820K88113
August, 1987
METRIBUZIN
Health Advisory
Office of Drinking Water
U.S. Environmental Protection Agency
DRAFT
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, Logifor 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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II. GENERAL INFORMATION AND PROPERTIES
CAS No. 21087-64-9
Structural Formula
4-Amino-6-(1,1-dimethylethyl)-3-methylthio-1,2,4-triazin-5(4H)-one
Synonyms
0 Bayer 6159; Bayer 6443H; Bayer 94337; Lexone; Sencor; Sencoral;
Sencorer; Sencorex
Uses
o
Herbicide used for the control of a large number of grass and broadleaf
weeds infesting agricultural crops (Meister, 1983).
Properties (CHEMLAB, 1985)
Chemical Formula CQH14ON4S
Molecular Weight 214.28
Physical State (at 25°C) white crystalline solid
Boiling Point —
Melting Point 125-126°C
Density —
Vapor Pressure (25°C) 10~5 nraHg (20°C)
Specific Gravity
Water Solubility (25eC) 1,200 mg/L
Log Octanol/Water Partition -5.00 (calculated)
Coefficient
Taste Threshold
Odor Threshold —
Conversion Factor —
Occurrence
0 Metribuzin has been found in 1,517 of 3,580 surface water samples
analyzed and in 54 of 240 ground water samples (STORET, 1987). These
samples were collected at 407 surface water locations and 204 ground
water locations; metribuzin was found in 14 states. The 85th
percentile of all nonzero samples was 4.79 ug/L in surface water and
0.1 ug/L in ground water sources. The maximum concentration found in
surface water was 22.79 Ug/L and in ground water, 1.25 ug/L.
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0 Metribuzin has been found in Iowa ground water resulting from
agricultural uses; typical positives were 1 to 4.3 ppb (Cohen et al.,
1986).
Environmental Fate
0 The rate of hydrolysis of metribuzin is pH dependent. During a
28-day test, little or no degradation was observed at pH 6 or 9 at
25°C, or at pH 6 at 37°C or 52°C (Day et al., 1976).
o 14c-Metribuzin on silty clay soil degraded, with a half-life of 15
days, when exposed to natural sunlight (Khasawinah, 1972). The half-life
in control samples kept in the dark was 56 days. After 10 weeks,
20.6, 6.5 and 7.0% of the applied radioactivity was present in the
irradiated soil as 6-t-butyl-l,2,4-triazin-3,5-(2H,4H)-dione (DADK),
6-t-butyl-3-(methylthio)-l,2,4-trizin-5(4H)-one (DA) and parent compound,
respectively. A substantial portion of the applied radioactivity
(56%) was bound to the soil. In the dark control, 4.6, 16.9, 44.0 and
34% of the applied radioactivity was present as DADK, DA, parent or
bound compound, respectively.
0 Under aerobic conditions, metribuzin at 10 ppm degraded with a
half-life of 35-63 days in silt loam and sandy loam soils treated
with a 50% wettable powder (WP) formulation, and 63 days in soils
treated with a 4-lb/gal FlC formulation (Pither and Gronberg, 1976).
Degradates found were: 6-t-butyl-l,2,4-triazin-3,5-(2H,4H)-dione
(DADK); 4-amino-6-butyl-l-2,4,-triazin-3,5-(2H,4H)-dione (DK); and
6-t-butyl-3-(methylthio)-l,2,4-triazin-5-(4H)-one (DA).
0 14c-Metribuzin residues degraded slowly in silty clay soil under
anaerobic conditions with a half-life of more than 70 days (Khasawinah,
1972). After 10 weeks of incubation, 10, 10.9, 57, and 19% of the
applied radioactivity was present as DADK, DA, parent compound or
bound to the soil, respectively.
