&EPA
United States Prevention, Pesticides EPA 738-R-04-011
Environmental Protection and Toxic Substances November 2004
Agency (7508C)
Reregistration Eligibility
Decision (RED)
Ethoxyquin
-------
REREGISTRATION ELIGIBILITY DECISION (RED)
for
Ethoxyquin
CASE 0003
Includes chemicals:
055501 1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline
Approved by:
Debra Edwards, Ph. D.
Director
Special Review and Reregistration Division
Date:
-------
Ethoxyquin Team
Office of Pesticide Programs:
Health Effects Division
David Hrdy
Abdallah Khasawinah
Dave Jaquith
Jerry Stokes
Biological and Economics Analysis Division
Jihad Alsadek
Registration Division
Cynthia Giles- Parker
Special Review and Reregistration Division
Tom Brennan
-------
Executive Summary
The U.S. Environmental Protection Agency (EPA or the Agency) has completed the
reregistration eligibility decision for the pesticidal uses of ethoxyquin for post-harvest/ indoor uses on
pears. The decision includes a comprehensive assessment of the required data and the use patterns of
currently registered products.
The Agency has conducted a risk assessment for the active ingredient ethoxyquin to support a
reregistration eligibility and tolerance reassessment decision for this pesticide. The risk assessment
team, using a streamlined process for lower risk pesticides, selected relevant toxicity endpoints and
estimated doses for risk assessment of various exposure conditions. The acute and chronic dietary
risks are both below the Agency's level of concern. Although ethoxyquin has not been determined to
be a carcinogen and no cancer data are available, a bounding endpoint Q\ of 0.04 (mg/kg/day)"1 as a
possible dietary endpoint for ethoxyquin was assessed as a conservative estimate considering the lack
of data. The 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 risk assessment scenarios were done because the waste water from the
drench application onto the fruit is recycled and there is very low likelihood of water contamination
from the registered indoor use of ethoxyquin. In addition, no products are registered that would result
in residential exposure of ethoxyquin. Potential worker exposure occurs while mixing/loading the
chemical during treatment, and while sorting/packing/culling after the application to pears. The
Agency's assessment shows that mixers/loaders must wear gloves to obtain an acceptable margin of
exposure above 100, the Agency's level of concern. The mixer/loader lifetime cancer risk is 2. IxlO"6
and does not exceed the Agency's level of concern. The estimates of exposure for the
sorting/packing/culling of pears were derived from residue chemistry data, surface area calculations,
and a scientific literature study. The margin of exposure level is greater than 1800 and does not
exceed the Agency's level of concern. Lifetime cancer risk for workers handling fruit is l.SxlO"7, and
also does not exceed the Agency's level of concern.
Based on the current uses, no aggregate exposure risk assessments were conducted. Because
there are no outdoor uses and low likelihood of water exposures, risk to non-target species or
endangered species is not anticipated, and no ecological risk assessment was conducted.
The Agency has found that sufficient data are available to create a safety finding for the
current uses. The single current tolerance on pears for ethoxyquin is reassessed, and the products
containing ethoxyquin are eligible for reregistration provided that a label change stating that
mixers/loaders are required to wear gloves is added.
-1-
-------
I. Determination of Reregistration Eligibility for Ethoxyquin
Section 4(g)(2)(A) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) calls
for the Environmental Protection Agency (EPA or the Agency) to determine, after submission of
relevant data concerning an active ingredient, whether products containing the active ingredient are
eligible for reregistration. This is determined in the reregistration eligibility decision (RED). The
EPA has reviewed all relevant data and assessed the potential risks posed by exposure to ethoxyquin.
Based on this assessment, EPA has determined that ethoxyquin is eligible for reregistration and
tolerance reassessment provided that the label change outlined in this document is adopted.
Accordingly, should a registrant fail to implement the label change identified in this document, the
Agency may take further regulatory action for ethoxyquin.
n. Chemical Overview
A. Regulatory History
Developed by Monsanto in the 1950's, Ethoxyquin is used primarily, under Food and Drug
Administration regulation 21 CFR § 172.140, as a preservative in animal feed for stabilizing fat
soluble vitamins (such as vitamins A and E) to maintain the quality of feed. Ethoxyquin has a feed-
additive tolerance in certain dehydrated crops such as such as alfalfa, clover, grasses, and sorghum to
retard the destruction of carotene and vitamin E (published by the FDA under 21 CFR § 573.400). It
is also used as an antioxidant for the preservation of color in the production of chili powder, paprika,
and ground chili (21 CFR § 172.140 ), and as a stabilizer and anti-degradation agent for rubber ( 21
CFR § 177.2600).
