United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508C)
EPA-738-F-98-017
NOVEMBER 1998
R.E.D. FACTS
Pesticide
Reregistration
Use Profile
Regulatory
History
IPRODIONE
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 develops any mitiga-
tion measures or regulatory controls needed to effectively reduce each pesti-
cide'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 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
2335, iprodione [3-(3,5-dichlorophenyl)-N-(l-methylethyl)-2,4-dioxo-l-
imidazolidinecarboxamide].
Iprodione is a contact and/or locally systemic fungicide registered for use
on a variety of field, fruit, and vegetable crops, including almonds, grapes,
peaches, potatoes, rice, berries, onions, peanuts, lettuce, golf courses, lawns,
and ornamentals. There are currently 70 tolerances for iprodione. These end-
use patterns for the current formulations have been classified for outdoor use
only, applications include aircraft (fixed-wing and helicopter), airblast sprayer,
chemigation, groundboom, high- and low-pressure handwand, backpack
sprayer, and tractor-drawn spreader. Iprodione is formulated as a liquid, dry
flowable, wettable powder, and granular.
Iprodione was first registered in the U.S. in 1979 as a fungicide. Rhone-
Poulenc Ag Co., is the current manufacturer of iprodione. A data call-in was
issued in September 1991. Currently, 21 iprodione products are registered,
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along with 18 Special Local Needs registrations (SLNs). Product
concentrations range from 1.5% active ingredient to 95% active ingredient.
Human Health Toxicity
AsS6SSm6nt In studies using laboratory animals, iprodione generally has been shown to be
of low acute toxicity. It is slightly toxic by the eye, dermal and oral routes and
has been placed in Toxicity Category III (the second lowest of four categories)
for these effects. In acute inhalation and as a dermal sensitizer, iprodione is
practically non-toxic (Category IV).
Iprodione was not mutagenic in several studies. Iprodione has been classified
as a Group B2, or "likely," human carcinogen, based on evidence of tumors in
both sexes of mouse (liver) and in the male rat (Leydig cell). A Q* of 4.39 x
10"2 was used for estimating carcinogenic risk (Leydig cell).
The endpoints selected for both the acute (decreased anogenital distance
(AGD)) and the chronic (histopathology of male reproductive system) risk
assessments are based on developmental and reproductive effects. It was
determined that the additional lOx Safety Factor for the protection of infants
and children (as required) by FQPA should be reduced to 3x and the rationale
for reducing the lOx factor to 3x are as follows: no enhanced susceptibility was
seen in rat and rabbit developmental and the two generation reproduction study
in rats; the critical endpoint for acute dietary risk assessment (decreased AGD)
was seen at a high dose (120 mg/kg/day) and there were only marginal
differences in the degree of decreased AGD between the doses 20 mg/kg/day,
120 mg/kg/day, and 250 mg/kg/day thus indicating the "true" NOEL could be
higher than the one established at 20 mg/kg/day; the proposed mode of action
of iprodione is disruption of testosterone biosynthesis; the use of a realistic
dietary exposure data (refined using monitoring data and percent crop treated).
The Agency used the developmental NOEL of 20 mg/kg/day based on AGD in
male fetuses to assess acute dietary risk. The acute reference dose (RfD) for
iprodione is 0.06 mg/kg/day. The Agency used the toxicity/carcinogenicity
NOEL of 6.1 mg/kg/day to assess the chronic dietary risk for iprodione based
on histopathological lesions in the male reproductive system and effects of the
adrenal glands. The chronic RfD for iprodione is 0.02/kg/day.
Iprodione is structurally related to vinclozolin and procymidone. Each of these
three pesticides can metabolize to 3,5-dichloroaniline (3,5-DCA). FQPA
requires EPA to estimate cumulative risk from consumption of food and water
containing 3,5-DCA derived from iprodione, vinclozolin, and procymidone. A
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Q* of 6.38 X 10"2 (mg/kg/day) in human equivalents has been calculated for p-
chloroaniline. This Q* is based on the spleen sarcoma rate in male rats from a
bioassay study, linearized low-dose multistage model, and the 3/4s interspecies
scaling factor.
