[Federal Register Volume 62, Number 95 (Friday, May 16, 1997)]
[Rules and Regulations]
[Pages 26954-26960]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-12912]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300492; FRL-5718-4]
RIN 2070-AB78
Pyridaben; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes time-limited tolerances with an
expiration date of May 31, 2001 for residues of the pesticide pyridaben
[2-tert-butyl-5-(4-tert-butylbenzylthio)-4-chloropyridazin-3(2H)-one]
in or on the food commodities apples, wet apple pomace, pears, citrus,
citrus oil, almonds, almond hulls, meat, milk and fat. A petition was
submitted by BASF Corporation to EPA under the Federal Food, Drug, and
Cosmetic Act (FFDCA) as amended by the Food Quality Protection Act of
1996 (Pub. L. 104-170) requesting the tolerance. These tolerances will
expire and are revoked on May 31, 2001.
DATES: This regulation becomes effective May 16, 1997. Objections and
[[Page 26955]]
requests for hearings must be received by EPA on or before July 15,
1997.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300492], 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-300492], should be submitted to: Public
Information and Records Integrity Branch, Information Resources and
Services Division, (7506C), 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. 1132, CM#2, 1921
Jefferson Davis Highway, Arlington, VA.
A copy of objections and hearing requests filed with the Hearing
Clerk may also be submitted electronically by sending electronic mail
(e-mail) to: OPP[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 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-300492]. 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: Marion Johnson Jr. Product
Manager (PM) 10, 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.
210, CM #2, 1921 Jefferson Davis Highway, Arlington, VA (703) 305-6788,
e-mail: [email protected].
SUPPLEMENTARY INFORMATION: EPA issued a notice, in the March 12, 1997
Federal Register (62 FR 11450)(FRL-5592-7), which announced that BASF
Corporation had submitted pesticide petitions (PP) 5F4543 (on citrus),
and 6F4651 (on apples), 6F4741 (on pears), and 6F4721 (on almonds).
Pesticide petitions 5F4543, 6F4651, 6F4741 and 6F4721 requested that
the Administrator, pursuant to section 408 of the Federal Food, Drug,
and Cosmetic Act (FFDCA), 21 U.S.C 346a, amend 40 CFR part 180 to
establish tolerances for residues of the pesticide pyridaben [2-tert-
butyl-5-(4-tert-butylbenzylthio)-4-chloropyridazin-3(2H)-one; EPA
Chemical No. 129105; CAS No. 96489-71-3] in or on the food commodities:
apples, wet apple pomace, pears, citrus, dried citrus pulp, citrus oil,
almonds, and almond hulls. The proposed tolerance levels for pyridaben
and its metabolites are:
------------------------------------------------------------------------
Parts per
Commodity million
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Almond hulls............................................... 4.0
Almonds.................................................... 0.05
Apple pomace, wet.......................................... 1.0
Apples..................................................... 0.6
Citrus..................................................... 0.5
Citrus oil................................................. 10
Citrus pulp, dried......................................... 1.5
Milk....................................................... 0.01
Fat........................................................ 0.05
Meat....................................................... 0.05
Meat by-products........................................... 0.05
Pears...................................................... 0.75
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As required by section 408(d) of the FFDCA, as recently amended by
the Food Quality Protection Act, Pub. L. 104-170, BASF included in the
notice of filing a summary of the petitions and authorization for the
summary to be published in the Federal Register in a notice of receipt
of the petition. The summary of the petitions prepared by the
petitioner contained conclusions and assessments to support its
conclusions that the petition complied with FQPA elements set forth in
section 408(d)(3) of the FFDCA.
There were no comments received in response to the notice of
filing.
I. Statutory Background
Section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21
U.S.C. 301 et seq., as amended by the Food Quality Protection Act of
1996, (FQPA) Pub. L. 104-170) authorizes the establishment of
tolerances (maximum residue levels), exemptions from the requirement of
a tolerance, modifications in tolerances, and revocation of tolerances
for residues of pesticide chemicals in or on food commodities and
processed foods. Without a tolerance or exemption, food containing
pesticide residues is considered to be unsafe and therefore
``adulterated'' under section 402(a) of the FFDCA, and hence may not
legally be moved in interstate commerce. For a pesticide to be sold and
distributed, the pesticide must not only have appropriate tolerances
under the FFDCA, but also must be registered under section 3 of the
Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA, 7 U.S.C.
