United States
                  Environmental Protection
                  Agency	
                       Office of Prevention, Pesticides
                       And Toxic Substances
                       (H-7508W)	
EPA-738-F-94-019
September 1994
                  R.E.D.   FACTS
                  Hexazinone
      Pesticide
Registration
     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 years ago 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 imposes
any regulatory controls that are needed to effectively manage each
pesticide's risks.  EPA then reregisters pesticides that can be used without
posing unreasonable risks to human health or the environment.
     When a pesticide is eligible for reregistration, EPA announces this and
explains why in a Reregistration Eligibility Decision (RED) document. This
fact sheet summarizes the information in the RED document for
reregistration case 0266, hexazinone.

     Hexazinone is a herbicide  used to control a broad spectrum of weeds
including undesirable woody plants in alfalfa, rangeland and pasture,
woodland, pineapples, sugarcane and blueberries. It is also used on
ornamental plants, forest trees and  other non-crop areas. Hexazinone is
registered for pre-emergent, post-emergence,  layby, directed spray and
basal soil applications.  It is used as a non-selective herbicide in non-
cropland areas and as a selective herbicide in reforestation practices.
     Hexazinone products are formulated as granulars, pellets/tablets,
emulsifiable concentrates, ready-to-use liquids, soluble concentrates/solids
and a technical grade active ingredient.  Products are applied using aerial or
ground equipment or by hand, or using a hand-held, boom, knapsack or
power sprayer.
     Use practice limitations prohibit application of hexazinone through any
type of irrigation system.  The pesticide also cannot be applied within 30 to
60 days before grazing, harvest or feeding.
    Regulatory        Hexazinone is the common name for 3-cyclohexyl-6-(dimethylamino)-
        HJStorv   1-methyl-1,3,5 triazine-2,4(lH,3H)-dione.  Hexazinone was first registered
                  as a pesticide in the U.S. in 1975 for general weed control in non-cropland
    Use Profile

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Human  Health
  Assessment
areas.  Use in the culture of Christmas and forest trees was added in 1977,
and uses on sugarcane and alfalfa were conditionally registered in 1980 and
1981, respectively.
      EPA issued one Registration Standard for hexazinone in February
1982  (NTIS #PB87-110292), and a second in September 1988  (NTIS
#PB89-126080).  These documents summarized available data supporting
the registration of hexazinone products, and required additional product
chemistry, residue chemistry,  toxicology, ecological effects and
environmental fate data.
      EPA's Office of Drinking Water issued a drinking water Health
Advisory (HA) for hexazinone in August 1988.  A lifetime HA was
established at 200 ppb for an adult consuming 2 liters of water per day.  For
a 10 kg child, a one- and ten-day HA was determined to be 2 mg/L.
      Currently, 20 end-use pesticide products and one technical grade,
manufacturing use product containing hexazinone are registered.

Toxicity
      Hexazinone is classified as a Group D carcinogen—a chemical that is
not classifiable as to human carcinogenicity.  Animal data presented to EPA
is equivocal—it is not entirely negative, but not convincingly positive.  The
Agency has concluded that the evidence cannot be interpreted as  showing
either the presence or  absence of a carcinogenic effect.  Since  hexazinone
has not been found to induce cancer,  food and feed additive regulations are
not prohibited by the Delaney Clause of the Federal Food, Drug, and
Cosmetic Act (FFDCA). The Reference Dose  (RfD) approach was used to
assess human risk from  exposure to hexazinone.
      In acute toxicity studies using laboratory animals, hexazinone has been
shown to be a severe eye irritant and has been placed in Toxicity Category I
(the highest of four levels) for primary eye irritation.  It is slightly toxic
through the acute oral route (Toxicity Category III)  and very mildly toxic
through the acute dermal and acute inhalation routes (Toxicity Category
IV).   Hexazinone is  only mildly toxic for skin irritation potential (Toxicity
Category IV) and is not a skin sensitizer.
      Some treatment-related  effects were found in developmental toxicity
studies using rats and rabbits, at the high dose levels.  Similarly,  some
effects were noted in a reproductive toxicity study at the mid- and high dose
levels. Hexazinone was positive in one mutagenicity study  but negative in
the remaining studies.  There are no other acute or chronic toxicological
endpoints of concern.
Dietary Exposure
      People may be exposed to residues of hexazinone through their diet.
EPA reassessed existing tolerances or maximum residue limits (please see
40 CFR 180.396) for blueberries, pineapple and sugarcane at the time of
this RED.  Tolerances for meat, meat byproducts and milk cannot be

