530R86107
WATER
T T IT V
L, 1 1 I
ADVISORY
METRIBUZIN
CritEria and Standards Division
Office of Water Regulations and Standards
United States
n vir a
nrnental Protection Rgency
MRRCH 1 9 8 G
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WATER QUALITY ADVISORY
Number 7 .
METRIBUZIN
Criteria and Standards Division
Office of Water Regulations and Standards
United States Environmental Protection Agency
The advisory concentration for Metribuzin in ambient water for the
protection of freshwater aquatic life is estimated to be 100 ug/L. No
saltwater toxicological data were reviewed and no advisory concentra-
tion for the protection of saltwater aquatic organisms has been
estimated. Care should be taken in the application of this advisory,
- with consideration of its derivation, as stated in the attached
J support document.
"i
A value given to protect aquatic life can be derived from no
x observed effect levels (NOEL), the lowest concentration found in the
"l data which has been observed to cause acute or chronic toxicity or
^ other experimental data which may be applicable. When there is no
^-' valid experimental evidence, a value may be derived from a model which
uses structure-activity relationships (SAR) as its basis. The advisory
concentrations should be used with caution, since they are derived
x from minimal experimental evidence, or in the case of SAR derived
values, no data on the specific chemical.
The advisory concentration for Metribuzin in ambient water for the
protection of human health is estimated to be 5,250 ug/L, based on
data and information which are available to U.S. EPA. Care should be
taken in the application of this advisory, with consideration of its
derivation, as stated in the attached support document.
An advisory concentration can be derived from a number of sources:
The Office of Drinking Water Health Effects Advisories; Acceptable
Daily Intake(ADI) values from EPA; Office of Pesticides and Toxic
Substances risk assessments; Carcinogen Assessment Group(CAG) cancer
risk estimates; risk estimates derived from the open literature; or
other sources which will be given in the support document. The
advisory concentrations derived from these sources will vary in
confidence and usefulness, based on the amount and quality of data
used as well as the assumptions behind the original estimates. The
user is advised to read the background information carefully to
determine the strengths or deficiencies of the values given in the
advisory.
U.S. Environmental Protection Agency
Region 5, Library (PI.-12J)
77 West Jackson Boulevatd, 12th Floor
Chicago, IL 60604-3590
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HUMAN HEALTH AND AQUATIC LIFE LITERATURE
SEARCH AND DATA BASE EVALUATION FOR
METRIBUZIN
U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF WATER REGULATIONS AND STANDARDS
CRITERIA AND STANDARDS DIVISION
WASHINGTON, D.C. 20460
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HUMAN HEALTH AND AQUATIC LIFE
LITERATURE SEARCH AND DATA
BASE EVALUATION FOR
METRIBUZIN
U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF WATER REGULATIONS AND STANDARDS
CRITERIA AND STANDARDS DIVISION
WASHINGTON, D.C. 20460
INTRODUCTION
Metribuzin is a member of the triazine class of pesticides (heter-
ocyclic nitrogen compounds) with the chemical formula 4-amino-6-tert-
butyl-3-(methylthic)-as-triazine-5(4H)-one (McEwen and Stephenson,
1979). It is a white crystalline solid with a melting point of 125-
126.5 c. Metribuzin is soluble in methanol, ethanol, glycol ether
acetate, and water (1,200 ppm). The compound is a methylthiotriazine
developed in the early 1970's for controlling grasses and broadleaf
weeds in soybeans and tomatoes, but is also registered for use in
wheat, barley, peas, lentils, sugarcane, alfalfa, sainfoin and aspara-
gus (McEwen and Stephenson, 1979).
Metribuzin controls the growth of grasses and broadleaf weeds by
inhibitinoPhotosystem II of photosynthesis (McEwen and Stephenson,
1979). -4Pfcs produced under the trade names Sencor and Lexone by
Bayer AG., Federal Republic of Germany; E.I. Dupont de Nemours and
Co., USA; and by Mobay Chemical Corporation, USA. Metribuzin is
moderately persistent in soils with half-lives ranging from 15 to 377
days depending upon moisture, temperature, exposure to sunlight, and
soil composition (Hyzak and Zimdahl, 1974; Schmidt, 1974). Smith and
Hayden (1982) found 18 to 20 percent of the applied dose in the upper
10 cm of clay loam and heavy clay soils after a period of 22 weeks.
