[Federal Register Volume 64, Number 71 (Wednesday, April 14, 1999)]
[Rules and Regulations]
[Pages 18333-18339]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-9061]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300830; FRL-6071-3]
RIN 2070-AB78
Pyriproxyfen (2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine;
Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes a tolerance for residues of
pyriproxyfen in or on pome fruits, walnuts and apple pomace, wet.
Valent U.S.A. Corporation requested this tolerance under the Federal
Food, Drug, and Cosmetic Act, as amended by the Food Quality Protection
Act of 1996.
DATES: This regulation is effective April 14, 1999. Objections and
requests for hearings must be received by EPA on or before June 14,
1999.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300830], must be submitted to: Hearing
Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M St.,
SW., Washington, DC 20460. Fees accompanying objections and hearing
requests shall be labeled ``Tolerance Petition Fees'' and forwarded to:
EPA Headquarters Accounting Operations Branch, OPP (Tolerance Fees),
P.O. Box 360277M, Pittsburgh, PA 15251. A copy of any objections and
hearing requests filed with the Hearing Clerk identified by the docket
control number, [OPP-300830], must also be submitted to: Public
Information and Records Integrity Branch, Information Resources and
Services Division (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. In person,
bring a copy of objections and hearing requests to Rm. 119, Crystal
Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA.
A copy of objections and hearing requests filed with the Hearing
Clerk may be submitted electronically by sending electronic mail (e-
mail) to: opp-docket@epa.gov. Copies of objections and hearing requests
must be submitted as an ASCII file avoiding the use of special
characters and any form of encryption. Copies of objections and hearing
requests will also be accepted on disks in WordPerfect 5.1/6.1 file
format or ASCII file format. All copies of objections and hearing
requests in electronic form must be identified by the docket control
number [OPP-300830]. No Confidential Business Information (CBI) should
be submitted through e-mail. Electronic copies of objections and
hearing requests on this rule may be filed online at many Federal
Depository Libraries.
FOR FURTHER INFORMATION CONTACT: By mail: Joseph Tavano, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. Office
location, telephone number, and e-mail address: Rm. 222, Crystal Mall
#2, 1921 Jefferson Davis Hwy., Arlington, VA, (703) 305-6411,
tavano.joseph@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: In the Federal Register of March 27, 1998
(63 FR 14926) (FRL-5579-6), EPA issued a notice pursuant to section 408
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a as
amended by the Food Quality Protection Act of 1996 (FQPA) (Pub. L. 104-
170) announcing the filing of a pesticide petition (PP 7F4882) for
tolerance by Valent U.S.A. Corporation, 1333 N. California Blvd.,
Walnut Creek, CA 94596 This notice included a summary of the petition
prepared by Valent U.S.A. Corporation, the registrant. There were no
comments received in response to the notice of filing.
The petition requested that 40 CFR 180.510 be amended by
establishing a tolerance for residues of the insecticide, pyriproxyfen,
in or on pome fruits, walnuts and apple pomace, wet at 0.2, 0.02 and
0.8 part per million (ppm) respectively.
I. Background and Statutory Findings
Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a
tolerance (the legal limit for a pesticide chemical residue in or on a
food) only if EPA determines that the tolerance is ``safe.'' Section
408(b)(2)(A)(ii) defines ``safe'' to mean that ``there is a reasonable
certainty that no harm will result from aggregate exposure to the
pesticide chemical residue, including all anticipated dietary exposures
and all other exposures for which there is reliable information.'' This
includes exposure through drinking water and in residential settings,
but does not include occupational exposure. Section 408(b)(2)(C)
requires EPA to give special consideration to exposure of infants and
children to the pesticide chemical residue in establishing a tolerance
and to ``ensure that there is a reasonable certainty that no harm will
result to infants and children from aggregate exposure to the pesticide
chemical residue....''
[[Page 18334]]
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. For further discussion of the
regulatory requirements of section 408 and a complete description of
the risk assessment process, see the final rule on Bifenthrin Pesticide
Tolerances (62 FR 62961, November 26, 1997) (FRL-5754-7).
II. Aggregate Risk Assessment and Determination of Safety
Consistent with section 408(b)(2)(D), EPA has reviewed the
available scientific data and other relevant information in support of
this action. EPA has sufficient data to assess the hazards of
pyriproxyfen, 2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine and to
make a determination on aggregate exposure, consistent with section
408(b)(2), for a tolerance for residues of pyriproxyfen on pome fruits,
walnuts and apple pomace, wet at 0.2, 0.02 and 0.8 ppm respectively.
EPA's assessment of the dietary exposures and risks associated with
establishing the tolerance follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children. The nature of the toxic effects caused by pyriproxyfen, 2-[1-
methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine are discussed in this unit.
