820K88001
August, 1987
TERBUFOS
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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P - S - CH2 - S - C - CH3
Terbufos August, 1987
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II. GENERAL INFORMATION AND PROPERTIES
CAS No. 13071-79-9
Structural Formula
CH3
CH3CH20
CH3CH20
S-[[(1,1-Dimethylethyl)thio]methyl]0,0-diethyl phosphorodithioate
Syroryms
0 Counter; Cortraver (Meister, 1986).
Uses
0 Cortrol of corr rootworm and other soil insects and nematodes infesting
corn. Control of sugarbeet maggots in sugarbeets; green bug on
grain sorghum (Meister, 1986).
Properties (Windholz et al., 1983; Meister, 1986)
Chemical Formula CgHoiOoPSi
Molecular Weight 288.41
Physical State (room temp.) Clear, slightly brown liquid
Boiling Point 69°C/0.01 mm Hg
Melting Point -29.2°C
Density (246C) 1.105
Vapor Pressure (25°C) 34.6 mPa
Specific Gravity —
Water Solubility (25°C) 15 mg/L
Log Octanol/Water Partition 595
Coefficient
Taste Threshold
Odor Threshold
Conversion Factor ~
Technical 87 to 97% pure
Occurrence
0 Terbufos has been found in 444 of 2,016 surface water samples
analyzed and in 9 of 283 ground water samples (STORET, 1987).
Samples were collected at 55 surface water locations and 261 ground
water locations, and terbufos was found in 5 states. The 85th
percentile of all nonzero samples was .10 ug/L in surface water and
3 ug/L in ground water sources. The maximum concentration found
was 2.25 ug/L in surface water and 3 ug/L in ground water.
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Terbufos August, 1987
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Ervirormertal Fate
Forthcoming from OPP, EPA
III. PHARMACOKINETICS
Absorption
0 North (1973) reported that 83% of a single oral dose of technical
14c-terbufos (0.8 mg/kg) was excreted in the urine of rats 168 hours
after dosing. (The carbon atom of the thiomethyl portion of
terbufos was radiolabeled.) An additional 3.5% was recovered in
feces. This study indicates that terbufos was well absorbed (about
80 to 85%) from the gastrointestinal tract.
Distribution
0 North (1973) reported that maximum residues of cholinesterase-inhib-
iting compounds (phosphorylated metabolites), resulting from a single
oral dose of technical 14C-terbufos (0.8 mg/kg) given to rats, were
found in rat liver (0.08 ppm) 6 hours after dosing. In the same
study, residues of hydrolysis (nonphosphorylated metabolites) products
reached a maximum in rat kidney 12 hours after dosing (0.9 ppm).
After 168 hours, each body tissue in the rat contained less than
0.1 ppm radiolabeled) terbufos.
Metabolism
0 North (1973) reported that terbufos was extensively metabolized in
the rat. 14C-Radiolabeled terbufos was administered in a single dose
to 16 male wistar rats at a dose level of 0.8 mg/kg via gavage.
Examination of urine extracts by thin-layer chromatography (TLC)
showed the presence of 10 radiometabolites in the rat urine. Approxi-
mately 96% of the radioactivity present in the urine was composed of
an S-methylated series of metabolites, which result from the cleavage
of the sulfur-phosphorus bond, methylation of the liberated thiol group
and oxidation of the resulting sulfide to sulfoxides and sulfones.
Of the remaining radioactivity, about 2% was composed of various
oxidation products of the intact parent organophosphorus compound and
2% was an unknown metabolite.
Excretion
North (1973) reported that technical terbufos and its metabolites
were rapidly excreted in the urine of the rat. Radiolabeled terbufos
was administered in a single dose to male Wistar rats at a dose level
of 0.8 mg/kg by gavage. Of all the radioactivity recovered in the
urine, 50% was excreted after 15 hours. After 168 hours, the termina-
tion of the test, 83% of the terbufos was excreted via the urine and
3.5% was recovered in the feces.