136 et seq.).
Section 408 was substantially amended by the FQPA. Among other
things, the FQPA amends the FFDCA to bring all EPA pesticide tolerance-
setting activities under a new section 408 with a new safety standard
and new procedures. New section 408(b)(2)(A)(i) 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 food, drinking water, and from pesticide use
in gardens, lawns, or buildings (residential and other indoor uses) 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....''
II. Risk Assessment and Statutory Findings -- Background
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. First, EPA determines the
toxicity of pesticides based primarily on toxicological studies using
laboratory animals. These studies address many adverse health effects,
including (but not limited to) reproductive effects, developmental
toxicity, toxicity to the nervous system, and carcinogenicity. For many
of these studies, a dose response relationship can be determined, which
provides a dose that causes adverse effects (threshold effects) and
doses causing no observed effects (the ``no-observed effect level'' or
``NOEL'').
Once the studies have been evaluated and the observed effects have
been determined to be threshold effects, EPA generally divides the NOEL
from the study with the lowest NOEL by an uncertainty factor (usually
100 or more) to determine the Reference Dose (RfD). The RfD is a level
at or below which daily aggregate exposure over a lifetime
[[Page 26956]]
will not pose appreciable risks to human health. An uncertainty factor
(sometimes called a ``safety factor'') of 100 is commonly used since it
is assumed that people may be up to 10 times more sensitive to
pesticides than the test animals, and that one person or subgroup of
the population (such as infants and children) could be up to 10 times
more sensitive to a pesticide than another. In addition, EPA assesses
the potential risks to infants and children based on the weight of the
evidence of the toxicology studies and determines whether an additional
uncertainty factor is warranted. An aggregate daily exposure to a
pesticide residue at or below the RfD (expressed as 100 percent or less
of the RfD) is generally considered by EPA to pose a reasonable
certainty of no harm. For threshold effects other than those assessed
under the RfD, EPA generally calculates a margin of exposure (MOE). The
MOE is a measure of how close the exposure comes to the NOEL. The NOEL
is selected from a study of appropriate duration and route of exposure.
The MOE is the NOEL from the selected study divided by exposure. MOEs
greater than 100 are generally considered to show a reasonable
certainty of no harm.
Lifetime feeding studies in two species of laboratory animals are
conducted to screen pesticides for cancer effects. When evidence of
increased cancer is noted in these studies, the Agency conducts a
weight of the evidence review of all relevant toxicological data
including short term and mutagenicity studies and structure activity
relationship. Once a pesticide has been classified as a potential human
carcinogen, different types of risk assessments (e.g., linear low dose
extrapolations or margin of exposure calculation based on the
appropriate NOEL) will be carried out based on the nature of the
carcinogenic response and the Agency's knowledge of its mode of action.
In examining aggregate exposure, FFDCA section 408 requires that
EPA take into account available and reliable information concerning
exposure from the pesticide residue in the food in question, residues
in other foods for which there are tolerances, and other non-
occupational exposures, such as where residues leach into groundwater
or surface water that is consumed as drinking water and exposures
resulting from indoor and outdoor residential uses. Dietary exposure to
residues of a pesticide in a food commodity are estimated by
multiplying the average daily consumption of the food forms of that
commodity by the tolerance level or the anticipated pesticide residue
level. The Theoretical Maximum Residue Contribution (TMRC) is an
estimate of the level of residues consumed daily if each food item
contained pesticide residues equal to the tolerance. The TMRC is a
``worst case'' estimate since it is based on the assumptions that food
contains pesticide residues at the tolerance level and that 100 percent
of the crop is treated by pesticides that have established tolerances.
If the TMRC exceeds the RfD or poses a lifetime cancer risk that is
greater than approximately one in a million, EPA attempts to derive a
more accurate exposure estimate for the pesticide by evaluating
additional types of information which show, generally, that pesticide
residues in most foods when they are eaten are well below established
tolerances.
