United States
                        Environmental Protection
                        Prevention, Pesticides
                        And Toxic Substances
September 2004
&EFW   R.E.D.    FACTS
     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
     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. To implement provisions of the Food
Quality Protection Act of 1996, EPA considers the special sensitivity of infants and
children to pesticides, as well as aggregate exposure of the public to pesticide
residues from all sources, and the cumulative effects of pesticides and other
compounds with common mechanisms of toxicity. The Agency develops any
mitigation measures or regulatory controls needed to effectively reduce each
pesticide's risks. EPA then reregisters pesticides that meet the safety standard of
the FQPA and can be used without posing unreasonable risks to human health or
the environment.
     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 0012,
         Use Profile
     Carboxin is a systemic fungicide used to control seed and seedling diseases
(smut, rot, blight) on barley, beans, canola, corn, cotton, oats, onions, peanuts, rice,
rye, safflower, sorghum, soybeans, triticale, and wheat.  Formulations include
wettable powder, dust, flowable concentrate, emulsifiable concentrate, and ready-
to-use liquid. Carboxin is applied to seeds prior to planting both by commercial
seed treaters and on-farm applicators. Approximately 200,000 Ibs of carboxin are
used annually throughout the U.S.; 140,000 for commercial use, and 60,000 for
on-farm use. There are no registered residential uses for carboxin.

     Carboxin was first registered as a pesticide in the U.S. in 1968. EPA issued
a Registration Standard for carboxin in August, 1981 (PB82-132994). Carboxin
Product and Residue Chemistry Reregistration Standards updates were issued in
October, 1991. Data Call-in (DCI) Notices for carboxin were issued by the
Agency in 1991,  1995 and  1997.  The tolerance reassessment decision for
carboxin was completed  in December 2002.

Human Health
      Carboxin has been shown to have low acute toxicity.  Toxicity Categories,
which range from I (most toxic) to IV (least toxic), were in for the oral route of
exposure, IV for inhalation, and m for dermal. Carboxin is a slight eye irritant
(Toxicity Category HI), is not a skin irritant (Toxicity Category IV), and is negative
for dermal sensitization. The mechanism of toxicity for carboxin has not been fully
investigated; however the primary target organs appear to be the liver and kidney.
In carcinogenicity studies in rats and mice, carboxin did not demonstrate any
significant evidence of carcinogenic potential.
                     Dietary Exposure
                           The Agency has assessed the dietary risk posed by carboxin and determined
                     that exposure to carboxin from food and water are well below the Agency's level
                     of concern for all populations
                           The chronic dietary exposure estimates for carboxin are below the Agency's
                     level of concern (<100% cPAD) for the U.S. Population and all population
                     subgroups: All supported commodities were less than 36% cPAD.  An acute
                     dietary risk assessment was not required since no acute dietary toxicity end-point of
                     concern was identified.  Tolerances for residues of carboxin in/on food and feed
                     commodities are currently established under 40 CFR  180.301.  Tolerances have
                     been reassessed for barley, bean, canola, cattle, corn, cottonseed, egg, goat, hog,
                     horse, milk, oat, onion, peanut, poultry, rice, safflower, sheep, sorghum, soybean,
                     and wheat products, and are detailed in the RED.
                           The residues of concern in drinking water are carboxin and its sulfoxide
                     degradate. Since no monitoring data were available to assess residues of carboxin
                     and carboxin sulfoxide in drinking water, the Agency used the FIRST and SCI-
                     GROW models to determine surface water and groundwater estimated
                     environmental concentrations (EECs). The surface water EEC (0.63 ppb) and
                     groundwater EEC (0.095 ppb) were less than the DWLOC (26) indicating that
                     chronic exposure to carboxin in food and drinking water from surface water or
                     groundwater sources are below the Agency's level of concern.
                     Occupational and Residential Exposure
                           The results of the worker exposure assessment indicate that workers are
                     unlikely to encounter unacceptable occupational exposure to carboxin.  There are
                     no registered residential uses for carboxin and therefore no potential for residential
                     exposure from pesticidal uses of carboxin.
                           Workers may be exposed to carboxin via dermal and inhalation routes during
                     loading, treating, and planting activities.  Seven major exposure scenarios were
                     identified as representative of carboxin uses: (1) on farm seed treatment with dry

