820K88002
ujgust, 1987
TERBACIL
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
anv one of these models is able to predict risk more accurately than another.
Because each model is based on differing assumptions, the estimates chat are
derived can differ by several orders of magnitude.
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Terbacil August, 1987
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II. GENERAL INFORMATION AND PROPERTIES
CAS No. 5902-51-2
Structural Formula
Cl
5-Chloro-3-(1,1-dimethylethyl)-6-methyl-2,4(lH,3H)-pyrimidinedione
Synonyms
0 Sinbar; Turbacil (Meister, 1983).
Uses
0 Herbicide used for the selective control of annual and perennial weeds
in crops such as sugarcane, alfalfa, apples, peaches, blueberries,
strawberries, citrus, pecans and mint (Meister, 1983).
Properties (Meister, 1983)
Chemical Formula • CgHj 302N2C1
Molecular Weight 216.65
Physical State (at 25°C) White crystals
Boiling Point (at 25 mm Hg)
Melting Point 175-177°c
Vapor Pressure (54CC) 5.4 x 10~6 mm Hg
Specific Gravity —
Water Solubility (25°C) 710 mg/L
Log Octanol/Water Partition -1.41
Coefficient
Taste Threshold
Odor Threshold
Conversion Factor
Occurrence
0 Terbacil was not sampled at any water supply stations listed in the
STORET database (STORET, 1987). No information was found in available
literature on the occurrence of terbacil.
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Environmental Fate
0 14c-Terbacil at 5 ppm was stable (less than 2% degraded) in buffered
aqueous solutions at pH 5, 7, and 9 for 6 weeks at 15°C in the dark
(Davidson et al. 1978).
0 After 4 weeks of irradiation with UV light (300 to 400 run), about 16%
of the applied 14c-terbacil (5 ppm) was photodegraded in distilled
water (pH 6.2) (Davidson et al., 1978).
0 Soil metabolism studies indicate that terbacil is persistent in soil.
At 100 ppm, terbacil was slowly degraded in an aerobic sandy loam
soil (80% remained after 8 months) (Marsh and Davies, 1978). Terbacil
at 8 ppm had a half-life of about 5 months in aerobic loam soil
(Zimdahl et al., 1970). 14c-Terbacil at 2 ppm had a half-life of
2 to 3 months in aerobic silt loam and sandy loam soils (Rhodes, 1975;
Gardiner, 1964; Gardiner et al., 1969). The formation of carbon
dioxide is slow; for example, 28% of the applied 14c-terbacil at 2.88
ppm on sandy loam soil degraded to carbon dioxide in 600 days (Wolf,
1973; Wolf, 1974; Wolf and Martin, 1974).
0 Degradation of terbacil in an anaerobic soil environment is also slow.
In anaerobic silt loam and sandy soils, 14c-terbacil at 2.1 ppm was
slightly degraded (less than 5% after 60 days) in the dark (Rhodes,
1975). Only trace amounts of 14C-terbacil, applied at 2.88 ppm, were
degraded to 14c-carbon dioxide after 145 days in an anaerobic environment
when metabolized by microbes in the dark (Rhodes, 1975). At least
90% of the lable remained as terbacil after 90 days of incubation in
both sterile and nonsterile soils. Small amounts (0.8 to 1.5% of the
label of carbon dioxide were evolved from nonsterile soil, whereas
0.01% was evolved from sterile soil (Rhodes, 1975).
0 Terbacil was mobile in soil columns of sandy loam and fine sandy soil
(Rhodes, 1975; Mansell et al., 1972). However, in a silt loam soil
column, only 0.4% of the applied 14C-terbacil leached with 20 inches
of water (Rhodes, 1975). In an aged soil column leaching study of
the leaching characteristics of degradates, about 52% and 4% of the
applied radioactivity in aged sandy loam and silt loam soils leached,
respectively (Rhodes, 1975). Terbacil phytotoxic residues were
mobile to depths of 27.5 to 30 cm in a sandy soil column treated with
terbacil at 5.6 kg/ha and eluted with 10 or 20 cm water (Marriage,
1977). Terbacil was negligibly adsorbed to soils ranging in texture
from sand to clay (Davidson et al., 1978; Liu et al., 1971; Rao and
Davison, 1979). Terbacil was adsorbed (54%) to a muck soil (36%
organic matter) (Liu et al., 1971).
