevens et al.,
1970). Concentrations detected in soils ranged from less than 0.01
to 0.48 ppm. Trifluralin residues were detected in only 3.5% of the
1,729 agricultural soils sampled in 1969 (Wiersma et al., 1972).
0 Trifluralin was detected at a maximum concentration of 0.25 ppm.
Residues of volatile nitrosamines (dimethylnitrosoamine, N-nitro-sodi-
propylamine, or N-butyl-N-ethyl-N-nitrosoamine) were not detected in
water samples taken from ponds and wells located in or near fields that
had been treated with trifluralin at various rates (Day et al., 1977).
III. PHARMACOKINETICS
Absorption
0 Emmerson and Anderson (1966) indicated that trifluralin is not readily
absorbed from the gastrointestinal (GI) tract and that the fraction
that is absorbed is completely metabolized. Of an orally administered
dose (100 mg/kg), only 11 to 14% was excreted in the bile after 24
hours, indicating low GI absorption.
\
Distribution
8 No information was found in the available literature on the distri-
bution of trifluralin.
Metabolism
0 Four metabolites of trifluralin were identified in rats. Twelve rats
were given 100 mg/kg CFj-trifluralin in corn oil by gavage for 2
weeks. The metabolites, identified by thin-layer chromatography,
were produced by removal of both propyl groups or dealkylation and
reduction of a nitro group to an amine {Emmerson and Anderson, 1966).
0 An in vitro study using rat hepatic microsomes indicated that trifluralin
undergoes aliphatic hydroxylation of the N-alkyl substituents,
N-dealkylation and reduction of a nitro group (Nelson et al., 1976).
0 There are insufficient data to characterize the general metabolism of
trifluralin in animals (U.S. EPA, 1986a).
Excretion
Rats given an oral dose (100 mg/kg) of 14CF3-trifluralin excreted
virtually all of the dose within 3 days. The radioactivity was
excreted during the first 24 hours. Approximately 78% of the dose
was eliminated in the feces and 22% in the urine (Emmerson and
Anderson, 1966).
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Trifluralin August, 1987
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IV. HEALTH EFFECTS
Humans
Short-term Exposure
0 The Pesticide Incident Monitoring System database revealed 105
incident reports involving trifluralin from 1966 to April of 1981.
Of the 105 reports, 49 cases involved humans exposed to trifluralin
alone. Twenty-seven cases involved human exposure to mixtures con-
taining trifluralin. The remaining incidents involved nonhuman
exposures (U.S. EPA, 1981a).
0 Among reports of human exposure to trifluralin alone, one fatality
was reported. A 9-year-old girl suffered cardiac arrest following
the ingestion of an unknown amount of trifluralin (U.S. EPA, 1981a).
0 Verhalst (1974) reported that the symptoms observed in trifluralin
poisonings appeared to be related to the solvent used (e.g., acetone
or xylene) rather than trifluralin itself.
Long-term Exposure
0 The majority of reported trifluralin exposure cases were occupational
in nature. Trifluralin exposure has resulted in dermal and ocular
irritation in humans. Other reported symptoms include respiratory
involvement, abdominal cramps, nausea, diarrhea, headache, lethargy
and parasthesia following dermal or inhalation exposure. Specific
exposure levels or durations were not reported (U.S. EPA, 1981a).
Animals
Short-term Exposure
0 The acute oral toxicity of trifluralin is low. The following oral
LD50 values have been reported: mice >5 g/kg; rats >10 g/kg; dogs,
rabbits and chickens >2 g/kg (Meister, 1983; RTECS, 1985).
0 An inhalation LC50 value (41% trifluralin; species not specified) of
>2.44 mg/L/hour was reported (U.S. EPA, 1985c). No other information
was available.
Dermal/Ocular Effects
0 The results of a primary dermal-irritation study in the rabbit were
negative. No dermal irritation was observed at 72 hours following
application of a 41.2% trifluralin solution (U.S. EPA, 1985c).
e Treflan, containing 10% trifluralin, was tested for sensitization in
female guinea pigs. A dose of 50 mg was applied to the skin of
12 animals, three times a week for 2 weeks. No dermal irritation or
contact sensitization developed during this time (BLANCO, 1984a).
