United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508C)
EPA-738-F-00-021
October 2000
R.E.D. FACTS
Pesticide
Reregistration
Vinclozolin
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. 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 2740, vinclozolin.
Use Profile Vinclozolin is a fungicide used to control various diseases on raspberries, chicory
grown for Belgian endive, lettuce, kiwi, canola, snap beans, dry bulb onions,
ornamentals, and turf. Import tolerances have been established to permit
importation of vinclozolin-treated cucumbers, sweet peppers and wine. Vinclozolin
is formulated as a dry flowable and extruded granular which may be applied with
aerial, chemigation, or ground equipment (broadcast, band, or soil drench); as a dip
treatment on ornamental bulbs and corms, cut flowers, rose budwood, or nursery
stock; and with thermal foggers in greenhouses.
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Regulatory Vmclozolin has been registered in the United States since 1981 for use as a
History fungicide. A Data Call-In (DCI) was issued in 1991 for vinclozolin requiring the
submission of additional data on product and residue chemistry, toxicity,
environmental fate, and ecological effects. Subsequent DCIs were issued in 1995
and 1996 requiring additional environmental fate and ecological toxicity studies.
Also, the Agricultural Data Call-In (AGDCI) was issued in 1995, which required
data to help estimate postapplication occupational exposure. The Reregistation
Eligibility Decision (RED) reflects a reassessment of all data which were submitted
in response to the DCIs.
In April 1997, the risks from all uses were reevaluated under the Food Quality
Protection Act (FQPA) when a new use for this chemical was proposed by BASF
Corporation (succulent beans). The estimated dietary cancer risks were above the
level generally regarded as negligible. As a result, previously registered uses were
voluntarily canceled by the registrant and the Agency has revoked the related
tolerances, namely for tomatoes, plums, prunes, and grapes (except wine grapes).
To reduce exposure to children, residential uses of vinclozolin were deleted and turf
and ornamental applications limited to commercial and industrial sites. Following this
mitigation, a three-year time-limited tolerance was established for succulent beans in
1997.
In June 1998, after EPAs decision to retain the FQPA safety factor of 10X, BASF
requested voluntary cancellation of its vinclozolin uses on stone fruits and
strawberries to reduce dietary exposure to vinclozolin residues. The Agency
published a Federal Register notice announcing the use deletions on July 30, 1998.
At that time, BASF also requested use rate reductions for turf and agreed to phase
out its liquid formulations, as well as phase-in water soluble packaging for the
remaining formulations. Revocation of the stone fruit and strawberry tolerances will
be proposed in an upcoming Federal Register notice.
On July 18, 2000 the Agency established 3 year time-limited tolerances for
vinclozolin and its metabolites containing the 3,5-DCA moiety on succulent beans,
canola, eggs, milk, and the meat, fat, and meat byproducts of cattle, goats, hogs,
horses and sheep. In order to mitigate risk associated with the added uses, EPA
accepted a proposal submitted by the registrant which includes the following actions
to occur over the next 4 years: A phase out of all domestic food uses of vinclozolin
except for use on canola, and revocation of all import tolerances except for wine
grapes. The Agency published the proposed use deletions in the Federal Register
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for public comment on September 20, 2000 (65 FR 56894, FRL-6744-2). On
September 18, 2000, EPA received objections to the newly-issued tolerances on
succulent beans and canola. Once EPA finalizes its response to the objections, it
will amend its reregistration and reassessment decisions, if any such amendment is
necessary.
In addition to the use cancellations, BASF also initiated measures at that time to
mitigate risks identified through the reregistration process including cancellation of
the use on ornamental plants due to postapplication risk concerns and new
restrictions on turf use based on non-dietary risks to children. Use on sod farm turf
was prohibited (except for transplant onto golf courses) and application to turf was
restricted to golf courses and industrial sites.
In an effort to promote transparency and public acceptance in regulatory decision
making, the Agency, in cooperation with the U.S. Department of Agriculture
(USDA), is working to modify the reregistration process. Until a final process is
established, an interim process is being used to provide opportunities for
stakeholders to ask questions and provide input on risk assessments and risk
mitigation strategies, via conference calls and other formats. Consistent with this
process, a conference call was conducted on June 1, 2000 with EPA, USDA, the
registrant, and other stakeholders (e.g., growers, commodity groups, land grant
universities) to discuss the basis of the calculated risks of vinclozolin, the Agency's
risk concerns, and the registrant's voluntary cancellation and phase-out proposal.