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reassessed until a cattle feeding study is completed.  However, sufficient
data were available to conduct a risk assessment, and the Agency believes
that the existing tolerances are protective until data are available for
reassessment.
     The Reference Dose (RfD) or amount believed not to cause adverse
effects if consumed daily over a 70-year lifetime is 0.05 mg/kg/day based
upon a No Observable Effect Level (NOEL) of 5 mg/kg/day in a one-year
feeding study in dogs.  EPA calculated  that the Anticipated Residue
Contribution (ARC) for the overall U.S. population  from all hexazinone
tolerances equals  7% of the RfD.  The  ARC for the  subgroup most highly
exposed, non-nursing infants age less than 1 year, represents 40% of the
RfD, while the ARC for children age 1 to 6 years is 20% of the RfD.
EPA's  calculations overestimate exposure, however,  by assuming 100% of
crop treated for all commodities.  Actual dietary risk from hexazinone is
believed to be minimal.  When current  residue chemistry data gaps are
filled, however, dietary exposure estimates for hexazinone could change.
     Hexazinone concentrates in certain processed fractions of alfalfa,
pineapple and sugarcane. EPA has determined that establishing food and
feed additive tolerances for these commodities is appropriate and consistent
with the Delaney  Clause of the FFDCA, and that such tolerances must be
established for alfalfa meal, pineapple processing residue and sugarcane
molasses.
     EPA's Office of Water has issued a lifetime Health Advisory (HA)
which sets a maximum level of 0.21 mg/L, or 200 ppb allowable in
drinking water. No international CODEX Maximum Residue Limits are
established for hexazinone so compatibility with U.S. tolerances is not an
issue.
Occupational and Residential  Exposure
     Based  on current use  patterns, workers may be exposed to hexazinone
during and after applications in agricultural and other settings.  In  assessing
handler and  post-application exposure,  Agency concerns are predominantly
related to skin contact. Hexazinone is poorly absorbed through the skin, so
little or no absorption is anticipated.  Therefore, no  changes  in  personal
protective equipment (PPE) required by the Worker  Protection  Standard
(WPS) are being imposed at this time.  However, the Restricted Entry
Interval (REI) is being changed from 24 to 48 hours because hexazinone  is
in Toxicity Category I for primary eye irritation.
     There  are no residential uses of hexazinone, so residential exposure is
not expected.
Human Risk Assessment
     Hexazinone generally is of relatively low acute toxicity but is a severe
eye irritant (Toxicity Category I).  It is  not classifiable as to human
carcinogenicity (Group D carcinogen) and does not cause other toxic effects
of concern.

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                          The dietary risk posed by hexazinone is expected to be minimal. Most
                     tolerances were reassessed and other existing tolerances are considered
                     protective until confirmatory data are available for reassessment.  A lifetime
                     Health Advisory sets a maximum level of exposure to hexazinone from
                     drinking water.
                          Exposure to workers and other applicators generally is not expected to
                     pose undue risks, due to hexazinone's overall low acute toxicity. However,
                     based on toxicity concerns regarding primary eye irritation, a 48-hour rather
                     than a 24-hour REI is required.