                     formulations - open transfer system, (2) on farm seed treatment with liquid
                     formulations - closed transfer system, (3) loading and applying liquid with
                     commercial seed-treatment equipment, (4) bagging and otherwise handling treated
                     seeds with commercial equipment, (5) commercial sewer stitching bags of seed, (6)
                     multiple commercial seed treatment activities and (7) loading and planting treated
                           Worker risk is measured by a Margin of Exposure (MOE) which determines
                     how close the occupational exposure comes to the No Observable Adverse Effect
                     Level (NOAEL) taken from an animal study. A MOE of 100  or greater for both
                     the dermal and inhalation route is considered to be adequately protective for
                     carboxin.  The results of the worker exposure assessment indicate that all potential
                     exposure scenarios result in MOEs greater than or equal to the target MOE of 100
                     at the baseline level of protection for all routes of exposure  (i.e., dermal, inhalation,
                     and aggregate dermal and inhalation).
FQPA Considerations
      No Special FQPA Safety Factor is necessary to protect the safety of infants
and children because there is no quantitative or qualitative evidence of increased
susceptibility following in utero or postnatal exposure in any of the developmental or
reproductive studies, and the toxicity endpoints selected are protective of
pre/postnatal toxicity following acute and chronic exposures.
      Carboxin is classified as "not likely to be carcinogenic to humans " according
to the EPA Draft Proposed Guidelines for Carcinogen Risk Assessment (July 2,

Environmental Fate
      Carboxin is a very mobile compound that degrades rapidly in soil by aerobic
metabolism with a mean half-life of 1.25 days. Carboxin degraded much more
slowly in anaerobic soil with a half-life of 128 days. In both aerobic and anaerobic
soil studies, the predominant degradate was carboxin sulfoxide which forms
quickly, is more persistent, and is more mobile than the parent compound. Based
on the structure of carboxin sulfoxide, the toxicity of the sulfoxide degradate is likely
comparable to that of the parent compound carboxin.
      There was no evidence of degradation by hydrolysis at any pH for carboxin.
Aqueous photolysis is rapid with a half-life of 1.5 hours under a xenon arc lamp.
Photolysis is not expected to be a major route of dissipation in the field as planted
seed is generally buried some depth below the surface, but may contribute to
dissipation after it has entered surface water bodies. Degradation in the anaerobic
phase in soil was much slower with a mean degradation half-life of 129 days.
There is some evidence that carboxin may degrade by direct oxidation in aqueous
systems when dissolved oxygen is present. Limited information on aquatic

                      metabolism show slower degradation rates anaerobically (245 days) than
                      aerobically (31 days).  In two anaerobic soil metabolism studies conducted for
                      carboxin sulfoxide, the major degradate formed was carboxin, indicating that
                      carboxin can reform from the sulfoxide under anaerobic conditions.

                      Ecological Effects
                            Mammals and birds in the field may be exposed to carboxin by ingesting
                      treated seeds or by other routes, such as incidental ingestion of contaminated soil,
                      dermal contact with treated seed surfaces and soil during activities in the treated
                      areas, inhalation of pesticide vapor and contaminated paniculate, and ingestion of
                      drinking water contaminated with the pesticide.
                            Based on the ecological effect studies,  carboxin is practically nontoxic to
                      terrestrial animals and ranges from moderately to slightly toxic to aquatic animals on
                      an acute exposure basis. No data were available to gauge the acute toxicity of
                      carboxin to estuarine/marine fish. Following chronic exposure, mallard ducks
                      (Anas platyrhynchos) exhibited reductions in the number of eggs laid, viable
                      embryos, live 3-week embryos, normal hatchlings and 14-day survivors at 700
                      mg/kg/day Chronic exposure to rats (Rattus norvegicus) resulted in reduced
                      growth (decreased body weight) of offspring. Based on environmental
                      concentrations in surface water, no acute LOCs are exceeded for aquatic animals
                      or plants.  No chronic toxicity data were available for the Agency to review and
                      based on the use pattern, no chronic exposure for aquatic animals and plants is
                            The Agency has developed the Endangered Species Protection Program to
                      identify pesticides whose use may cause adverse impacts on endangered and
                      threatened species, and to implement mitigation measures that address these
                      impacts. Thus far, the  only endangered seed-eating animal that requires risk
                      mitigation is the Attwater's Prairie Chicken (Tympanuchus cupido attwaterf).
                            EPA will continue to evaluate whether currently identified and/or additional
                      endangered species may be impacted by exposure to carboxin and is working with
                      other federal, state, and local agencies to refine the endangered species risk
                      assessment with the goal of developing reasonable and prudent alternatives to
                      mitigate risks to endangered species.

