United States
                  Environmental Protection
                       Prevention, Pesticides
                       And Toxic Substances
                       (7508W)   .  ,
February 1998
                  R.E.D.   FACTS
Re registration
    Use Profile
     All pesticides sold or distributed in the United States must be
registered by EPA, based on scientific studies showing that they can be
used without posing unreasonable risks to people or the environment.
Because of advances in scientific knowledge, the law requires that
pesticides which were first registered before November 1, 1984, be
reregistered to ensure that they meet today's more stringent standards.
         In evaluating pesticides for reregistration, EPA obtains and
reviews a complete set of studies from pesticide producers, describing the
human health and environmental effects of each pesticide. The Agency
edevelops any mitigation measures or regulatory controls needed to
effectively reduce each pesticide's risks. EPA then reregisters pesticides
that can be used without posing unreasonable risks to human health or the
     When a pesticide is eligible for reregistration, EPA explains the basis
for its decision in a Reregistration Eligibility Decision (RED) document.
This fact sheet summarizes the information in the RED document for
reregistration case 0181, metribuzin.

     Metribuzin is a herbicide used to selectively control certain broadleaf
weeds and grassy weed species on a wide range of sites including vegetable
and field crops, turf grasses (recreational areas), and non-crop areas.
Formulations include wettable powder, emulsifiable concentrate, water
dispersible granules (dry flowable), and flowable'concentrate. Metribuzin
is applied by various methods including aerial, chemigation, and ground  .

     Metribuzin was first registered as a pesticide in the U.S. in 1973.
EPA issued a Registration Standard for metribuzin in July 1985 (PB86-
174216). Data Call-Ins (DCIs) were issued in 1991 and 1995 requiring
additional product chemistry, environmental fate and groundwater, and
ecological effects data. Currently 86 metribuzin products are registered.
     On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA)
was signed into law. FQPA amends both the Federal Food, Drug, and
Cosmetic Act (FFDCA), and the Federal Insecticide, Fungicide, and
Rodenticide Act (FIFRA). The FQPA amendments went into effect
immediately and were considered during this reregistration decision.

Human  Health   Toxicity
  Assessment         In studies using laboratory animals, metribuzin generally has been
                    shown to be of low acute toxicity. It is slightly toxic by the oral and
                    inhalation routes and has been placed in Toxicity Category III (the second
                    lowest of four categories) for this effect.  It is practically non-toxic by the
                    dermal route of exposure and has been placed in Toxicity Category IV (the
                    lowest of four categories).
                        '  A 21-day dermal toxicity study and a 21-day inhalation toxicity study
                    were used to assess subchronic toxicity.  In the dermal toxicity study,
                    minimal systemic changes were noted at the highest dose level and no
                    dermal irritation was noted at any dose level. In the inhalation study,
                    systemic toxicity was observed at 720 mg/m3 air (0.720 mg/L), and was
                    based on clinical signs of toxicity, increased liver enzyme activities, and
                    increased organ weights. Results of three developmental toxicity studies
                    and one  reproduction study suggest that although metribuzin is not
                    considered a developmental toxicant it is associated with developmental
                    toxicity effects.  There was a lack of evidence for carcinogenieity in the
                    following studies:  1) a mouse study in which there were no increases in
                    tumor incidences at dosing levels up to 438 mg/kg/day for males and 567
                    mg/kg/day for females; 2) a rat study in which the observed pituitary
                    adenomas and carcinomas were not statistically significant at dosing levels
                    up-to 14.36 mg/kg/day for males and 20.38 mg/kg/day for females; and .3)
                    another rat study which indicated no evidence for carcinogenieity at dosing
                    levels up to 42.2 mg/kg/day for males and 53.6 mg/kg/day for females.
                    Available data also suggest that metribuzin is not mutagenic.
                    Dietary Exposure
                          People may be exposed to residues of metribuzin through the diet.
                    Tolerances were reassessed for metribuzin and three of its primary
                    metabolites.  Tolerances have been established in 40 CFR 18.0.332 for the
                    following commodities:  asparagus; barley, grain; barley, straw; carrots;
                    corn, fodder; corn, forage; grass; grass, hay; lentils (dried); lentils, forage;
                    peas; peas (dried), peas, forage; peas, vine hay; sainfoin, hay; soybeans;
                    soybeans, forage; soybeans, hay; sugarcane; tomatoes; wheat forage; wheat,
                    grain; and wheat straw. Additional confirmatory information are needed
                    before several established tolerances for animal commodities can be
                    reassessed. When these tolerances for animal commodities are reassessed,
                    a separate dietary exposure assessment will be made.
                     Occupational Exposure
                          Based  on current use patterns, handlers (mixers, loaders, and
                     applicators) may be exposed to metribuzin during and after normal use of
                     liquid, wettable powder, and dry-flowable formulations.  Since minimal
                     systemic changes were noted at the highest dose level in a 21-day dermal
                     toxicity study, a short-term or intermediate term dermal  risk assessment was