Ethoxyquin was initially registered as a pesticide in 1965 as an antioxidant used as a deterrent
of scald in pears and apples through a pre- harvest spray and post- harvest post- harvest dip or spray.
Scald is a physiological disorder of fruit which results in the discoloration of large areas of the fruit. It
is currently registered for use on pears through a post-harvest indoor application via a drench and/or
impregnated wrap. Four products are registered; one emulsifiable concentrate and three impregnated
materials. There are two companies, Decco, Ceraxagri, Inc. and Wrap Pack Inc., who are ethoxyquin
registrants.
B. Chemical Identification
• Common Name: Ethoxyquin
• Case number: 0003
• Basic manufacturer: Ceraxagri, Inc.
-2-
-------
Table 1. Ethoxyquin Structure and Nomenclature
Chemical Structure
Empirical Formula
Molecular Weight
Common name
lUPACname
CAS name
CAS Registry Number
PC Code
End-use product/EP
Chemical Class
Known Impurities of Concern
C,H,oC
H
N CH3
CH3
C14H19NO
217.34
Ethoxyquin
l,2-dihydro-2,2,4-trimethylquinolin-6-yl ethyl ether
6-ethoxy- 1 ,2-dihydro-2,2,4-trimethylquinoline
91-53-2
55501
Deccoquin, Pear Wrap I, Pear Wrap III
Quinoline
None
C. Use Profile and Estimated Use of Pesticide
Ethoxyquin is registered for use as an antioxidant to control scald (browning) in pears. It can
be 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). Additionally, applications can be
made as a non-split application, split application, or wrapped as noted below:
-3-
-------
Application Method Rates (ppm)
Non-split application (Single Application)*
- drenching; spray (brush bed or conveyor rolls); or 2700 ppm
- combined (w/ packout wax treatment)
Split application (Double Application)*
- drenching (applied within 2 days of harvest), and 1000 ppm
- line spray (stored pears washed & packed) 1700 ppm
Impregnated Wrap (Wrap within 1 week post-harvest) 1000 ppm
* These two methods of application are not to be used in combination with one another.
Additionally, the maximum application rate must not exceed 2700 ppm.
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 as a minor use chemical.
HI. Summary of Human Health and Environmental Risk Assessments
The Health Effects Division (HED) Risk Assessment (29 July 2004, Hrdy) details the EPA's
human health risk findings and conclusions for ethoxyquin. This technical support document is
available on the Internet at htt|3i//wwa,epa,ggvMQcketand in the Office of Pesticide Program's
(OPP) public docket for viewing. The OPP docket is located in Room 119, Crystal Mall #2, 1801
South Bell Street, Arlington, VA, and is open Monday through Friday, excluding legal holidays, from
8:30 AM to 4:00 PM.
A. Human Health Risk Assessment
The ethoxyquin risk assessment was done using a streamlined process for lower risk/ exposure
pesticide chemicals. The toxicology and risk assessment teams evaluated the entire toxicological
database, the information on use patterns, and the exposures to ethoxyquin. Relevant toxicity
endpoints and doses for the risk assessment of various exposure conditions were selected; no endpoint
relevant to the general population was identified. Ethoxyquin has been the subject of numerous
studies because of its wide use as an antioxidant. 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 III), dermal (Category
IE), 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. Extensive human experience from the use of this chemical showed strong
-4-
-------
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. Dogs are more susceptible to ethoxyquin toxicity than rats with elevated liver enzymes and
microscopic findings in the liver occurring at doses as low as 4 mg/kg/day over a 90 day feeding
period. Studies indicate that ethoxyquin is not a teratogen or a developmental toxicant in rats or
rabbits; ethoxyquin did not cause developmental effects in rats tested at doses of 350 mg/kg/day
during gestation, or in rats at doses as high as 500 mg/kg of a 67% ethoxyquin formulation, and no
developmental effects were seen in rabbits where the maximum dose of 3 mg/kg/day was
administered.