0 Data from field dissipation studies showed that terbacil persistence
in soil varied with application rate, soil type and rainfall. In
the field, terbacil phytotoxic residues persisted in soil for up to
16 months following a single application of terbacil. Residues were
found at the maximum depths sampled (3 to 43 inches) (Gardiner, undated
a,b; Gardiner et al., 1969; Isom et al., 1969; Isom et al., 1970; Liu
et al., undated; Mansell et al., 1977; Mansell et al., 1979; Morrow
and Mccarty, 1976; Rahman, 1977; Rhodes, 1975).
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Terbacil August, 1987
8 Phytotoxic residues resulting from multiple applications of terbacil
persisted for 1 to more than 2 years following the final application
(Skroch et al., 1971; Tucker and Phillips, 1970; Benson, 1973;
Doughty, 1978).
0 Terbacil has not been found in ground water; however, its soil
persistence and mobility indicate that it has the potential to get
into ground water.
III. PHARMACOKINETICS
Absorption
0 No information was found in the available literature on the absorption
of terbacil.
Distribution
0 No information was found in the available literature on the distribution
of terbacil.
Metabolism
0 No information was found in the available literature on the metabolism
of terbacil.
Excretioji
0 No information was found in the available literature on the excretion
of terbacil.
IV. HEALTH EFFECTS
Humans
No information was found in the available literature on the health
effects of terbacil in humans.
Animals
Short-term Exposure
0 It was not possible to perform an acute oral toxicity study in dogs
because repeated emesis prevented dosing with terbacil in amounts in
excess of 5,000 mg/kg (Paynter, 1966). However, in a dog receiving
one oral dose of terbacil at 250 mg/kg followed 5 days later by a
dose of 100 mg/kg, emesis, diarrhea and mydriasis were noted.
* -In rats (details not available), the LD50 was between 5,000 and 7,500
mg/kg (Sherman, 1965). At 2,250 mg/kg, inactivity, weight loss and
incoordination were noted.
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Dermal/Ocular Effects
0 Hood (1966) reported that no compound-related clinical or pathological
changes were observed when terbacil was applied to the clipped dorsal
skin of rabbits (five males, five females) at a dose level of 5,000
rag/kg (as a 55% aqueous paste), for 5 hours/day, 5 days/week for
3 weeks (15 applications). The parameters observed included body
weight, dermal reaction, organ weights and histopathology.
0 Reinke (1965) reported that no dermal reactions were observed when
terbacil was administered to the intact dorsal skin of 10 guinea pigs
as a 15% solution in 1:1 acetoneidioxane containing 13% guinea pig fat.
0 Reinke (1965) reported no observed sensitization in ten albino guinea
pigs when terbacil was administered nine times during a 3-week period,
with half of the animals in each group receiving dermal applications
on aoraded dorsal sHn and the others receiving intradermal injections.
After 2 wee is, the animals were challenged by application of terbacil
to intact and abraded skin. The challenge application was repeated
2 weeks later.
Long-term Exposure
0 Wazeter et al. (1964) administered terbacil, 82.7% (a.i.), in the
diet to Charles River pathogen-free albino rats (20/sex/level) at
levels of 0, 100, 500 or 5,000 ppm of a.i. for 90 days. This corresponds
to doses of about 0, 5, 25 or 250 mg/kg/day based on the dietary
assumptions of Lehman (1959). The parameters observed included body
weight, food consumption, hematology, liver function tests, urinalyses,
organ weights and gross and histologic pathology. No adverse effects
with respect to behavior and appearance were noted. All rats survived
to the end of the study. No effect on body weight gain was observed
in either sex when terbacil was administered at 5 or 25 mg/kg/day.
