United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508C)
EPA-738-F99-016
September 1999
R.E.D. FACTS
Folpet
Pesticide
Reregistration
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 0630,
folpet.
Use Profile Folpet is a fungicide used to control scab (sphaceloma) on avocados; wood
rot fungi, mold/mildew, and spoilage fungi on wood and other surfaces.
Formulations include liquid, ready to use, 0.3 to 0.7%; wettable powder, 44
to 50%; and technical, solid 88%.
Folpet is applied by dip treatment, foliar treatment, soaking, spraying, and as
a paint additive, wood surface treatment, and high volume spray.
Regulatory Folpet was first registered as a pesticide in the U.S. in 1948. EPA issued a
History Registration Standard for folpet in June 1987. A January 1993 Data Call-In (DCI)
required additional data.
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Currently, four folpet manufacturing use products are registered and twelve
end-use products are registered. The registrant has requested voluntary
cancellation of two end-use products, EPA registrations 66222-8 and 7401-231,
which have been suspended for lack of supporting data. The cancellations are being
processed. The proposed cancellation was published in the Federal Register on
August 4, 1999 for a 180 day comment period. The RED assumes that these uses
will be canceled in the near future.
Human Health
Assessment
Toxicity
In studies using laboratory animals, folpet generally has been shown to be of
low acute toxicity. However, it is moderately toxic by the inhalation route and has
been placed in Toxicity Category n (the second highest of four categories) for this
effect. Folpet has also been placed in Toxicity Category n for eye irritation.
Dietary Exposure
People may be exposed to residues of folpet through the diet. Tolerances or
maximum residue limits have been established for apples, avocados, cranberries,
cucumbers, grapes, lettuce, melons, onion (dry bulb), strawberries, and tomatoes
(see 40 CFR 180.191). EPA has reassessed the folpet tolerances and found that
tolerances for apples, cranberries, cucumbers, grapes, lettuce, melons, onion (dry
bulb), strawberries, and tomatoes must be converted to import tolerances because
the US registrations for these commodities are being canceled. Also, a new
tolerance must be established for raisins because folpet concentrates in raisins. The
avocado tolerance is being amended to indicate that it is limited to a regional
registration for the state of Florida.
The Codex Alimentarius Commission has established temporary maximum
residue limits (TMRL) for folpet on cucumber, grapes, potatoes, and strawberries.
EPA has assessed the dietary risk posed by folpet, considering food and
water sources of potential residues, and quantifying dietary exposure on acute and
chronic bases. For the acute dietary (food only) assessment, EPA used a
probablistic exposure analysis, finding that the acute population adjusted dose
(aPAD) was below the Agency's level of concern. A risk estimate that is less than
100% of the acute population adjusted Dose (acute PAD)—that is, the dose at
which an individual could be exposed on any given day and no adverse health
effects would be expected—does not exceed the Agency's risk concern. At the
99.9th percentile, exposure to the most sensitive sub-group (females age 13-50)
was found to be about 25% of the aPAD for folpet.
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EPA also assessed the chronic (non-cancer) dietary risk using average field
trial data and percent crop treated information. The Agency found that the chronic
population adjusted dose (cPAD) was below the Agency's level of concern. A
risk estimate that is less than 100% of the cPAD—the dose at which an individual
could be exposed and not expect an adverse health effect—does not exceed the
Agency's risk concern. For all subgroups, the exposure is less than 1% of the
cPAD for folpet.
In addition, EPA assessed the dietary cancer risk from residues in food using
the same exposure information as used in the chronic (non-cancer) assessment and
a cancer potency factor or Qx* of 0.00186 (mg/kg/day)"1. The Agency found a
cancer risk of 9.8 x 10"8 for folpet, which is less than the Agency's level of concern
of 1 x 10-6.
The dietary risk from water, as well as the aggregate risk assessment for
folpet is discussed in the FQPA Considerations portion of this factsheet.
Occupational and Residential Exposure
Based on current use patterns, handlers (mixers, loaders, and applicators)
may be exposed to folpet during and after normal use of the wettable powder and
liquid ready to use formulations in agricultural, residential, and manufacturing
settings.
Human Risk Assessment
Folpet generally is of medium acute toxicity but causes developmental
effects in animal studies and has been classified as a Group B2, probable human
carcinogen. Food crop uses are registered including avocados in the US and
apples, cranberries, cucumbers, grapes, lettuce, melons, onions, strawberries, and
tomatoes imported from other countries However, dietary exposure to folpet
residues in foods is extremely low, as is the cancer risk posed to the general
population.
Of greater concern is the risk posed to folpet handlers, particularly
mixers/loaders who come into contact with folpet while adding it to paint during
manufacture. Exposure and risk to workers will be mitigated by the use of PPE
required by the WPS, supplemented by a dust/mist respirator and chemical
resistant gloves as required by this RED. Post-application reentry workers will be
required to observe a 24-hour Restricted Entry Interval, which is set by the WPS.
For folpet, a 24-hour REI is required because folpet is classified as Toxicity
Category n for acute inhalation toxicity and for eye irritation.