Ethoxyquin has not been tested for its carcinogenic potential. In a two-year study, the 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 etal (1987) study where feeding male Fisher 344 rats ethoxyquin at 0.5% formulation (5000
ppm, equivalent to 250 mg/kg/day) for 23 weeks caused severe damage to the kidneys and produced
many hyperplastic and putative preneoplastic tubules. A number of authors, especially Gaylor and
Krewski, have concluded that the association between maximum tolerated dose (MTD) and cancer
potency is sufficiently robust and can be used to estimate boundaries on cancer potency (refer to
Human Health Risk Assessment Document for further reference). The Gaylor and Krewski
estimation method is applicable to ethoxyquin, as suggested by the Manson etal study that produced
putative preneoplastic tubules in male rats.
-5-
-------
Table 2. Summary of lexicological Endpoints and Other Factors Used in the Risk Assessment of the Ethoxyquin
Exposure
Scenario
Dose (mg/kg/day)
*Special FQPA Safety Factor
and Level of Concern for Risk
Assessment
I. ml point for Risk Assessment
Dietary Risk Assessments
Acute Dietary
Chronic Dietary
all populations
NOAEL = >3
mg/kg/day
UF=100
Acute RfD = 0.03
mg/kg/day
NOAEL= 2 mg/kg/day
UF=100
Chronic RID = 0.02
mg/kg/day
FQPASF = 1
aPAD= acute RfD
FQPA SF
= 0.03 mg/kg/day
FQPASF = 1
cPAD= chronic RfD
FQPA SF
= 0.02 mg/kg/day
Developmental study in rabbits (published) where the
maximum dose tested of 3 mg/kg/day had no
developmental effects
90-day subchronic study in dogs
LOAEL = 4 mg/kg/day based on elevated liver
enzymes and microscopic findings in the liver
(cytoplasmic vacuolation and minimal hepatocelular
necrosis).
Non-Dietary Risk Assessments
Dermal. All
durations
Cancer
NOAEL= 2 mg/kg/day
(Oral)
100% absorption is
assumed
Residential: not required
Occupational
LOCforMOE=100
90-day subchronic study in dogs
LOAEL = 4 mg/kg/day based on elevated liver
enzymes and microscopic findings in the liver
(cytoplasmic vacuolation and minimal hepatocelular
necrosis).
There are no guideline studies assessing this effect in animals. It is structurally similar to l,2-dihydro-2,2,4-
trimethylquinoline which showed evidence of carcinogenicity (kidney tumors) in male rats. Ethoxyquin is also a
nephrotoxin in male rats. A theoretical upper bound Q'j for ethoxyquin was calculated to be 0.04 (mg/kg/day)"1.
There is low concern (and no residual uncertainty) for pre- and/or postnatal toxicity resulting
from exposure to ethoxyquin. The available data show no indication of increased susceptibility
(quantitative or qualitative) to rats or rabbits to in utero exposure. A developmental neurotoxicity
study is not required as there was no evidence of neurotoxicity or neuro pathology from the available
studies. The special FQPA safety factor is reduced to IX in risk assessments for this chemical.
1. Dietary Risk From Food
Acute, chronic, and cancer dietary risk assessments were conducted using the Lifeline Model
Version 2.0 and the Dietary Exposure Evaluation Model (DEEM-FCID™, Version 2.03), which use
food consumption data from the USDA's Continuing Surveys of Food Intakes by Individuals (CSFII)
from 1994-1996 and 1998. The acute reference dose had a safety factor of 100 applied (10X for
interspecies variation and 10X for intraspecies variation). The chronic reference dose had a safety
factor of 100 applied (lOx for interspecies variation and 10X for intraspecies variation). The
ethoxyquin dietary assessment included food exposure from EPA registered pesticidal use in pears as
well as ethoxyquin's FDA approved uses as an antioxidant in feeds (e.g., meat, poultry, eggs) and as a
food preservative (e.g, spices).
-6-
-------
The toxicity endpoints selected and risk results for relevant exposure scenarios are
summarized in table 3 and 4 below. Exposure estimates are expressed in mg/kg body weight/day, and
risk is expressed as a percent of the acute/chronic Population Adjusted Dose (a/cPAD). The aPAD is
the dose at which a person could be exposed to on any given day and no adverse health effects would
be expected. The cPAD is the dose at which an individual could be exposed over the course of a
lifetime and no adverse health effects would be expected. A risk that is less than 100% of the acute or
chronic PAD does not exceed EPA's risk concern.