 not required.  However, an inhalation risk assessment is required based on
 clinical signs of toxicity, increased liver enzyme activities, and increased
 organ weights observed in a 21-day inhalation study.  Based on the use
 patterns and potential exposures, ten exposure scenarios for handlers were  '
 identified and assessed for metribuzin.
 Human Risk Assessment
      Metribuzin generally is of low acute tpxicity, and although it does
 show developmental effects in animal studies, it is not considered a
 developmental toxicant.  It has been classified as a Group D chemical, not
 classifiable as to human carcinogenicity.  Many food and feed crop uses are
 registered; however, dietary exposure to metribuzin residues in food and
 feed are not of concern. Also, the cancer risk posed to the general
 population is not  of concern.
      Of greater concern is the inhalation exposure risk posed to metribuzin
 handlers, particularly mixers/loaders/applicators,  and field workers. This
 concern was identified for mixing and loading wettable powders for aerial
 and chemigation applications at 6 Ibs active ingredient (ai)/acre.  Exposure
 and risk to workers will be mitigated by the use of PPE required by the
 WPS, as well as additional risk mitigation measures described below. Post-
 application reentry workers will be required to observe a  12-hour Restricted
 Entry Interval.                             .                  '
     The Agency has reassessed metribuzin food and feed related
 tolerances under the standards of the FQPA  and determined that, based on
 available information, there is a reasonable certainty that no  harm will result
 to infants and children or to the general population from aggregate  exposure
 to metribuzin residues. The only type of exposures evaluated were dietary
 and drinking water routes, since significant non-occupational exposures are
 unlikely with metribuzin use.       ,                            ,
     The Agency believes that the acute and chronic total dietary (food
 source and drinking water source) risks from metribuzin are  minimal. The
 total acute dietary (food and drinking water  source) risk assessment was
 performed for the sub-population females (13+ years). The MOE was 1200
 (rounded to two significant digits). Metribuzin's acute dietary MOE greatly
 exceeds 100; therefore, the Agency considers the  MOE to be sufficiently
 protective for acute total dietary risk.
     EPA has also assessed the chronic dietary risk posed by metribuzin.
 For the overall U.S. population and 22 subgroups, exposure from all current
 metribuzin tolerances represents 3 6% of the Reference Dose (RfD), or
 amount believed not to cause adverse effects if consumed daily over a 70-
year lifetime.  1% of the RfD is reserved for exposure to residues of
 metribuzin in drinking water; therefore,  the total chronic dietary risk is 37%
of the RfD for the general population. The exposure level of residues of
metribuzin in food commodities in the most highly exposed subgroup,
children (1-6 years), is 75% of the RfD. For this subgroup, 4% of the RfD