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FQPA Considerations
The Agency has determined that the established tolerances for folpet, 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, and that
there is a reasonable certainty of no harm for infants and children. The safety
determination for infants and children considers the factors noted above for the
general population, but also 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 folpet residues in this
population subgroup.
In determining whether or not infants and children are particularly susceptible
to toxic effects from folpet residues, EPA considered the completeness of the
database for developmental and reproductive effects, the nature of the effects
observed, and other information.
Based on the current data requirements, folpet has a complete database for
developmental and reproductive toxicity. Reliable studies cited earlier in this
document indicate limited concern for special sensitivity of young organisms to
folpet (see Section inb). However, the Agency has determined that the Safety
Factor can be reduced to 3X based on the developmental and reproductive toxicity
studies available for folpet, as described previously in Section ni(B)l(d) of this
document. The Agency has retained a 3X FQPA safety factor to ensure adequate
protection of infants and children. This FQPA safety factor applies only to females
13-50 for acute and short-term exposures. Therefore, the Agency has concluded
that a total uncertainty factor of 300 is adequate to protect infants and children.
This uncertainty factor was incorporated into the risk assessment.
At this time, the Agency does not know how to apply the information in its
files concerning common mechanism issues to most risk assessments; however,
there are pesticides for which the common mechanism issues can be resolved. For
example, there are pesticides that are lexicologically dissimilar to existing chemical
substances, in which case the Agency can conclude that it is unlikely that a pesticide
shares a common mechanism of activity with other substances. There are also
pesticides that produce a common toxic metabolite, in which case common
mechanism of activity will be assumed.
In the case of folpet, the Agency is aware of a proposed common mechanism
of carcinogenicity with captan. Captan and folpet share a common metabolite,
thiophosgene, which is believed to be responsible for the carcinogenic effects
observed with both compounds. Thiophosgene is a highly reactive, short-lived
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species which is produced in the gut and believed to cause tumors through the
irritation of the duodeum. Because it is so short lived, its residues cannot be
quantified. Without measurable residues of the common metabolite, it is difficult at
this time to relate exposures of captan to those of folpet since the rate of formation
of thiophosgene may be different for both compounds. However, assuming that the
carcinogenic effects observed in both pesticides are due solely to the metabolite
thiophosgene, the Agency believes it is reasonable to add the estimated cancer risks
from the individual aggregate risks from both folpet and captan to obtain a worse
case estimate. When this is done, the risks do not exceed the Agency's level of
concern.
The Agency considers residential postapplication exposure to folpet from its
use in sealants and coatings to be negligible because dermal and inhalation
exposures are likely to be minimal. Therefore, EPA has considered only residential
handler exposure together with dietary and drinking water exposures in its
aggregate risk assessment.
In assessing acute aggregate dietary risk, EPA used a NOAEL of 10
mg/kg/day from a developmental study in rabbits. Because the selected endpoint is
from a developmental toxicity study, the sub-population of females, 13-50 years
old, is the subgroup of interest. EPA estimates that residues of folpet in diets of
females 13-50 years old accounts for 25% of the acute PAD. This leaves 75% of
the acute PAD for aggregate risk. The DWLOC corresponding to 75% of the
acute PAD is 670 ppb. Because the modeled ground water concentration is only
0.06 ppb and the modeled peak surface water concentration is 156 ppb, aggregate
acute exposure and risk are not of concern.
Short and intermediate term aggregate risk estimates do not exceed the
Agency's level of concern. Short and intermediate term aggregate risk estimates
considered only two potential homeowner exposure scenarios: application of
Ready-to-Use paint or stain with either a paint brush or an airless sprayer. The
highest exposure, from the airless sprayer, represents a short-term MOE of 407.
The chronic dietary exposure from folpet represents less than 1% of the chronic
PAD. This leaves 99% of the PAD available for aggregate risk, which corresponds
to short-term DWLOC of 228 ppb available for water. The modeled 56-day
GENEEC value is 1 ppb, and the modeled concentration of folpet in groundwater
is 0.06 ppb. Because the short-term DWLOC is greater than the modeled
concentrations of folpet in surface or groundwater, the short-term aggregate risk is
not of concern.
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Environmental
Assessment
In assessing chronic aggregate dietary risk, the Agency used the same
exposure assumptions for estimating the chronic (non-cancer) and cancer risk. The
drinking water assessment used modeling, as above, to predict ground and surface
water concentrations of folpet. Chronic dietary (food) exposure to the US
population accounts for less than 1% of the chronic PAD. This leaves 99% of the
chronic PAD for aggregate risk. The DWLOC corresponding to 99% of the
chronic PAD is 890 ppb, which is far greater than the modeled groundwater
concentration of 0.06 ppb and the modeled surface water concentration of 3 ppb.
Therefore, the Agency concludes that the aggregate chronic exposure and risk from
residues in food and water are not of concern.
Ecological Effects Risk Assessment
The ecological risk assessment and risk mitigation recommendations for
folpet are based on the present limited use of folpet. At present, the only potential
ecological risks are from the use of folpet on avocados in Florida. Only a very
small percentage of Florida avocados are treated with folpet.