Dietary Exposure
People may be exposed to residues of iprodione through the diet and drinking
water. Tolerances were reassessed for iprodione and have been established in
40 CFR 180.399 for the following commodities: almonds, hulls; almonds,
nutmeat; apricots; beans, dried, vine hay; beans, dry; beans, forage; beans,
succulent; blueberries; boysenberries; broccoli; caneberries; carrots; cherries
(sour); cherries (sweet); Chinese mustard; currants; garlic; ginseng; grapes;
kiwi fruit; lettuce; nectarines; onions, dry bulb; peaches; peanuts; peanut
forage; peanut hay; plums; potatoes; prunes; raspberries; rice grain; rice straw;
strawberries; cattle, fat, kidney, liver, meat, meat byproducts; eggs; goats, fat,
kidney, liver, meat, meat byproduct; hogs, fat, kidney, liver, meat, meat
byproduct, horses, fat, kidney, liver, meat, meat byproduct; milk; poultry, fat,
liver, meat, meat byproduct; and, sheep, fat, kidney, liver, meat, meat
byproduct.
Occupational and Residential Exposure
Handlers (mixers, loaders, and applicators) of iprodione may be exposed to
iprodione during and after normal use of liquid, wettable powder, dry flowable,
and granular formulations. For dermal exposure, no short- and intermediate-
term dermal risk for iprodione. For inhalation exposure, the current use of
iprodione does not indicate a concern for long-term exposure or risk. Based on
the use patterns and potential exposures, nineteen exposure scenarios for
handlers were identified and assessed for iprodione. Rhone-Poulenc has
voluntarily canceled all residential uses of iprodione.
Human Risk Assessment
The Agency was concerned about the cancer risk and the acute dietary risk
posed by exposure to iprodione. The target Margin of Exposure (MOE) for
acute dietary risk is 300; MOEs above 300 are not considered to be of
concern. Acute MOEs for iprodione are calculated for females 13+ only, as
discussed previously. With risk mitigation measures in place, the MOE for the
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acute risk from food and drinking water for iprodione is 351, which the Agency
considers acceptable.
Aggregate cancer risk from iprodione (from dietary, residential and water
exposure) with risk mitigation measures in place is 1.8 x 10"6, which is within
the range that the Agency currently considers acceptable.
With personal protective equipment (PPE) in place, risk to handlers of
iprodione are considered acceptable. The Agency has also determined that a
restricted-entry interval (REI) of 24-hours reduces the post-application risks
posed by iprodione to workers.
The cumulative carcinogenic risk estimate for consumption of food and wine
containing residues of 3,5-DCA as a result of use of iprodione, vinclozolin, and
procymidone is 9.5 X 10"7.
Environmental Environmental Fate
AsSGSSmGnt The major routes of dissipation are hydrolysis in neutral and alkaline
environments (half-life pH 7 = 4.7 days; pH 9 = 27 minutes) and microbial
degradation under both aerobic and anaerobic conditions. The overall result of
these mechanisms of dissipation appears to indicate that iprodione has low to
intermediate persistence in the environment. The results obtained in the field
confirm the expected low persistence of iprodione (t1/2 = 3-7 days).
Despite the fact that iprodione is mobile to highly mobile in some soils, it is
unlikely that it will leach to ground water because of its rapid degradation in
the environment. In addition, because iprodione is typically applied as a foliar
treatment, degradation/metabolism on the plant surface and/or absorption by
plants will further mitigate the potential for ground water contamination.
Ecological Effects
For acute exposure, iprodione is practically nontoxic to slightly toxic to birds,
practically nontoxic to small mammals, relatively nontoxic to bees, moderately
toxic to freshwater fish, moderately toxic to estuarine and marine fish, and
moderately to highly toxic to estuarine and marine invertebrates. Chronic
toxicity studies established the following No Observable Effect Concentration
(NOEC) values and ecological endpoints affected: 300 ppm for birds
(decreased hatchling body weight), 500 ppm for small mammals (decreased
fetal weight); > 0.26 ppm for freshwater fish (larval survival);
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> 0.17 ppm for freshwater invertebrates (offspring/female, mean percentage
survival, growth); > 3.5 ppb for estuarine and marine invertebrates
(offspring/female/reproductive day).
Ecological Effects Risk Assessment
EPA is generally concerned about the ecological effects to terrestrial wildlife
and aquatic organisms posed by exposure to iprodione. The risk assessment
for iprodione shows various levels of concern regarding avian risk and
mammalian risk from broadcast applications of granular and nongranular
products used on turf and ornamentals. In addition, most agricultural uses
present acute and chronic risks of varying levels to endangered and
nonendangered aquatic organisms, with turf and rice demonstrating the higher
risks. In general, the risks to invertebrates are greater than the risks to fish.
The turf and rice uses present high acute risks for nonvascular aquatic plants.
With risk mitigation measures in place, the Agency considers these risks
acceptable.
Risk Mitigation To lessen human health risk, residential risk, worker risk, and ecological
effects posed by iprodione, Rhone-Poulenc has requested changes to its
iprodione registrations, including the following mitigation measures.
