[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: [email protected]. 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, 
[email protected].

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, [email protected]. 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:
    [email protected].

    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