0 Metribuzin adsorption was significantly correlated to soil organic
matter, clay and bar soil water contents (Savage, 1976). Calculated
K<3 values ranged from 0.27 for a sandy loam soil (0.75% organic
matter, 11% clay and 12% bf 0.33 bar soil water content), to 3.41 for
a clay soil (42% organic matter, 71% clay and 42% of 0.33 bar soil
water content).
o 14c-Metribuzin residues were very mobile in Amarillo sandy loam and
Louisiana Commerce silt loam soils; after leaching 12-inch soil
columns with 20 inches of water, 96.6 and 91.6% of the applied radio-
activity, respectively, was found in the leachate (Houseworth and
Tweedy, 1973). !4C-Metribuzin residues were relatively immobile in
Indiana silt loam and New York muck soils; after leaching 12-inch
soil columns, 90.6 and 89.4% of the applied radioactivity was detected
in the top 3 cm of the Indiana silt loam and New York muck, soil
columns, respectively. No radioactivity was detected in column
leachates.
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0 14c-Metribuzin residues (test substance not characterized) aged 30
days were moderately mobile in an Amarillo sandy loam soil column;
after leaching a 12-inch column with 22.5 inches of water, 7.3% of
the applied radioactivity was found in the leachate (Tweedy and
Houseworth, 1974). In the soil column, 85.2% of the applied radio-
activity remained within the top 2 inches.
o 14c-Metribuzin residues (test substance not characterized) were
intermediately mobile in sandy clay loam and silt loam soils
(Rf 0.61 to 0.62) and mobile in sandy, sandy loam, and two silty
clay soils (Rf 0.68 to 0.77), based on soil thin-layer chromatography
(TIC) tests (Thornton et al. , 1976). 14c-Metribuzin residues (test
substance not characterized) were intermediately mobile in sand (Rf
0.61), sandy clay loam (Rf 0.64), two silty clay soils (Rf 0.62 and
0.71), silt loam (Rf 0.66) and sandy loam (Rf 0.82) soils, based on
soil TLC tests (Obrist and Thorton, 1979). 14c-Metribuzin (purity not
specified) at 1.5 ug/spot had low mobility (Rf 0.13 to 0.26) in two
muck soils and intermediate mobility (Rf 0.42 to 0.53) in six mineral
soils ranging in texture from sand to clay, based on soil TLC plates
developed in water (Sharon and Stephenson, 1976).
0 In the field, metribuzin dissipates with half-lives of less than
1 month to 6 months. Three metribuzin degradates were detected:
6-t-butyl-l,2,4-triain-3,5-(2H,4H)-dione (DADK); 4-amino-6-t-butyl-
l,2,4-triazin-3,5-(2H,4H)-dione (DK); and 6-t-butyl-3-(methylthio)l,2,4-
triazin-5-(4H)-one (DA). Soil type and characteristics, chemical
formulation or application rates did not discernibly affect the
dissipation rate of metribuzin (Stanley and Schumann, 1969; Finlayson,
1972; Rockwell, 1972a; Rockwell, 1972b; Rockwell, 1972c; Rowehl,
1972a; Rowehl, 1972b; Schultz, 1972; Mobay Chemical, 1973; Fisher,
1974; Murphy, 1974; United States Borax and Chemical Corp., 1974;
Potts et al., 1975; Analytical Biochemistry Laboratories, 1976;
Ballantine, 1976; and Ford, 1979).
III. PHARMACOKINETICS
Absorption
0 A study was conducted in four dogs using oral dosing of radiolabeled
metribuzin (Khasawinah, 1972) to evaluate absorption, distribution
and metabolites. Analysis of blood samples showed a peak level
at 4 hours.
Distribution --
0 No information was found in the available literature on the distribution
of metribuzin.
Metabolism
0 No information was found in the available literature on the metabolism
of metribuzin.
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Excretion
0 Khasawinah (1972) reported that 52 to 60% of the administered dose of
metribuzin in dogs was excreted in the urine and 30% in the feces.