Environmental   Environmental Fate
   AsSGSSITIGnt        Based on laboratory data and confirmed by field and forestry data,
                     hexazinone appears to be persistent and mobile in soil and aquatic
                     environments. The degradates of hexazinone also are believed to be
                     persistent and mobile. Hexazinone was reported in runoff water up to 6
                     months post-treatment in a forestry dissipation study. Therefore, field and
                     laboratory data indicate that hexazinone may be of concern for both
                     groundwater and surface water contamination.
                          Hexazinone has been detected in ground water (at levels well below
                     the Health Advisory) in Hawaii,  Florida,  Maine and North Carolina.
                     Hexazinone also can contaminate surface water by spray drift at application,
                     and for several months post-application via runoff.  It is not expected to
                     accumulate in fish but does accumulate in crops grown on treated soil.
                     Ecological Effects
                          Hexazinone is practically non-toxic  to birds on an acute oral  and
                     subacute  dietary basis. It is practically non-toxic to freshwater fish and
                     freshwater  invertebrates in acute exposures.  Hexazinone is practically
                     nontoxic to mollusks, slightly toxic to crustaceans, and relatively non-toxic
                     to honey  bees.
                     Ecological Effects Risk Assessment
                          Exposure of non-target organisms to hexazinone can result from direct
                     application, spray drift from treated areas, and runoff from treated areas.
                     Such exposure would be chronic as well as acute.
                          Hexazinone exceeds the levels of concern (LOG) for terrestrial and
                     aquatic plants, at all application rates, using aerial and ground equipment.
                     Contamination of aquatic sites adjacent to treated areas could be of great
                     ecological significance and may be exacerbated by the persistence and
                     mobility of hexazinone.
                          Aquatic plants are  an important component of the ecosystem. Algae
                     are the link between solar radiation, aquatic animals and humans, which are
                     dependent on the oxygen produced by algae during photosynthesis.  Algae
                     are responsible for maintaining the quality of the aquatic habitat for fish,
                     while at the same time providing food for fish either directly or indirectly.
                     Effects to aquatic plants expected from the use of hexazinone may  alter

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aquatic ecosystems, the severity of which is dependent on the frequency of
application and the nature of the receiving body of water.
     Hexazinone also exceeds the LOG for small mammals at several of the
higher application rates.
Risk to Endangered Species
     Hexazinone exceeds the endangered species LOCs for grass- and
insect-eating mammals at use rates of 3.6 pounds active ingredient per acre
(Ib ai/acre) or greater.  It also exceeds the LOCs for both aquatic and
terrestrial plants at all use rates.
Risk Mitigation Measures
     Hexazinone exceeds the levels of concern for both aquatic and
terrestrial plants,  and exceeds levels of concern for small mammals at
several of the higher application  rates.  Hexazinone also is likely to have a
significant impact on ground water quality. In areas where irrigation water
is contaminated with hexazinone or where ground water discharges to
surface water, hexazinone residues in water could pose  a threat to plants.
Therefore, the following risk  mitigation measures are required:
      •     All hexazinone product labels must carry a  ground water
           advisory;
      •     Registrants must report any domestic hexazinone ground water
           detections at any levels to EPA;
      •     The registrant must prepare  a report summarizing ongoing
           research regarding ground water detections  in the State of
           Maine;
      •     The registrant also must submit to EPA the  educational materials
           under development regarding product stewardship and
           addressing the potential for ground water contamination from
           use of hexazinone;
      •     A prospective ground water  monitoring study must be conducted
           to determine the potential for hexazinone to leach to ground
           water;
      •     To address surface water concerns, precautionary label language
           will be required;
      •     To address the risk to nontarget plants and small mammals,  the
           maximum application rate must be reduced  from 13.5 Ib ai/acre
           to 8 Ib ai/acre.
      •     To inform the user of best management practices to minimize
           spray drift, EPA is preparing labeling statements that  may be
           required in the future for all aerially-applied hexazinone
           products;
      •     To address endangered aquatic and terrestrial plant species as
           well as endangered small mammal concerns, endangered species
           precautionary labeling will be required in the future;

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                                    Hexazinone may be classified as a Restricted Use Pesticide for
                                    ground water concerns once the Agency's Ground Water
                                    Restricted Use Rule is finalized.
    Additional Data
            Required
  Product Labeling
Changes Required
     The Agency is requiring additional generic data on hexazinone's
residue chemistry, ecological effects and environmental fate. The following
confirmatory generic studies are required:  residue analytical methods
(ruminant only), magnitude of the residue grass hay and alfalfa seed
screenings, magnitude of the residue in meat/milk, storage stability  (alfalfa
and Metabolite C for grass),  rotational crops (sorghum and leafy vegetable),
seed germination/seedling emergence (cucumber, onion, pea), vegetative
vigor (cucumber), batch equilibrium, aquatic sediment  dissipation, spray
drift, and a prospective groundwater monitoring study.
     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.