Consistent with sections 408(b)(2)(D), EPA has reviewed the
available scientific data and other relevant information in support of
this action. EPA has also assessed the toxicology database for
pyridaben in its evaluation of application for registration on citrus,
apples, pears and almonds. EPA has sufficient data to assess the
hazards of pyridaben and to make a determination on aggregate exposure,
consistent with section 408(b)(2), for granting time-limited tolerances
for residues of pyridaben on apples at 0.6 ppm, wet apple pomace at 1.0
ppm, pears at 0.75 ppm, citrus at 0.5 ppm, dried citrus pulp at 1.5
ppm, citrus oil at 10.0 ppm, milk at 0.01 ppm, meat at 0.05 ppm, meat
by-products at 0.05 ppm, fat at 0.05 ppm, almonds at 0.05 ppm, almond
hulls at 4.0 ppm. EPA's assessment of the database, dietary exposures
and risks associated with establishing these tolerances follows.
III. Toxicology Database
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 pyridaben are
discussed below.
1. A battery of acute toxicity studies placing technical pyridaben
in toxicity category II for acute oral toxicity and category III and IV
for the remaining studies.
2. Pyridaben was administered in the diet to CD rats at dosages of
0, 30, 65, 155 and 350 ppm for 13 weeks. The NOEL was determined to be
65 ppm (4.94 mg/kg/day) for males; 30 ppm (2.64 mg/kg/day) for females.
The lowest observed effect level (LOEL) was determined to be 155 ppm
(11.55 mg/kg/day) for males based on reduced body weight gain, food
consumption, food efficiency and altered clinical pathology parameters;
65 ppm (5.53 mg/kg/day) for females based on reduced body weight gain
and food efficiency.
3. In a 13 week feeding study in dogs, Pyridaben was administered
in capsules to beagle dogs at dosages of 0, 0.5, 1.0, 4.0 or 16.0 mg/
kg/day. The NOEL was 1.0 mg/kg/day for males and females and the LOEL
was 4.0 mg/kg/day for males and females based on an increased incidence
of clinical signs and decreased body weight gain.
4. In a 21 day dermal study, rats received repeated topical
applications of pyridaben to about 10% of the body surface area at
dosages of 30, 100, 300 and 1,000 mg/kg for 21 days produced body
weight decreases in the 300 mg/kg/day females and in the 1,000 mg/kg/
day males and females. The NOEL was 100 mg/kg/day and the LOEL was 300
mg/kg/day based on decreased body weight gain in females.
5. In a 12-month chronic feeding study in dogs pyridaben was
administered in capsules at dosages of 0, 1.0, 4.0, 16.0 or 32.0 mg/kg/
day. The NOEL was determined to be < 1.0 mg/kg/day and the LOEL was
1.0 mg/kg/day based on increased incidence of clinical
signs in both sexes and decreased body weight gain in females at 1.0
mg/kg/day.
6. Pyridaben was administered in capsules to beagle dogs at dosages
of 0 and 0.5 mg/kg/day for 1 year. The NOEL was determined to be < 0.5
mg/kg/day for males and females and the LOEL was 0.5 mg/kg/
day for males and females based on an increased incidence of clinical
signs in both treated sexes and decreased weight gain in the treated
females.
7. Pyridaben was administered in the diet to CD-1 mice at dosages
of 0, 2.5, 8.0, 25 or 80 ppm for 78 weeks. There was no evidence of a
carcinogenic effect of the chemical. The NOEL was determined to be 25
ppm (2.78 mg/kg/day) for males and females and a LOEL of 80 ppm (8.88
and 9.74 mg/kg/day for males and females, respectively). The MTD was
determined to be 80 ppm for males and females based on decreased body
weight gain, decreased food efficiency and changes in organ weights and
histopathology (males).
8. Pyridaben was administered in the diet to groups of Wistar rats
for 104 weeks at doses of 0, 4, 10, 28 or 80 ppm to assess
carcinogenicity. Additional groups received doses of 0, 4, 10, 28 or
[[Page 26957]]
120 ppm for 104 weeks (with an interim sacrifice at 53 weeks) to assess
chronic toxicity. There was no treatment-related neoplastic or non-
neoplastic pathology in either phases of the study. The NOEL was
determined to be 28 ppm in males (1.13 mg/kg/day) and 28 ppm (1.46 mg/
kg/day) in females. The LOEL was determined to be 120 ppm (5.00 mg/kg/
day) in males and 120 ppm (6.52 mg/kg/day) in females based on
decreased body weight gain in males and females and decreased ALT
levels in males in the chronic toxicity phase. There was no evidence of
a carcinogenic effect of this chemical.