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Terbufos
August, 1987
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IV. HEALTH EFFECTS
Humans
0 Petersor et al. (1984) reported the results of farm worker exposure
to Courter 15-G (a 15% granular formulation of terbufos). Five
farmers (one loader, one flagger and three scouts) were exposed for
varying time periods (loader, 5 minutes; flagger, 15 minutes;
scouts, twice for 30 minutes) during a typical workday while Counter
15-G was applied aerially to a young corn crop. The mean exposure
via inhalation was <0.25 ug/hour, the sensitivity of the monitoring
method, for all samples collected. The exposure values for the five
farm workers were: 331 ug/hour for the loader, 0 ug/hour for the
flagger, 381 ug/hour for scouts (after 3 days) and 250 ug/hour for
scouts (after 7 days). All of the farm workers were men and weighed
between 65..9 and 90.9 kg. Analysis of urinary metabolites showed no
indication of any adverse effects to any of the exposed workers. All
urinary alkyl phosphate analyses were negative (detection level,
0.1 ppm), indicating no significant absorption of terbufos. Plasma
and red blood cell cholinesterase values of the exposed workers
showed no significant (95% confidence level) decrease in activity
when compared to pre-exposed samples, indicating no adverse physiological
effects from exposures.
0 Devine et al. (1985) reported results similar to Peterson et al'. (1984)
for 11 farmers who were exposed to terbufos during a typical workday
while planting corn and applying Counter 15-G. The average estimated
dermal exposure was 72 ug/hour, and the estimated respiratory exposure
was 11 ug/hour. The results of urinary alkyl phosphate analyses were
all negative, showing no detectable absorption of terbufos. Plasma
and red blood cell cholinesterase (ChE) values of the exposed farmers
showed no significant difference in activity when compared to pre-
exposure or control values, indicating no adverse physiological
effects from the exposure. The report concluded that, based on the
study results, the use of Counter 15-G does not present a significant
hazard, in terms of acute toxicity, to farmers using this product for
the control of corn insects.
Animals
Short-term Exposure
0 Parke and Terrell (1976) reported that the acute oral 1*050 value
of technical-grade (86%) terbufos in wistar rats was 1.73 rag/kg.
Terbufos was administered in doses of 1.0 to 3.0 mg/kg via gavage in
corn oil to a total of 50 rats (10/sex/dose). Average weight of the
rats ranged from 200 to 300 g. The lowest dose (1.0 mg/kg) did not
result in any mortality. Observed effects to the rats weres respir-
atory depression, piloerection, clonic convulsions, exophthalmus,
ptosis, lacrimation, hemorrhage and decreased motor activity.
0 Consultox Laboratories (1975) reported that the acute oral LD5Q value of
technical-grade (86%) terbufos in male wistar rats was 1.5 mg/kg.
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Terbufos August, 1987
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Terbufos was administered by gavage ir doses of 0.50 to 2.5 mg/kg to a
total of 50 rats (10/sex/dose) at ar average weight of 200 ± 20 g.
No mortality was reported at the low dose (0.50 mg/kg). Ter> percent
mortality was reported at the 0.75-mg/kg dose. Other effects reported
were: salivation, diuresis, diarrhea, disorientation, chromodocryorrhea,
piloerection and body tremors.
8 American Cyanamid (1972a) reported acute oral 1,050 values (for 96.7%
technical-grade terbufos) in dogs, mice and rats of 4.5 mg/kg (male)/
6.3 mg/kg (female), 3.5 mg/kg (male)/9.2 mg/kg (female), and
4.5 mg/kg (male)/ 9.0 mg/kg (female), respectively. No details were
given as to age, weight or route of exposure.
0 American Cyanamid (1972b) reported additional acute oral LDso values
in male Wistar rats and female CF1 mice of 1.6 mg/kg and 5.0 mg/kg,
respectively. Other effects reported included cholinesterase inhibition
in both sexes.
0 Berger (1977) reported that plasma ChE was inhibited by as much as
79% in eight beagle dogs that were dosed via corn oil with
0.05 mg/kg/day technical terbufos for 28 days. Red blood cell ChE
was not inhibited at the dose tested.