Females administered 250 mg/kg/day gained slightly less weight (15%)
than controls. Males at this level showed no effect. No compound-
related hematological or biochemical changes were found, and urinalyses
were normal at all times. No gross or microscopic pathological
changes were noted in animals administered terbacil at 5 or 25 mg/kg/day.
Morphological changes in animals receiving the highest dose level
were limited to the liver and consisted of statistically significant
increases in liver weights. This change was accompanied by a moderate-
to-marked hypertrophy of hepatic parenchymal cells associated with
vacuolation of scattered hepatocytes. Similar microscopic changes,
but with reduced severity, were found in one rat at the 25 mg/kg/day
level. This study identified a Lowest-Observed-Adverse-Effect-Level
(LOAEL) of 25 mg/kg/day and a No-Observed-Adverse-Effect-Level (NOAEL)
of 5 mg/kg/day.
0 Goldenthal et al. (1981) administered terbacil (97.8% a.i.) in the
diet to CD-I mice (80/sex/level) at levels of 0, 50, 1,250 or 5,000 to
7,500 ppm for 2 years. Based on the dietary assumptions of Lehman
(1959), 1 ppm in the diet of mice is equivalent to 0.15 mg/kg/day;
therefore, these levels correspond to doses of about 0, 7.5, 187 or
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Terbacil August, 1987
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750 to 1,125 mg/kg/day. The 5,000-ppm dose level was increased
slowly to 7,500 ppm by week 54 of the study. Mortality was signifi-
cantly higher (p <0.05) in mice at the high dosage levels throughout
the study. No changes considered biologically important or compound-
related occurred in the hematological parameters. An increased
incidence of hepatocellular hypertrophy was seen microscopically in
male and female mice administered 750 to 1,125 mg/kg/day and in male
mice administered 187 mg/kg/day. An increased incidence of hyperplastac
liver nodules also occurred in male mice administered 750 to 1,125
ing/kg/day. Female mice from the 187-mg/kg/day group and both male
and female mice from the 7.5-mg/kg/day group were free of compound-
related microscopic lesions. This study identified a LOAEL of
187 mg/kg/day and a NOAEL of 7.5 mg/kg/day.
Wazeter et al. d967b) administered terbacil (80% a.i.) in the diet
to CD albino rats (36/sex/level) at levels of 0, 50, 250 or 2,500 ppm
to 10,000 ppm of a.i. for 2 years. Based on the dietary assumptions
of Lehman (1959), 1 ppm in the diet of a rat corresponds to
0.05 mg/kg/day; therefore, these dietary levels correspond to doses
of about 0, 2.5, 12.5 or 125 to 500 mg/kg/day. The 2,500 ppm level
was increased slowly to 10,000 ppm by week 46 of the study. No
adverse compound-related alterations in behavior or appearance occurred
in any test group. No significant differences in body weight gain in
males and females administered 2.5 or 12.5 mg/kg/day were observed.
Rats administered 125 to 500 mg/kg/day exhibited a significantly
lower rate of body weight gain. This difference occurred early and
became more pronounced with time in the female rats than in the male
rats. Maximum differences were 14 to 17% in the male rats and 24 to
27% in the females when compared to the controls. No compound-related
gross pathological lesions were seen at necropsy in rats from any
groups. The only compound-related variation in organ weights was a
slight increase in liver weights among rats from the 125- to
500-mg/kg/day dose level at final sacrifice. Histological changes
were observed in the livers of rats fed terbacil at 12.5 mg/kg/day
for 1 year and in the high-dose group fed 125 to 500 mg/kg/day for
1 and 2 years. These changes consisted of enlargement and occasional
vacuolation of centrilobular hepatocytes. No compound-related microscopic
changes were observed in livers or in any tissues examined in rats from
the 12.5-mg/kg/day group sacrificed after 2 years. Due to an outbreak
of respiratory congestion observed in all study groups at week 27,
all animals were placed on antibiotic treatment (tetracycline hydrochloride)
at a dose level of 25 mg/kg/day in drinking water for 1 week. In the
29th week, all rats were administered 50,000 units of penicillin G
intra-muscularly and 1/16 g of streptomycin. Some rats still exhibiting
respiratory congestion were administered a second dose on the following
day. This study identified a LOAEL of 125 to 500 mg/kg/day, based on
irreversible histological changes in the liver, and a NOAEL of
12.5 mg/kg/day.