9. Pyridaben was administered to female Sprague-Dawley rats from
days 6 through 15 of gestation at dosages of 0, 2.5, 5.7, 13.0 or 30.0
mg/kg/day. Maternal toxicity was evidenced by decreased body weight/
body weight gain and food consumption in the 13 and 30 mg/kg/day
groups. The Maternal NOEL is 4.7 mg/kg/day (82% of 5.7 mg/kg/day); The
Maternal LOEL is 13.0 mg/kg/day based on decreased body weight/weight
gain and food consumption during the dosing period. The Developmental
NOEL is 13.0 mg/kg/day; a Developmental LOEL of 30 mg/kg/day based on
decreased fetal body weight and increased incomplete ossification in
selected bones.
10. A study was performed in Himalayan rabbits in which the test
compound was administered to groups of female pregnant rabbits by
dermal application at dose levels of 0, 70, 170, or 450 mg/kg/day from
gestational days 6 to 19, inclusive. The Maternal toxicity, observed at
70 mg/kg/day, was manifested by moderate to severe skin reactions. At
``170 mg/kg/day, there was body weight loss and food consumption and
moderate to severe skin reactions in 50% of the animals. In addition,
the severity of skin reactions increased in a time-and dose-dependent
manner. The maternal systemic NOEL is 70 mg/kg/day. Developmental
toxicity observed at 450 mg/kg/day (HDT) consisted of increase in the
incidence of fetuses with incompletely ossified skull. The
developmental NOEL was 170 mg/kg/day.
11. New Zealand white rabbits were dosed with 0, 1.5, 5, or 15 mg/
kg/day pyridaben from day 6 through 19 of gestation. Maternal toxicity
was evidenced by a dose-dependent decrease in body weight gain and food
consumption at al dose levels. There was also increase incidence of
abortions and clinical signs (few feces) in the 15 mg/kg/day group.
There was no evidence that the chemical had a developmental effect at
any of the tested levels. the maternal NOEL was < 1.5 mg/kg/day and the
Maternal LOEL was < 1.5 mg/kg/day based on decreases in body weight
gain and food consumption at all dose levels. The developmental NOEL
was > 15 mg/kg/day and the Developmental LOEL was > 15 mg/kg/day.
12. In a standard two-generation reproduction study, CD rats were
administered pyridaben in the diet at doses of 0, 10, 28 or 80 ppm.
There was no effect on reproductive parameters on the dose levels
tested. The Parental/Systemic NOEL is 28 ppm (2.20 and 2.41 mg/kg/day
for males and females, respectively). The parental/systemic LOEL is 80
ppm (6.31 and 7.82 mg/kg/day for males and females, respectively) based
on decreased body weights, body weight gains and food efficiency. The
reproductive NOEL is 80 ppm in males and females. The
reproductive LOEL is > 80 ppm in males and females.
13. Mutagenicity studies including Ames testing, in vitro
cytogenicity (chinese hamster lung cell), in vivo micronucleus assay
(mouse) and DNA damage/repair (E. coli) showed no mutagenic activity
associated with pyridaben.
14. In an acute neurotoxicity study, rats were dosed once with 0,
50, 100 and 200 mg/kg body weight (active ingredient equivalents: 44.3,
79.6, and 190 mg/kg for males and 0, 44.5, 99.7, and 190 mg/kg body
weight for females). The animals were observed for mortality and
clinical signs of toxicity for 14 days post-dosing. No treatment
related gross or microscopic neuropathologic findings were present. The
NOEL for systemic toxicity is 50 mg/kg/day in both sexes. The LOEL for
systemic toxicity is 100 mg/kg in males and females based on the
clinical signs of toxicity, and decreased food consumption and body
weight gain. Based on the findings of this study (screening battery),
the LOEL for neurobehavioral effects was established at 200 mg/kg in
males (FOB findings and motor activity); no LOEL was established for
females (>HDT).