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0 In a similar study, a 95% technical trifluralin solution was shown to be
a potential skin sensitizer in guinea pigs using the Buehler topical-
patch method (U.S. EPA, 1985c).
0 A 14-day study in which rabbits were exposed to 2 mL/kg trifluralin
topically produced diarrhea and slight dermal erythema in exposed
animals. No other effects were reported (BLANCO, 1979).
0 Technical-grade trifluralin applied as a powder to rabbit eyes was
reported as nonirritating. Slight conjunctivitis developed but
cleared within a week (U.S. EPA, 1985c).
0 When applied as a liquid to rabit eyes, technical trifluralin produced
corneal opacity that cleared in 7 days (U.S. EPA, 1985c).
Long-term Exposure
0 In a modified subacute study, female Harlan-Wistar rats were given 0,
Oc05f 0.1 or 0.2% (0, 500, 1,000 or 2,000 ppm) trifluralin in their
diet for 3 months. Assuming that 1 ppm in the diet of rats equals
0.05 mg/kg/day (Lehman, 1959), these levels correspond to doses of
0, 25, 50 and 100 mg/kg/day. Physical appearance, behavior, body and
organ weights, mortality and clinical chemistries were monitored in
progeny from 10 females. No significant effects were observed in
survival or appearance. Liver weights in progeny continuously fed
diets of 0.1% and 0.2% trifluralin were increased over those of control
animals. The study identified a No-Observed-Adverse-Effect-Level
(NOAEL) in progeny of 0.05% (25 mg/kg) trifluralin (BLANCO, 1977a).
0 In a 90-day study, male F344 rats were fed dietary levels of 0 (n = 60),
0.005% (n = 60), 0.02% (n = 45), 0.08% (n = 45), 0.32% (n * 45) and
0.64% (n = 45). These concentrations are equivalent to dose levels of
0, 50, 200, 800, 3,200 and 6,400 ppm trifluralin, respectively (BLANCO,
1985). Assuming that 1 ppm in the diet of a rat equals 0.05 mg/kg/day
(Lehman, 1959), these levels correspond to doses of 0, 2.5, 10, 40,
160 and 320 mg/kg/day. After 90 days, alpha-1, alpha-2 and beta-
globulin levels were significantly increased in all treatment groups.
Other effects included increased aspartate transaminase, urinary
calcium, inorganic phosphorus and magnesium at levels y\ 60 mg/kg/day.
A Lowest-Observed-Adverse-Effect-Level (LOAEL) of 2.5 mg/kg/day (the
lowest dose tested) can be identified from this study.
0 Sixty weanling BarIan rats were fed 0, 20, 200, 2,000 or 20,000 ppm
trifluralin in the diet for 729 days (24 months). Assuming that
1 ppm in the diet of a rat equals 0.05 mg/kg (Lehman, 1959), these
concentrations correspond to doses of 0, 1, 10, 100 or 1,000 mg/kg/day.
No significant effects were observed in growth rate, mortality or
food consumption of treated animals at the three lower dose levels.
Animals in the highest dose group (1,000 mg/kg/day) were significantly
smaller than controls and ranked lower in food consumption. No effects
on hematology were noted. Animals in the high-dose group displayed a
slight proliferation of the bile ducts. No other histopathological
effects were observed. A NOAEL of 2,000 ppm (100 mg/kg/day) was
reported (BLANCO, 1966a).