Dermal/Ocular Effects
0 Kruger et al. (1973) conducted a subacute dermal toxicity test in
New Zealand White rabbits. Technical-grade terbufos was administered
at doses varying from 0.004 to 0.1 mg/kg to the shaved, abraded backs
of male and female rabbits (2.5 to 3.5 kg). All animals survived the
30-day test and showed no adverse effects with regard to food and
water intake, elimination, behavior, pharmacological effects and
weight gain differences. There were no observed changes in hemato-
logical determinations (hematocrit, total erythrocyte and total
leukocyte levels). Minor changes reported were increased numbers of
eosinophils and basophils in all groups, occasional minimal edema
that abated by day 21, and occasional mild erythema. All observed
changes occurred on intact and abraded skin sites.
0 American Cyanamid (1972a,b) conducted a series of tests with 96.7
and 85.8% terbufos using New Zealand White rabbits. Twenty male
rabbits (2.56 to 2.73 kg) were administered doses of 0.4 to 3.5 mg/kg
terbufos to their shaved backs. Dermal contact with terbufos was
maintained for 24 hours. The dermal LDgQ value was 1.0 mg/kg. An
acute dermal test with 96.7% terbufos resulted in an LDso of 1.1 mg/kg
in male rabbits (no other details were given). In another test with
96.7% terbufos, 0.5 mL (500 mg) of terbufos was applied to the backs
of rabbits; all of these animals died within 24 hours after dosing.
0 American Cyanamid (1972a) reported the results of an application of
0.1 mg of technical-grade (96.7%) terbufos to the'eyes of New Zealand
albino rabbits. All animals died within 2 to 24 hours after dosing.
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Long-term Exposure
c Daly et al. (1979) administered terbufos (90% active ingredient
(a.i.)) in the diet to groups of male and female Sprague-Dawley rats
(10/sex/group, 24 to 39 days old, 95 to 150 g) at levels of 0, 0.125,
0.25, 0.5 or 1.0 ppm (estimated doses of 0, 0.01, 0.02, 0.04 or 0.08
nig/kg/day based on feed conversions given by the authors) for 90
days. Body weights and food consumption were measured weekly. Blood
samples were obtained weekly and analyzed for plasma, erythrocyte and
brain ChE. Body organs were weighed and analyzed for histopathology.
The No-Observed-Adverse-Effect-Level (NOAEL) was determined to be
0.02 mg/kg/day, based on the absence of effects on ChE. The statistically
significant Lowest-Observed-Adverse-Effect-Level (LOAEL) was determined
to be 0.046 mg/kg based on the observed 17% decrease in plasma ChE in
females. There were no depressions of erythrocyte or brain ChE at
the highest dose tested (0.09 mg/kg/day). In addition, gross postmortem
observations and histopathologic evaluation of selected tissues
revealed no findings related to the test substance. Systemically, the
LOAEL for increased liver weight in females and for a dose-related
increase in liver extra-medullary hematopoiesis was 0.046 mg/kg/day.
The systemic NOAEL based on absence of liver effects was determined to be
0.02 mg/kg in this study.
0 Morgareidge et al. (1973) administered technical-grade terbufos in
the diet to groups of male and female beagle dogs (four/sex/group,
10 to 13 months old, 9.0 to 13.8 kg) at levels of 0.0025, 0.01 and 0.04
mg/kg/day, 6 days a week for 26 weeks. Plasma, red blood cell and
brain ChE levels, body weight and food, urinalysis, gross necropsy
examination and histopathology were evaluated. Observed effects
included a decrease in ChE activity in plasma at all dose levels;
however, decreased ChE activity was statistically significant only
for doses of 0.01 mg/kg/day and above. At 0.01 mg/kg/day, plasma ChE
was inhibited by 26% and red blood cell ChE was inhibited by 14%.
The systemic NOAEL was determined to be greater than the highest dose
tested (0.04 mg/kg/day). No statistical analyses were performed on
body weight changes, food consumption, hematology, clinical chemistry,
urinalyses and organ weight data. The LOAEL (based on ChE effects)
determined by the study was 0.01 mg/kg/day and the NOAEL was determined
to be 0.0025 mg/kg/day.