15. In a subchronic neurotoxicity study pyridaben was administered
to CD rats at dietary levels of 0, 30, 100, and 350 ppm (0, 2.5, 8.5
and 28.8 mg/kg/day in males and 0, 2.8, 9.3 and 31.1 mg/kg/day in
females, respectively) for 13 weeks. No neuropathological effects were
observed. The LOEL was established at 350 ppm (28.8 mg/kg/day in males
and 31.1 mg/kg/day in females). The NOEL was established at 100 ppm
(8.5 mg/kg/day in males and 9.3 mg/kg/day in females.
B. Toxicology Profile
1. Toxicity endpoint for dietary exposure--i. Chronic effects. A
reference dose (RfD) has been estimated for pyridaben at 0.005 mg/kg/
day based on a NOEL of 0.5 mg/kg/day (lowest dose tested) observed in a
1 year dog study for body weight gain reduction. An uncertainty factor
of 100 was utilized to account for both interspecies and intraspecies
variability.
ii. Acute toxicity. To assess acute dietary exposure, the Agency
used a toxicity endpoint of 50 mg/kg/day, the NOEL for the acute oral
neurotoxicity study in rats.
iii. Carcinogenicity. Based on the available carcinogenicity
studies in two rodent species, the Agency has classified pyridaben as a
Group ``E'' for carcinogenicity (no evidence of carcinogenicity). There
was no evidence of carcinogenicity in an 18-month feeding study in mice
and a 2-year feeding study in rats at the dose levels tested.
2. Toxicity endpoints for non-dietary exposure--i. short- and
intermediate-term risk. As part of the hazard assessment process, the
Agency reviews the available toxicological database to determine the
endpoints of concern. For pyridaben, the Agency does not have a concern
for a short-term or intermediate-term assessment since the available
data do not indicate any evidence of significant toxicity by the dermal
or inhalation routes. Therefore, a short-term or intermediate-term
assessment was not required. Since there are no residential uses or
exposure, a residential risk assessment is not required.
ii. Chronic non-dietary exposure. As part of the hazard assessment
process an endpoint of concern was determined for the chronic non-
dietary assessment. However, during the exposure assessment process,
the exposures which would result from the use of pyridaben was
determined to be of an intermittent nature. The frequency and duration
of these exposures do not exhibit a chronic exposure pattern. The
exposures do not occur often enough to be considered a chronic exposure
i.e., a continuous exposure that occurs for at least several months.
Therefore, a chronic occupational assessment was not required.
C. Aggregate Exposure
1. Food and feed uses. For purposes of assessing the potential
chronic dietary exposure from the use of pyridaben on citrus, apples,
almonds and pears, EPA has estimated aggregate exposure based on
Anticipated Residue Contribution (ARC). For plant commodities,
anticipated residue levels were calculated from field trials conducted
at the maximum proposed
[[Page 26958]]
use rate and minimum pre-harvest interval (PHI), and the ratio of
organosoluble residues to pyridaben residues. The ARC for processed
commodities was based upon the average residue level for that commodity
from field trials conducted at the maximum proposed use rate and
minimum PHI, the ratio of organosoluble residues to pyridaben residues,
and the concentration factor for the processed commodity. In some
cases, adjustments for degradation of residues prior to analysis was
taken into account. Anticipated residue levels were utilized for
livestock feedstuffs to determine the dietary burden for ruminants, as
well as for ruminant edible commodities. The proposed pyridaben
tolerances result in an ARC that is up to 74 percent of the reference
dose for the most sensitive subpopulation. The general population is
11.8 percent of the RfD.
The endpoint for acute dietary risk assessment is the NOEL (50 mg/
kg/day) from an acute oral neurotoxicity study in rats. The effects at
the LOEL of 100 mg/kg/day were clinical signs of toxicity, and a
decrease in food consumption and body weight gain. The DRES detailed
acute analysis estimates the distribution of a singe -day exposure for
the overall U.S. population and certain subgroups. For acute dietary
risk for the population subgroup with the highest exposure, non-nursing
infants (<1 year), the estimated margin of exposure (MOE) is 1,250. The
margin of exposure (MOE) is a measure of how close the high end
exposure comes to the LOEL and is calculated as the ratio of the NOEL
to the exposure (NOEL/exposure = MOE). Generally, acute dietary margins
of exposure greater than 100 tend to cause no dietary concern. The
Agency considers the acute and chronic dietary risks to be acceptable.