Also, a close-out conference call was conducted on September 25, 2000 with
many of the same participants from the June 1st conference call, to discuss the
additional risk management decisions and resultant changes to the vinclozolin labels.
Human Health
Assessment
Toxicity
Vinclozolin generally has been shown to have low acute oral/dermal/inhalation
toxicity. Vinclozolin is not an irritant to the eye/skin but can act as a skin sensitizer.
The principal toxic effects induced by vinclozolin and/or its metabolites are related
to its antiandrogenic activity. Androgens are the principal male steroid hormones,
such as testosterone, which stimulate the development and maintenance of the
male reproductive system and secondary sex characteristics. Studies show that
vinclozolin may have minimal antiandrogenic activity at relevant dose levels but that
at least two vinclozolin metabolites occur in mammals, plants, and soil and are
responsible for much of the antiandrogenic activity attributable to vinclozolin.
Vinclozolin exerts its effects most dramatically during the developmental stages of
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animals ultimately resulting in reproductive effects. At low dose levels in rats (>3
mg/kg/day), the most androgen sensitive effects are noted, such as decreased
prostate weight, weight reduction in other sex organs, nipple/areolas development,
and decreased ano-genital distance in male rats. At higher dose levels, the
reduction in male sex organ weight is exacerbated, and sex organ malformations
are seen, such as reduced penis size, ectopic testes, vaginal pouches, hypospadias,
and additional ambiguities of the urogenital system. In some studies reduced
fertility from the hypospadias, delayed puberty and kidney stones were noted.
Since the androgen receptor is widely conserved across species lines, anti-
androgenic effects would be expected in humans. However, the human
consequence of many of the low dose effects in male rats such as reduced ano-
genital distance, areola and nipple development, and reduced prostate weight is
unknown. Vmclozolin and/or its metabolites cause Leydig cell (testicular) tumors
in rats. There is also evidence in the published literature that vinclozolin may affect
the development and function of the neuroendocrine system. The Agency has also
determined that vinclozolin's terminal metabolite, 3,5-dichloroaniline (3,5-DCA),
should be regulated based on potential carcinogenic concerns. 3,5-DCA is a
common metabolite of two related fungicides, iprodione and procymidone.
Dietary Exposure
People may be exposed to residues of vinclozolin and its metabolites containing
the 3,5-dichloroaniline moiety through the diet. Tolerances or maximum residue
limits have been established in 40 CFR §180.380 for: succulent beans; Belgian
endive tops; cucumbers; wine grapes; kiwifruit; leaf and head lettuce; dry bulb
onions; bell peppers; raspberries; stonefruits except plums/fresh prunes;
strawberries; canola; milk; cattle fat, meat, and meat byproduct; eggs; poultry fat,
meat and meat byproduct; sheep fat, meat and meat byproduct; goat fat, meat and
meat byproduct; hog fat, meat and meat byproduct; horses fat, meat, and meat
byproduct.
The following tolerances do not need to be amended at this time: wine grapes,
canola and the animal products associated with canola in feed. All other tolerances
will be proposed for revocation within the next few years after use cancellation.
Risk From Food
For vinclozolin, acute, chronic and carcinogenic dietary risk from food is not of
concern. Cancer dietary risk from 3,5-DCA in food is also not of concern (<1 x
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Risk From Food + Drinking Water
Model estimates of potential drinking water exposure from ground and surface
water sources are not of concern for vinclozolin. Based on screening-level
models, carcinogenic dietary risk from vinclozolin-derived 3,5-DCA in drinking
water is above the Agency's level of concern. 3,5-DCA exhibits fate properties
(high mobility and persistence) of pesticides which may be found in ground and
surface waters.
Risk From Non-dietary Exposure
There are no vinclozolin pesticide products registered for use by homeowners.
Vinclozolin can, however, be occupationally used in a manner that may lead to
post-application exposures to golfers playing on treated golf courses and
homeowners and their families coming into contact with or playing on sod which
has been previously treated on a sod farm. No chronic exposures or exposures
of sufficient duration to cause cancer were identified. The short-/intermediate-term
risk to golfers of all age ranges is below the Agency's level of concern. Risks to
toddlers playing on treated sod fall beneath the Agency's level of concern 24 days
after application. To mitigate the unacceptable risk resulting from exposure before
the 24 day period has elapsed, the registrant has submitted label amendments
deleting use on sod farms (except for transplant onto golf courses), and has begun
the immediate restickering of all product in the channels of trade to require a 24
day period before sod can be harvested. Although the Agency's level of concern
would have been exceeded, the risk reduction measures implemented by the
registrant immediately reduce risk such that it is below the Agency's level of
concern.