0 Rapp et al. (1974) administered technical-grade terbufos in the diet
to groups of Long-Evans rats (six/sex/dose, weanlings, 122 to 138.8 g)
at levels of 0.25, 1.0, 2.0, 4.0, and 8.0 ppm for 2 years. These doses
correspond to 0.0125, 0.05, 0.1, 0.2 and 0.4 mg/kg/day (Lehman, 1959.
The original high doses (2.0 ppm) were increased to 4.0 and then to
8.0 ppm for males, and were increased from 2.0 to 4.0 to 8.0 and then
reduced to 4.0 ppm for females. Body weight and food consumption
were measured weekly. Hematology, clinical chemistry and urinalyses
were also performed. Red blood cell ChE and brain ChE were significantly
inhibited at 0.05 mg/kg/day (20% inhibition for brain ChE and 43% for
red blood cell ChE in females) and above. Red blood'cell ChE was
also inhibited at 0.0125 mg/kg/day (12% in males and 15% in females).
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Terbufos August, 1987
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At the high dose (0.1 to 0.4 mg/kj/day), there was a noticeable inhibition
in mean body weight and mean food consumption. Mortality rates were
24 and 27% (males and females, respectively) at the high dose,
19% (males) at the mid-dose and 10% (males) at the low dose. The
incidence of exophthalmia was in high-dose females (exophthalmia was
also noted in low- and mid-dose control females). This study did not
establish a NOAEL. The LOAEL was equivalent to the lowest dose
tested (0.0125 mg/kg/day).
0 McConnell (1983) administered technical-grade terbufos in the diet to
groups of Long-Evans rats (60/dose/sex) at levels of 0.25, 1.0, 2.0,
4.0 and 8.0 ppm for 2 years. These doses are equivalent to 0.0125,
0.05, 0.1, 0.2 and 0.4 mg/kg/day (Lehman, 1959). The original high
dose (2.0 ppai) was increased to 4.0 and then 8.0 ppm for males after the
first 3 months, and increased from 2.0 to 4.0 to 8.0 and then reduced
to 4.0 ppm for females after the first 3 months. At the end of the
2-year study, tissues were prepared for microscopic examination.
Mortality occurred in all groups (control and test) due to broncho-
pneumonia, with mortality rates ranging from 17 to 35% in controls
and low-dose groups, respectively. Mortality rates at the high dose
(0.4 mg/kg/day) were 58% and 43% in male and female rats, respectively.
Other effects reported were gastric ulceration and/or erosion of
glandular and nonglandular stomach mucosa in high-dose rats. No
similar effect was seen in lowand mid-dose rats. Acute bronchopneumonia
and granuloma of lungs occurred in high-dose rats more frequently
than in low-dose, mid-dose or control rats. The authors reported
that lung inflammation did not appear directly associated with the
compound. No LOAEL or NOAEL was established in this study.
0 Shellenberger (1986) administered technical-grade terbufos (89.6% a.i.)
in capsule form to groups of beagle dogs (six/sex/dose, 6.8 to 7.5 kg,
5 to 6 months old) at doses of 0, 0.015, 0.060, 0.090, 0.120, 0.240 and
0.480 mg/kg/day for 1 year. High doses were eventually reduced to
0.090 and 0.060 mg/kg/day after the 8th week of the study. Body
weight and food consumption were measured together with assessment of
urinalyses, organ weights and cholinesterase levels. One male and one
female at the high dose and one female at 0.240 mg/kg/day were found
dead. At the two highest doses (0.240 and 0.480 mg/kg/day), decreased
body weights and food consumption were observed. Mean erythrocytic
parameters of high-dose males and females were significantly reduced at
3 months but not at 6 months jr at termination of the study. Plasma
ChE activity was significantly inhibited to 55% of controls at 0.015
mg/kg/day. Slight inhibition of erythrocyte ChE activity occurred at
0.120 mg/kg/day in females but not in males. No inhibition of erythrocyte
ChE in males or females was observed at the lower doses. Brain ChE
activities were similar for both sexes at all dose levels. Urinalyses and
organ weight data revealed no significant differences. The report
suggests that the NOAEL was 0.120 mg/kg/day in males and 0.090 mg/kg/day
in females.