In conducting this exposure assessment, EPA has made conservative
assumptions-- 100 percent of the apples, citrus, almonds and pears will
contain pyridaben residues. This will result in an overestimate of
human exposure.
2. Potable water. The Agency does not have drinking water
monitoring data available to perform a quantitative drinking water risk
assessment for pyridaben at this time. Based on the available
environmental fate data, conservative estimates produced by the Generic
Expected Environmental Concentration (GENEEC) model and Leaching Index,
environmental concentrations of pyridaben in surface water and the
leaching potential of pyridaben have been derived. Pyridaben has been
assessed as immobile and thus unlikely to leach to groundwater. For
surface water, the GENEEC model estimates body-weight based on chronic
exposure values for pyridaben to be 9.7 x 10-7 mg/kg/day
for the whole U.S. population and 1.8 x 10-6 mg/kg/day for
non-nursing infants (< 1 year). These values represent < 0.1% of the
RfD. As GENEEC is a conservative screening tool and the exposure
estimates for both adults and children are well below 1% of the RfD,
the Agency concludes that the potential for chronic dietary exposure
through drinking water in insignificant.
3. Non-dietary uses. EPA has not estimated non-dietary exposure for
pyridaben since there are no chronic or acute residential risks
expected from the citrus, apple, pear and almond uses. The only other
registered use is limited to commercial greenhouse for non-food
ornamental plants. The potential for non-occupational exposure to the
general population is, thus, not expected to be significant.
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.'' While the Agency has some information
in its files that may turn out to be helpful in eventually determining
whether a pesticide shares a common mechanism of toxicity in a
meaningful way, EPA is commencing a pilot process to study this issue
further through the examination of particular classes of pesticides.
The Agency hopes the results of this pilot process will enable it to
apply common mechanism issues to its pesticide risk assessments. At
present, however, the Agency does not know how to apply the information
in its files concerning common mechanism issues to risk assessments,
and therefore believes that in most cases, there is no available
information concerning mechanism that can be scientifically applied to
tolerance decisions. Where it is clear that a particular pesticide may
share a significant common mechanism with other chemicals, a tolerance
decision may be affected by common mechanism issues. The Agency expects
that most tolerance decisions will fall into the area in between, where
EPA can not reasonably determine whether a pesticide does or does not
share a common mechanism of toxicity with other chemicals (and, if so,
how that common mechanism should be factored into a risk assessment).
In such circumstances, the Agency will reach a tolerance decision based
on the best, currently available and useable information, without
regard to common mechanism issues. However, the Agency will also
revisit such decisions when the Agency learns how to apply common
mechanism information to pesticide risk assessments.
In the case of pyridaben, it is structurally similar to other
members of the pyridazinone class of pesticides (i.e. pyrazon and
norflurazon). However, since EPA has determined that it does not now
have the capability to apply the information in its files to a
resolution of common mechanism issues in a manner that would be useful
in a risk assessment, this tolerance determination does not take into
account common mechanism issues. The Agency will reexamine the
tolerance for pyridaben, if reexamination is appropriate, after the
Agency has determined how to apply common mechanism issues to its
pesticide risk assessments.
IV. Determination of Safety for Infants and Children
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 analysis or through using
uncertainty (safety) factors in calculating a dose level that poses no
appreciable risk to humans. In either case, EPA generally defines the
level of appreciable risk as exposure that is greater than 1/100 of the
no observed effect level in the animal study appropriate to the
particular risk assessment. This hundredfold uncertainty (safety)
factor/margin of exposure (safety) is designed to account for combined
inter-and intra-species variability. EPA believes that reliable data
support using the standard hundredfold margin/factor not the additional
tenfold margin/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 margin/factor.
In assessing the potential for risk to infants and children to
residues of pyridaben, EPA considered data from oral developmental
toxicity studies in the rat and rabbit, as well as data from
[[Page 26959]]
a 2-generation reproduction study in the rat. The developmental
toxicity studies are designed to evaluate adverse effects on the
developing organism resulting from pesticide exposure during prenatal
development to the mothers. Reproduction studies provide information
relating to effects from exposure to the pesticide on the reproductive
capability of mating animals and data on systemic toxicity.