Wazeter et al. (1966) administered terbacil (80% a.i.) in the diet to
young purebred beagle dogs (4 to 6 months old, four/ sex/dose) at
dose levels of 0, 50, 250 or 2,500 to 10,000 ppm of a.i. for 2 years.
Based on the dietary assumptions of Lehman (1959), 1 ppm in the diet
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Terbacil August, 1987
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of a dog corresponds to 0.025 mg/kg/day; therefore, these dietary
levels correspond to approximately 0, 1.25, 6.25 or 62.5 to
250 mg/kg/day. The 2,500-ppm level was gradually increased to
10,000 ppm from week 26 to week 46 of the study. All animals underwent
periodic physical examinations, hematologic tests, and determinations
of 24-hour alkaline phosphatase, prothrombin time, serum glutamate
oxaloacetate transaminase (SCOT), serum glutamate pyrurate transaminase
(SGPT) and cholesterol. No adverse compoundrelated alterations in
behavior or appearance occurred among any of the control or treated
dogs. No mortalities occurred during the 2-year course of treatment.
Although there were some fluctuations in body weight throughout the
study, these were not considered to be compound-related. No alterations
in hematology, plasma biochemistry or urinalysis were observed. No
compound-related gross or microscopic pathological changes were seen
in any of the dogs sacrificed after 1 or 2 years of feeding. A
slight increase in relative liver weights and elevated alkaline
phosphatase occurred in dogs from the 62.5- to 250-mg/kg/day group
and the 6.25-mg/kg/day group, which were sacrificed after 1 or
2 years. Also at 6.25 mg/kg/day, there was an increase in thyroid-
to-body weight ratio. This study identified a NOAEL of 1.25 mg/kg/day
(50 ppm) and a LOAEL of 6.25 mg/kg (250 ppm).
Reproductive Effects
0 Wazeter et al. (1967a) administered terbacil (80% a.i.) in the diet
to male and female rats of three generations (10 males and 10 females
per level per generation) at dietary levels of 0, 50 or 250 ppm of
a.i. 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
dietary levels correspond to doses of about 2.5 or 12.5 mg/kg/day.
Each parental generation was administered terbacil in the diet for
100 days prior to mating. No abnormalities in behavior, appearance
or food consumption of the parental rats were observed in any of the
three generations. Males at the 12.5 mg/kg/day level in all three
generations exhibited reduced body weight gains. Females in all
three generations were similar to controls in body weight gain. No
abnormalities were observed in the breeding cycle of any of the three
generations relative to the fertility of the parental male and female
rats, development of the embryos and fetuses, abortions, deliveries,
live births, sizes of the litters, viability of the newborn, survival
of the pups until weaning o- growth of the pups during the nursing
period. Gross examination of pups surviving at weaning from both
litters of all three generations did not reveal any evidence of
abnormalities. No compound-related histopathological lesions were
observed in any of the tissues examined from weanlings of the F^
litter. This study identified a NOAEL of 2.5 mg/kg/day and a LOAEL
of 12.5 mg/kg/day.