IV. HEALTH EFFECTS
Humans
No information was found in the available literature on the health
effects of metribuzin in humans.
Animals
Short-term Exposure
0 Crawford and Anderson (1974) reported the acute oral LD50 values
following the administration of technical metribuzin to guinea pigs
and rats as 245 and 1,090 mg/kg, respectively, for male animals,
and 274 and 1,206 mg/kg, respectively, for females.
0 Mobay Chemical (1978) reported the acute oral LD50 values for a
wettable granular formulation of metribuzin to be 2,379 and
2,794 mg/kg for male and female rats, respectively.
0 Mobay Chemical (1978) reported the acute dermal LD50 for a wettable
granular formulation of metribuzin to be >5,000 mg/kg for both male
and female rats.
0 Mobay Chemical (1978) reported the acute (1-hour) inhalation LC5Q in
rats for a wettable granular formulation to be >20 mg/L.
Dermal/Ocular Effects
0 In studies conducted by Mobay Chemical (1978), metribuzin (wettable
granular) was determined to be a very slight irritant to rabbit eyes
and skin.
Long-term Exposure
0 Loser et al. (1969) administered metribuzin to Wistar rats (15/sex/dose)
for 3 months in their feed at levels of 0, 50, 150, 500 or 1,500 ppm
(about 2.5, 7.5, 25 or 75 mg/kg/day, bashed on calculations in Lehman
et al., 1959). Following treatment, food consumption, growth, body
weight, organ weight, clinical chemistry, hematology, urinalysis and
histopathology were measured. No significant efects on these parameters
were observed in either sex at 50 ppm (2.5 mg/kg/day). Among females,
enlarged livers were found in the 150, 500 or 1,500 ppm (7.5, 25 or
75 mg/kg/day) dosage groups (p <0.05), and thyroid glands were also
enlarged in the 500 or 1,500 ppm (25 or 75 mg/kg/day) groups (p <0.05
and p <0.01, respectively). In the males, enlarged thyroids were
reported among the 500 (25 mg/kg/day) (p <0.05) and 1,500 ppm
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(75 mg/kg/day) (p <0.01) dosage groups, while an enlarged heart was
reported at 1,500 ppm (75 mg/kg/day) (p <0.05). At 1,500 ppm
(75 mg/kg/day), lower body weights (p <0.01) were reported in both
sexes when compared to untreated controls.
0 In studies conducted by Lindberg and Richter (1970), beagle dogs
(four/sex/dose) administered oral doses of 50, 150 or 500 ppm (about
1.25, 3.75 or 12.5 mg/kg/day, based on calculations in Lehman et al.,
1959) technical metribuzin for 90 days showed no significant differences
in body weights, food consumption, behavior, mortality, hematologic
findings, urinalysis, gross pathology or histopathology.
e Loser and Mirea (1974) reported that dietary concentrations of 1.5,
2 or 20 mg/kg/day metribuzin did not significantly affect physical
appearance, behavior, mortality, hematologic clinical chemistry,
urinalysis or histopathology in rats (40/sex/dose) fed technical
metribuzin in the diet for 24 months. The body weights of females at
the 20 mg/kg/day dose level were usually lower (p <0.05) than those of
controls; at the end of the test period, however,, no significant
differences were noted.
0 Hayes et al. (1981) administered technical metribuzin in the diet
to albino CD mice (50/sex/dose) at 200, 800 or 3,200 ppm (about 30,
120 or 480 mg/kg/day, based on calculations in Lehman et al., 1959)
for 24 months. Following treatment, feed consumption, general behavior,
body and organ weights, mortality, hematology and histopathology were
analyzed. No adverse effects were observed in these parameters in
either sex at 800 ppm (120 mg/kg/day). However, a significant
(p <0.05) increase in absolute and relative liver and kidney weights
was observed in female mice receiving 3,200 ppm (480 mg/kg/day).