Risk Mitigation         The Agency has determined that the current risk mitigation strategies for
                      carboxin are acceptable. Carboxin is a very mobile compound that degrades
                      rapidly in  soil, and is not registered for aquatic application.  There are no registered
                      residential uses for carboxin and therefore no potential for residential exposure from
                      pesticidal uses of carboxin. All potential occupational exposure scenarios result in
                      MOEs greater than or  equal to the target MOE of 100 at the baseline level of
                      protection for all routes of exposure (i.e., dermal, inhalation, and aggregate dermal

Additional Data
and inhalation).  Mammals and birds in the field may be exposed to carboxin by
ingesting treated seeds or by other routes, but the predicted exposure from these
routes are below the Agency's LOCs.
     The Agency's initial assessment suggested that eight endangered species may
potentially be impacted by carboxin: the Delmarva fox squirrel (Sciurus niger
cinereus\ six species of kangaroo rat (Dipodomys spp.), and the Attwater's
Prairie Chicken  (Tympanuchus cupido attwaterf).  Based on information
provided by the U.S. Fish and Wildlife Service, the endangered species profile, and
communications with refuge managers, risk mitigation is required only for the
Attwater's Prairie Chicken (Tympanuchus cupido attwaterf).  The Agency will
issue new or revised County Specific Bulletins for the Attwater's Prairie Chicken to
be issued in Austin, Colorado, and Galveston Counties in Texas. The bulletins will
require minimum planting depths (rice 0.5 inch, cotton 1.5 inch) and subsequent
discing for carboxin-treated seed planted within one mile of the U.S. Fish and
Wildlife Service's Attwater Prairie Chicken National Wildlife Refuge and The
Nature Conservancy's Texas City Preserve.
     In conjunction with  other local and federal agencies, EPA will continue to
evaluate whether currently identified and/or additional endangered species may be
impacted by exposure to carboxin.

     EPA  requires additional generic studies for carboxin to confirm its regulatory
assessments and conclusions.
     Most data requirements are satisfied for the 97% carboxin T/TGAI;
however, additional data are required:








                                 Description of Production Process

                                 UVTVisible Absorption

                                 Sediment and Soil Adsorption/Desorption
                                 for Parent and Degradates

                                 Soil Column Leaching

                                 Photodegradation of Parent and Degradates
                                 in Soil

                                 Acute Toxicity Test for Estuarine and Marine

                                 Fish Early-Life Stage Toxicity Test

                                 Daphnid Chronic Toxicity Test

                                 Residue Analytical Method

                                Crop Field Trials
                                28-Day Inhalation Toxicity
                                Additional product chemistry data are required for the carboxin 75%
                           formulation intermediate (FI).
                                The Agency is uncertain regarding the endocrine disrupting potential of
                           carboxin and, once the appropriate testing protocols have been established for
                           examining endocrine disruption, carboxin may be subject to this battery of tests.

   Product Labeling        AH carboxin end-use products must comply with EPA's current pesticide
             Changes   product labeling requirements and with the following. For a comprehensive list of
Red U i red                labeling requirements, please see the carboxin RED document.
             For More
      The use of currently registered products containing carboxin 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
      Carboxin 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 carboxin 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 Records Integrity Branch, Information Resources
and Services Division (7502C), 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 Service Center for Environmental Publications (EPA/NSCEP), PO Box
42419, Cincinnati, OH 45242-2419, telephone 1-800-490-9198;  fax  513-489-
      Following the comment period, the carboxin RED document also will be
available from the National Technical Information Service (NTIS), 5285  Port Royal
Road, Springfield, VA 22161, telephone 1-800-553-6847, or 703-605-6000.

      For more information about EPA's pesticide reregistration program, the
carboxin RED, or reregistration of individual products containing carboxin, please
contact the Special Review and Reregistration Division (7508C), 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 Pesticide  Information Center (NPIC).  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. Their internet address is http://npic.orst.edu.