August, L988
TEBUTHIURON
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. Healtn
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.
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. Hi is 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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GENERAL INFORMATION AND PROPERTIES
CAS No. 34014-18-1
Structural Formula VT
N—N CH3
?3 // \\ l
H3C - c C C N — C-NH- CH3
I «'
ch3 s 0
N-[5-(1,1-Dimethyl ethyl>-1,3,4-thiadiazol-2-yl]-N,N1-dimethylurea
Synonyms
0 Combine; Herbic; Graslan; Perflan; Spike.
Uses
° Herbicide for total vegetation woody plant control in noncropland
areas and for brush and weed control in rangeland (Meister, 1983).
Properties (Meister, 1983)
Chemical Formula
Molecular Weight
Physical State (25°C)
Boiling Point
Melting Point
Density
Vapor Pressure (25°C)
Specific Gravity
Water Solubility (25°C, pH 7)
Log Octanol/Water Partition
Coefficient
Taste Threshold
Odor Threshold
Conversion Factor
CgH-j gON^jS
228 (calculated)
White crystalline, odorless powder;
colorless solid
159 to 1 61 °C
2 x 10~® mm Hg
2,500 mg/L
1.79
Occurrence
° No occurrence data has been found in the STORET database (STORET, 1988).
Environmental Fate
° Tebuthiuron is resistant to hydrolysis. 1^C-Tebuthiuron, at 10
and 100 ppm, did not degrade during 64 days of incubation in sterile
aqueous solutions at pH 3, 6 and 9 in the dark at 25°C (Mosier and
Saunders, 1976).
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° After 23 days of irradiation with artificial light (20-vr black light),
tebuthiuron accounted for 87 to 89% of the applied radioactivity in
deionized (pH 7.1) and natural (pH 8.1) water treated with thiadiazole
ring-labeled 14C-tebuthiuron at 25 ppm (Elanco Products Company, 1972;
Rainey and Magnussen, 1976b). After 15 days of irradiation with a
black light or a sunlamp, tebuthiuron accounted for approximately
82 and 53%, respectively, of the applied compound in natural water
treated with 14C-tebuthiuron at 2.5 ppm.
° Thiadiazole ring-labeled 1^C-tebuthiuron in loam soil degraded from
8 ppm immediately post-treatment to 5.7 ppa at 273 days posttreatment
indicating a half-life greater than 273 days (Rainey and Magnussen,
1976a, 1978).
o 14c-Tebuthiuron, at 1.0 ppm, degraded with a half-life of greater
than 48 weeks in a loam soil maintained under anaerobic conditions in
the dark at 23°C (Berard, 1977). U-[5-(1,1-Dimethylethyl)-1,3,4-
thiadiazol-2-yl]-N-methylurea was the ma)or degradate.
° Ring-labeled 14C-tebuthiuron was very mobile {>94% of that applied
was found in the leachate) in a 12-inch column of Lakeland £ine sand
soil leached with 20 inches of water (Holzer et al., 1972). It was
mobile in columns of loamy sand (approximately 73% at 6 to 10 inches),
loam (approximately 84% at 1 to 8 inches) and muck (100% at 0 to 4
inches) soils leached with 4 to 8 inches of water.
° Based on column leacning studies, tebuthiuron is mobile to very mobile
in loam, loamy sand, and Lakeland sand soils and has low mobility m
silty loam soil (Day, 1976a).
° 14c-Tebuthiuron residues aged 30 days were mobile in a column of
sandy loam soil; 39% of 14c-residues were found in the soil and 40%
of ^C-residues were in the leachate (Day, 1976b).
° 14C-Tebuthiuron degraded with half-lives of greater than 33 months
in field plots in California (loam soil), 12 to 15 months in Louisiana
(clay soil), and 12 to 15 months in Xndiana (loam soil). The three
sites were treated with thiadiazole ring-labeled 14C-tebuthiuron at
8.96f 2*24 and 8.96 kg/ha, respectively (Rainey and Magnussen, 1976a,
1978). H-[5-(1,1-Dime thyle thy1)-1,3,4-thiadiazol-2-yl]-N-methylurea
was the major degradate at all three sites. Radioactivity was detected
in the 15- to 30-cm depth of soil (10.2% of the applied compound at
18 months) at the California site, in the 30- to 45-cm depth of soil
(1.3% of the applied compound at 33 months) at the Louisiana site,
and in the 30- to 45-cn depth of soil (4.7% of the applied compound
at 15 months) at the Indiana site. 14c-Tebuthiuron residues did not
appear to accumulate in silt loam soil in Louisiana after three
applications of 14C-tebuthiuron (0.84 kg/ha at zero time; 1.4 kg/ha at
22 and 73 weeks).