Photodegradation was found to accelerate the disappearance of metri-
buzin in soil (3-fold) and water (10-fold) (Schmidt, 1974). Tempera-
ture also affected the rate of degradation of metribuzin with half-
lives of 377 days at 5 C, 46 days at 20 C, and 16 days at 35 C (Hyzak
and Zimdahl, 1974). A half-life of 43 days at 18 C in field soils
correlated well with the laboratory results (Hyzak and Zimdahl, 1974).
Metribuzin is slowly degraded by microbes in soil and readily adsorbs
to clay and organic matter which increases its persistence in soils
causing carry-over of residues from year to year (McEwen and
Stephenson, 1977).
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SCOPE OF SEARCH
Computerized literature searches and printed abstracts of TOXLINE,
TOXBACK, NTIS and the Toxicology Data Base were used as primary
sources for identifying data on aquatic toxicity and human health
effects, focusing primarily on laboratory studies of dose-response of
aquatic organisms and mammalian species. The quality assurance/
quality control measures used in these studies were evaluated for
their use of positive and negative controls, replication, and chemical
analysis of test concentrations. Additionally, the quality-of experi-
mental methods were evaluated by comparison to guidelines established
by the U.S. EPA in "Guidelines and Methodology Used in Preparation of
Health Effect Assessment Chapters of the Consent Decree Water Quality
Criteria Documents" (FR 45:79347, November 28, 1980) and the "Guide-
lines for Deriving Numerical National Water Quality Criteria for the
Protection of Aquatic Life and Their Uses" (Stephan et al., 1985).
Data other than dose-response relationships (e.g., metabolic
studies, field observations, and bioaccumulation) were also collected
to provide ancillary information relevant to aquatic toxicity and
human health effects.
SUMMARY OF FINDINGS
Aquatic Toxicity
Metribuzin inhibited the growth of several species of fresh water
algae (Table l). At levels of 0.1 ppm, growth was significantly
inhibited in a blue green algae (Anacystis nidulans) culture but
variable (12-55 percent of controls) in four other species of algae
(Eley et al., 1983; Arvik et al., 1973). Significant inhibition of
algal growth also occurred from metribuzin at 0.05 ppm (Arvik et al.,
1973). Metribuzin also bioconcentrates in algae 59 times the levels
in water (Freitag et al., 1982).
Levels of metribuzin at 40 ppm resulted in no toxicity to daphnids
(U.S. Dept. of Interior, 1981), and only one source was found that
reported an acute toxicity value (10 ppm) for fishes (Schmidt, 1974).
However, this information was taken from an abstract and neither the
species, duration of exposure, nor the quality assurance measures of
the study were reported. Exposure of metribuzin to catfish finger-
lings at 10 ppm for 48 hours resulted in only 10 percent mortality
(McCorkel et al., 1977), while levels of 2*20 ppm shoved no toxic
effect to the same species (Chambers and Fabacher, 1975). Exposure of
rainbow trout to 40 ppm DCPA resulted in no toxicity; however, neither
the duration nor the quality assurance measures of the study were
reported (U.S. Dept. Interior, 1981). A bioconcentration factor of 11
was found for golden orfes exposed to 50 ppb metribuzin in water for a
period of 3 days (Freitag et al., 1982).
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Health Effects
The values of acute toxicity for metribuzin to rats and mice are
fairly consistent for similar routes of exposure (Table 2). Oral LD50
(estimated dose at which 50 percent mortality occurs) values ranged
from 2,000 to 2,500 rag/kg metribuzin in three different studies
(Loeser and Kimmerle, 1972; Schmidt, 1974; Kasimov, 1980). Oral
exposure of metribuzin was more toxic to mice than rats (Loeser and
Kimmerle, 1972; Kasimov, 1980). A single intraperitoneal injection of
metribuzin resulted in a mean LD50 value of 210 mg/kg for mice (Bleeke
et al., 1985). Single intraperitoneal injections of metribuzin in
mice at 200-250 mg/kg resulted in increased serum glutamicpyruvic
transaminase, decreased glutathione, and increased necrotic lesions in
the liver. After a single injection of 50 mg/kg metribuzin effects
in the livers of mice were observed (Bleeke et al., 1985). Ingestion
of 0.5 to 25 ppm metribuzin in the diet for 3 months had no observable
effect on rats (Schmidt, 1974; Kasimov, 1980). After an 8-day expo-
sure of metribuzin to rats by stomach intubation (1 ppm), 85 percent
of the dose was excreted. Less than 0.1 percent had been retained in
liver, lung, and adipose tissue (Freitag et al., 1982). A summary of
the toxic effects for metribuzin to algae and animals is presented in
Figure 1.