is reserved for exposure to residues of metribuzin in drinking water;
therefore, total chronic dietary risk is 79% of the RfD. It appears that total
chronic dietary risk from food and drinking water sources is low.
     EPA does not have, at this time, available data to determine whether
metribuzin has a common mechanism of toxicity with other substances or
how to include this pesticide in a cumulative risk assessment. Unlike other
pesticides for which EPA has followed a cumulative risk approach based on
a common mechanism of toxicity, metribuzin does not appear to produce a
toxic metabolite produced by other substances. For the purposes of this
tolerance action, therefore, EPA has not assumed that metribuzin has a
common mechanism of toxicity with other substances.
Environmental Assessment
     An evaluation of the estimated exposure of metribuzin to the
environment and the toxicity of metribuzin to nontarget organisms is
required  to assess the potential risk to the environment posed by metribuzin
 'Exposure of metribuzin to the environment is assessed  by reviewing fate
lab and field tests, and estimating terrestrial residues and aquatic
concentrations with the use of models. Toxicity of metribuzin to nontarget
organisms is extrapolated from lab studies conducted on a few species of
birds, mammals, aquatic organisms, and plants.
Environmental Fate
     Based on available data, the primary routes of degradation of .
metribuzin and its primary degradates are microbial metabolism and
photolytic degradation on soil. These compounds will be available for
leaching to ground water and.runoff to surface water in many use
conditions because the\ are not volatile. Once in ground water, metribuzin
is expected to persist due to its stability to hydrolysis and the lack of light
penetration. Con\crscl>, residues of metribuzin are not  likely to persist in
clear, well-mixed, shallow surface water with good light penetration since
parent metribuzin degrades rapidly by aqueous photolysis.
Ecological Effects
      Laboratory study results indicate that metribuzin is moderately toxic
to avian  species on an acute oral basis, practically non-toxic to avian
species on a subacute dietary basis, slightly-toxic to small mammals on an
acute oral basis, practically non-toxic to bees on an acute contact basis,
slightly toxic to practically non-toxic to freshwater fish on an acute basis,
moderately  to slightly toxic to aquatic invertebrates on an acute basis,
slightly toxic to estuarine/marine fish and invertebrates on an acute basis,
and highly toxic to nontarget plants.
Ecological Effects Risk Assessment
      There is potential acute and chronic risk concern for avian species,
including endangered species, for metribuzin application rates of 4 pounds

 Risk Mitigation
Additional Data
 (lb) active ingredient (ai) per acre or higher.  Also acute and chronic risks
 are likely for mammalian species, including endangered species, for rates of
 1 lb ai/acre or higher. Additionally, risks are likely for nontarget terrestrial
 and aquatic .plant species, including endangered species, for rates of 0.5 lb
 ai/acre or higher.
      Although presently there are ground water advisories on metribuzin
 product labels, the Agency is still concerned with potential ground water
 contamination from metribuzin use.. Data currently available to the Agency
 indicate that metribuzin and its degradates are very mobile and highly
 persistent, and thus have the potential to contaminate ground water and
 surface water; however, the persistence of parent metribuzin in surface
 water may be lessened by its susceptibility to photolytic degradation.
 Metribuzin use could adversely affect ground-water quality, especially in
 vulnerable areas. Detections have been reported in the "Pesticides in
 Ground Water Database" (EPA, 19,92) and other studies., These ground
 water contamination concerns are enhanced by metribuzin's widespread use

      To lessen the risks to  birds, mammals, and nontarget plants posed by
 metribuzin, EPA is taking the following risk mitigation measures.
  prohibiting aerial application on asparagus and tomatoes;
 o reducing the application rate of metribuzin being applied to sugarcane via
 aerial and chemigation methods from 6.0 lb ai/acre to 2.0 lb ai/acre;
 o adding specific spray drift labeling requirements.
      To lessen the potential risks to humans posed by metribuzin, EPA is
 taking the following risk mitigation measures.
 o reducing the application rate of metribuzin being applied to sugarcane via
 aerial and chemigation methods from 6.0 lb ai/acre to 2.0 lb ai/acre;
 o prohibiting the use of low-pressure or high volume hand wand equipment.
     To reduce the likelihood of metribuzin and its primary degradates
 contaminating ground and surface water, EPA is taking the following risk
 o specifying on the label Best Management Practices;
 o determining areas that are vulnerable to ground-water contamination by
 metribuzin and recommending risk mitigation measures.