1. Acute toxicity. Acute toxicity studies with technical
pyriproxyfen: Oral LD50 in the rat is >5,000 milligram/
kilogram (mg/kg) for males and females - Toxicity Category IV; dermal
LD50 in the rabbitat >2,000 mg/kg - Toxicity Category IV;
inhalation LC50 in the rat is >1.3 mg/L (highest dose
attainable) - Toxicity Category III; primary eye irritation in the
rabbit (mild irritatant) - Toxicity Category III; primary dermal
irritation in the rabbit (not an irritant: non-irritating to the skin
under conditions of test))- Toxicity Category IV. Pyriproxyfen is not a
sensitizer.
2. Subchronic toxicity. In the subchronic feeding study in rats,
the no-observed effect level (NOAEL) was 27.68 mg/kg/day. The lowest
oberved effect level (LOAEL) was 141.28 mg/kg/day, based upon higher
mean total cholesteral and phospholipids, decreased mean RBCs,
hematocrit and hemoglobin counts and increased relative liver weight.
In the subchronic feeding study in dogs, the NOAEL was 100 mg/kg/
day and the LOAEL was 300 mg/kg/day. The effects were based on
increased absolute and relative liver weight in males and
hepatocellular hypertrophy in females. These findings were also
observed at 1,000 mg/kg/day and may represent adaptive changes at both
300 mg/kg/day and the limit dose of 1,000 mg/kg/day.
In a 21-day dermal study in rats, the NOAEL for systemic effects
was >1,000 mg/kg/day (limit dose). The LOAEL for systemic effects was
not established in this study. No dermal or systemic toxicity was
observed at any dose tested.
3. Chronic toxicity/carcinogenicity. In a 1-year chronic feeding
study in dogs, the NOAEL was 100 mg/kg/day. The LOAEL was 300 mg/kg/day
based on decreased weight gain, increased absolute and relative liver
weight, mild anemia, increased cholesterol and triglycerides.
The oncogenicity study in mice the NOAEL and LOAEL for systemic
toxicity in males are 600 ppm and 3,000 ppm, respectively, based on an
renal lesions in males. The technical grade test material was given to
male and female CD-1 mice in diet for 18 months at 0, 120, 600, or
3,000 ppm. No statistically significant increase in tumor incidence
relative to controls were observed in either sex at any dose up to
3,000 ppm HDT.
In the chronic feeding/oncogenicity study in rats, the NOAEL
(systemic) was 35.1 mg/kg/day and the LOAEL (systemic) was 182.7 mg/kg/
day. The technical grade test material was administered to male and
female Sprague-Dawley rats in diet for 24 months at 0, 120, 600, or
3,000 ppm. A decrease of 16.9% in body weight gain in females at 3,000
ppm 182.7 mg/kg/day was basis for the systemic LOAEL.
4. Developmental toxicity. In the developmental study in rabbits,
the maternal NOAEL/LOAEL for maternal toxicity were 100 and 300 mg/kg/
day based on premature delivery/abortions, soft stools, emaciation,
decreased activity and bradypnea. The developmental NOAEL was
determined to be 300 mg/kg/day and developmental LOAEL was determined
to be undetermined; no dose related anomalies occurred in the 4
remaining litters studied at 1,000 mg/kg/day.
In the developmental study in rats, a maternal NOAEL/LOAEL were
determined to be 100 mg/kg/day and 300 mg/kg/day, respectively. These
findings were based on increased incidences in mortality and clinical
signs at 1,000 mg/kg/day with decreased in food consumption, body
weight, and body weight gain together with increases in water
consumption at 300 and 1,000 mg/kg/day. The developmental NOAEL/LOAEL
were 100 mg/kg/day and 300 mg/kg/day based on the increase of skeletal
variations at 300 mg/kg/day and above.
5. Reproductive toxicity. In a 2-generation reproduction study in
rats, the systemic NOAEL was 1,000 ppm (87 mg/kg/day). The LOAEL for
sytemic toxicity was 5,000 ppm (453 mg/kg/day). Effects were based on
decreased body weight, weight gain and food consumption in both sexes
and both generations, and increased liver weights in both sexes
associated with liver and kidney histopathology in males. The
reproductive NOAEL was 5,000 ppm. A reproductive LOAEL was not
established.
6. Mutagenicity-- Studies on gene mutation and other genotoxic
effects. In a Gene Mutation Assay (Ames Test)/Reverse Mutation, finding
was determined as negative for induction of gene mutation measured as
the reversion to histine protrophy of 5 S.typhimurium strains and
E.Coli WP2 uvra at doses from 10 to 5,000 g/plate with and
without S-9 activation. The highest dose was insoluble. A Gene Mutation
assay in Mammalian Cells was found to be negative f or mutagencity in
CHO (Chinese hamster ovary) V79 cells with and without metabolic
activation yp to cytotoxic doses (300 g/mL). In a Structural
Chromosomal Aberration Assay in vivo, findings proved nonclastogenic in
CHO cells both with and without S-9 activation up to cytotoxic doses
300 g/mL. In Other Genotoxicity Assays, an increase in
unscheduled DNA synthesis was not induced both with and without
activation in HeLa cells exposed up to insoluble doses ranging to 6.4
g/mL without activation and 51.2 g/mL with
activation.