Developmental Effects
0 E.I. DuPont (1984a) administered terbacil by gavage as a 0.5% suspen-
sion in methyl cellulose to groups of 18 female New Zealand white
rabbits (5 months old) from days 7 to 19 of gestation at dose levels
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Terbacil August, 1987
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of 0, 30, 200 or 600 mg/kg/day. Maternal mortality was significantly
increased (p £0.05) at the 600-mg/kg/day level. Additional indicators
of maternal toxicity at 600-mg/kg/day were a significant increase
(p_<0.05) in adverse clinical signs (anorexia and liquid or semi-solid
yellow, orange or red discharges found below the cages) and a significant
decrease (p <0.05) in body weight gain. Mean body weight gains and
the incidence of adverse effects were similar in controls and in the
30- and 200-mg/kg/day groups. Fetal toxicity at doses of 600 mg/kg/day
included a significant decrease (p _
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Terbacil August, 1987
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since genetic assays did not indicate the induction of chromosomal
breakage or loss.
Carcinogenicity
0 Goldenthal et al. (1981) administered terbacil (97.8% a.i.) in the
diet to CD-1 mice (80/sex/level) at levels of 0, 50, 1,250 or
5,000 to 7,500 ppm for 2 years. These levels correspond to doses of
about 0, 7.5, 187 or 750 to 1,125 mg/kg/day (Lehman, 1959). The
5,000-ppm dose level was increased slowly to 7,500 ppm by week 54 of
the study. The authors reported no increased incidence of cancer in
the treated animals.
0 Wazeter et al. (1967b) administered terbacil (80% a.i.) in the diet
to CD albino rats (36/sex/level) at levels of 0, 50, 250 or 2,500 to
10,000 ppm of active ingredient for 2 years. These levels
correspond to doses of about 0, 2.5, 12.5 or 125 to 500 mg/kg/day
(Lehman, 1959). The authors reported no evidence of compound-related
carcinogenic effects.
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:
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 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 terbacil. It is, therefore,
recommended that the Ten-day HA value for a 10-kg child, 0.24 mg/L (240 ug/L),
calculated below, be used at this time as a conservative estimate of the
One-day HA value.
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Ten-day Health Advisory
The dietary reproductive study in rats by Wazeter et al. (1967a) has
been selected to serve as the basis for the Ten-day HA value for terbacil.
It identifies a LOAEL of 12.5 mg/L, based on a reduced body weight gain in
the males in all three generations, and a NOAEL of 2.5 mg/kg/day, yielding
a Ten-day HA of 0.25 mg/L (see calculation below). The teratology study in
rats by Culik et al. (1980) provides support for this conclusion. This teratology
study identifies a LOAEL of 23 mg/L (no doses lower than 23 mg/kg/day were
tested) and essentially the same Ten-day HA value (0.23 mg/L) can be derived
from this LOAEL by using an uncertainty factor of 1,000.
The Ten-day HA for a 10-kg child is calculated as follows:
Ten-day HA = (2.5 mg/kg/day) (10 kg) = 0.25 mg/L (250 ug/L)
(100) (1 L/day)
where:
2.5 mg/kg/day = NOAEL, based on absence of reduced body weight gain in
male rats.
10 kg = assumed body weight of a child.
100 = uncertainty factor, chosen in accordance with 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 Advisory
The dietary reproductive study in rats by Wazeter et al. (1967a) has been
selected to serve as the basis for the Longer-term HA values for terbacil. A
NOAEL of 2.5 mg/kg/day is identified in this study. A 90-day subchronic study
in rats (Wazeter et al., 1964) identifying a NOAEL of 5 mg/kg/day supports
this conclusion.
The Longer-term HA for a 10-kg child is calculated as follows:
Longer-term HA = (2.5 mg/kg/day) (10 kg) = 0<25 mg/L (250 ug/L)
(100) (1 L/day)
where:
2.5 mg/kg/day = NOAEL, based on absence of reduced body weight gain
in male rats.
10 kg = assumed body weight of a child.
100 = uncertainty factor, chosen in accordance with 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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The Longer-term HA for a 70-kg adult is calculated as follows:
Longer-term HA = (2.5 mg/kg/day) (70 kg) „ Q.875 mg/L (875 ug/L)
(100) (2 L/day)
where:
2.5 mg/kg/day = NOAEL, based on absence of reduced body weight gain
in male rats.