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III. PHARMACOKINETICS
Absorption
° Morton and Hoffman (1976) reported that 94 to 96% of a single oral
dose of tebuthiuron (10 mg/kg) was excreted in the ur.ine of rats,
rabbits and dogs. In mice, 66% was excreted in the urine, and 30% in
the feces, these data indicate that tebuthiuron was well absorbed
(about 70 to 96%) from the gastrointestinal tract.
Distribution
° No quantitative data were found in the available literature on the
tissue distribution of tebuthiuron in exposed animals.
° Adams et al. (1982) administered tebuthiuron in the diet to 20
pregnant Wistar rats at levels of 100 or 200 ppm for 6 days prior
to delivery. Forty-eight hours after delivery, radiolabeled tebu-
thiuron was reintroduced into the diet at the same levels as before.
Radioactive label was detected in the milk at mean levels of 2.7 and
6.2 ppm for the 100- and 200-ppm groups, respectively.
Metabolism
° Morton and Hoffman (1976) reported that tebuthiuron was metabolized
extensively by mice, rats, rabbits and dogs. Tebuthiuron was
administered by gavage to male and female ICR mice, Harlan rats,
Dutch-Beli-®d rabbits and beagle dogs at a dose of 10 mg/kg. Examin-
ation of urine extracts by thin-layer chromatography (TLC) showed the
presence of eight radioactively labeled metabolites in rat, rabbit
and dog urine and seven in mouse urine. Small amounts of unchanged
tebuthiuron also were detected in each case (except for the mouse).
The ma^or metabolites were formed by N-demethylation of the substituted
urea side-chain in each species examined. Oxidation of the dimethylethyl
group also occurred in all species examined.
Excretion
° Morton and Hoffman (1976) reported that tebuthiuron was excreted
rapidly in the urine of several species. Radiolabeled tebuthiuron
was administered to male and female ICR mice, Harlan rats, Dutch-
Belted rabbits and beagle dogs at a dose of 10 mg/kg by gavage.
Elimination of radioactivity was virtually complete within 72 hours
and recovery values at 96 hours were 96.3, 94.5, 94.3 and 95.7% in
the mouse, rat, rabbit and dog, respectively. In the rats, rabbits
and dogs, the radioactivity was excreted almost exclusively in the
urine. In the mice, 30% of the radioactivity was excreted in the
feces.
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HEALTH EFFECTS
Humans
" No information on the health effects of tebuthiuron in humans was
found in the available literature.
Animals
Short-term Exposure
° Todd et al. (1974) reported the acute oral LD50 values of tebuthiuron
in rats, mice and rabbits to be 644, 579 and 286 mg/kg, respectively.
In cats, oral doses of 200 mg/kg were not lethal, while 500 mg/kg
given orally was not lethal to dogs, quail, ducks or chickens.
0 Todd et al. (1972a) supplied 40 weanling Sprague-Dawley rats <105-146g)
with food containing tebuthiuron (purity not stated) at levels of
2,500 ppm for 15 days. At various time periods, 5 rats were necropsied
and evaluated. Based on the dietary assumptions of Lehman (1959),
1 ppm in the diet of a rat is equivalent to 0.05 mg/kg/day; therefore,
this level corresponds to 125 mg/kg/day. The animals were observed
for an additional 15-day recovery period. All the animals exhibited
reduced body weight gain during the treatment period. Light and
electron microscopic evaluation revealed formation of vacuoles containing
electron-dense bodies and myeloid figures in pancreatic acinar cells.
This condition was rapidly reversed during the recovery period.
Dermal/Ocular Effects
0 Todd et al. (1974) administered 200 mg/kg tebuthiuron to the shaved,
abraded backs of male and female New Zealand White rabbits. During
the study, one rabbit died following development of diarrhea and
emaciation. All surviving rabbits gained weight over the 14-day
observation period and were without signs of dermal irritation.