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Trifluralin August, 1987
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0 In a 2-year chronic carcinogenic!ty study with F344 rats, doses
greater than 128 mg/kg/day in males and 154 mg/kg/day in females were
reported to produce overt toxicity. Groups of 60 animals/sex/dose
were fed dietary levels of 0.08, 0.3 or 0.65% (30, 128 or 272 mg/kg/day
for males, and 37, 154 or 336 mg/kg/day for females) trifluralin. Body
weights of the high-dose groups were significantly decreased in both
sexes. This may be related to the decreased food consumption observed
in those groups. Increased blood urea nitrogen (BUN) levels and
increased liver and testes weights were note in the two high-dose
groups. Kidney and heart weights were significantly decreased in
females in the 0.3- and 0.65%-trifluralin groups. Other noncarcino-
genic effects included decreased hemoglobin values and erythrocyte
counts in both sexes of the high-dose group (ELANCO, 1980a). This
study appears to identify a NOAEL of 0.08% trifluralin (30 to 37 mg/kg/day)
0 B6C3F1 mice (40/sex/group) were exposed to dose levels of 40, 180 or
420 mg/kg/day trifluralin in the diet for 2 years. Animals exposed
to the two higher levels exhibited decreased body weight and renal
toxicity. Other noncarcinogenic effects included decreased erythrocytic
and leukocytic values in the high-dose group, increased BUN and
alkaline phosphatase levels in the 180- and 420-mg/kg/day group,
decreased kidney weights in the two high-dose groups and decreased
spleen and uterine weights with increased liver weights in the high-
dose group (ELANCO, 1980b). No effects were noted at the low-dose
level (40 mg/kg/day).
0 Occasional emesis and increased liver-to-body weight ratios were
observed in dogs (three/sex/dose) fed 25 mg/kg/day trifluralin for 3
years. No adverse effects were observed in animals fed 10 mg/kg/day
(Worth, 1970). An intermediate dose was not tested.
Reproductive Effects
0 In a four-generation reproduction study (ELANCO, 1977b), rats were
given 0, 200 or 2,000 ppm trifluralin in the diet (0, 10 or 100
nig/kg/day). A reproductive NOAEL of 200 ppm (10 mg/kg/day) was
identified. The number of animals used in the study was not reported.
However, a review of this study (U.S. EPA, 1985c) indicated that an
insufficient number of animals were used and that several other
deficiencies in the study may have compromised the integrity of the
results.
0 In a 3-year feeding study in dogs a NOAEL of 10 mg/kg/day was
identified in adults (ELANCO, 1967). Dogs (three/sex/dose) were
given 10 or 25 mg/kg/day trifluralin in the diet. When bred after 2
years of exposure, no differences in litter size, survival or growth
of the pups were reported. An occasional emesis and increased liver
weights were reported in adults in the 25-mg/kg/day group.
Developmental Effects
0 Female rabbits (number not specified) were fed 0, 100, 225, 500, or
800 mg/kg/day by gavage during pregnancy (ELANCO, 1984b). No adverse
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Trifluralin August, 1987
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reproductive effects were observed at the two lower dose levels.
The 500 and 800 mg/kg/day levels resulted in anorexia, aborted litters
and decreased live births. The NOAEL for maternal effects was identi-
fied as 225 mg/kg/day.
0 Rabbits (number not specified) exposed to 100, 225 or 500 mg/kg/day
trifluralin during pregnancy exhibited anorexia and cachexia at all
dose levels (U.S. EPA, 1985c). Aborted litters were observed at the
two high-dose levels. Fetotoxicity as evidenced by decreased fetal
weight and size was observed at the high-dose level.
0 In a rabbit teratology study, a total of 32 mated females were given
up to 1,000 mg/kg/day trifluralin by gavage (BLANCO, 1966b). Specific
dose increments were not reported. Animals were dosed until the 25th
day of gestation and then sacrificed. Does in the 1,000 mg/kg/day
group weighed slightly less than controls. Two fetuses were found to
be underdeveloped in the high-dose group; however, this was not
considered by the investigators to be treatment related. Average
litter size and weight were not significantly affected. The authors
reported that their results identified a safe level of 1,000 mg/kg/day.
0 Rabbit does (number per group not specified) were given 100, 225, 500
or 800 mg/kg/day trifluralin by gavage during pregnancy (ELANCO, 1984b)
The 500 and 800 mg/kg/day levels resulted in decreased live births,
cardiomegaly and wavy ribs in the progeny. No effects on progeny were
observed at 225 mg/kg/day or less (ELANCO, 1984b).
Mutagenicity
0 Anderson et al. (1972) reported that trifluralin did not induce point
mutations in any of the three microbial systems tested. No further
details were provided in the review.