0 In studies conducted by Loser and Mirea (1974), four groups of beagle
dogs (four/sex/dose) were administered metribuzin in the diet at dose
levels of 0, 25, 100 or 1,500 ppm (about 0, 0.625, 2.5 or 37.5 mg/kg/day,
based on calculations in Lehman, 1959) for 24 months. Following
treatment, food consumption, general behavior and appearance, clinical
chemistry, hematology, urinalysis, body and organ weights and histo-
pathology were evaluated. No toxicologic effects were reported in
animals administered 100 ppm metribuzin (2.5 mg/kg/day) or less for
any of the parameters measured. Necrosis of the renal tubular cells,
slight iron deposition as well as slight hyp°rglycemia and temporary
hypercholesterolemia were noted in animals administered 1,500 ppm
(37.5 mg/kg/day).
Reproductive Effects -~
0 In a 3-generation reproduction study. Loser and Siegmund (1974)
administered technical metribuzin in the feed at dose levels of 0,
35, 100 or 300 ppm (about 0, 1.75, 5 or 15 mg/kg/day, based on
calculations in Lehman et al., 1959) to FB30 (Elberfeld breed) rats
during mating, gestation and lactation. Following treatment,
fertility, lactation performance and pup development were evaluated.
No treatment-related effects were reported at any dose tested.
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Developmental Effects
0 Unger and Shellenberger (1981) administered technical metribuzin by
gastric intubation to pregnant female rabbits (16 to 17/dose) on days
6 through 18 of gestation at daily doses of 15, 45 or 135 mg/kg/day.
Following treatment, there was a statistically significant (p <0.05)
decrease in body weight gain in the high-dose does (135 mg/kg). No
maternal toxicity was reported in animals administered metribuzin at
levels of 45 mg/kg/day or less. No treatment-related effects were
reported at any dose level in fetuses based on gross, soft tissue and
skeletal examinations.
0 Machemer (1972) reported no maternal toxicity, embryotoxicity or
teratogenic effects following oral administration (via stomach tube)
of technical metribuzin to FB30 rats (21 to 22/dose) on days 6 through
15 of gestation at dose levels of 5, 15, 50 or 100 mg/kg/day.
Mutagenicity
0 Metribuzin showed no mutagenic activity in several bacterial assays
(Inukai and lyatomi, 1977; Shirasu et al., 1978) or in dominant
lethal tests in mice (Machemer and Lorke, 1974, 1976). The results
of microbial point mutation assays (Machemer and Lorke, 1974) did not
indicate a mutagenic potential for metrirazin in the test systems
utilized. The results of dominant lethal mutations in mice or
chromosomal aberrations in hamster spermatogonia at dose levels of
300 mg/kg and 100 mg/kg, respectively, did not indicate any mutagenic
effects of metribuzin.
Carcinogenicitjy
0 Hayes et al. (1981) conducted studies in which technical metribuzin
was administered in the diet to albino CD-1 mice (50/sex/dose) at 200,
800 or 3,200 ppm (30, 120 or 380 mg/kg/day) for 24 months. Minimal
toxic effects were observed at the high-dose level in the form of
increased liver weight and changes in the hematocrit and hemoglobin
measurements. Although some increase in the number of tumor-bearing
animals was observed in low- and mid-dose animals, significant
increases in the incidence of specific tumor types were not observed
at any dose level. It was concluded that, under the conditions of the
test, there was no increase in the incidence of tumors in mice.
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) = /L ( /L)
(UF) x ( L/day) y/
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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 a One-day HA for metribuzin. It is therefore recommended
that the Ten-day HA value for a 10-kg child (4.5 mg/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 Unger and Shellenberger (1981) has been selected to serve
as the basis for determination of the Ten-day HA for metribuzin. In this
study, pregnant rabbits (16 or 17/dose) that were administered technical
metrizubin by gastric intubation at dosage levels of 0, 15, 45 or 135 mg/kg/day
on days 6 through 18 of gestation showed a statistically significant (p <0.05)
decrease in body weight gain at the 135-mg/kg dose. No maternal toxicity was
reported at or below the 45-mg/kg dose. No treatment-related effects were
reported at any dose level in fetuses based on gross, soft tissue and skeletal
examinations. The NOAEL identified in this study was, therefore, 45 mg/kg/day.
