United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508C)
EPA-738-F-04-011
February 2005
SEPA R.E.D. FACTS
Imazalil
Pesticide
Reregistration
Use Profile
All pesticides sold or distributed in the United States must be registered by
EPA (the Agency), 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 (FQPA) 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 current human health
and safety standards 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 and the Amendment to the 2003
Imazalil RED for reregistration case 2325, imazalil.
Imazalil is a systemic fungicide for post harvest use on bananas, citrus, and
preplanting seed treatments of barley and wheat. Its only nonfood use is for
chicken hatchery treatments. There are no residential or public health uses.
Approximately 6000 Ibs. a.i. of imazalil are used annually. It can be applied by
seed treatment equipment, drenches, waxing and foaming equipment, handwand
sprayers and smoke canisters. There are 15 registered products including two
technical grade products. Formulations include Magnate technical (98.50-98.94%
active ingredient), one impregnated material (14.9% a.i.), four liquids (up to 31%
a.i.), seven emulsifiable concentrates (up to 68.25% a.i.), and a flowable
concentrate (10% a.i.). Impregnated material is used in smoke generators.
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Regulatory
History
Imazalil was first registered by Janssen Pharmaceutica (FIFRA Section 3) in
1983. Since then, imazalil has continuously had one or more FIFRA Section 3
registrations for postharvest use on citrus fruits against various fungi. In 1984, the
Agency first registered imazalil for use as a seed treatment, and in 1990 for use in
chicken hatcheries.
EPA completed the tolerance reassessment for imazalil on July 12, 2002.
The Agency concluded that there is a reasonable certainty of no harm to any
population subgroup from aggregate exposure to imazalil from dietary (food and
water) exposure and all other non-occupational sources for which there is reliable
information.
Human Health
Assessment
Toxicity
Imazalil is classified as "Likely to be carcinogenic in humans," according to
EPA's July 1999 Draft Guidelines for Carcinogenic Assessment. Carcinogenicity
studies in rodents indicate imazalil is carcinogenic to male Swiss albino mice and
Wistar rats based on a significant increase in liver adenomas and combined
adenomas/carcinomas. Based on current science policy and absent information
supporting a mode of action in test animals, EPA quantified the human cancer risk
by a linear low-dose (Qi*) extrapolation. The most potent unit risk,
Q /(mg/kg/day)"1 for imazalil based on male mouse liver adenoma and/or carcinoma
combined tumor rates is 6.1 x 10"2 (mg/kg/day)"1 in human equivalents. In rats, there
was also an increased incidence of combined thyroid follicular cell
adenomas/carcinomas. In addition, imazalil is placed in Category II, II, and IV for
oral, dermal and inhalation toxicity respectively. It is highly irritating to the eye
(Category I), but is not a skin irritant (Category IV) or a dermal sensitizer.
Dietary Risks
EPA determined that there is a reasonable certainty that no harm to any
population subgroup will result from aggregate exposure to imazalil when
considering dietary (food and water) exposure and all other non-occupational
sources of pesticide exposure for which there is reliable information. Both acute and
chronic dietary exposure were below the Agency's level of concern.
For acute dietary exposure, the most sensitive group, females 13-50 years of age,
was 15% of the acute Population Adjusted Dose (aPAD) at the 99.9th percentile.
For chronic dietary exposure, the most highly exposed group was children 1-6 years
old at 3% of the chronic Population Adjusted Dose (cPAD). Imazalil was not
expected to reach drinking water sources at high concentrations due to its immobility.
Drinking water models showed that the estimated environmental concentration (EEC)
for groundwater was negligible. The acute surface water EEC of 0.072 ppb is less
than the acute drinking water level of comparison (aDWLOC) of 500 ppb, while the
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chronic surface water EEC of 0.037 ppb is less than the chronic drinking water level
of comparison (cDWLOC) of 25 ppb, thus drinking water exposure is below the
Agency's level of concern. The lifetime cancer risk estimate, largely associated with
the use of imazalil on citrus, was 2.0 X 10"6, and thus presents no concern to the
Agency. This estimate did not include water because water was well below the
Agency's level of concern and is not expected to contribute significantly to exposure.