0 Trifluralin was tested for genotoxicity in several in vivo and
in vitro systems (ELANCO, 1983). No reverse mutations were observed
in Salmonella typhimurium or Escherichia coli when incubated with 25
to 400 mg trifluralin/plate without activation; trifluralin was also
negative when tested at levels of 50 to 800 mg/plate with activation.
Negative results were obtained in mouse lymphoma L5178Y TK+ cells
incubated with 0.5 to 20 ug/mL trifluralin with and without activation.
An in vivo sister-chromatid exchange study in Chinese Hamster Ovary
(CHO) cells following exposure to 500 mg/kg trifluralin was also
negative.
Carcinogenicity
0 NCI (1978) conducted bioassays on B6C3Fi mice and Osborne-Mendel rats
using technical-grade trifluralin (which contained 84 to 88 ppm of the
contaminant dipropylnitrosamine). Two dietary -levels were used in
each bioassay. Mice (50/sex/group) were exposed to trifluralin at
dose levels of 2,000 or 3,444 ppm (males) or 3,740 or 5,192 ppm
(females) for 78 weeks and observed for an additional 13 weeks after
exposure. A significant close-related increase in hepatocellular
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carcinoma was observed in female mice (0/20 control, 12/47 low dose,
21/44 high dose). An increased incidence of alveolar/ bronchiolar
adenomas was also observed (0/19 control, 6/43 low dose, 3/30 high
dose) in female mice. Squamous cell carcinomas in the forestomach of
a few treated female mice were also observed. Although the incidence
of squamous cell carcinoma in the forestomach was not statistically
significant when compared to pooled and matched controls, NCI deemed
this finding to be treatment related, since it was an unusual type of
lesion. Male mice were not significantly affected by trifluralin
exposure.
0 Rats (50/sex/group) were exposed to two levels of trifluralin in the
feed (4,125 or 8,000 ppm for males; 4,125 or 7,917 ppm for females)
for 78 weeks followed by a 33-week observation period (NCI, 1978).
Assuming 1 ppm in the diet of rats equals 0.05 mg/kg/day (Lehman,
1959), these doses correspond to 206 or 400 mg/kg/day. Several
neoplasms were observed and compared to pooled and matched controls.
These neoplasm types were reported to occur spontaneously in the
Osborne-Mendel strain and were not considered treatment related by
NCI.
0 In a 2-year feeding study, B6C3F1 mice were given 563, 2,250 or 4,500
ppm trifluralin (assuming 1 ppm in the diet of a mouse equals 0.15
mg/kg/day, these doses correspond to 40, 180 or 420 mg/kg/day (Lehman,
1959) in the diet (ELANCO, 1980b). Levels of a nitrosamine contaminant
of trifluralin, NDPA, were below the 0.01-ppm analytical detection
limit. A total of 40 animals/sex/treatment group was used. At the
lowest dose level, 40 mg/kg/day, no adverse effects were observed in
either sex. Decreased body weight and renal effects were noted in
mice in the mid- and high-dose groups. Pathology revealed progressive
glomerulonephritis in females of the high-dose group. Hepatocellular
hyperplasia and hypertrophy were also observed in the treated mice.
The specific dose level was not reported. No evidence of increased
incidence or decreased latency for any type of neoplasm was found in
any of the mice.
0 Trifluralin was administered to F344 rats (60/sex/group) at dose
levels of 813, 3,250 or 6,500 ppm [assuming 1 ppm in the diet of a
rat equals 0.05 mg/kg/day (Lehman, 1959), these doses correspond to
30, 128 or 272 mg/kg/day for males and 37, 154 or 336 mg/kg/day for
females] in the diet for 2 years (ELANCO, 1980a). A significant
increase in malignant renal neoplasms and thyroid tumors in male rats
and in neoplasms of the bladder in both sexes was reported. A high
incidence (20/30) of renal calculi was also observed in animals in
the high-dose groups.
V. QUANTIFICATION OF TOXICOLOGICAL EFFECTS
Health Advisories (HAs) are generally determined for one-day, ten-day,
longer-term (approximately 7 years) and lifetime exposures if adequate data
are available that identify a sensitive noncarcinogenic end point of toxicity.