While a reproductive end point is not the most appropriate basis for derivation
of an HA for a 10-kg child, this study is the only one available for the
appropriate duration.
Using a NOAEL of 45 mg/kg/day, the Ten-day HA for a 10-kg child is
calculated as follows:
Ten-day HA = (45 mg/kg/day) (10 kg) = 4.5 mg/L (4,500 ug/L)
(100) (1 L/day)
where:
45 mg/kg/day = NOAEL, based on absence of body weight reduction in
rabbits exposed to metribuzin via gastric intubation
on days 6 through 18 of 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 Advisory
The study by Loser et al. (1969) has been selected to serve as the basis
for the Longer-term HA for metribuzin. In this study, rats (15/sex/dose)
were fed diets containing metribuzin at doses of 50, 150, 500 or 1,500 ppm
(about 2.5, 7.5, 25 or 75 mg/kg/day based on calculations in Lehman et al.,
1959) for 90 days. Thyroid glands were enlarged in males in the 500 or
1,500 ppm (25 or 75 mg/kg/day) dosage groups, while the heart was enlarged at
the 1,500 ppm (75 mg/kg/day) dose level. In females, enlarged livers were
detected in the 150, 500 or 1,500 ppm (7.5, 25 or 75 mg/kg/day) dosage groups,
and the thyroid was enlarged in the 500 or 1,500 ppm (25 or 75 mg/kg/day)
dosage groups. Body weights were reduced in both sexes at 1,500 ppm
(75 mg/kg/day), compared to untreated controls. The NOAEL identified in this
study was, therefore, 50 ppm (2.5 mg/kg/day). Lindberg and Richter (1970)
determined a NOAEL of 12.5 mg/kg/day in dogs; however, this study was'not
chosen, since the NOAEL was higher than the LOAEL of 7.5 mg/kg/day identified
by Loser et al. (1969) in the rat.
Using a NOAEL of 2.5 mg/kg/day, 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 increased absolute organ
weights in rats exposed to metribuzin via the diet
for 90 days.
10 kg = assumed body weight of a child.
1 00 = 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.
Using a NOAEL of 2.5 mg/kg/day, the Longer-term HA for a 70-kg adult is
calculated as follows:
Longer-term HA = (2.5 mg/kg/day) (70 kg) = 0<875 /L (875 /L)
(100) (2 L/day)
where:
2.5 mg/kg/day = NOAEL, based on absence of increased absolute organ
weights in rats exposed"to metribuzin via the diet
for 90 days.
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.
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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 study by Loser and Mirea (1974) has been selected to serve as the
basis for the Lifetime HA for metribuzin. In this study, dogs (four/sex/dose)
were administered metribuzin in the diet at dose levels of 0, 25, 100 or
1,500 ppm (0, 0.625, 2.5 or 37.5 mg/kg/day) for 24 months. Necrosis of the
renal tubular cells was reported as well as slight and temporary changes in
certain clinical chemistry parameters (e.g., blood glucose and cholesterol)
at the high-dose level. No other toxicologic effects were reported. Based
on this information, a NOAEL of 100 ppm (2.5 mg/kg/day) and a LOAEL of
1,500 ppm (37.5 mg/kg/day) were reported. Loser and Mirea (1974) reported a
NOAEL of 20 mg/kg/day in rats. This study was not selected because no dose-
related toxicologic responses were observed, and the rat may be less sensitive
than the dog. Hayes et al. (1981) determined a NOAEL of 120 mg/kg/day in
mice; however, this value exceeded the LOAEL (37.5 mg/kg/day) reported by Loser
and Mirea (1974).