7. Metabolism. The results of the metabolism studies are as
follows: Acceptable Rats were orally dosed with 14C-labeled
pyriproxyfen at 2 or 1,000 mg/kg and at repeated oral doses 14 daily
doses of unlabeled pyriproxyfen at 2 mg/kg followed by administration
of a single oral dose of labeled pyriproxyfen at 2 mg/kg. Most
radioactivity was excreted in the feces 81-92% and urine 5-12% over a 7
day collection period. Expired air was not detected. Tissue
radioactivity levels were very low less than 0.3% except for fat.
Examination of urine, feces, liver, kidney, bile and blood metabolites
yielded numerous > 20 identified metabolites when compared to synthetic
standards. The major biotransformation
[[Page 18335]]
reactions of pyriproxyfen include: (1) Oxidation of the 4' - position
of the terminal phenyl group; (2) Oxidation at the 5' - position of
pyridine; (3) Cleavage of the ether linkage and conjugation of the
resultant phenols with sulfuric acid.
8. Neurotoxicity. Neurotoxicity has not been observed in any of the
acute, subchronic, chronic, developmental or reproductive studies
performed with pyriproxyfen.
B. Toxicological Endpoints
1. Acute toxicity. An acute dietary dose and endpoint was not
identified in the database. The Agency concludes that there is a
reasonable certainty of no harm from acute dietary exposure.
2. Short- and intermediate-term toxicity. Doses and endpoints were
not identified for short and intermediate-term dermal and inhalation
exposure. The Agency concludes that there are reasonable certainties of
no harm from these exposures.
3. Chronic toxicity. EPA has established the RfD for pyriproxyfen,
2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine at 0.35 mg/kg/day. This
Reference Dose (RfD) is based on a NOAEL of 35.1 mg/kg/day and an
uncertainty factor (UF) of 100. The NOAEL was established from the
combined chronic feeding/oncogenicity study in rats where the the LOAEL
was 3,000 ppm, based on a 16.9% decrease in body weight gain in females
when compared to controls.
4. Carcinogenicity. Pyriproxyfen is classified as Category E: not
carcinogenic in two acceptable animal studies.
C. Exposures and Risks
1. From food and feed uses. Tolerances have been established (40
CFR 180.510) for the residues of pyriproxyfen, in or on a variety of
raw agricultural commodities. In todays action tolerances will be
established for the residues of pyriproxyfen, in or on the raw
agricultural commodities: pome fruits, walnuts and apple pomace, wet at
0.2, 0.02 and 0.8 ppm respectively. Risk assessments were conducted by
EPA to assess dietary exposures from pyriproxyfen as follows:
i. Acute exposure and risk. Acute dietary risk assessments are
performed for a food-use pesticide if a toxicological study has
indicated the possibility of an effect of concern occurring as a result
of a 1-day or single exposure. No acute dietary endpoint and dose was
identified in the toxicology data base for pyriproxyfen, therefore the
Agency concludes that there is a reasonable certainty of no harm from
acute dietary exposure.
ii. Chronic exposure and risk. The chronic dietary exposure
analysis from food sources was conducted using the RfD of 0.35 mg/kg/
day. The RfD is based on the NOAEL of 35.1 mg/kg/day in male and female
rats from the Chronic Feeding/Oncogenicity study in rats and an
uncertainty factor of 100 applicable to all population subgroups.
In conducting this chronic dietary risk assessment, EPA has made
very conservative assumptions: 100% of pome fruits and walnuts having
pyriproxyfen tolerances will contain pyriproxyfen residues and those
residues will be at the level of the established tolerance. This
results in an overestimate of human dietary exposure. Thus, in making a
safety determination for this tolerance, EPA is taking into account
this conservative exposure assessment.