Based on current data requirements, the database relative to pre-
and post natal toxicity is complete. These data taken together suggest
minimal concern for developmental or reproductive toxicity and do not
indicate any increased pre- or post-natal sensitivity. Therefore, EPA
concludes that reliable data support use of a hundredfold safety factor
and an additional tenfold safety factor is not needed to protect the
safety of infants and children. Therefore, no outstanding data
requirements exist.
V. Determination of Safety for U.S. Population Including Infants
and Children
1. Chronic dietary exposure/risk. A chronic dietary exposure/risk
assessment was performed for pyridaben using a RfD of 0.005 mg/kg/day.
Using the exposure assumptions previously described, and based on the
completeness and reliability of the toxicity data base, EPA has
concluded that aggregate exposure to pyridaben from its us on apples,
pears, citrus and almonds will utilize 11.8 percent of the RfD for the
general population and 74% for non-nursing infants < 1 year old which
is the most exposed subpopulation. EPA generally has no concern for
exposures below 100 percent of the RfD because the RfD represents the
level at or below which daily aggregate dietary exposure over a
lifetime will not pose an appreciable risk to human health.
2. Aggregate risks. Based upon the available data and assumptions
used for dietary and water exposure and risk estimates, the population
group estimated to be the most highly exposed to pyridaben is non-
nursing infants (< 1 year old), with a risk estimate from combined
sources equaling 74 percent of the RfD. (Dietary exposure contributes
74% of the RfD and drinking water contributes less than 1% of the RfD).
EPA therefore concludes that there is reasonable certainty that no harm
will result to Consumers, including infants and children from aggregate
exposure of pyridaben residues.
VI. Other Considerations
A. Endocrine Effects
No evidence of such effects were reported in the toxicology studies
described above. There is no evidence at this time that pyridaben
causes endocrine effects.
B. Metabolism in Plants and Animals
The metabolism of pyridaben in plants and animals is adequately
understood for the purpose of this tolerance. There are no Codex
maximum residue levels established for residues of pyridaben on the
proposed commodities. There is a practical analytical method available
for determination of residues of pyridaben. Adequate enforcement
methodology (gas chromatography/electron capture detector) for plant
and animal commodities is available to enforce the tolerances. As a
condition of registration, EPA has requested that revisions and
clarifications be made to the submitted methodology, and that the
animal commodity method be improved. Once this method has been
submitted, EPA will provide information on this method to FDA. In the
interim, the analytical method is available to anyone who is interested
in pesticide residue enforcement from: By mail, Calvin Furlow, Public
Information and Records Integrity Branch, Information Resources and
Services Division, (7506C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. Office
location and telephone number: Crystal Mall #2, Rm 1128, 1921 Jefferson
Davis Hwy., Arlington, VA 703-305-5805.
VII. Summary of Findings
Tolerances are time limited to allow for development and review of
additional residue field trials, long term storage stability studies,
and revised analytical enforcement methodology. The analysis for
pyridaben using anticipated residue levels shows that the proposed uses
will not cause exposure to exceed the levels at which EPA believes
there is an appreciable risk. All population subgroups examined by EPA
are exposed to pyridaben residues at levels below 100 percent of the
RfD for chronic effects. Based on the information and data considered,
EPA concludes that the proposed time-limited tolerances will be safe.
Therefore the tolerances are established as set forth in this document.
VIII. Objections and Hearing Requests
The new FFDCA section 408(g) provides essentially the same process
for persons to ``Object'' to a tolerance regulation issued by EPA under
the new section 408(d) 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 its current procedural regulations with appropriate adjustments to
reflect the new law.
Any person may, by July 15, 1997, 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 above (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 rulemaking. 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). 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
[[Page 26960]]
may be disclosed publicly by EPA without prior notice.
IX. Public Docket
The official record for this rulemaking, as well as the public
version, has been established for this rulemaking under docket control
number [OPP-300492] (including comments and data submitted
electronically as described below). 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 official rulemaking record is located at the address in
``ADDRESSES'' at the beginning of this document.
Electronic comments can be sent directly to EPA at:
[email protected]
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption. Comment and data
will also be accepted on disks in Wordperfect 5.1 file format or ASCII
file format. All comments and data in electronic form must be
identified by the docket control number [OPP-300492]. Electronic
comments on this proposed rule may be filed online at many Federal
Depository Libraries.