Using this study, the Lifetime HA is calculated as follows:
Step 1: Determination of the Reference Dose (RfD)
RfD = (2.5 mg/kg/day) = Q. 025_ mg/kg/day
(100)
where:
2.5 mg/kg/day = NOAEL, based on absence of organ toxicity and clinical
chemistry effects in dogs exposed to metribuzin via
the diet for 24 months.
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1 00 = 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 = (0.025 mg/kg/day) (70 kg) _ 0<875 mg/day (875 ug/L)
(2 L/day)
where:
0.025 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 = (0.875 mg/L) (20%) = 0.175 mg/L (175 ug/L)
where:
0.875 mg/L = DWEL.
20% = assumed relative source contribution from water.
Evaluation of Carcinogenic Potential
0 In a study by Hayes et al. (1981), metribuzin was administered in the
feed of mice (50/sex/dose) at dose levels of 200, 800 or 3,200 ppm
(30, 120 or 480 mg/kg/day) for 24 months. Following treatment, the
incidence of tumor formation was analyzed in a variety of tissues.
Neoplasms of various tissues and organs were similar in type,
localization, time of occurrence and incidence in control and treated
animals. It was concluded that under the conditions of the test,
there was no increase in the incidence of tumors in mice.
0 The International Agency for Research on Cancer has not evaluated the
carcinogenic potential of metribuzin.
0 Applying the criteria described in EPA's guidelines for assessment
of carcinogen risk (U.S. EPA, 1986), metribuzin may be classified in
Group D: not classified. This category is used for substances with
inadequate animal evidence of carcinogenicity.
VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
0 A Threshold Limit Value-Time-Weighted Average (TLV-TWA) of 5 mg/m3
was determined, based on animal studies substantiated by repeated
inhalation tests, a safety factor of 5, and assuming a total pulmonary
absorption (ACGIH, 1984).
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VII. ANALYTICAL METHODS
0 Analysis of metribuzin is by a gas chromatography (GC) method appli-
cable to the determination of certain organonitrogen pesticides in
water samples (U.S. EPA, 1985). 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 GC and measurement
is made with a thermionic bead detector. The method detection limit
for metribuzin is 0.46 ug/L.
VIII. TREATMENT TECHNOLOGIES
0 Available data indicate that granular-activated carbon (GAC) adsorption
and a conventional treatment scheme will remove metribuzin from water.
0 Whittaker (1980) experimentally determined adsorption isotherms for
metribuzin on GAC.
0 Whittaker (1980) reported the results of GAC columns operating under
bench-scale conditions. At a flow rate of 0.8 gpm/sq ft and an empty
bed contact time of 6 minutes, metribuzin breakthrough (when effluent
concentration equals 10% of influent concentration) occurred after
112 bed volumes (Bv).
0 In the same study, Whittaker (1980) reported the results for four
metribuzin bi-solute solutions when passed over the same GAC continuous
flow column.
0 Another study investigated the effectiveness of two different GAC
columns in removing metribuzin from contaminated wastewater (Whittaker,
et al., 1982). One type of GAC showed breakthrough for metribuzin
(6 mg/L) from an initial concentration of 140 mg/L after 50 gallons
of the wastewater had been treated. No pesticide was found in the
effluent from the second type of GAC.
0 Conventional water treatment, coagulation and sedimentation with alum
and an anionic polymer removed more than 50% of the metribuzin present
(Whittaker et al., 1980). The optimum alum dosage was 200 mg/L. Also
equivalent dosages of ferric chloride were found to be equally effective.
0 Treatment technologies for the removal of metribuzin from water are
available and have been reported to be effective. However, selection
of individual or combinations of technologies to attempt metribuzin
removal from water must be by a case-by-case technical evaluation,
and an assessment of the economics involved.
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Metribuzin August, 1987
-13-
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