70 kg = assumed body weight of an adult.
100 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal study.
2 L/day = assumed daily water consumption of an adult.
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 wit! lifetime exposure to this chemical.
The 2-year dog feeding study by Wazeter et al. (1966), selected to serve
as the basis for the Lifetime HA value for terbacil, identifies a NOAEL of
1.25 mg/kg/day, based on relative liver weight increases and an increase in
alkaline phosphatase. A number of other studies provide information that
supports the conclusion that the overall NOAEL for lifetime exposure of rats,
mice and dogs to terbacil is less than 25 mg/kg/day. These include a 2-year
feeding study in mice that identifies a NOAEL of 7.5 mg/kg/day for liver
changes (Goldenthal, 1981) and a 2-year feeding study in rats that identifies
a NOAEL of 12.5 mg/kg/day for lower body weight gain and liver effects (Wazeter
et al., 1967b).
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Using a NOAEL of 1.25 mg/kg/day, the Lifetime HA is calculated as follows:
Step 1: Determination of the Reference Dose (RfD)
RfD = (1.25 mg/kg/day) = 0.0125 mg/kg/day
doo) y y
where:
1.25 mg/kg/day = NOAEL, based on slight increase in relative liver
weight and elevated alkaline phosphatase.
100 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal study.
Step 2: Determination of the Drinking Water Equivalent Level (DWEL)
DWEL = (0.0125 mg/kg/day) (70 kg) = 0<44 mg/L (440 ug/L}
(2 L/day)
where:
0.0125 mg/kg/day = RfD.
70 kg = assumed body weight of adult.
2 L/day = assumed daily water consumption of an adult.
Step 3: Determination of the Lifetime Health Advisory
Lifetime HA = (0.44 mg/L) (20%) = 0.09 mg/L (90 ug/L)
where:
0.44 mg/L = DWEL.
20% = assumed relative source contribution from water.
Evaluation of Carcinogenic Potential
0 The Interritional Agency for Research on Cancer has not evaluated the
carcinogenic potential of terbacil.
0 Applying the criteria described in EPA's guidelines for assessment of
carcinogenic risk (U.S. EPA, 1986), terbacil may be classified in
Group E: evidence of noncarcinogenicity for humans. This category is
used for substances that show no evidence of carcinogenicity in at
least two adequate animal tests or in both epidemiologic and animal
studies. Studies by Goldenthal et al. (1981) and Wazeter et al.
(1967b) reported no induction of any carcinogenic effect in mice or
rats, respectively, administered terbacil in the diet for 2 years.
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VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
0 Tolerances have been established for residues of terbacil in or on
many agricultural commodities by the U.S. EPA
Office of Pesticide Programs
(U.S. EPA, 1985a).
VII. ANALYTICAL METHODS
0 Analysis of terbacil is by a gas chromatographic method applicable
to the determination of certain organonitrogen pesticides in water
samples (U.S. EPA, 1985b). This method requires a solvent extraction
of approximately 1 L of sample with methylene chloride using a
separatory funnel. The methylene chloride extract is dried and exchanged
to acetone during concentration to a volume of 10 mL or less. The
compounds in the extract are separated by gas chromatography, and
measurement is made with a thermionic bead detector. The method
detection limit for terbacil has not been determined.
VIII. TREATMENT TECHNOLOGIES
0 Treatment technologies currently available have not been tested for
their effectiveness in removing terbacil from drinking water.
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IX. REFERENCES
Benson, N.R. 1973. Efficacy, leaching and persistence of herbicides in
apple orchards. Bulletin No. 863. Washington State University, College
of Agriculture Research Center.
Culik, R., C.K. Wood, A.M. Kaplan et al.* 1980. Teratogenicity study in
rats with 3-tert-butyl-5-chloro-6-methyluracil. Haskell Laboratory
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