X. Regulatory Assessment Requirements
Under Executive Order 12866 (58 FR 51735, October 4, 1993), this
action is not a ``significant regulatory action'' and, since this
action does not impose any information collection requirements as
defined by the Paperwork Reduction Act, 44 U.S.C. 3501 et seq., it is
not subject to review by the Office of Management and Budget. In
addition, this action does not impose any enforceable duty or contain
any unfunded mandate as described in the Unfunded Mandates Reform Act
of 1995 (Pub. L. 104-4), or require prior consultation with State
officials as specified by Executive Order 12875 (58 FR 58093, October
28, 1993), or special considerations as required by Executive Order
12898 (59 FR 7629, February 16, 1994).
Because tolerance established on the basis of a petition under
section 408(d) of FFDCA do not require issuance of a proposed rule, the
regulatory flexibility analysis requirements of the Regulatory
Flexibility Act (RFA), 5 U.S.C. 604(a), do not apply. Prior to the
recent amendment of the FFDCA, EPA had treated such rulemakings as
subject to the RFA; however, the amendments to the FFDCA clarify that
no proposal is required for such rulemakings and hence that the RFA is
inapplicable. Nonetheless, the Agency has previously assessed whether
establishing tolerances or exemptions from tolerance, raising tolerance
levels, or expanding exemptions adversely impact small entities and
concluded, as a generic matter, that there is no adverse impact. (46 FR
24950, May 4, 1981).
Under 5 U.S.C. 801(a)(1)(A) of the Administrative Procedure Act
(APA) as amended by the Small Business Regulatory Enforcement Fairness
Act of 1996 (Title II of Pub. L. 104-121, 110 Stat. 847), EPA submitted
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 General Accounting Office prior to publication of the
rule in today's Federal Register. This rule is not a ``major rule'' as
defined by 5 U.S.C. 804(2) of the APA as amended.
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: May 7, 1997.
Stephen L. Johnson,
Acting Director, Office of Pesticide Programs.
Therefore, 40 CFR Chapter I is amended as follows:
PART 180-- [AMENDED]
1. In part 180:
a. The statutory authority for part 180 continues to read as
follows:
Authority: 21 U.S.C. 346a and 371.
b. By revising Sec. 180.494 to read as follows:
Sec. 180.494 Pyridaben; tolerance for residues.
(a) General. Time limited tolerances are established for residues
of the insecticide pyridaben [2-tert-butyl-5-(4-tert-butylbenzylthio)-
4-chloropyridazin-3(2H)-one] on the following plants, and of the
insecticide pyridaben and its metabolites (2-tert-butyl-5-[4-(1-
carboxy-1-methylethyl)benzylthio]-4-chloropyridazin-3(2H)-one) and (2-
tert-butyl-4-chloro-5-[4-(1,1-dimethyl-2-hydroxyethyl)benzylthio]-
chloropyridazin-3(2H)-one) on animals, as indicated in the following
table. The tolerances will expire and are revoked on the dates
specified in the following table.
------------------------------------------------------------------------
Parts
Commodity per Expiration/
million Revocation Date
------------------------------------------------------------------------
Almonds..................................... 0.05 5/31/2001
Almond hulls................................ 4.0 do.
Apple....................................... 0.6 do.
Apple pomace, wet........................... 1.0 do.
Cattle, fat................................. 0.05 do.
Cattle, meat................................ 0.05 do.
Cattle, meat by-products.................... 0.05 do.
Citrus...................................... 0.5 do.
Citrus oil.................................. 10.0 do.
Citrus pulp, dried.......................... 1.5 do.
Goat, fat................................... 0.05 do.
Goat, meat.................................. 0.05 do.
Goat, meat by-products...................... 0.05 do.
Hog, fat.................................... 0.05 do.
Hog, meat................................... 0.05 do.
Hog, meat by-products....................... 0.05 do.
Horse, fat.................................. 0.05 do.
Horse, meat................................. 0.05 do.
Horse, meat by-products..................... 0.05 do.
Milk........................................ 0.01 do.
Pears....................................... 0.75 do.
Sheep, fat.................................. 0.05 do.
Sheep, meat................................. 0.05 do.
Sheep, meat by-products..................... 0.05 do.
------------------------------------------------------------------------
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 97-12912 Filed 5-15-97; 8:45 am]
BILLING CODE 6560-50-F