CR1IIBIA EVALUATION AND RECOMMENDATIONS
Aquatic Life
No water-quality criteria for metribuzin was found in the litera-
ture search or in various water-quality criteria documents. The lack
of adequate dose-response data makes a numerical calculation of a
criterion impossible. Although little information is available on
dose-response relationships metribuzin does not appear very toxic to
fish and daphnids but may be significantly toxic to fresh water algae.
Levels of 40 ppm metribuzin resulted in no toxicity to daphnids and
rainbow trout, and 20 ppm resulted in no toxic effects in catfish
fingerlings (U.S. Dept. of Interior, 1981; Chambers and Fabacher,
1975). Additionally, bioconcentration of metribuzin by fishes does
not appear to be significant (llx) even at levels of 50 ppb in water
(Freitag et al., 1982). However, metribuzin inhibited the growth of
certain species of algae at 0.05 ppm and was significantly concen-
trated (59x) by one green algal species (Arvik et al., 1973; Freitag
et al., 1982). Therefore, the toxicity of metribuzin to fresh water
algae may be the most important consideration in determining a water
quality criterion to protect aquatic life. Because levels of 50 and
100 ppb resulted in moderate growth inhibition (12-76 percent of
controls) of algae and 0.1 ppm resulted in total inhibition of growth,
a level of 0.1 ppm might be an appropriate maximum level allowable to
protect fresh water algae. A concentration of 0.1 ppm would probably
be safe for daphnids and fishes as this concentration represents 0.25
percent of a no toxic effect concentration (40 ppm) for daphnia and 10
percent of the LC50 for fish reported by Schmidt (1974).
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Health Effects
The available information on metribuzin suggests that the long-
term feeding study with rats is the most appropriate parameter to use
in deriving a water quality criterion to protect human health. These
data were available through a secondary reference (ACGIH, 1984). in
the study, a dietary concentration of 100 ppm did not produce any
effects, but 300 ppm did. The 300 ppm concentration is regarded as a
LOEL or a lowest observed effect level and may be transformed to a
daily dosage by multiplying the LOEL by a constant 0.05 (FR 45:79353)
for the rat. The dosage is, therefore, 15 mg/kg/day. Current U.S.
EPA methodology (FR 45:79355) indicates that a LOEL, LOAEL, or NOAEL
from a long-term feeding study is appropriate for calculating an
acceptable daily intake (ADI) level. The ADI may be calculated as
follows:
ADI = (150 mg/kg/day) (70 kg)
100
ADI = 10.5 mg/day
where:
15 mg/kg/day = LOEL
70 kg = average body weight of an adult
= uncertainty factor when adequate chronic
toxicity data are available/ but no
studies of human ingestion are available.
A proposed advisory level for metribuzin in water, taking into effect
ingestion of water only, is derived as:
Advisory = 10.5 mg/day
2 I/day
Advisory =5.25 mg/L
where:
10.5 mg/day = ADI
2 I/day = average daily drinking water volume for adult.
This water quality advisory does not take into account additional
exposures that may result from dietary exposure to metribuzin through
ingestion of contaminated fish. The only bioconcentration factor
found, 11, would probably not change the advisory significantly if it
were used in the calculations.
There is almost a complete lack of data for appropriate acute and
chronic studies of metribuzin for aquatic organisms and a lack of
chronic studies of mammals for human health effects. The kinds of
data required for calculating water quality criteria are summarized in
Tables 3 and 4. Of 14 tests needed, only one was found to be appro-
priate for use in deriving a water quality criterion for freshwater
life. This value involves exposure of metribuzin to freshwater algae
8
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TABLE 3. DATA REQUIREMENTS FOR CALCULATION OF AQUATIC LIFE
INTERIM CRITERIAMETRIBU2IN
Criterion Requirements
Aquatic Toxicity
Available
Data
Acute Test Results from tests on:
A salmonid (class Osteichthyes) NO
A warm water species commercially NO
commercially or recreationally
important (class Osteichthyes)
Another family in the phylum YES
Chordata (fish, amphibian, etc.)
A planktonic crustacean NO
(cladoceran, copepod, etc.)
Benthic crustacean (ostracod, NO
isopod, scud, crayfish, etc.)
Insect (mayfly, dragonfly, NO
damselfly, stonefly, mosquito,
etc.)