The existing pyriproxyfen tolerances (published and pending) result
in a Theoretical Maximum Residue Contribution (TMRC) that is equivalent
to the following percentages of the RfD: US. Population (48 states)
0.8%; Hispanics 1.0%; Non-hispanic blacks 0.9%; Non-hispanic other than
black or white 1.2%; All infants (< 1="" year)="" 1.1%;="" nursing="" infants="">< 1="" year="" old)="" 0.8%;="" non-nursing="" infants="">< 1="" year="" old)="" 1.2%;="" children="" (1-6="" years="" old)="" 2.2%;="" children="" (7-12="" years="" old)="" 1.3%;="" females="" (13+/nursing)="" 1.0%.="" the="" subgroups="" listed="" above="" are:="" (1)="" the="" u.s.="" population="" (48="" states);="" (2)="" those="" for="" infants="" and="" children;="" and="" (3)="" the="" other="" subgroups="" for="" which="" the="" percentage="" of="" the="" rfd="" occupied="" is="" greater="" than="" that="" occupied="" by="" the="" subgroup="" u.s.="" population="" (48="" states).="" 2.="" from="" drinking="" water--="" i.="" acute="" exposure="" and="" risk.="" as="" previously="" stated,="" no="" acute="" dietary="" endpoint="" was="" identified="" for="" assessment="" of="" acute="" dietary="" risk.="" thus="" the="" agency="" concludes="" that="" there="" is="" a="" reasonable="" certainty="" of="" no="" harm="" from="" acute="" dietary="" exposure.="" ii.="" chronic="" exposure="" and="" risk.="" following="" opp's="" interim="" approach="" for="" addressing="" drinking="" water="" exposure="" in="" tolerance="" decision="" making="" issued="" on="" 17-nov-1997,="" the="" generic="" expected="" environmental="" concentration="" (geneec)="" model="" and="" the="" screening="" conccentration="" in="" ground="" water)="" (sci-="" grow)="" model="" were="" run="" to="" produce="" estimates="" of="" pyriproxyfen="" concentrations="" in="" surface="" and="" ground="" water="" respectively.="" the="" primary="" use="" of="" these="" models="" is="" to="" provide="" a="" coarse="" screen="" for="" sorting="" out="" pesticides="" for="" which="" opp="" has="" a="" high="" degree="" of="" confidence="" that="" the="" true="" levels="" of="" the="" pesticide="" in="" drinking="" water="" will="" be="" less="" than="" the="" human="" health="" drinking="" water="" levels="" of="" comparison="" (dwlocs).="" a="" human="" health="" dwloc="" is="" the="" concentration="" of="" a="" pesticide="" in="" drinking="" water="" which="" would="" result="" in="" unacceptable="" aggregate="" risk,="" after="" having="" already="" factored="" in="" all="" food="" exposures="" and="" other="" non-occupational="" exposures="" for="" which="" opp="" has="" reliable="" data.="" for="" chronic="" (non-cancer)="" exposure="" to="" pyriproxyfen="" in="" surface="" and="" ground="" water,="" the="" drinking="" water="" levels="" of="" concern="" are="" 12,000="">g/L for U.S. Population and 3,400 g/L for children
(1-6 yrs). To calculate the DWLOC for chronic (non-cancer) exposure
relative to a chronic toxicity endpoint, the chronic dietary food
exposure (from DEEM) was subtracted from the RfD to obtain the
acceptable chronic (non-cancer) exposure to pyriproxyfen in drinking
water. DWLOCs were then calculated using default body weights and
drinking consumption figures.
Estimated average concentrations of pyriproxyfen in surface and
ground water are 0.14 parts per billion (ppb) and 0.006 ppb,
respectively. The estimated average concentrations of pyriproxyfen in
surface and ground water are less than OPP's level of concern for
pyriproxyfen in drinking water as a contribution to chronic aggregate
exposure. Therefore, taking into account present uses and uses proposed
in this action, OPP concludes with reasonable certainty that residues
of pyriproxyfen in drinking water (when considered along with other
sources of exposure for which OPP has reliable data) would not result
in unacceptable levels of aggregate human health risk at this time.
3. From non-dietary exposure. Pyriproxyfen is the active ingredient
in many registered residential (indoor, non-food) products for flea and
tick control. Formulations include foggers, aerosol sprays,
emulsifiable concentrates, and impregnated materials (pet collars).
i. Acute exposure and risk. An acute dietary dose and endpoint was
not identified. Thus the risk from aggregate exposure is considered to
be negligible.
ii. Chronic exposure and risk. With the exception of the pet collar
uses, consumer use of pyriproxyfen typically results in short-term,
intermittent exposures. Hence, chronic residential post-application
exposure and risk assessments were conducted to estimate the potential
risks from pet collar uses.
The risk assessment was conducted using the following assumptions:
application rate of 0.58 mg ai/day (product label), average body weight
for a 1 to 6 year old child of 10 kg, the active ingredient dissipates
uniformly through 365 days (the label instruct to change collar once a
year), 1% of the
[[Page 18336]]
active ingredient is available for dermal and inhalation exposure per
day. The assessment also assumes an absorption rate of 100%. This is a
conservative assumption since the dermal absorption was estimated to be
10%.
The estimated chronic term MOE was 61,000 for children, and 430,000
for adults. An adequate MOE is 100. The risk estimates indicate that
potential risks from pet collar uses do not exceed the Agency's level
of concern.
iii. Short- and intermediate-term exposure and risk. The Agency
concludes that there is reasonable certainty of no harm from short term
and intermediate-term dermal and inhalation occupational and
residential exposure due to the lack of significant toxicological
effects observed.
4. Cumulative exposure to substances with common mechanism of
toxicity. Section 408(b)(2)(D)(v) 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 pyriproxyfen has a common mechanism of toxicity with other
substances or how to include this pesticide in a cumulative risk
assessment. Unlike other pesticides for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity,
pyriproxyfen does not appear to produce a toxic metabolite produced by
other substances. For the purposes of this tolerance action, therefore,
EPA has not assumed that pyriproxyfen 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 final rule
for Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997).