Because of the highly conservative nature of the assessment, 95th percentile was deemed
acceptable. Acute and chronic dietary exposure analyses was created using a Tier I, highly
conservative assessment using tolerance level residues and 100% crop and feed treated.
Females 13- 49 years of age was the population of interest for the aPAD, as the endpoint is
based on developmental effects. The overall acute dietary risk from residues in foods was 14 % of the
aPAD at the 95th percentile of exposure for the females 13-49 years old sub-population.
Table 3. Ethoxyquin Acute Dietary Exposure Analysis
Population Subgroup
Females 13^9 years old
aPAD
(mg/kg/day)
0.03
95th Percentile
Exposure
(mg/kg/day)
0.004311
% aPAD
14
The overall chronic dietary risk from residues in foods was based on the General U.S.
population, and young children, the population of interest because they are the most exposed The
average dietary exposure for the general U.S. Population was 5% of the cPAD, 15% of the cPAD for
all infants (< 1 year old), and 14% of the cPAD for children 1 to 2 years of age.
Table 4. Ethoxyquin Chronic Dietary Exposure and Risk
Population
Subgroup*
General U.S.
Population
All Infants (< 1
year old)
Children 1-2
years old
cPAD
(mg/kg/day)
0.02
0.02
0.02
Chronic Dietary
Dietary
Exposure
(mg/kg/day)
0.001064
0.003066
0.00287
%cPAD*
5
15
14
Both the acute and chronic endpoint analyses were below the Agency's level of concern.
-7-
-------
2. Hypothetical Cancer Dietary Exposure Results and Characterization
Cancer risks are calculated by multiplying the 70 year exposure estimate for the U.S.
population by the Q\ , and are expressed as a probability of developing cancer. Ethoxyquin has been
determined to not be a carcinogen and no adequate guideline studies for rats and mice have been
submitted for carcinogenic potential of ethoxyquin. To ensure safety in the absence of ethoxyquin
specific carcinogen!city studies, a bounding Q\ of 0.04 (mg/kg/day)"1 was created using the Q*
bounding estimation procedure and the maximum tolerated dose (MTD) of ethoxyquin.
a. Residue Data Used for Cancer Assessment
The hypothetical cancer assessment included 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 assessment was performed using field trial results of 1.31 ppm
of ethoxyquin present on pears after 14 days, and was refined, to match the use pattern of ethoxyquin,
by the fraction of fresh non- Bartlett pears. USD A Agricultural Statistics for 2003 were used to adjust
for the 45% of pears that were cultivated in U.S. that are non-Bartlett pears. The assessment only
included spices that were dried; ethoxyquin is not applied to fresh herbs and spices. The inclusion of
all dried spices is considered conservative since ethoxyquin is registered for use on only chili and
paprika.
b. Results
Using tolerances to represent ethoxyquin residues in foods including the food preservative use
in spices and the antioxidant use in feeds from which secondary residues may result in meat and
poultry, 100% of the non-Bartlett pear variety crop, the refined assessment produced a estimated
cancer risk of less than 2 x 10"6.
Table 5. Ethoxyquin Hypothetical Cancer Risk Estimated
Population Subgroup
US General Population (EPA and FDA
regulated uses)
Q*
(mg/kg/day)1
0.04
Exposure
(mg/kg/day)
0.001065
Estimated Lifetime
Cancer Risk
1.9 E-6
Q* is the estimated slope factor for ethoxyquin from the bounding estimation Q* estimation method.
-------
Because only a small percentage of livestock feeds are treated, further refinement of the
assessment could be made through the use of field trial data, FDA monitoring data for pears and
livestock feeds, or the percent of crop treated for the pears and livestock feeds. Factors that lead to the
conclusion for refinement include:
- Upper bound estimate of potency (Qj*)
- Tolerance (upper bound) residues for spices, meat products, and eggs
- High- end residue value for pears
- Assumption that all pears that could be treated are treated
- Assumption that all dried spices are treated while only paprika and chili are actually treated
- Assumption of 100% crop treated for meat products and eggs
Given these high end inputs and assumptions, the EPA concludes that potential cancer risk is below
the Agency's level of concern.
2. Dietary Risk from Water
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.
3. Residential Risks
A residential exposure assessment was not performed because there are no registered products
containing ethoxyquin that would result in residential exposure.