The HAs for noncarcinogenic toxicants are derived using the following formula:
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HA = (NOAEL or LOAEL) x (BW) = /L ( ug/L)
(UF) x ( L/day)
where?
NOAEL or LOAEL = No- or Lowest-Observed-Adverse-Effect-Level
in mg/kg bw/day.
BW = assumed body weight of a child (10 kg) or
an adult (70 kg).
UF = uncertainty factor (10, 100 or 1,000), in
accordance with NAS/ODW guidelines.
L/day = assumed daily water consumption of a child
(1 L/day) or an adult (2 L/day).
One-day Health Advisory
No information was found in the available literature that was suitable
for determination of the One-day HA value for trifluralin. Therefore, it is
recommended that a modified DWEL (0.025 mg/L, calculated below) for a 10-kg
child be used as a conservative estimate for the One-day HA value.
For a 10-kg child, the adjusted DWEL is calculated as follows:
DWEL = (0-0025 mg/kg/day) (10 kg) = 0<025 mg/L
1 L/day
where:
0.0025 mg/kg/day » Rfd (see Lifetime Health Advisory Section).
1 0 kg = assumed body weight of a child.
1 L/day = assumed daily water consumption of a child.
Ten-day Health Advisory
No information was found in the available literature that was suitable
for determination of the Ten-day HA value for trifluralin. It is, therefore,
recommended that a modified JWEL (0.025 mg/L) for a 10-kg child be used as a
conservative estimate for the Ten-day HA value.
Longer-term Health Advisory
No information was found in the available literature that was suitable
for determination of the Longer-term HA value for trifluralin. It is, therefore,
recommended that a modified DWEL (0.025 mg/L) for a 10-kg child be used as a
conservative estimate for a Longer-term exposure.
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Lifetime Health Advisory
The Lifetime HA represents that portion of an individual's total exposure
that is attributed to drinking water and is considered protective of noncar-
cinogenic adverse health effects over a lifetime exposure. The Lifetime HA
is derived in a three-step process. Step 1 determines the Reference Dose
(RfD), formerly called the Acceptable Daily Intake (ADI). The RfD is an esti-
mate of a daily exposure to the human population that is likely to be without
appreciable risk of deleterious effects over a lifetime, and is derived from
the NOAEL (or LOAEL), identified from a chronic (or subchronic) study, divided
by an uncertainty factor(s). From the RfD, a Drinking Water Equivalent Level
(DWEL) can be determined (Step 2). A DWEL is a medium-specific (i.e., drinking
water) lifetime exposure level, assuming 100% exposure from that medium, at
which adverse, noncarcinogenic health effects would not be expected to occur.
The DWEL is derived from the multiplication of the RfD by the assumed body
weight of an adult and divided by the assumed daily water consumption of an
adult. The Lifetime HA is determined in Step 3 by factoring in other sources
of exposure, the relative source contribution (RSC). The RSC from drinking
water is based on actual exposure data or, if data'are not available, a
value of 20% is assumed for synthetic organic chemicals and a value of 10%
is assumed for inorganic chemicals. If the contaminant is classified as a
Group A or B carcinogen, according to the Agency's classification scheme of
carcinogenic potential (U.S. EPA, 1986), then caution should be exercised in
assessing the risks associated with lifetime exposure to this chemical.
The ELANCO (1985) study has been selected to serve as the basis for the
Lifetime HA value for trifluralin. F344 rats were fed diets containing
0.005, 0.02, 0.08, 0.32 or 0.64% trifluralin (2.5, 10, 40, 160 or 320
mg/kg/day) for 90 days. Significant increases in urinary alpha-1, alpha-2,
and beta-globulins were observed in all treated animals. A NOAEL was not
identified. Other longer-term studies report NOAELs at higher doses.
Using a LOAEL of 2.5 mg/kg/day, the Lifetime HA is calculated as follows:
Step 1: Determination of the Reference Dose (RfD)
RfD = (2.5 mg/kg/day) = 0.0025 mg/kg/day
(1,000) y
where:
2.5 lug/kg/day = LOAEL, based on increased urinary globulins in rats
consuming a trifluralin diet for 3 months.
1,000 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a LOAEL from an animal study.