D. Aggregate Risks and Determination of Safety for U.S. Population
1. Acute risk. An acute dietary dose and endpoint was not
identified. Thus the risk from acute aggregate exposure is considered
to be negligible.
2. Chronic risk. Using the conservative exposure assumptions
described above, EPA has calculated that the percentage of the RfD that
will be utilized by dietary (food) exposure to residues of pyriproxyfen
is 0.8 percent for the U.S. Population. The major identifiable subgroup
with the highest aggregate exposure is children (1-6 years old). See
discussion below. Chronic residential exposure to pyriproxyfen from pet
collars is estimated to increase total pyriproxyfen exposure only
marginally. Despite the potential for exposure to pyriproxyfen in
drinking water, EPA does not expect the aggregate exposure to exceed
100% of the RfD.
This determination is based on a comparison of estimated
concentrations of pyriproxyfen in surface and ground water to levels of
concern for pyriproxyfen in drinking water. The estimates of
pyriproxyfen in surface and ground water are derived from water quality
models that use conservative assumptions regarding the pesticide
transport from the point of application to surface and ground water.
Because EPA considers the aggregate risk resulting from multiple
exposure pathways associated with the pesticide's uses, levels of
concern in drinking water may vary as those uses change. If new uses
are added in the future, EPA will reassess the potential impact of
pyriproxyfen in food and drinking water as part of the aggregate
chronic risk assessment process.
3. Short- and intermediate-term risk. No significant toxicological
effects were observed in the animal studies that could be attributed to
short- or intermediate-term exposure. Thus, the risk from short- and
intermediate-term exposure is negligible.
4. Aggregate cancer risk for U.S. population. Pyriproxyfen is
classified as Category E: not carcinogenic in two acceptable animal
studies.
5. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
from aggregate exposure to pyriproxyfen residues.
E. Aggregate Risks and Determination of Safety for Infants and Children
1. Safety factor for infants and children-- i. In assessing the
potential for additional sensitivity of infants and children to
residues of pyriproxyfen, EPA considered data from developmental
toxicity studies in the rat and rabbit and a 2-generation reproduction
study in the rat. The developmental toxicity studies are designed to
evaluate adverse effects on the developing organism resulting from
maternal pesticide exposure gestation. Reproduction studies provide
information relating to effects from exposure to the pesticide on the
reproductive capability of mating animals and data on systemic
toxicity.
FFDCA section 408 provides that EPA shall apply an additional
tenfold margin of safety for infants and children in the case of
threshold effects to account for pre-and post-natal toxicity and the
completeness of the database unless EPA determines that a different
margin of safety will be safe for infants and children. Margins of
safety are incorporated into EPA risk assessments either directly
through use of a margin of exposure (MOE) analysis or through using
uncertainty (safety) factors in calculating a dose level that poses no
appreciable risk to humans. EPA believes that reliable data support
using the standard uncertainty factor (usually 100 for combined inter-
and intra-species variability) and not the additional tenfold MOE/
uncertainty factor when EPA has a complete data base under existing
guidelines and when the severity of the effect in infants or children
or the potency or unusual toxic properties of a compound do not raise
concerns regarding the adequacy of the standard MOE/safety factor.
ii. Developmental toxicity studies. In the rat developmental study,
the developmental NOAEL was 100 mg/kg/day and the maternal NOAEL was
100 mg/kg/day. Therefore, there was no prenatal developmental toxicity
in the presence of maternal toxicity. Similarly in rabbits, the
prenatal developmental NOAEL was 300 mg/kg/day and the maternal NOAEL
was 300 mg/kg/day. Therefore, prenatally exposed fetuses were not more
sensitive to the effects of pyriproxyfen than maternal animals.
iii. Reproductive toxicity study. In the rat reproduction study,
the parental NOAEL of 1,000 ppm was identical to the pup NOAEL of 1,000
ppm and decreased body weight was seen in both pup and parental
animals. This finding demonstrates that there are no extra
sensitivities with respect to pre- and post-natal toxicity between
adult and infant animals.
iv. Pre- and post-natal sensitivity. The oral perinatal and
prenatal data demonstrated no indication of increased sensitivity of
rats or rabbits to in utero and postnatal exposure to pyriproxyfen.
v. Conclusion. The 10X factor for infants and children (as required
by FQPA) was removed, since there was no special sensitivity for
infants and children and the data base is complete. For chronic dietary
risk assessment, a UF of 100 is adequate for protection from exposure
to pyriproxyfen.
2. Acute risk. An acute dietary dose and endpoint was not
identified. Thus the risk from acute aggregate exposure is considered
to be negligible.
3. Chronic risk. Using the exposure assumptions described in this
unit, EPA has concluded that aggregate exposure to pyriproxyfen from
food will utilize 2.2% of the RfD for infants and
[[Page 18337]]
children. EPA generally has no concern for exposures below 100% of the
RfD because the RfD represents the level at or below which daily
aggregate dietary exposure over a lifetime will not pose appreciable
risks to human health. Despite the potential for exposure to
pyriproxyfen in drinking water and from non-dietary, non-occupational
exposure, EPA does not expect the aggregate exposure to exceed 100% of
the RfD.
