United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508C)
EPA-738-F-04-006
November 2004
R.E.D. FACTS
Pesticide
Reregistration
Ethoxyquin
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 humans 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 ethoxyquin (Chemical Code
No. 055501; Case No. 0003).
Use Profile
Ethoxyquin is registered for use as an antioxidant to control scald
(browning) in pears. It is applied post-harvest by spraying/drenching, paper
wrapping, or a combination thereof. Currently only two formulation types are
registered for this chemical, which includes an emulsifiable concentrate (1
product) and an impregnated wrap (3 products). Production of ethoxyquin is
estimated to be less than 25,000 Ibs. active ingredient over the past five years
(averaging less than 5,000 Ibs. active ingredient per year); hence, ethoxyquin is
being considered a minor use chemical. Ethoxyquin is also regulated by the Food
and Drug Administration for its use as a preservative in animal feed, dehydrated
crops and sorghum, and as a antioxidant for the preservation of color in the
production of chili powder, paprika, and ground chili.
Regulatory Ethoxyquin was developed by Monsanto in the 1950's. Ethoxyquin was
History initially registered as a pesticide in 1965 as an antioxidant used as a deterrent of
scald in pears through post-harvest indoor application via a drench and/or
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Human Health
Assessment
impregnated wrap. There are three companies, Decco, Ceraxagri, Inc., and Wrap
Pack, Inc., who are ethoxyquin registrants.
Toxicity
The ethoxyquin risk assessment was done using a streamlined process for
lower risk/ exposure pesticide chemicals. Although the ethoxyquin toxicology
database is not complete, the toxicology database provides adequate information
for evaluating and characterizing the risks under FIFRA and FQPA for the limited
use of this chemical. Ethoxyquin has low to moderate acute toxicity by the oral
(Category in), dermal (Category in), and inhalation (Category III) exposure
routes. It is not an eye irritant (Category IV), and it produces minimal irritation to
the skin (Category IV). Tests in animals show it to have a weak sensitizing
potential, and extensive human experience from the use of this chemical showed
strong association with contact dermatitis that ceased upon discontinuation of
working in an ethoxyquin environment. The primary target organs affected by
ethoxyquin in experimental animals are the liver and the kidneys, and studies
indicate that ethoxyquin is not a teratogen or a developmental toxicant in rats or
rabbits. There is low concern (and no residual uncertainty) for pre- and/or
postnatal toxicity resulting from exposure to ethoxyquin.
Ethoxyquin has not been tested for its carcinogenic potential, though a
closely related chemical, l,2-dihydro-2,2,4-trimethylquinoline, showed some
evidence of carcinogenic activity in rats. The only suggestion of a potential
carcinogenic effect for ethoxyquin came from a Manson et al (1987) study. For
more information please see the accompanying RED document.
Dietary Risks
The ethoxyquin dietary assessment included food exposure from EPA
registered pesticidal use in pears as well ethoxyquin's FDA approved uses as an
antioxidant in feeds (e.g., meat, poultry, eggs) and as a food preservative (e.g.,
spices). In the assessment, the Agency concluded that the residue of concern
remains the parent ethoxyquin (40 CFR § 180.178). The current tolerance for
ethoxyquin (l,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline) is in pears for pre or
post- harvest use. The Agency is proposing the tolerance expression be amended
for post-harvest use only. The Codex MRL residue definition and the U.S.
tolerance definition will be compatible after amending the ethoxyquin tolerance
expression. For the overall U.S. population and all subgroups as measured by the
Population Adjusted Dose (PAD), both the acute and chronic endpoint analyses
were below the Agency's level of concern.
To ensure safely in the absence of ethoxyquin- specific carcinogenicity
studies, a bounding Q*l of 0.04 (mg/kg/day)"1 was created as a possible dietary
endpoint for ethoxyquin, and included an assessment of the FIFRA use on pears,
the FDA regulated uses on spices as a food preservative and the antioxidant use in
feeds from which secondary residues may result in meat, poultry, and eggs. The
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conservative assessment produced an estimated cancer risk of less than 2 x 10"6
which does not exceed the Agency's level of concern.
No drinking water scenarios are presented because ethoxyquin is indoor use
only and waste water from the drench application onto the fruit is commonly
recycled. There is very low likelihood of water contamination from the registered
indoor use of ethoxyquin. A residential exposure assessment was not performed
because there are no registered products containing ethoxyquin that would result
in residential exposure.
Worker Risks
Occupational assessment was based on non- cancer and potential cancer risk
for ethoxyquin handlers and post- application workers. Non- cancer risk for
potentially exposed populations is measured by a Margin of Exposure (MOE),
which determines how close the occupational exposures come to a No Observed
Adverse Effect Level (NOAEL). Potential occupational exposure scenarios include
mixing/ loading for post-harvest treatments using drench/spray application methods,
exposure during post-harvest sorting/packing/culling pears following ethoxyquin
treatment, and handling treated pears wrapped in impregnated paper.