Phylum other than Arthropoda/ NO
Chordata (Rotifera, Annelida,
Mollusca)
Another family of insect NO
Acute-chronic ratios with species from
three different families:
One fish
One invertebrate
Acutely sensitive freshwater
animal species
NO
NO
NO
Acceptable test results from a test with:
Freshwater algae YES
A vascular plant NO
Bioaccumulation factor with a fresh- YES
water species (if a maximum permissible
tissue concentration is available)
Data
Acceptability
NO
(not native U.S. species)
YES
NO
(not native U.S. species)
10
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TABLE 4. DATA REQUIREMENTS FOR CALCULATION OF HUMAN HEALTH
INTERIM CRITERIA--METRIBUZIN
Criterion Requirements
Aquatic Toxicity
Nonthreshold:
Available
Data
Carcinogen NO
Tumor incidence tests (incidence NO
of tumor formation signficantly
more than the control for at least
one dose level), or
Data set which gives estimate NO
of carcinogenetic risk, or
Lifetime average exposure tests, or NO
Human epidemiology studies NO
(if available, not required)
Threshold:
Non-carcinogens NO
No observed adverse effect level NO
(at least 90-day), or
Lowest observed effect level YES
Lowest observed adverse effect level NO
Acceptable Daily Intake:
Daily water consumption YES
Daily fish consumption YES
Bioconcentration factor NO
Non-fish dietary intake YES
Daily intake by inhalation NO
Threshold Limit Value:
(Based on 8-hour time-weighted YES
average concentrations in air)
Inhalation Studies:
Available pharmokinetic data NO
Measurements of absorption NO
efficiency
Comparative excretion data YES
Data
Acceptability
YES
(ACGIH, 1984)
YES
(EPA assumption)
YES
(EPA assumption)
YES
(EPA assumption)
YES
(ACGIH, 1984)
NO
11
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LITERATURE CITED
ACGIH. 1984. TLVs, Threshold limit values for chemical substances
and physical agents in the work environment and biological exposure
indices with intended>changes for 1984-85. lSBN:0-9367-54-6. Ameri-
can Conference of Governmental Industiral Hygienists. Cincinnati,
Ohio.
Arvik, J., D. L. Hyzak, and R. L. Zimdahl. 1973. Effect of metri-
buzin and two analogs on five species of algae. Weed Science 21:ITS-
ITS.
Bleeke, M. S., M. T. Smith, and J. E. Casida. 1985. Metabolism and
toxicity of metribuzin in mouse liver. Pesticide Biochemistry and
Physiology 23:123-130.
Chambers, H., and D. L. Fabacher. 1975. Acute toxicity of pesticides
to channel catfish fingerlings. Mississippi Agricultural Forest
Experimental Station 37:1 Abstract.
Eley, J. H., J. F. McConnell, and R. H. Catlett. 1983. Inhibition of
metribuzin on growth and phtosynthesis of the blue-green alga
Anacystis nidulans. Environmental and Experimental Botany 23:365-368.
Federal Register (FR). 1980. U.S. Government Printing Office, Wash-
ington, D.C., November 28, 45(231) :79347-79356.
Freitag, D., H. Geyer, A. Karus, R. Viswanthan, D. Kotzias, A. Attar,
W. Klein, and F. Korte. 1982. Ecotoxicological profile analysis VII.
Screening chemicals for their environmental behavior by comparative
evaluation. Ecotoxicology and Environmental Safety 6:60-81.
Hyzak, D. L., and R. L. Zimdahl. 1974. Rate of degradation of metri-
buzin and two analogs in soil. Weed Science 22:75-79.
Kasimov, R. A. 1980. Toxicology of Sencor. Zdravookhr Tadzh 6:11-13
Abstract.
Loeser, E., and G. Kimmerle. 1972. Acute and subchronic toxicity of
Sencor active ingredient. Pflanzenschutz-Nachr. 25:186-209 Abstract.
McCorkel, F. M., J. E. Chambers, and J. 0. Yarbrough. 1977. Acute
toxicities of selected herbicides to fingerling channel catfish,
Ictalurus punctatus. Bulletin of Environmental Contamination and
Toxicology. 18:267-270.
McEwen, F. L. and G. R. Stephenson. 1979. The use and significance
of Pesticides in the environment. John Wiley and Sons, Inc. New York.
pp 124-133.
Schmidt, R. R. 1974. Sencor in the biosphere. Nachrictenbl. Deut.
Pflanzenschutzdients 26:69-71 Abstract.
12
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U.S. Environmental Protection ARency
Region 5, Library (PL-12J)
77 West Jackson Boulevard, 12th Floor
Chicago, 11 60604-3590
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of Environmental Contamination and Toxicology 29:243-247.
w' ?' I* Mount' D' J- Hansen, J. H. Gentile, G. A.
Protection Agency
96"05"
servioe-
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