Reproductive Effects
0 Smith and Kasner, (1972a) administered technical terbufos via the diet
to Long-Evans and Blue Spruce rats (10 males/dose, weighing 276.3 g; 20
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Terbufos August, 1987
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feraales/dose, weighing 185.6 g) for a period of 6 months at levels
of 0, 0.25 and 1 ppn. These levels correspond to doses of 0, 0.0125
and 0.05 mg/kg/day, based on a conversion factor of 0.05 for rats
(Lehman, 1959). The first parental generation (FQ) was. dosed for 60
days. No reproductive effects were observed in males or females at
any dose tested. The authors concluded that the reproductive NOAEL
was greater than 0.05 mg/kg/day, the highest dose tested.
Developmental Effects
0 MacKenzie (1984) administered terbufos (87.8% a.i.) by gavage to
groups of 18 female New Zealand White rabbits (3.5 kg) at levels of
0, 0.1, 0.2 and 0.4 ing/kg/day on days 7 to 19 of gestation. Reproductive
indices monitored were female mortality, corpora lutea or implants,
sex ratio, implantation efficiency, fetal body weight, fetal mortality
and steletal development. Cesarean sections were performed on day 29
of gestation. Survival of adult female rabbits was 100% in controls
and in the 0.2-mg/kg/day dose group; 89% in the 0.1-mg/kg/day dose
group; and 67% in the high-dose (0.4 mg/kg/day) group. There were
no statistically significant dose-related differences in mean body
weight, weight changes or gravid uterine weights, mean number of
corpora lutea, implantation efficiency, sex ratio, fetal body weight
or number of live or resorbing fetuses. The incidence of fetuses
with accessory left subclavian artery was significantly greater in
the high-dose (0.4 mg/kg/day) group. The incidence of an extra
unilateral rib and of chain fusion of sternebrae was significantly
lower in the high-dose group than in the controls. According to the
author, terbufos appears to be maternally toxic at 0.4 mg/kg/day, the
highest dose tested.
0 Rodwell (1985) administered terbufos (87.8% a.i.) via gavage to
groups of 25 Charles River female rats (226 to 282 g, 71-days old) at
doses of 0.05, 0.10 and 0.20 mg/kg/day on days 6 to 15 of gestation.
Cesareans sections were performed on day 20; half of the fetuses were
stained for skeletal evaluation. Parent survivability, body weight
and embryonic and fetal development were all assessed. All parents
survived the test. No changes in general appearance or behavior were
observed. Slightly decreased mean body weights were observed during
days 12 to 16 and following treatment in the 0.10- and 0.20-mg/kg/day
dose groups. The study demonstrates that terbufos is slightly
maternally t'^xic at dose levels of 0.10 and 0.20 mg/kg/day. A NOAEL
of 0.05 mg/kg/day, the lowest dose tested, was identified.
Mutagenicity
0 Thilager et al. (1983) reported that Chinese hamster ovary cells
tested with and without S-9 rat liver activation at concentrations of
100, 50, 25, 10, 5 and 2.5 nL/mL (ppm) terbufos did not cause any
significant increase in the frequencies of chromosomal aberrations.
Only a concentration of 100 nL/mL proved to be cytotoxic.
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Terbufos August, 1987
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0 Allen et al. (1983) conducted mutagenicity tests with terbufos
(87.8% a.i.) in the presence of metabolic activation and Chinese
hamster ovary cells and in the absence of S-9 activation. Initial
tests were conducted with doses of 100 to 10 ug/L, and then followed up
with activation at doses of 50, 42, 33, 25, 10 and 5 mg/ml. Terbufos
proved to be cytotoxic at 75 to 100 ug/mL with activation and at 50
to 70 mg/mL without activation. There were no increases in the
frequency of chromosomal aberrations. The authors concluded that
terbufos reflected a negative mutagenic potential.