     All hexazinone end-use products must comply with  EPA's current
pesticide  product labeling requirements, and with the following:
Worker Protection Standard (WPS) - EPA has evaluated the 24-hour
interim REI established by the WPS and concluded that it should be changed
to 48 hours because hexazinone is in Toxicity Category I for primary eye
irritation. The new 48-hour  REI must be inserted  into the standardized REI
statement required by PR Notice 93-7.
     The PPE for  early entry under the 48-hour REI for hexazinone is
coveralls, chemical resistant gloves, shoes plus socks, and protective
eyewear.  These PPE must be inserted into the early entry PPE statement
required by PR Notice 93-7.
Ground Water Labeling Advisory - All products must carry the following
advisory:
     "This chemical is known to leach through soil into ground water under
     certain conditions as a result of agricultural use.  Use of this chemical
     in areas where soils are permeable, particularly where the water table
     is shallow, may result in ground water contamination."
Surface Water Labeling - The technical manufacturer of hexazinone is in
the process of consolidating label language relating to surface and ground
water for all of their hexazinone products.  After the Agency has reviewed
and approved these label amendments, all hexazinone labels must carry this
labeling.
Other Ground  Water Requirements
     •     Registrants must report any  domestic hexazinone ground water
           detections at any  levels to the Agency.
     •     The registrant must prepare and submit a report summarizing
           the ongoing research in Maine regarding ground water

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 Regulatory
Conclusion
   For More
Information
           detections in blueberry use areas. This report must be submitted
           within one year from receipt of the RED document.  The
           registrant also must prepare a one year follow-up to the original
           report.
      •     The registrant also must submit an analytical method or immuno
           assay for detection of hexazinone in ground water, within one
           year after receipt of the RED document.
      •     The registrant is required to submit educational materials that
           are currently being developed to the Agency. These materials
           should be in specific regard to product stewardship and should
           address the  potential for ground water contamination from use of
           hexazinone.
Risk to Non-Target Plants and Small Mammals - To mitigate the risk to
non-target plants and small mammals, registrants must reduce the maximum
application rate from 13.5  Ib ai/acre to 8 Ib ai/acre.
Spray Drift Label Advisory - The Agency is preparing spray drift labeling
statements to inform users of management practices that would minimize
spray drift from the target site.  This future labeling may be required for all
hexazinone products that may be applied aerially to agricultural crops.
Endangered Species Statement -  EPA is working with the Fish and
Wildlife Service and other  Federal and State agencies to develop a program
to avoid jeopardizing the continued existence of identified species by the use
of pesticides. When this program goes into effect, endangered species
precautionary labeling will be required.

      The use of currently  registered products containing hexazinone 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.
      Hexazinone 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 hexazinone 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 Response and Program Resources
Branch,  Field Operations Division (7506C), Office of Pesticide Programs
(OPP), US EPA, Washington, DC 20460, telephone 703-305-5805.
      Electronic copies of the RED and this fact sheet can be downloaded
from the  Pesticide Special Review  and Reregistration Information System at
703-308-7224, and also can be reached on the Internet  via
FEDWORLD.GOVand EPA's gopher server, EARTH1.EPA.GOV.

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     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  45242-0419, telephone
513-489-8190, fax 513-489-8695.
     Following the comment period, the hexazinone RED document 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 hexazinone RED, or reregistration of individual products containing
hexazinone, 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, between 8:00 am and 6:00 pm Central Time, Monday
through Friday.

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