4. Short- or intermediate-term risk. Short-term and intermediate-
term dermal and inhalation risks are judged to be negligible due to the
lack of significant toxicological effects observed.
5. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to infants and children from aggregate exposure to pyriproxyfen
residues.
III. Other Considerations
A. Metabolism In Plants and Animals
The nature of the residue in plants is understood. Acceptable
metabolism studies using 14C-labeled pyriproxyfen (phenyl
and pyridyl rings) have been performed in apple RACs and cotton RACs.
Metabolism of pyriproxyfen in apples proceeds through hydroxylation and
cleavage of the phenoxy ether linkage. Primary metabolites formed are
further metabolized to more polar products by oxidation or conjugation
reactions. Similar metabolic pathways were observed for the metabolism
of pyriproxyfen in cotton, goats, and hens.
The HED Metabolism Assessment Review Committee (MARC) has
determined that there are no pyriproxyfen metabolites of toxicological
or regulatory concern in plants thus, tolerances based on the parent
only are appropriate.
There are no poultry feed items associated with pome fruits and
walnuts. Therefore, no secondary residues are expected to occur in
poultry eggs, fat, meat, and meat byproducts as a result of the
proposed uses on pome fruits and walnuts.
Valent submitted data from studies investigating the metabolism of
Ph-14C uniformly ring labeled and Py-14C in
pyridine ring 2 and 6 positions pyriproxyfen in lactating goats. Two
goats were fed 10 ppm of the Ph-14C pyriproxyfen daily for 5
days, while two other goats were fed 10 ppm of the Py-14C
pyriproxyfen daily for 5 days, with 1 control goat. Urine, feces and
milk samples were obtained twice daily. After sacrifice at 6 hours
after last dose, samples of blood, heart, kidneys, liver, loin muscle,
rear leg muscle, omental and perirenal fat, gastrointestinal tract and
contents were collected for 14C analysis.
The majority (62-76%) of the 14C-pyriproxyfen ingested
by goats was excreted in urine and feces, with residue levels in feces
being higher than in urine. Approximately 25 to 32% of the administered
14C-pyriproxyfen was found in goat tissues, with the large
majority located in the gastrointestinal tract. These studies show that
metabolism of phenyl-14C pyriproxyfen in goats proceeds
through hydroxylation of the phenoxyphenyl and pyridyl rings, sulfation
of the 4'-OH phenoxyphenyl moiety, and cleavage of the ether linkage.
Metabolism of pyridyl-14C pyriproxyfen in goats proceeds
through hydroxylation of the phenoxyphenyl and pyridyl rings, sulfation
of the 4'-OH phenoxyphenyl moiety, cleavage of the ether linkage and
oxidation of the side chain. Therefore the nature of the residue in
ruminants is adequately understood.
Should future crop uses increase the maximum dietary burden in
animals to the point that tolerances are needed in animal commodities,
the residue of concern will be pyriproxyfen and the free and sulfate
forms of 4'-OH-PYR.
B. Analytical Enforcement Methodology
The proposed enforcement methods for residues of pyriproxyfen on
plant commodities has not been subjected to a complete Agency method
validation at this time. The EPA validation laboratory at Beltsville is
currently being relocated, and consequently, the laboratory is not
operational at this time. The method trial requests have been received
and a validation is scheduled. In the interim, EPA has conducted a
preliminary review of the apple and walnut methods that indicates that
they appears to be suitable for enforcement purposes pending the
outcome of the actual method validation. Given that the registrant has
provided concurrent fortification data to demonstrate that the methods
are adequate for data collection purposes and has provided the Agency
with a successful Independent Laboratory Validation, coupled with EPA's
preliminary review, EPA concludes that the methods are suitable as
enforcement methods to support tolerances associated with a conditional
registration only. As a condition of the registration, the Agency will
require successful method validations and the registrant will be
required to make any necessary modifications to the methods resulting
from the laboratory validation.
C. Magnitude of Residues
Adequate residue data were provided to support tolerances of 0.2
ppm forpome fruits and 0.02 ppm for walnuts.
Processing data provided for apples indicated concentration of
residues in wet apple pomace. Based on the available field trial data
the highest average field trial (HAFT) for apples is 0.16 ppm for
residues of pyriproxyfen. The maximum pyriproxyfen residues in apple
pomace based on the HAFT and the average concentration factor 4.9x
would be 0.78 ppm. Therefore, the proposed tolerance of 0.8 ppm for
pyriproxyfen residues in/on wet apple pomace is adequate.
There are no processed commodities associated with pears and
walnuts andtherefore no tolerances for processed commodities are
required.