0 Godeket al. (1983) conducted a rat hepatocyte primary culture/DNA
repair test with terbufos (87.8% a.i.) at doses ranging from 100 to
33 ug/well (a well contains 2 mL of media). Unscheduled DNA repair
synthesis was quantified by a net nuclear increase of black silver
grains for 50 cells/slide. This value was determined by taking a
nuclear count and three adjacent cytoplasmic counts (100 ug/well was
cytotoxic). The results for terbufos were negative in the rat hepato-
cyte primary culture/DNA repair test. These findings are based on
the inability of terbufos to produce a mean grain count of 5 or
greater than the vehicle-control mean grain count at any level. The
authors concluded that terbufos reflected a negative mutagenic
potential.
Carcinogenicity
0 Smith and Kasner (1972b) administered technical terbufos in the diet
to groups of mice (15/sex/dose) at levels of 0, 0.5, 2.0 and 8.0 ppm
for 18 months. These doses correspond to.0.075, 0.3 and 1.2 mg/Jq/day
(Lehman, 1959). The authors reported no signs of tumors or neoplasia.
Effects noted include alopecia and signs of ataxia; exophthalmia in
males, corneal cloudiness and opacity and eye rupture. Organ tissues
examined were liver, kidney, heart and lung. No pathological changes
in these four organs were observed.
0 Rapp et al. (1974) administered technical terbufos in the diet to
groups of Long-Evans rats (six/sex/dose) at levels of 0, 0.25, 1.0,
2.0, 4.0 and 8.0 ppn for 2 years. These doses correspond to 0.0125,
0.05, 0.1, 0.2 and 0.4 mg/kg/day (Lehman, 1959). There were no
indications of tumorigenic effects at any dose tested.
McConnell (1983) administered technical terbufos in the diet to
groups of Long-Evans rats (60/sex/dose) at levels of 0, 0.25, 1.0,
2.0, 4.0 and 8.0 ppm for 2 years. These doses correspond to 0,
0.125, 0.05, 0.1, 0.2 and 0.4 mg/kg/day (Lehman, 1959). The author
concluded that the compound had no effect on tumorigenesis.
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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Terbufos August, 1987
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HA = (NOAEL or LOAEL) x (BW) = mg/L ( /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 the determination of the One-day HA value for terbufos. It is, therefore,
recommended that the Ten-day HA value for a 10-kg child (0.005 mg/L, calculated
below) be used at this time as a conservative estimate of the One-day HA value.
Ten-day Health Advisory
The teratogenicity study in rats by Rodwell (1985) has been selected to
serve as the basis for the Ten-day HA value for terbufos. Pregnant rats
administered terbufos via gavage at a level of 0.05 mg/kg/day showed no
clinical signs of toxicity in the adult animals and no reproductive or terato-
genic effects in the fetuses. The study identified a NOAEL of 0.05 mg/kg/day.
These results are supported by the results of studies by MacKenzie (1984)
with rabbits and by Smith and Kasner (1972a) with rats.
Using a NOAEL of 0.05 mg/kg/day, the Ten-day HA for a 10-kg child is
calculated as follows:
Ten-day HA = (0.05 mg/kg/day) (10 kg) = 0>005 /L (5 /L)
(100) (1 L/day)
where:
0.05 mg/kg/day = NOAEL, based on the absence of clinical signs of
toxicity and the lack of reproductive or teratogenic
effects in rats exposed to terbufos via gavage for
10 days during gestation.
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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Longer-term Health Advisories
No suitable studies were available to serve as the basis for the Longer-
term HA value for terbufos. It is recommended, however, that the modified
Drinking Water Equivalent Level (DWEL) (adjusted for a 10-kg child) be used as
a conservative estimate for a longer-term exposure. Accordingly, the Longer-term
HA for a 10-kg child is 0.00025 mg/L and the Longer-term HA for an adult is
0.00088 mg/L.