Step 2: Determination of the Drinking Water Equivalent Level (DWEL)
DWEL = (0.0025 mg/kg/day) (70 kg) = 0.088 mg/L (87 u /L)
(2 L/day)
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where:
0.0025 mg/kg/day » RfD.
70 kg = assumed body weight of an adult.
2 L/day = assumed daily water consumption of an adult.
Step 3: Determination of the Lifetime Health Advisory
Lifetime HA - (0.088 mg/L) (20%) = Q.0017 mg/L (2 ug/L)
10
where:
0.088 mg/L = DWEL.
20% = assumed relative source contribution from water.
10 = additional uncertainty factor per ODW policy to
account for possible carcinogenicity.
Evaluation of Carcinogenic Potential
8 Applying the criteria described in EPA's guidelines for assessment
of carcinogenic risk (U.S. EPA, 1986b), trifluralin may be classified
in Group C: possible human carcinogen. This category is used for
substances that show limited evidence of carcinogenicity in animals
and inadequate evidence in humans.
0 In an NCI (1978) study of female B6C3F1 mice, a significant dose-
related increase in hepatocellular carcinomas and alveolar adenomas
was observed when the animals were exposed to 33 or 62 mg/kg/day
trifluralin in the diet for 78 weeks. The trifluralin used in this
study contained 84 to 88 ppm dipropylnitrosamine. Male rats, when
exposed to 30, 128 or 272 mg/kg/day trifluralin in the diet for 2
years, exhibited significant increases in the incidences in kidney,
urinary bladder and thyroid tumors (BLANCO, 1980a).
0 The evidence from the ELANCO (1980a) and NCI (1978) studies indicates
that trifluralin has carcinogenic potential. Based ( n the results of
the ELANCO (1980a) study, the U.S. EPA Carcinogen Assessment Group
(CAG) has prepared a quantitative risk estimate of trifluralin exposure
(U.S. EPA, 1981b). The CAG estimated a potency factor (q^*) of 7.66 x
10-3 mg/kg/day based on the combined incidence of tumors in male rats.
Assuming that a 70-kg human adult consumes 2 liters of water a day
over a 70-year lifespan, the estimated cancer risk would be 10-4,
10-5 and 10~6 at concentrations of 500, 50 and 5 ug/L, respectively.
VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
0 Residue tolerances from 0.05 to 2.0 ppm trifluralin have been established
for a variety of agricultural commodities (U.S. EPA, 1985).
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NAS (1977) has calculated an ADI of 0.1 rag/kg bw/day with a Suggested-
No-Adverse-Response-Level (SNARL) of 700 ug/L.
VII. ANALYTICAL METHODS
Determination of trifluralin is by a liquid-liquid extraction gas
chromatographic procedure applicable to the determination of organo-
chlorine pesticides in water samples (Standard Methods, 1985).
Specifically, the procedure involves extraction with a mixed solvent,
diethyl ether/hexane or methylene chloride/hexane. The extract is
concentrated by evaporation, and the compounds are separated by gas
chromatography. Detection and measurement are accomplished by the
use of an electron-capture detector. Additional confirmatory identi-
fication can be made through the use of two unlike columns or by mass
spectrometry.
VIII. TREATMENT TECHNOLOGIES
Available data indicate that reverse osmosis (RO), granular-activated
carbon (GAC) adsorption conventional treatment and possibly air
stripping will remove trifluralin from water.
U.S. EPA investigated the amenability of a number of compounds, including
trifluralin, to removal by GAC. No system performance data were given.
Conventional water treatment techniques of coagulation with alum,
sedimentation and filtration proved to be 100% effective in removing
trifluralin from contaminated water (Nye, 1984).
Sanders and Seibert (1983) determined experimentally water solubility,
vapor pressure, Henry's Law Constant and volatilization rates for
trifluralin; 100% of the compound volatilized under laboratory
conditions.
Treatment technologies for the removal of trifluralin from water are
available and have been reported to be effective. However, selection
of individual or combinations of technologies to attempt trifluralin
removal from water must be based on a case-by-case technical evaluation,
and an assessment of the economics involved.
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Programs.
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