Acute and chronic risks to birds and mammals from folpet are not of
concern, even at maximum label application rates and frequencies. Folpet also
does not appear to pose a risk to honeybees or other insects.
Folpet is highly toxic to most aquatic animal species tested. Based on
toxicity test results and results of conservative modeling of folpet concentrations in
water, airblast application of folpet to avocados in Florida are expected to exceed
high acute risk LOCs for all aquatic animals. Because folpet is applied directly to
leaves of avocado trees, only a small amount of folpet will be available for long
range spray drift to water. Chronic LOCs are not expected to be exceeded for fish
or aquatic invertebrates.
Folpet degrades rapidly in water to the degradates, PI and PAL The
degradate PI has been shown to be only slightly toxic to aquatic animals. No
toxicity data are available on PAL However, since PAI is not expected to be
lexicologically significant and usage is limited to two counties in Florida, no
additional data will be required at this time. However, if the use pattern changes,
the Agency may reconsider this position.
The current spray drift label advisory should be continued. Additional drift
mitigation practices may be identified following review of the Spray Drift Task
Force database.
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A full plant exposure and risk assessment cannot be done with the existing
data. Because of the limited use area, no additional data or mitigation are required
at this time. However, additional aquatic plant testing would be required with any
expansion of folpet use.
Endangered Species
The Agency has concerns about the exposure of threatened and endangered
species to folpet. Levels of concern (LOG) are expected to be exceeded for
aquatic organisms exposed to single or multiple applications of this fungicide. There
are a number of endangered species in avocado growing regions in Florida. These
include the Everglades snail kite, whose primary diet consists of apple snails.
Although folpet is highly toxic to aquatic invertebrates, such as apple snails, the
nearest avocado groves are approximately 3 miles from the Everglades. Therefore,
the most likely route of exposure to snails would be long range spray drift, which is
unlikely to occur but cannot be quantified at this time. The current spray drift label
advisory should be continued. Additional drift mitigation practices may be identified
following review of the Spray Drift Task Force database. After its review of the
new studies, the Agency will determine whether a reassessment of the potential
risks to nontarget organisms is warranted.
Risk Mitigation
To lessen the risks posed by folpet, EPA is requiring the following mitigation
measures for folpet-containing products:
Gloves and dust/mist respirator or equivalent engineering controls are
required to lessen the risks to workers adding the wettable powder to
paints and stains during the manufacturing process; and
An Environmental Hazard warning is required to lessen risks to
nontarget aquatic organisms. Specific label language is provided in
Section V of the RED.
Additional Data
Required
EPA is requiring the following additional generic studies for folpet to confirm
its regulatory assessments and conclusions:
Guideline 830.7050,UV/Visible Absorption for the PAI
Guideline 860.1200, Direction for Use
Guideline 860.1380, Storage Stability for avocados, cucumber, and
melon
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Guideline 860.1480, Magnitude of the Residue in Meat and Milk (Ruminant
Feeding Study)
Guideline 850.1300, Chronic Daphnia Toxicity
Guideline 870.3700, Prenatal Developmental Toxicity in the New
Zealand White Rabbit
Guideline 875(series), Exposure Monitoring for application with wood
dip and paint roller.
These data are confirmatory; i.e., they are not expected to change the
conclusions of this RED.
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 reregi station.
P rod U Ct La be I i n g All folpet end-use products must comply with EPA's current pesticide
Required product labeling requirements and with the following. For a comprehensive list of
labeling requirements, please see the folpet RED document.
PPE for workers adding wettable powder to sealants and coatings during
manufacturing process: Chemical resistant gloves and a dust/mist respirator are
required. If available, engineering controls such as closed loading systems are an
adequate substitute for the PPE.
REI: Since folpet is in toxicity category n for inhalation exposure and eye
irritation, a 24-hour restricted entry interval (REI) is required for avocado
harvesters. Early entry PPE is required for any workers who enter treated avocado
orchards before the 24-hour REI.
Environmental Hazard Statement: "This chemical is highly toxic to fish and other
aquatic organisms. Do not apply directly to water. Do not contaminate water
when disposing of equipment, washwater, or rinsate."
Regulatory
Conclusion
The use of currently registered products containing folpet in accordance with
approved labeling will not pose unreasonable risks or adverse effects to humans or
the environment. Therefore, the Agency has determined that all supported folpet
products are eligible for reregistation under the conditions specified in this RED.
Products containing folpet for use on avocados and in coatings and sealants are
eligible for reregistation. As mentioned previously, the registrants are not
supporting other folpet uses and have requested voluntary cancellation of
agricultural, ornamental, and greenhouse registrations (EPA Registration numbers
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For More
Information
66222-8 and 7401-231). These unsupported uses were suspended due to lack of
supporting data and are ineligible for reregistration.
Folpet 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 folpet 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
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 45242-2419, telephone
1-800-490-9198; fax 513-489-8695.
Following the comment period, the folpet RED document also will be
available from the National Technical Information Service (NTIS), 5285 Port Royal
Road, Springfield, VA 22161, telephone 703-605-6000.
For more information about EPA's pesticide reregistration program, the
folpet RED, or reregistration of individual products containing folpet, 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 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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