A feeding study on lactating dairy cows was submitted. Using
proposed tolerances for animal feed items, the calculated maximum
theoretical dietary burdens for beef and dairy cattle are 1.69 and 1.29
ppm, respectively. Based on the dietary burdens, the dosing levels of
3, 9, and 30 ppm in the study represent 2x, 5x, and 18x the maximum
theoretical dietary burden to beef cattle, and 2x, 7x, and 23x the
maximum theoretical dietary burden to dairy cattle. Typically,
tolerances are required on all animal commodities having detectable
residue levels at a 10x dosing rate or below. For the computed MTDB of
1.69 ppm in beef cattle, this would include the 3 and 9 ppm dosing
levels. The only commodity having detectable pyriproxyfen residues at
these levels was fat: 0.01 - 0.03 ppm. Since the MTDB calculation is
based on a nutritionally unbalanced diet and includes contributions
from some animal feed items that are used only regionally, the Agency
will not require the establishment of pyriproxyfen tolerances in fat at
this time. However, should future new uses include additional animal
feed items, tolerances on animal commodities will be needed.
D. International Residue Limits
There are no CODEX, Canadian, or Mexican tolerances for
pyriproxyfen residues in/on pome fruits or walnuts. Therefore,
international harmonization is not an issue at this time.
E. Rotational Crop Restrictions
The Agency has determined that rotational crop studies are not
required for uses of pesticides on pome fruits or walnuts
[[Page 18338]]
IV. Conclusion
Therefore, the tolerances are established for residues of
pyriproxyfen in pome fruits, walnuts and apple pomace, wet at 0.2 ,
0.02, and 0.8 ppm, respectively.
V. Objections and Hearing Requests
The new FFDCA section 408(g) provides essentially the same process
for persons to ``object'' to a tolerance regulation as was provided in
the old section 408 and in section 409. However, the period for filing
objections is 60 days, rather than 30 days. EPA currently has
procedural regulations which govern the submission of objections and
hearing requests. These regulations will require some modification to
reflect the new law. However, until those modifications can be made,
EPA will continue to use those procedural regulations with appropriate
adjustments to reflect the new law.
Any person may, by June 14, 1999, file written objections to any
aspect of this regulation and may also request a hearing on those
objections. Objections and hearing requests must be filed with the
Hearing Clerk, at the address given under the ``ADDRESSES'' section (40
CFR 178.20). A copy of the objections and/or hearing requests filed
with the Hearing Clerk should be submitted to the OPP docket for this
regulation. The objections submitted must specify the provisions of the
regulation deemed objectionable and the grounds for the objections (40
CFR 178.25). Each objection must be accompanied by the fee prescribed
by 40 CFR 180.33(i). EPA is authorized to waive any fee requirement
``when in the judgement of the Administrator such a waiver or refund is
equitable and not contrary to the purpose of this subsection.'' For
additional information regarding tolerance objection fee waivers,
contact James Tompkins, Registration Division (7505C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. Office location, telephone number, and e-mail
address: Rm. 239, Crystal Mall #2, 1921 Jefferson Davis Hwy.,
Arlington, VA, (703) 305-5697, tompkins.jim@epa.gov. Requests for
waiver of tolerance objection fees should be sent to James Hollins,
Information Resources and Services Division (7502C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460.
If a hearing is requested, the objections must include a statement
of the factual issues on which a hearing is requested, the requestor's
contentions on such issues, and a summary of any evidence relied upon
by the requestor (40 CFR 178.27). A request for a hearing will be
granted if the Administrator determines that the material submitted
shows the following: There is genuine and substantial issue of fact;
there is a reasonable possibility that available evidence identified by
the requestor would, if established, resolve one or more of such issues
in favor of the requestor, taking into account uncontested claims or
facts to the contrary; and resolution of the factual issues in the
manner sought by the requestor would be adequate to justify the action
requested (40 CFR 178.32). Information submitted in connection with an
objection or hearing request may be claimed confidential by marking any
part or all of that information as CBI. Information so marked will not
be disclosed except in accordance with procedures set forth in 40 CFR
part 2. A copy of the information that does not contain CBI must be
submitted for inclusion in the public record. Information not marked
confidential may be disclosed publicly by EPA without prior notice.
VI. Public Record and Electronic Submissions
EPA has established a record for this regulation under docket
control number [OPP-300830] (including any comments and data submitted
electronically). A public version of this record, including printed,
paper versions of electronic comments, which does not include any
information claimed as CBI, is available for inspection from 8:30 a.m.
to 4 p.m., Monday through Friday, excluding legal holidays. The public
record is located in Room 119 of the Public Information and Records
Integrity Branch, Information Resources and Services Division (7502C),
Office of Pesticide Programs, Environmental Protection Agency, Crystal
Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA.
Objections and hearing requests may be sent by e-mail directly to
EPA at:
opp-docket@epa.gov.
E-mailed objections and hearing requests must be submitted as an
ASCII file avoiding the use of special characters and any form of
encryption.
The official record for this regulation, as well as the public
version, as described in this unit will be kept in paper form.