Residential and Other Nonoccupational Risks
There are no registered residential uses of imazalil and thus residential
exposure is not expected.
FQPA Considerations
EPA has determined that there is a reasonable certainty that no harm to any
population subgroup will result from aggregate exposure to imazalil when considering
dietary (food and water) exposure and all other nonoccupational sources of pesticide
exposure for which there is reliable information.
EPA did not perform a cumulative risk assessment as part of this
reassessment of imazalil because the Agency has not determined that there are any
other chemical substances that have a similar mechanism of toxicity.
Worker Risks
Occupational workers can be exposed to a pesticide through mixing, loading,
and/or applying a pesticide, or re-entering treated sites. Occupational handlers of
imazalil include the following: individual farmers or growers who mix, load, and/or
apply pesticides and professional or custom agricultural applicators. Non-cancer
risk for all of these potentially exposed populations is measured by a Margin of
Exposure (MOE) which determines how close the occupational exposure comes to
a No Observed Adverse Effect Level (NOAEL) taken from an animal study. For
imazalil, MOEs greater than 100 do not exceed the Agency's level of concern.
With additional personal protective equipment (PPE) and label changes, all worker
exposure scenarios have MOEs greater than 100. Cancer risk estimates ranged
from 2.0 x 10"3 to 1.0 x 10"7 using conservative exposure assumptions. The
following scenarios have cancer risk estimates that exceed the Agency's level of
concern.
• Handlers lighting smoke generators. Cancer risk was calculated at 2.0 x
10"3 based on the assumption that exposure lasted one minute and the entire
contents of the canister were released immediately. The Agency believes this
over estimates exposure because it is industry practice to leave the area after
lighting the canister and the smoke is released over a couple of minutes.
Nonetheless, the Agency is requiring that labels instruct handlers to vacate
the area immediately after lighting the canister and prohibiting re-entry until
ventilation has occurred.
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Citrus handlers. Cancer risk was calculated at 7.0 x 10"4 based on fruit
packers wearing no PPE. The Agency believes this over estimates exposure
because calculations were based on an assumption of 100% dermal
exposure but recently submitted data show the potential transfer of pesticide
from citrus to handler is less than 2%. Therefore, exposure would be
reduced 50-fold.
• Loading/applying on-farm seed treatment. Cancer risk was calculated at
2.0 x 10"4 based on handlers wearing gloves using a dust formulation. The
Agency believes this over estimates exposure because imazalil is an
emulsifiable concentrate which is shown to have significantly lower dermal
exposures. Nonetheless, the Agency is requiring chemical resistant gloves
and aprons during on-farm seed treatment.
Environmental Ecological Fate
Assessment Imazalil is moderately water soluble, very stable to hydrolysis, photo
degrades relatively rapidly, degrades very slowly in soil under aerobic conditions, is
immobile in soils, is not expected to volatilize, and has a high octanol water partition
coefficient.
Ecological Risks
Based on the above environmental fate properties, and with consideration of
the product formulations, the application methods, and the application rates, EPA
believes that the immobile parent compound is not likely to be found in significant
concentrations in the environment. Although persistent in aerobic soil, the seed
treatment with a low application rate (0.01 Ibs. a.i./A) is the only use that comes in
contact with soil.
Risks to Terrestrial and Aquatic Organisms
Imazalil does not exceed acute or chronic levels of concern (LOCs) for
freshwater fish, invertebrate, avian, and mammalian species due to extremely low
exposure, which is attributable to the low application rate (0.01 Ibs. a.i./A) and the
seed treatment end-use (only 1% residue was left on soil surfaces). Imazalil is
practically non-toxic to seed eating avian and mammalian species. In addition to the
seed treatment, all other uses occur within contained areas or structures and no
exposure is expected.