     EPA is requiring the following additional generic studies for
 metribuzin to confirm its regulatory assessments and conclusions:
 1) magnitude of residue studies (alfalfa and field corn trials, and field
rotational crop studies, additional field trials for field corn and potatoes, and
data"for wheat aspirated grain fractions; 2) processing studies for sugarcane
and wheat; 3) certified limits (GLN 62-2) and analytical methods to verify

                      '  certified limits (GLN 62-3) for three impurities related to the active
                        ingredient in the 90% technical; 4) storage stability data for animal
                        commodity samples from the previously evaluated poultry and ruminant
                        feeding studies; 5) confined rotational crop and field rotational crop studies;
                        and 6) additional ground water information.
                             The Agency also is requiring product-specific data including product
                        chemistry and acute toxicity studies, revised Confidential  Statements of
                        Formula (CSFs), and revised labeling for reregistration.

Product Labeling        All metribuzin end-use products must comply with EPA's current
           Changes   pesticide product labeling requirements and with the following. For a
          R   uired   comprehensive list of labeling requirements, please see the metribuzin RED
                             o For tomatoes and asparagus uses: "Aerial application is
                             o For aerial application on sugarcane: "To assure that spray will not
                             adversely affect adjacent sensitive nontarget plant, apply this product
                             by aircraft at a minimum upwind distance of 400 ft from sensitive
                             o For all uses: "Low-pressure and high volume hand wand
                             equipment is prohibited."
                             o For the aerial and chemigation application methods of metribuzin
                             on sugarcane: A "maximum application rate of 2.0  Ib ai/acre" is
                             o Specific spray drift label requirements are added.
                             o Best Management Practices to help reduce ground and surface
                             water contamination.
          For More
     The use of currently registered products containing metribuzin in
accordance with approved labeling will not pose unreasonable risks or
adverse effects to humans or the environment. Therefore, all uses of these
products are eligible for reregistration under the conditions specified in this
     Metribuzin products will be reregistered once the required product-
specific data, revised Confidential Statements of Formula, and revised
labeling are received and accepted  by EPA.

     EPA is requesting public comments on the Reregistration Eligibility   ,
Decision (RED) document for metribuzin during a 60-day time period, as
announced in a Notice of Availability published in the Federal Register. To
obtain a copy of the RED document or to submit written comments, please
contact the Pesticide Docket, Public Information and Record Integrity

Branch, Informantion Resources and Services Division (7506C), Office of
Pesticide Programs (OPP), US EPA, Washington, DC 20460', telephone
     Electronic copies of the RED and this fact sheet are available on the
Internet.  See http://www.epa.gov/REDs. ~     '
     Printed copies of the RED and fact sheet can be obtained from EPA's
National Center for Environmental Publications and Information
(EPA/NCEPI), PO Box 42419, Cincinnati, OH 45242-2419, telephone 1-
800-490-9198; fax 513-489-8695.
     Following the comment period, the metribuziri RED document also
will be available from the National Technical Information Service (NTIS),
5285 Port Royal Road, Springfield, VA 22161, telephone 703-487-4650.
     For more information about EPA's pesticide reregistration program,
the metribuzin RED, or reregistration of individual products containing
metribuzin, please contact the Special Review and Reregistration Division
(7508W), OPP, US EPA, Washington, DC 20460, telephone 703-308-8000,
     For information about the health effects of pesticides, or for assistance
in recognizing and managing pesticide poisoning symptoms, please contact
the National Pesticides Telecommunications Network (NPTN). Call toll-
free 1-800-858-7378, from 6:30 am to 4:30 pm Pacific Time, or 9:30 am to
7:30 pm Eastern Standard Time, seven days a week.