Accordingly, EPA will transfer any copies of objections and hearing
requests received electronically into printed, paper form as they are
received and will place the paper copies in the official record which
will also include all comments submitted directly in writing. The
official record is the paper record maintained at the Virginia address
in ``ADDRESSES'' at the beginning of this document.
VII. Regulatory Assessment Requirements
A. Certain Acts and Executive Orders
This final rule establishes a tolerance under section 408(d) of the
FFDCA in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). This final rule does not contain
any information collections subject to OMB approval under the Paperwork
Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose any enforceable
duty or contain any unfunded mandate as described under Title II of the
Unfunded Mandates Reform Act of 1995 (UMRA) (Pub. L. 104-4). Nor does
it require any prior consultation as specficed by Executive Order
12875, entitled Enhancing the Intergovernmental Partnership (58 FR
58093, October 28, 1993), or special considerations as required by
Executive Order 12898, entitled Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations (59 FR 7629, February 16, 1994), or require OMB review in
accordance with Executive Order 13045, entitled Protection of Children
from Environmental Health Risks and Safety Risks (62 FR 19885, April
23, 1997).
In addition, since tolerances and exemptions that are established
on the basis of a petition under FFDCA section 408(d), such as the
tolerance/exemption in this final rule, do not require the issuance of
a proposed rule, the requirements of the Regulatory Flexibility Act
(RFA) (5 U.S.C. 601 et seq.) do not apply. Nevertheless, the Agency
previously assessed whether establishing tolerances, exemptions from
tolerances, raising tolerance levels or expanding exemptions might
adversely impact small entities and concluded, as a generic matter,
that there is no adverse economic impact. The factual basis for the
Agency's generic certification for tolerance actions published on May
4, 1981 (46 FR 24950), and was provided to the Chief Counsel for
Advocacy of the Small Business Administration.
B. Executive Order 12875
Under Executive Order 12875, entitled Enhancing the
Intergovernmental Partnership (58 FR 58093, October 28, 1993), EPA may
not issue a regulation that is not required by
[[Page 18339]]
statute and that creates a mandate upon a State, local or tribal
government, unless the Federal government provides the funds necessary
to pay the direct compliance costs incurred by those governments. If
the mandate is unfunded, EPA must provide to OMB a description of the
extent of EPA's prior consultation with representatives of affected
State, local, and tribal governments, the nature of their concerns,
copies of any written communications from the governments, and a
statement supporting the need to issue the regulation. In addition,
Executive Order 12875 requires EPA to develop an effective process
permitting elected officials and other representatives of State, local,
and tribal governments ``to provide meaningful and timely input in the
development of regulatory proposals containing significant unfunded
mandates.''
Today's rule does not create an unfunded Federal mandate on State,
local, or tribal governments. The rule does not impose any enforceable
duties on these entities. Accordingly, the requirements of section 1(a)
of Executive Order 12875 do not apply to this rule.
C. Executive Order 13084
Under Executive Order 13084, entitled Consultation and Coordination
with Indian Tribal Governments (63 FR 27655, May 19, 1998), EPA may not
issue a regulation that is not required by statute, that significantly
or uniquely affects the communities of Indian tribal governments, and
that imposes substantial direct compliance costs on those communities,
unless the Federal government provides the funds necessary to pay the
direct compliance costs incurred by the tribal governments. If the
mandate is unfunded, EPA must provide OMB, in a separately identified
section of the preamble to the rule, a description of the extent of
EPA's prior consultation with representatives of affected tribal
governments, a summary of the nature of their concerns, and a statement
supporting the need to issue the regulation.
In addition, Executive Order 13084 requires EPA to develop an
effective process permitting elected officials and other
representatives of Indian tribal governments ``to provide meaningful
and timely input in the development of regulatory policies on matters
that significantly or uniquely affect their communities.''
Today's rule does not significantly or uniquely affect the
communities of Indian tribal governments. This action does not involve
or impose any requirements that affect Indian tribes. Accordingly, the
requirements of section 3(b) of Executive Order 13084 do not apply to
this rule.
VIII. Submission to Congress and the Comptroller General
The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the Agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and the Comptroller General of the United
States. EPA will submit a report containing this rule and other
required information to the U.S. Senate, the U.S. House of
Representatives and the Comptroller General of the United States prior
to publication of the rule in the Federal Register. This rule is not a
``major rule'' as defined by 5 U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: March 30, 1999.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
PART 180-[AMENDED]
1. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 321(q), 346a, and 371.
2. In Sec. 180.510, paragraph (a), by alphabetically adding the
following commodities to the table to read as follows:
Sec. 180.510 Pyriproxyfen; tolerances for residues.
(a) * * *
------------------------------------------------------------------------
Commodity Parts per million
------------------------------------------------------------------------
Apple, pomace, wet........................ 0.8
* * * * * * *
Pome fruits............................... 0.2
Walnuts................................... 0.02
------------------------------------------------------------------------
* * * * *
[FR Doc. 99-9061 Filed 4-3-9; 8:45 am]
BILLING CODE 6560-50-F