Aggregate Risk
The short- and intermediate-term aggregate risk assessment includes exposure
from nonoccupational settings in addition to the dietary (food and water) exposure.
When aggregating food and water exposure with toddler's exposure to treated
sod, the sod pre-harvest interval (PHI) of 24 days results in short- and
intermediate-term aggregate risk below the Agency's level of concern. Food,
water, and adult/child golfer exposure do not exceed the Agency's level of concern
when aggregated.
EPA also considered the relative contribution of vinclozolin-, iprodione- and
procymidone-derived 3,5-DCA. The aggregate food-only cancer risk associated
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with 3,5-DCA derived from all three of these imide fungicides is not of concern
(<1 x 10"6). However, the vinclozolin- and iprodione-derived 3,5-DCA EECs
alone exceed the carcinogenic aggregate DWLOC indicating a potential for
concern.
Occupational Risk
Workers can be exposed to vinclozolin during handler activities such as mixing,
loading, applying and flagging, or by re-entering treated sites. Occupational risk
estimates were not considered for onions, raspberries and ornamentals because
the registrant has requested immediate cancellation. Only one handler scenario,
applying with an airblast sprayer (kiwi), indicates the need for an increase in
protection beyond current label requirements. Lettuce, kiwi and turf pose a
postapplication risk concern, i.e., the Agency does not believe that the currently
labeled REIs are of sufficient duration to protect workers from exposure to
residues of concern.
FQPA Considerations
EPA has determined that the established tolerances for vinclozolin, with
amendments and changes as specified in this document, meet the safety standards
under the FQPA amendments to section 408(b)(2)(C) of the FFDCA, that there
is a reasonable certainty of no harm for infants and children. The safety
determination for infants and children takes into account the possibility of increased
dietary exposure due to the specific consumption patterns of infants and children,
as well as the possibility of increased susceptibility to the toxic effects of vinclozolin
residues in this population subgroup.
In determining whether infants and children are particularly susceptible to toxic
effects from vinclozolin residues, EPA considered the completeness of the
database for developmental and reproductive effects, the nature of the effects
observed, and other information. For vinclozolin, the FQPA safety factor of 10
was retained because: (1) there is evidence of increased susceptibility to offspring
following in utero exposure to vinclozolin in the prenatal developmental toxicity
study in rats; and (2) a developmental neurotoxicity study in rats with an expanded
protocol is required for vinclozolin due to concern for the antiandrogenic
properties of vinclozolin and its metabolites.
In accordance with the Food Quality Protection Act (FQPA), the Agency is
examining whether, and to what extent, some or all members of the imide group of
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the dicarboximide class of fungicides, which include vinclozolin, iprodione and
procymidone, share a common mechanism of toxicity. Although there are data
suggesting that these dicarboximide fungicides induce some of the same
antiandrogenic effects, the mechanism by which they cause these toxic effects has
not been adequately evaluated. As a result, the Agency has not determined if it
would be appropriate to include them in a cumulative risk assessment. In addition,
there may be other compounds outside of this class of fungicides that may also be
considered antiandrogenic. Therefore, for the purposes of this risk assessment,
the Agency has assumed that vinclozolin does not share a common mechanism of
toxicity with the dicarboximide fungicides or other possible antiandrogens.
Environmental
Assessment
Environmental Fate
Vinclozolin dissipates in the environment by microbial-mediated hydrolysis, soil
metabolism, abiotic degradation, and transport with water. Metabolite B is a
common degradate of hydrolysis, soil metabolism, and photolysis. The other
principal degradation products of vinclozolin are 3,5-dichloroaniline and metabolite
E, which appears to be a degradation product of parent and metabolite B.
Metabolite E degrades to 3,5-dichloroaniline. Experimental evidence has shown
3,5-DCA to be resistant to degradation processes.
Vinclozolin and its principal degradates are potentially very mobile to slightly
mobile in soil. Metabolites B, E and 3,5-DCA may be transported with water
through the soil profile or with surface runoff. Residues are likely to be most
mobile in sandy soils low in organic matter.
In terrestrial field dissipation studies, vinclozolin dissipated with half-lives of 34 to
94 days. Half-lives for total residues (vinclozolin plus its dichloroaniline-containing
metabolites) were 179 to >1000 days. Persistence of total residues appeared to
be attributable to the resistance of 3,5-DCA to degradation and to the inclusion of
soil-bound residues in the data. Intermittent detections of residues were reported
at soil depths of 12-18, 18-24, and 24-30 inches. 3,5-DCA was detected
regularly deeper than 6 inches. Residues may accumulate and be available for
rotational crop uptake. Vinclozolin has a low potential to bioaccumulate in fish.