0 Todd et al. (1974) tested tebuthiuron for sensitization in 2- to
3-iaonth-old female albino guinea pigs. Each animal received topical
applications of 0.1 mL of an ethanolic solution containing 2% tebu-
thiuron to the region of the flank three times per week for 3 weeks.
Ten days after the last of the nine treatments, a challenge application
was made, followed by a second challenge 15 days after the first.
Tebuthiuron induced no dermal or systemic responses indicative of
contact sensitization.
0 Todd et al. (1974) instilled 0.1 mL (71 mg) of tebuthiuron into one
eye and conjunctival sac of each of six New Zealand White rabbits (2-
to 3-months old). No irritation of the cornea or iris was observed,
but there was slight transient hyperemia of the conjunctiva.
All eyes were normal by the end of the 7-day test period.
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Long-term Exposure
° Todd et al. (1972b) administered tebuthiuron (purity not stated) in
the diet to groups of male and female Harlan rats (1O/sex/group, 28-
to 35-days old, 74 to 156 g) at levels of 0, 40, 100 or 250 mg/kg/day
for 3 months. Body weights and food consumption were measured weekly.
Blood obtained prior to necropsy was evaluated for blood sugar, blood
urea nitrogen (BON) and serum glutamic-pyruvic transaminase (SGPT).
Sections of organs and tissues were prepared for gross and microscopic
evaluation. There were no clinical signs of toxicity or mortality in
any of the groups. A moderate reduction in body weight gain and a
decrease in efficiency of food utilization in males and females in
the highest dose group (250 mg/kg/day) was evident from week 1 of the
study. Tebuthiuron had no clinically important effects on any of the
hematological or clinical chemistry parameters measured. All rats
receiving 250 mg/kg/day tebuthiuron showed diffuse vacuolation of
the pancreatic acinar cells. The degree of this change ranged from
slight to moderate, but the effect was not associated with necrosis
or with the presence of an inflammatory response. One female rat
receiving 100 mg/kg/day tebuthiuron showed very slight pancreatic
changes. Based on these results, a No-Observed-Adverse-Effect-Level
(NOAEL) of 40 mg/kg/day and a Lowest-Observed-Adverse-Effect-Level
(LOAEL) of 100 mg/kg/day were identified.
° Todd et al. (1972c) administered tebuthiuron (purity not stated) in
gelatin capsules to groups of four beagle dogs (two/sex/group, 13- to
23-months old, 7 to 23 kg) at dose levels of 0, 12.5, 25 or 50 mg/kg/day
for 3 months. The physical condition of the animals was assessed
daily, and body weights were recorded weekly. Gross and microscopic
histopathology examinations were performed. Anorexia was noted,
especially in the high-dose animals, leading to some weight loss.
There was no mortality. Behavior and appearance were unremarkable at
all test levels. No abnormalities were seen in the hematological or
urinalysis studies. Clinical chemistry findings indicated increased
BUN in the 50-mg/kg females. In addition, this group and the 50-mg/kg
males exhibited increasing levels of alkaline phosphatase, up to
four-fold over those of controls; however, these levels had returned to
normal at the terminal sampling. There were no urinary abnormalities.
The 25-mg/kg females and males demonstrated increased thyroid-to-body
weight ratios, and the 50-mg/kg females also showed increased spleen-
to-body weight ratios. Histopathological findings were unremarkable.
The LOAEL was identified as 25 mg/kg, based on increased thyroid-to-
body weight ratios and increased alkaline phosphatase values. A
NOAEL of 12.5 mg/kg was identified.
0 Todd et al. (1976a) administered tebuthiuron (purity > 97%)
in the diet to groups of Harlan rats (40/sex/dose) for 2 years at
dietary levels of 0, 400, 800 or 1,600 ppm. Based on the dietary
assumptions of Lehman (1959), 1 ppm in the diet of a rat is equivalent
to 0.05 mg/kg/day; therefore, these doses correspond to 20, 40 or
80 mg/kg/day. Physical appearance, behavior, food intake, body
weight gain and mortality were recorded. Hematologic and blood
chemistry values were obtained throughout the study; urinalysis was
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also performed. At necropsy, organ weights were determined and
organs and tissues were examined grossly and histologically. Mortality
in exposed animals was similar to, or less than, that observed in the
control group. Variations in hematology, blood chemistry and urinalysis
data from all groups were slight and unrelated to the test compound.