4. Aggregate Risk
Aggregate exposure risk assessments were 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.
5. Occupational Handler and Post-Application Risks
Based on currently registered labels for ethoxyquin, EPA assessed potential occupational
scenarios for the chemical. Application rates were obtained from representative label rates for pears or
treated wrappers. Dermal absorption is assumed to be 100%. 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). Estimations of occupational cancer risk from ethoxyquin use were based on the following
assumptions:
-9-
-------
1 . Workers are exposed for 35 years over a 70 year life span.
2. Workers are exposed for 30 days per year.
3 . The Q*j for ethoxyquin is 0.04 per mg/kg/day .
Potential occupational exposure scenarios include:
1 . Mixing/loading for post-harvest treatments using drench/spray application methods.
2. Exposure during post-harvest sorting/packing/culling pears following ethoxyquin
treatment.
3 . Handling treated pears wrapped in impregnated paper.
a. Mixer/Loader
As a model for mixers and loaders, the throughput from a citrus operation was used. A large
citrus operation processes up to 2000 boxes. These boxes weigh approximately 90 Ibs. The
maximum application rate, 1 gallon of 52.2% product in 1999 gallons of waxing/rinsing solution,
results in an application rate of approximately 2700 ppm. The assumed rate for application of
ethoxyquin is 1 gallon per 8000-10,000 Ibs of fruit (using the citrus model).
The 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 1 00 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. 1x10 "6 and does not exceed the Agency's LOG.
b. Sorting/Packing/Culling
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
area calculations, and a study found in scientific literature. The estimated residues on the surfaces of
treated commodities were estimated using the following assumptions:
1 . A "standard" apple or pear has a diameter of 2-3/4 inches (~7 cm) and weighs 138
grams. It is assumed that pears have approximately the same characteristics as apples.
A medium size pear weighs 166 grams. For the purposes of this calculation pears are
assumed to be roughly spherical.
2. The treatment equipment for all post-harvest treatments with ethoxyquin is essentially
the same for pears as it is for citrus.
3. The average residue level in pears treated by both spray and wrapping is 0.873 ppm
4. All of the ethoxyquin in a pear is located on the surface.
5. The surface area of the palmar surface of the hands is 410 cm2. This area is considered
to be total area exposed in an 8 hour day.
-10-
-------
6. A study from the scientific literature indicates that less than 2 percent of material from
glass plates treated with a dust is transferred to the hands after repeated pressing (Refer
to the Human Health Risk Assessment document for further reference). The same
amount is assumed to be transferred from a pear, i.e., the hand pressed to glass plate
study is translated to grasping a fruit.
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 1.8xlO"7; this does not exceed the
Agency's LOG.
c. Impregnated Paper Handler
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 (PHED Surrogate Exposure Guide, AUG-1998). An
assessment of handling impregnated paper exposure is not presented in this document.
B. Environmental Risk Assessment
1. Risk to Non-Target Species
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.
2. Endangered Species Assessment
Because the pesticidal use pattern 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.
C. Cumulative Risk
Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish,
modify, or revoke a tolerance, the Agency consider "available information" concerning the cumulative
effects of a particular pesticide's residues and "other substances that have a common mechanism of
toxicity."
EPA does not have at this time available data to determine whether ethoxyquin has a common
mechanism of toxicity with other substances. Unlike other pesticides for which EPA has followed a
-11-
-------
cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common
mechanism of toxicity finding to ethoxyquin and any other substances, and ethoxyquin does not
appear to produce a toxic metabolite that is also produced by other substances. Therefore, for the
purposes of this tolerance reassesment, the Agency has not assumed that ethoxyquin has a common
mechanism of toxicity with other substances. For information regarding EPA's efforts to determine
which chemicals have a common mechanism of toxicity, and to evaluate the cumulative effects of
such chemicals, see the policy statements released by EPA's OPP concerning common mechanism
determinations and procedures for cumulating effects from substances found to have a common
mechanism on EPA's website at http://www.epa.gov/fedrgstr/EPA-PEST/2002/January/Day-16/.