Imazalil does not exceed levels of concern for endangered species. The
acute risk quotients (RQs) for freshwater fish (0.00005), invertebrate (0.00002),
avian (0.00003), and mammal species (0.0002) are all below the endangered
species LOG. Because of the extremely low exposure and relatively low toxicity to
freshwater organisms, all acute and chronic toxicity testing has been waived.
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RJS|< Dietary Risk
M it in at inn Although EPA determined that there is reasonable certainty that no harm to
any population subgroup will result from aggregate exposure to imazalil when
considering dietary (food and water) exposure for which there is reliable information,
the following risk mitigation measures and label changes are required in order to be
eligible for registration.
• This product may not be used when egg or poultry is present.
Occupational Risk
For the potential occupational risks associated with use of imazalil, the use of
chemical resistant gloves is necessary for the following scenarios:
• Mixing/loading liquid for on-farm seed treatment.
• Mixing/loading liquid for drenched application.
• Mixing/loading liquid for waxing equipment.
• Mixing/loading liquid for foaming equipment.
• Handling for commercial seed treatment.
• Mixing/loading and applying liquid with commercial seed treatment
equipment.
• Mixing/loading/applying seed treatment for on-farm seed treatment.
• Handling used smoke canisters for disposal.
To further address occupational risk concerns for imazalil use in chicken
hatcheries in which smoke canisters are used. The following label changes must be
made:
• All workers must immediately leave the treatment area after lighting the
smoke canister.
• All workers must be prohibited from reentering the treated area while smoke
is still visible.
• Workers must be prohibited from reentering unventilated areas for 12 hours
following application. For mechanically ventilated areas, workers may
reenter two hours after application.
In order to assure that workers are not exposed when imazalil is applied to
citrus in truck-beds, the following label statements must be added:
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• Stay outside the treatment area until citrus is treated and drained.
• The windows and doors of the transport vehicle must be closed prior to
treatment.
Ecological Risk
Based on the Agency's risk assessment, none of the RQ values exceed the
Agency's level of concern for either terrestrial or aquatic non-target organisms, and
minimal risk to the environment is expected. No environmental risk mitigation is
necessary at this time.
Additional Data The confirmatory data required to complete the generic data base and/or
Required refine the dietary, occupational and ecological risk assessments from the RED are
listed below. These studies include data requirements listed in the July 12, 2002
TRED.
OPPTS GLN 870.6300 Developmental Neurotoxicity in Rats
OPPTS GLN 870.6200 Acute Neurotoxicity Study in Rats
OPPTS GLN 870.6200 Subchronic Neurotoxicity Study in Rats
OPPTS GLN 860.1200 Direction for Use
OPPTS GLN 860.1340 Residue analytical method-Animal Commodities
OPPTS GLN 850.4400 Tier I aquatic plant growth studies with two species
of aquatic plants (Lema gibba and Selenastrum capricornutum ).
OPPTS GLN 830.7050 UV/Visible Light Absorption
Regulatory The use of currently registered products containing imazalil in accordance
Conclusion with approved labeling will not pose unreasonable risks or adverse effects to humans
or the environment if the risk mitigation measures and label changes outlined in the
RED and the Amendment to the Imazalil 2003 RED are implemented. Therefore,
all uses of these products are eligible for reregistration. These products will be
reregistered once the required product specific data, confidential statements of
formula (CSFs), and revised labeling are received and accepted by EPA. Products
which contain ingredients in addition to imazalil will be reregistered when all of their
other active ingredients also are reregistered.
For More To obtain a copy of the imazalil RED document, please contact the OPP
Information Public Docket (7502C), US EPA, Ariel Rios Building, 1200 Pennsylvania Avenue,
NW, Washington, DC 20460-0001, telephone: (703) 305-5805. Electronic copies
of the imazalil RED and all supporting documents are also available on the Agency's
website at htto://www.eva. zov/ovvsrrdl/rerezistration/status.htm.
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For more information about EPA's pesticide reregistration program or the
imazalil RED, please contact the U.S. EPA, OPP, Special Review and
Reregistration Division (7508C), Washington, DC 20460-0001, telephone: (703)
308-8000.
For more 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 (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://www.npic.orst.edu
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