Reduced body weight gain (10% or greater) was observed in the highest
dose group animals. There was also a slight increase in the kidney
weights of the high-dose males. Microscopic examination revealed a
low incidence of slight vacuolation of the pancreatic acinar cells in
animals in the highest dose group. Hie NOAEL for this study, based
on acinar vacuolation, was 40 mg/kg.
0 Todd et al. (1976b) administered tebuthiuron (purity not stated) in
the diet for 2 years to groups of Harlan ICR mice (40/sex/dose) at
levels of 0, 400, 800 or 1,600 ppm. Based on the dietary assumptions
of Lehman (1959), t ppm in the diet of a mouse is equivalent to 0.150
mg/kg/day; therefore, these dietary levels correspond to approximately
60, 120 or 240 ing/kg/day. Physical appearance, behavior, appetite,
body weight gain and mortality were recorded. Hematologic, blood
chemistry and organ weight values were obtained for animals surviving
the test period. Gross and microscopic evaluations were conducted on
organs and tissues obtained at necropsy. No important differences
were observed between treated and control groups for any of the
parameters evaluated. The vacuolation of pancreatic acinar cells
noted in the Todd (1976a) rat studies was not evident in this study
in mice. Based on this, the NOAEL for this study was identified as
240 mg/kg/day.
Reproductive Effects
0 Hoyt et al. (1981) studied the effects of tebuthiuron (98% active
ingredient) in a two-generation reproduction study in rats. Weanling
Wistar rats (25/sex/dose, Fq generation) were maintained on diets
containing tebuthiuron at 0, 100, 200, and 400 ppm based on the
active ingredient (0, 7, 14 or 28 mg/kg/day, based on actual food
consumption) for a period of 101 days preceding two breeding trials.
First generation (F^) offspring were maintained on the same diets for
a period of 124 days preceding two breeding trials. Spermatogenesis
and sperm morphology were examined in 10 Fq males per treatment
group. In addition, representative Fla and F2a weanlings and F-| adults
were necropsied and given histopathologic examinations after live-phase
observations were completed. No changes in the efficiency of food
utilization (EFU) were noted during the Fq growth period, but during
the F^ growth period, a statistically significant (p £0.05) depression
in cumulative (124 days) EFU values occurred in both male and female
rats receiving 28 mg/kg/day, EFU was not affected at the other dose
levels. A dose-related depression in mean body weight occurred among
female rats of the F^ generation receiving 14 or 28 mg/kg/day; mean
body weight was depressed significantly (p £0.05) only in the high-
dose females. In the 7 mg/kg/day group, body weights of either sex
were not affected. The reproductive capacity of the animals was not
affected at any level; no dose-related conditions or lesions were
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August, 1988
found in any offspring. In adult males from the Fq generation, no
dose-related histologic lesions were found, and sperm morphology and
spermatogenesis were normal. A LOAEL of 14 mg/kg/day was determined
for a lower rate of body weight gain during the 101-day pre-mating
period in F1 females, and a NOAEL of 7 mg/kg/day, the lowest dose
tested, was identified.
Developmental Effects
° Todd et al. (1972d) administered tebuthiuron (purity not stated) in
the diet to groups of 25 adult Histar-denved female rats (245 to
454 g) at levels of 0, 600, 1,200 or 1,800 ppm based on the active
ingredient (0, 30, 60 or 90 mg/kg/day, based on Lehman, 1959) on days
6 to 15 of gestation. Fetal and uterine parameters were normal and
the fetal defects that occurred were not attributed to the test
compound, ttie NOAEL for developmental effects was greater than
1,800 ppm, the highest dose tested.
° Todd et al. (1975) administered tebuthiuron (purity not stated) by
gavage to groups of 15 adult female Dutch-Belted rabbits at levels of
10 or 25 mg/kg/day on days 6 to 18 of gestation. No developmental or
toxic effects were observed.
Mutagenicity
° Hill (1984) reported that primary cultures of adult rat hepatocytes
incubated with concentrations of tebuthiuron ranging from 0.5 to
1,000 ug/mL did not exhibit unscheduled DNA synthesis.
0 Rexroat (1984) reported that tebuthiuron did not induce Salmonella
revertants (strains TA1535, 1537, 1538, 98 and 100) when tested at
concentrations ranging between 100 and 5,000 ug/plate, with or without
metabolic activation. It was concluded that tebuthiuron was not
mutagenic in the Ames Salmonella/mammalian microsome test for bacterial
mutation.