D. Endocrine Disrupter Effects
EPA is required under the Federal Food Drug and Cosmetic Act (FFDCA), as amended by
FQPA, to develop a screening program to determine whether certain substances (including all
pesticide active and other ingredients) "may have an effect in humans that is similar to an effect
produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator may
designate." Following the recommendations of its Endocrine Disrupter Screening and Testing
Advisory Committee (EDSTAC), EPA determined that there was scientific basis for including, as part
of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone
system. EPA also adopted EDSTAC's recommendation that the Program include evaluations of
potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that
effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA as
authority to require the wildlife evaluations. As the science develops and resources allow, screening
of additional hormone systems may be added to the Endocrine Disrupter Screening Program (EDSP).
There is no indication from existing data that ethoxyquin is an endocrine disrupter. When the
appropriate screening and/or testing protocols being considered under the Agency's EDSP have been
developed, ethoxyquin may be subjected to additional screening and/or testing to better characterize
effects related to endocrine disruption.
E. Tolerance Summary
A summary of the ethoxyquin tolerance reassessment is presented in the table below. A full
description of the tolerance reassessment can be found in the HED risk assessment document. 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.
-12-
-------
Table 6. Tolerance Reassessment Summary for Ethoxyquin
Commodity
Current Tolerance (ppm)
Tolerance Reassessment
(ppm)
Comment/correct
Commodity Definition
Tolerances Listed Under 40 CFR § 180. 178
Pear
3.0
3.0
Based on available residue
data that indicate residues of
ethoxyquin as high as 3.0 ppm
in or on pears.
[pear, post-harvest]
1. Codex Harmonization
The Codex Alimentarius Commission has established maximum residue limits (MRLs) for
ethoxyquin residues in/on pears at 3.0 ppm. The Codex MRL residue definition and the U.S.
tolerance definition will be compatible after amending the ethoxyquin tolerance expression.
IV. Confirmatory Generic Data Requirements
The generic database currently supports the use of ethoxyquin on pears, and 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 will 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
V. Label Changes
In order to be eligible for reregistration, all product labels are to be amended to incorporate
measures outlined in this 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. Table 7 describes how
language on the labels should be amended.
VL Attachment: Health Effects Division (HED) Risk Assessment for the Reregistration
Eligibility Decision for Ethoxyquin (7-29-04)
Table 7. Summary of Labeling Changes for Ethoxyquin
Description
Amended Labeling Language
-13-
-------
End Use Products Intended for Occupational Use
PPE Requirements for
Pesticide Handlers
Established by the RED1
for Liquid Formulations
"Some materials that are chemical-resistant to this product are (registrant inserts
correct chemical-resistant material). If you want more options, follow the
instructions for category [registrant inserts A,B,C,D,E,F,G,or H] "on an EPA
chemical-resistance category selection chart."
"Personal Protective Equipment (PPE)"
"Mixers, loaders and applicators and other handlers* must wear:
- long sleeved shirt and long pants and
-socks and shoes.
In addition, mixers and loaders must wear chemical resistant gloves [registrant: insert
appropriate glove material]."
*Persons sorting, packing, culling, or otherwise handling treated pears and persons
handling impregnated paper wrap are considered handlers and must wear the
required handler PPE.
NOTE: Employers must provide mixers and loaders with the appropriate type of
chemical-resistant gloves in clean and operating condition and replace or
appropriately clean the gloves after any day of use.
Immediately
following/below
Precautionary
Statements: Hazards
to Humans and
Domestic Animals
User Safety Requirements
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no such instructions
for washables exist, use detergent and hot water. Keep and wash PPE separately from
other laundry."
Precautionary
Statements: Hazards
to Humans and
Domestic Animals
immediately
following the PPE
requirements
-14-
-------
User Safety Recommendations
General Application
Restrictions
"User Safety Recommendations
Users should wash hands before eating, drinking, chewing gum, using tobacco, or using
the toilet.
Users should remove clothing/PPE immediately if pesticide gets inside. Then wash
thoroughly and put on clean clothing.
Users should remove PPE immediately after handling this product. Wash the outside of
gloves before removing. As soon as possible, wash thoroughly and change into clean
clothing."
"Do not apply this product in a way that will contact workers or other persons. Only
protected handlers may be in the area during application."
Precautionary
Statements under:
Hazards to Humans
and Domestic
Animals
Place in the Direction
for Use
1 PPE that is established on the basis of Acute Toxicity of the end-use product must be compared to the active ingredient PPE in this document. The more
protective PPE must be placed in the product labeling. For guidance on which PPE is considered more protective, see PR Notice 93-7.
-15-
------- |