• For iprodione use on strawberries, increase the pre-harvest interval from 0-
days to up to but not after first flower. In addition, the tolerance for
strawberries will be reduced to the limit of quantitation (0.05 ppm).
• For iprodione use on all stone fruit (apricots, cherries, nectarines, plums, and
prunes), increase the pre-harvest interval from 7-days to up to but not after
petal fall (approximately 45 - 90-day pre-harvest interval). In addition, the
tolerances for all stone fruit, including peaches, will be reduced to limit of
quantitation (0.05 ppm).
• For iprodione use on table grapes (fresh, cooked, canned, juice, raisin or
otherwise; mitigation does not include wine and sherry grapes), reduce the
application rate from 4 times per season to one application per season at
early- to mid-bloom. Tolerances remain unchanged consistent with the RED
(10 ppm).
• Cancellation by Rhone-Poulenc of all residential uses of iprodione.
• Limit the maximum number of applications on non-residential turf, lawn,
golf course, ornamental trees, and ornamental plants from "unlimited" to 6
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per year, with the maximum annual application of up to but no more than 24
Ibs. a.i..
Except for use of iprodione on golf courses, include label warnings requiring
a vegetative buffer strip of at least 25-feet for application of iprodione
adjacent to water bodies such as lakes, reservoirs, rivers, permanent streams,
marshes or natural ponds, estuaries, and commercial fish ponds.
For use on golf courses, the following statement will be included on the
label: "for golf courses only, do not apply to turf cut higher than 1" on golf
holes where water bodies are present."
Include label warnings to prevent application of iprodione when wind
direction is toward aquatic area.
Cancellation by Rhone-Poulenc of all herbaceous ornamental seed treatment
uses.
All wettable powder formulations must be packaged in water-soluable bags.
For rice use only, continue to include endangered species restrictions in the
state of Arkansas (for the fat pocketbook pearly mussel and its habitat).
Additional Data
Required
Additionally, there are a number of risk mitigation measures required in
the RED to protect mixers, loaders, applicators and workers. For a detailed
list, refer to Chapter IV of the Iprodione RED document. With the above
mitigation measures, and the agreed upon changes to labels by Rhone-Poulenc,
all uses of iprodione are eligible for reregi strati on.
The generic data base supporting the reregi strati on of iprodione for the
above eligible uses has been reviewed and determined to be substantially
complete. For confirmatory purposes, the following information is being
required:
- Pre and/or Post-Natal Exposure Study [GLN 83-3(a)];
- UV/Visible Absorption [OPPTS 870.7050];
- Density [GLN 63-7];
- Product Chemistry Reports [GLN 61/62];
- Aquatic Plant Growth Study [GLN 122-2];
- Aerobic Soil Metabolism [GLN 162-1];
- Leach/Adsorp/Desorption [163-1];
- Confined Rotational Crop Study [165-1];
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- Estimation of Dermal/Inhalation Exposure [GLN 231/232];
- Residue Analytical Methods [GLN 171-4(d)];
- Crop Field Trial Studies (strawberries, stone fruit) [GLN 171-4(k)];
- Surface Water Monitoring Study [Special Study];
Product Labeling All iprodione end-use products must comply with EPA's current
ChanQGS Required pesticide product labeling requirements and with those labeling requirements
imposed in the Iprodione RED. For a comprehensive list of labeling
requirements, please see section V of the Iprodione RED document.
Regulatory
Conclusion
The Agency has determined that existing uses of iprodione are eligible
for reregi strati on subject to conditions imposed in the RED. These include
removal of all residential uses of iprodione (residential turf, residential
ornamentals and residential vegetable/small fruit gardens) from product
registrations due to cancer risk concerns. Also, to protect handlers of granular
iprodione products, removal of belly grinder application method from
iprodione product registrations. Lastly, to mitigate risks to birds, removal of
herbaceous ornamental seed treatment from all iprodione registrations. Rhone-
Poulenc has already requested these changes to its iprodione registrations. All
other uses of iprodione are eligible for reregistration.
For More
Information
EPA is requesting public comments on the Reregistration Eligibility
Decision (RED) document for iprodione 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 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 45242-0419, telephone 513-
489-8190, fax 513-489-8695.
Following the comment period, the Iprodione RED document also will
be available from the National Technical Information Service (NTIS), 5285
Port Royal Road, Springfield, VA 22161, telephone 703-487-4650.
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For more information about EPA's pesticide reregi strati on program, the
Iprodione RED, or reregi strati on of individual products containing iprodione,
please contact the Special Review and Reregi strati on 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 Pesticides Telecommunications Network (NPTN). Call toll-free 1-
800-858-7378, between 9:30 am and 7:30 pm Eastern Standard Time, Monday
through Friday.
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