Ecological Effects
Results indicate that vinclozolin is practically nontoxic to birds, mammals, and
honey bees on an acute basis. Vinclozolin is moderately toxic to
freshwater/estuarine fish and freshwater/estuarine invertebrates on an acute basis.
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Vmclozolin and/or its metabolites have been shown in vitro and in vivo to be
potent mammalian anti-androgenic compounds, inhibiting androgen receptor
binding and gene expression. In addition to the adverse effects observed in the
male fetuses in the mammalian species, endocrine disruption effects in birds include
reduced egg laying, reduced fertility rate, and reduced hatching successes.
Ecological Effects Risk Assessment
The risk assessment for vinclozolin indicates low levels of acute risk to wildlife.
The Agency's level of concern has been exceeded for chronic effects to avian
species for most use sites. The registrant has already requested the phase-out of
all uses except turf and canola. For canola, all avian chronic RQs are below the
level of concern assuming average use rates. For turfgrass, the highest RQ is 2.7,
which is slightly above the LOG of 1.0. The registrant has undertaken several
mitigation measures on turf during the last few years which reduce risk to nontarget
species on turf. Chronic risk to aquatic organisms has not been assessed due to
lack of data.
Risk Mitigation BASF, the vinclozolin registrant, has already requested changes to its vinclozolin
registrations, including the phase-out of most uses and new restrictions on turf use.
In addition to these measures, EPA is recommending the following risk mitigation
measures to lessen the risks posed by vinclozolin.
• To address drinking water concerns, the registrants of vinclozolin and
iprodione should initiate a surface and ground water monitoring program.
Ground water and surface water advisory language is warranted on
vinclozolin product labels.
Only the extruded granular formulation packaged in water soluble bags is
eligible for reregistration.
Labels should specify enclosed cabs for airblast applicators.
• An advisory statement should be added informing crop advisors to wear
early entry PPE when entering treated sites during the REI.
• A label statement should be added to the 24(c) label for chicory informing
employers of chicory root workers that they must ensure that workers in the
chicory root spray area wear the PPE required for applicators. Employers
must provide, clean, and maintain all PPE.
• The REI for kiwi should be increased from 24 hours to 6 days. The REI
on sod farm turf should be increased from 12 hours to 5 days. The REI for
lettuce should be increased from 12 hours to 7 days. An exception to the 7
day REI may be established for applications to lettuce taking place within
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35 days of planting. Under this exception, workers may enter to perform
some tasks after 24 hours.
• A double notification statement must be included on labels. Workers will
be notified of applications orally and by posting.
Additional Data The following additional generic studies for vinclozolin are necessary to confirm its
regulatory assessments and conclusions:
The Agency has determined that a developmental neurotoxicity (DNT) study is
warranted; however, the kinds of perturbations likely to occur with
androgen/estrogen disrupter cannot be identified by the standard guideline DNT
study. Consequently, the DNT study will be due 3 years after the Agency
determines the protocol necessary to assess the relevant endpoints.
In additional to the water monitoring data, environmental fate studies will be
requested in order to better understand the persistence and mobility of the
degradates. Some ecotoxicity studies were required in a previous DCI and are
still outstanding. The registrant is in the process of submitting the studies.
Product Labeling All vinclozolin end-use products should comply with EPA's current pesticide
Changes product labeling requirements and with the label changes outlined in the RED
document.
Regulatory The use of currently registered products containing vinclozolin in accordance with
Conclusion 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. This decision takes into consideration the registrant's request to
cancel most currently registered uses of vinclozolin.
Vinclozolin products will be reregistered once the required product-specific data,
revised Confidential Statements of Formula, and revised labeling are received and
accepted by EPA.
For More EPA is requesting public comments on the Reregistration Eligibility Decision
Information (RED) document for vinclozolin 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
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Docket, Public Information and Records Integrity Branch, Information Resources
and Services Division (7502C), Office of Pesticide Programs (OPP), US EPA,
Washington, DC 20460, telephone 703-305-5805. 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 513-489-8695.
Following the comment period, the vinclozolin 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 vinclozolin
RED, or reregistration of individual products containing vinclozolin, 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 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.
Their Internet address is ace.orst.edu/info/nptn.
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