For mixing/loading, workers in the baseline assessment are assumed to be wearing
long sleeved shirts and long pants. A MOE =100 is sufficient to protect
occupational pesticide handlers. The mixer/loader scenario requires gloves be worn
in order to achieve a MOE above 100 with gloves; the MOE for the mixer/ loader
scenario is 1500 which does not exceed the Agency's LOG. The estimated lifetime
cancer risk for a mixer/loader wearing gloves is 2.1 x 10"6 and does not exceed the
Agency's LOG.
The Agency does not have data addressing the sorting/ packing/culling of
products following ethoxyquin treatment. The estimates of exposure were derived
from residue chemistry data, surface areas calculations, and a study found in
scientific literature. Though commonly worn, gloves are not required by label for
the sorting/packing/culling process. The scenario was assessed assuming no gloves.
The MOE for the above scenario is greater than 1800, therefore the risks for
sorting/packing/culling do not exceed the Agency's LOG. The estimated lifetime
cancer risk for workers handling treated fruit is 1.8 x 10"7; this does not exceed the
Agency's LOG.
Based on scenarios with true historical exposure data, exposure from
impregnated paper would not exceed (i.e. negligible in comparison to drench/spray
scenario) the exposure from handling treated pears after drenching/spraying.
FQPA Considerations
An aggregate exposure risk assessment was considered under FQPA, but
because residential and water exposures are not anticipated to result from any of
the current uses of ethoxyquin, the results are the same as the dietary risks, and
below the Agency's level of concern.
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In addition, unlike other pesticides for which EPA has followed a cumulative
risk approach based on a common mechanism of toxicity, EPA has not made a
common mechanism of toxicity finding as to ethoxyquin and any other substances,
and ethoxyquin does not appear to produce a toxic metabolite produced by other
substances. For the purpose of this reregistration decision, therefore, EPA has not
assumed that ethoxyquin has a common mechanism of toxicity with other
substances.
Environmental
Assessment
Ecological Risks
Because use patterns include only indoor uses, there is low likelihood of
outdoor or water exposures, and risks to non-target species are not anticipated.
Because the pesticidal use pattern of ethoxyquin includes only the indoor food
processing of pears, EPA has concluded that outdoor environmental or water
exposure is highly unlikely and any exposure to terrestrial wildlife or aquatic
organisms would be negligible. Therefore, EPA has determined that the
pesticidal uses of ethoxyquin discussed in the RED will have no effect on
federally listed endangered and threatened species.
Summary Th*8 Fact Sheet explains the Agency's decision regarding the reregistration
eligibility of the registered uses of ethoxyquin. The Agency has found that the
current uses of ethoxyquin are eligible for reregistration, provided the changes
specified in the RED are made to the packaging and labels.
Additional Data The generic database currently supports the use of ethoxyquin on pears, and
Red UJ red no confirmatory studies are required in the reassessment of the chemical ethoxyquin
for this use. Should a registrant petition for the use of ethoxyquin to be expanded, at
a minimum, the following data would be required:
- A Teratology study in rabbits
- A 2-generation reproduction study
- A chronic oncogenicity study in rats
- A carcinogenicity study in mice
- A 21/28 dermal toxicity study
Product Labeling All ethoxyquin end-use products must comply with EPA's current pesticide
ChanaeS Reauired product labeling requirements and with the following. For a comprehensive list of
labeling requirements, please see the Ethoxyquin RED document.
Regulatory
Conclusion
In order to be eligible for reregistration, all product labels are to be amended
to incorporate measure outlined in the attached RED document. Furthermore, many
of the existing labels for ethoxyquin need to be revised to provide clear use
directions. EPA has determined that all mixer/loaders of ethoxyquin post-harvest
application use must wear chemical resistant gloves.
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For More
Information
EPA is requesting public comments on the Reregistration Eligibility
Decision (RED) document for ethoxyquin during a 60-day time period, as
announced in a Notice of Availability published in the Federal Register. To obtain
a copy of the ethoxyquin RED document, please contact the OPP Public Docket
(7502C), US EPA, Ariel Rios Building, 1200 Pennsylvania Avenue, NW,
Washington, DC 20460-0001, telephone: (703) 305-5805. Electronic copies of the
ethoxyquin RED and all supporting documents are also available on the Agency's
website at http://www. cfpub. epa. gov/oppref/rereg/status, cjm ?show =rereg.
For more information about EPA's pesticide reregistration program or the
ethoxyquin 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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