° Neal (1984) reported that tebuthiuron did not induce sister chromatid
exchange i_n vivo in bone marrow cells of Chinese hamsters administered
oral doses of 200, 300, 400 or 500 mg/kg tebuthiuron.
° Cline et al. (1978) reported that histadine autotrophs of Salmonella
typhimurium (strains G46, TA1535, 100, 1537, 1538, 98, C3076 and
D3052) and tryptophan auxotrophs of Escherichia coli were not
reverted to the prototype by tebuthiuron at levels of 0.1 to 1,000
ug/mL, with or without metabolic activation.
Carcinogenicity
° Todd et al. (1976a) administered tebuthiuron (purity > 97%) in the
diet to groups of Harlan rats (40/sex/dose) at levels of 0, 400, 800
or 1,600 ppm based on the active ingredient (0, 20, 40 or 80 mg/kg/day,
based on Lehman, 1959) for 2 years. The authors reported no influence
of the test compound on the incidence of neoplasms at any dose level.
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° Todd et al. (1976b) administered tebuthiuron in the diet to groups
of Harlan ICR mice (40/sex/dose) at levels of 0, 400, 800 or 1,600
ppm (0, 60, 120 or 240 mg/kg/day, based on Lehman, 1959] for 2 years.
The authors reported no statistical evidence of increased incidence
of tumors at any dose level.
V. QUANTIFICATION OF TOXICOLOGICAL EFFECTS
Health Advisories (HAs) are generally determined for one-day, ten-day,
longer-term (up to 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:
HA = (NOAEL or LOAEL) X (BW) = mg/L ( ug/L)
(UF) x ( L/day)
where:
NOAEL or LOAEL ¦ No- or Lowest-Observed-Adverse-Effect Level
in nig/kg bw/day.
BW - assumed body weight of a child (10 kg) or
an adult (70 kg).
UF = uncertainty factor (10, 100, 1,000 or 10,000),
in accordance with EPA or KAS/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 the determination of the One-day HA value for tebuthiuron. It is therefore
recommended that the Ten-day value for a 10-kg child, 2.5 mg/L (3,000 ug/L,
calculated below), be used at this time as a conservative estimate of the
One-day HA value.
Ten-day Health Advisory
The study by Todd et al. (1975) has been selected to serve as the basis
for the Ten-day HA value for tebuthiuron because the NOAEL in the Dutch-Belted
rabbit was the lowest end point observed in a short-term developmental study.
This study identified a NOAEL of 25 mg/kg/day (the highest dose tested) based
on an absence of maternal toxicity. In another developmental study in rats
by Todd et al. (1972d), a NOAEL of 90 mg/kg/day (the highest dose tested) was
recorded. Since it is unknown whether the rabbit or the rat is more sensitive,
the lower NOAEL was conservatively chosen in deriving the 10-day HA.
Using a NOAEL of 25 mg/kg/day, the Ten-day HA for a 10-kg child is
calculated as follows:
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Ten-day HA = (25 mg/kg/day) (10 kg) = 2.5 mg/L (3,000 ug/L)
(100) (1 L/day)
where:
25 mg/kg/day = NOAEL, based on the absence of maternal toxicity in
Dutch-Belted rabbits exposed to tebuthiuron by diet.
10 kg = assumed body weight of a child.
100 = uncertainty factor, chosen in accordance with EPA
or NAS/ODW guidelines for use with a NOAEL from an
animal study.
1 L/day = assumed daily water consumption of a child.
Longer-term Health Advisories
The two-generation reproduction study in rats (Hoyt et al., 1981) has
been chosen to serve as the basis for the Longer-term HA for tebuthiuron.
In this study, four groups of Wistar rats (25/sex) were fed tebuthiuron
at 0, 7, 14, and 28 mg/kg/day in the diet for 101 days (F0 rats) or 121
days (rats) and then for a further period sufficient to mate, deliver,
and rear two successive litters of young to 21 days of age. No adverse
effects were reported- in this study except -for a lower body weight gain
during premating period in Fj_ females at the dietary levels of 14 and
28 mg/kg. The NOAEL was identified as 7 mg/kg/day. The chronic study
by Todd et al. (1976b) in mice was not selected because the weight loss
and vacuolization of pancreatic acinar cells noted in rats was not observed
in mice even at dose levels as high as 160 mg/kg/day, indicating that the
mouse is less sensitive than the rat. The subchronic (90-day) feeding
study in beagle dogs reported by Todd et al. (1972) was not selected
because the NOAEL (12.5 mg/kg/day) identified in that study was significantly
higher than that of tha rat study. In addition, the..duration<_of the rat
study was more appropriate for the derivation of a Longer-term HA.