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
noncarcinogenic 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, 1986a), then caution should be exercised in
assessing the risks associated with lifetime exposure to this chemical.
The 6-month feeding study in beagle dogs by Morgareidge et al. (1973)
has been selected to serve as the basis for the Lifetime HA value for terbufos.
In this study, beagle dogs were administered terbufos in the diet at doses of
0.0025, 0.01 and 0.04 mg/kg/day. At 0.01 mg/kg/day and above, plasma and red
blood cell ChE activity were significantly inhibited. At 0.01 mg/kg/day,
plasma ChE was inhibited by 26% and red blood cell ChE was inhibited by 14%.
These effects were not observed at 0.0025 mg/kg/day, which was identified as
the NOAEL. Other studies were not selected because a clear NOAEL was not
identifed or the respective NOAELs/LOAELs were an order of magnitude
higher than the NOAEL derived from the Morgareidge et al. (1973) study.
Using this study, the Lifetime HA is calculated as follows:
Step 1: Determination of the Reference Dose (RfD)
= (0-0025 mg/kg/day) = 0.000025 mg/kg/day
(100) y
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where:
0.0025 mg/kg/day = NOAEL, based on absence of inhibition of cholin-
esterase in beagles exposed to terbufos in the
diet for 6 months (180 days).
100 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a NOAEL from an animal study.
Step 2i Determination of the Drinking Water Equivalent Level (DWEL)
DWEL = (0.000025 mg/kg/day) (70 kg) = 0.00088 mg/L/day (0.88 ug/L)
(2 L/day)
where:
0.000025 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 = (0.00088 mg/L) (20%) = 0.00018 mg/L (0.18 ug/L)
where:
0.00088 mg/L = DWEL.
20% = assumed relative source contribution from water.
Evaluation of Carcinogenic Potential
0 The International Agency for Research on Cancer has not evaluated the
carcinogenic potential of terbufos.
0 The U. S. EPA's Cancer Assessment Group (CAG) has assessed the carcino-
genic potential of terbufos and has concluded that there are not
enough data to determine whether terbufos is carcinogenic.
0 Applying the criteria described in EPA's guidelines for assessment of
carcinogenic risk (U.S. EPA, 1986a), terbufos may be classified in
Group E: no evidence of carcinogenicity for humans. This group is for
substances that show no evidence of carcinogenicity in at least two
adequate animal tests in different species or in both epidemiologic
and animal studies. The studies by Smith and Kasner (1972b) on mice
and by Rapp et al. (1974) and McConnell (1983) on rats reported no
statistically significant influence on the incidence of neoplasms or
tumors at any dose level tested.
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VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
0 No other criteria, guidance or standards were found in the available
literature.
VII. ANALYTICAL METHODS
0 Analysis of terbufos is by a gas chromatographic (GC) method applicable
to the determination of certain nitrogen-phosphorus containing
pesticides in water samples (U.S. EPA, 1986b). In this method,
approximately 1 liter of sample is extracted with methylene chloride.
The extract is concentrated and the compounds are separated using
capillary collumn GC. Measurement is made using a nitrogen-phosphorus
detector. The method detection limit has not been determined for
this compound but it is estimated that the detection limits for the
method analytes are in the range of 0.1 to 2 ug/L.
VIII. TREATMENT TECHNOLOGIES
0 No data were found for the removal of terbufos from drinking water by
conventional treatment.
0 No data were found on the removal of terbufos from drinking water by
activated carbon adsorption. However, due to its low solubility and
high molecular weight, terbufos probably would be amenable to activated
carbon adsorption.
No data were found on the removal of terbufos from drinking water by
ion exchange. However, the structure of this ester indicates that it
is not ionic and thus probably would not be amenable to ion exchange.
0 No data were found for the removal of terbufos from drinking water by
aeration. However, the Henry's Coefficient can be estimated from
available data on solubility (10 to 15 mg/L) and vapor pressure
(0.01 mm Hg at 69°C). Terbufos probably would not be amenable to
aeration or air stripping because its Henry's Coefficient is
approximately 12 atm.
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