Using the NOAEL of 7 mg/kg/day, the Longer-term HA for a 10-kg child is
calculated as follows:
Longer-term HA « (7 mg/kg/day) (10 kg) = 0.7 mg/L (700 ug/L)
(100) (1 L/day)
where:
7 mg/kg/day » NOAEL, based on effects on the rate of weight gain in
rats exposed to tebuthiuron in the diet for 101 days.
100 - uncertainty factor, chosen in accordance with EPA
or NAS/ODW guidelines for use with a NOAEL from an
animal study.
1 L/day = assumed daily water consumption of a child.
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weight loss and vacuolation of pancreatic acinar cells noted in rats was not
observed in mice even at dose levels as high as 160 mg/kg/day, indicating
that the mouse is less sensitive than the rat.
Using the NOAEL of 7 mg/kg/day, the Lifetime HA is calculated as follows:
Step 1: Determination of the Reference Dose (Rf D)
RfD = (7 mg/kg/day) = o.07 mgAg/day
(100)
where:
7 mg/kg/day = NOAEL, based on effects on the rate of weight gain in
rats exposed to tebuthiuron in the diet for 101 days.
100 = uncertainty factor, chosen in accordance with EPA
or NAS/ODW guidelines for use with a NOAEL from an
animal study.
Step 2: Determination of the Drinking Water Equivalent Level (DWEL)
DWEL - (0.07 mg/kg/day) (70 kg) = 2.45 mg/L (2,000 ug/L)
(2 L/day)
where:
0.07 mg/kg/day «* RfD.
70 kg o assumed body weight of an adult.
2 L/day a assumed daily water consumption of an adult.
Step 3: Determination of the Lifetime Health Advisory
Lifetime HA = (2.45 mg/L) (20%) = 0.49 mg/L (500 ug/L)
where:
2.45 mg/L - DWEL.
20% *» assumed relative source contribution from water.
Evaluation of Carcinogenic Potential
° The International Agency for Research on Cancer has not evaluated the
carcinogenic potential of tebuthiuron.
0 Applying the criteria described in EPA's guidelines for assessment
of carcinogenic risk (U.S. EPA, 1986), tebuthiuron may be classified
in Group D: not classifiable as to human carcinogenicity. This
category is for substances with inadequate human and animal evidence
of carcinogenicity.
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VI. OTHER CRITERIA, GUIDANCE AMP STANDARDS
° No other criteria, guidance or standards were found in the available
literature.
VII. ANALYTICAL METHODS
° Analysis of tebuthiuron is by a gas chromatographic (GC) method
applicable to the determination of certain nitrogen-phosphorus-
contaimng pesticides in water samples (U.S. EPA, 1988). In this
method, approximately 1 liter of sample is extracted with methylene
chloride. The extract is concentrated and the compounds are separated
using capillary column GC. Measurement is made using a nitrogen
phosphorus detector. This method has been validated in a single
laboratory, and estimated detection limit for the analytes in the
method, such as tebuthiuron, is 1.3 ug/L.
VIII. TREATMENT TECHNOLOGIES
° No information on treatment technologies capable of effectively
removing tebuthiuron from contaminated water was found in the available
literature.
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REFERENCES
Adams, E., J. Magnussen, J. Qnmerson et al.* 1982. Radiocarbon levels in the
milX of lactating rats given 14C-tebuthiuron (compound 75503) in the diet.
Eli Lilly and Company, Greenfield, IN. Unpublished study. MRID 00106081.
Berard, D.F.* 1977. 1^c-Tebuthiuron degradation study in anaerobic soil.
Prepared and submitted by Eli Lilly and Co., Greenfield, IN.
MRID 00900098.
Cline, J.C., G.Z. Thompson and R.I. McMahon.* 1978. The effect of Lilly Com-
pound 75503 (tebuthiuron) upon bacterial systems known to detect mutagenic
events. Eli Lilly and Company, Greenfield, IN. Unpublished study.
MRID 000416090.
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