[Federal Register Volume 66, Number 50 (Wednesday, March 14, 2001)]
[Rules and Regulations]
[Pages 14852-14861]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-6330]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-301103; FRL-6766-6]
RIN 2070-AB78
Pyriproxyfen; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes a tolerance for residues of the
insecticide, pyriproxyfen [2-[1-methyl-2-(4-
phenoxyphenoxy)ethoxy]pyridine] in or on all food items in food
handling establishments where food and food products are held,
processed and/or prepared at 0.1 ppm. McLaughlin Gormley King Company
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 March 14, 2001. Objections and
requests for hearings, identified by docket control number OPP-301103,
must be received by EPA on or before May 14, 2001.
ADDRESSES: Written objections and hearing requests may be submitted by
mail, in person, or by courier. Please follow the detailed instructions
for each method as provided in Unit VI. of the SUPPLEMENTARY
INFORMATION. To ensure proper receipt by EPA, your objections and
hearing requests must identify docket control number OPP-301103 in the
subject line on the first page of your response.
FOR FURTHER INFORMATION CONTACT: By mail: Joseph Tavano, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460;
telephone number: (703) 305-6411; and e-mail address:
[email protected].
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be affected by this action if you are an agricultural
producer, food manufacturer, or pesticide manufacturer. Potentially
affected
[[Page 14853]]
categories and entities may include, but are not limited to:
------------------------------------------------------------------------
Examples of Potentially
Categories NAICS Affected Entities
------------------------------------------------------------------------
Industry 111 Crop production
112 Animal production
311 Food manufacturing
32532 Pesticide manufacturing
------------------------------------------------------------------------
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in the table could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether or not this action might apply to certain entities. If you have
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.
B. How Can I Get Additional Information, Including Copies of this
Document and Other Related Documents?
1. Electronically.You may obtain electronic copies of this
document, and certain other related documents that might be available
electronically, from the EPA Internet Home Page at http://www.epa.gov/.
To access this document, on the Home Page select ``Laws and
Regulations'', ``Regulations and Proposed Rules,'' and then look up the
entry for this document under the ``Federal Register--Environmental
Documents.'' You can also go directly to the Federal Register listings
at http://www.epa.gov/fedrgstr/. To access the OPPTS Harmonized
Guidelines referenced in this document, go directly to the guidelines
at http://www.epa.gov/opptsfrs/home/guidelin.htm. A frequently updated
electronic version of 40 CFR part 180 is available at http://www.access.gpo.gov/nara/cfr/cfrhtml_00/Title_40/40cfr http://www.access.gpo.gov/nara/cfr/cfrhtml_00/Title_40/40tab_00.html, a
beta site currently under development.
2. In person. The Agency has established an official record for
this action under docket control number OPP-301103. The official record
consists of the documents specifically referenced in this action, and
other information related to this action, including any information
claimed as Confidential Business Information (CBI). This official
record includes the documents that are physically located in the
docket, as well as the documents that are referenced in those
documents. The public version of the official record does not include
any information claimed as CBI. The public version of the official
record, which includes printed, paper versions of any electronic
comments submitted during an applicable comment period is available for
inspection in the Public Information and Records Integrity Branch
(PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Hwy.,
Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The PIRIB telephone number is (703) 305-5805.
II. Background and Statutory Findings
In the Federal Register of February 29, 2000 (65 FR 16608) (FRL-
6493-8), 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) (Public Law 104-170)
announcing the filing of a pesticide petition (PP) for tolerance by
McLaughlin Gormley king Company, 8810 Tenth Avenue North, Minneapolis,
MN 55427-4372. This notice included a summary of the petition prepared
by McLaughlin Gormley King Company, 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,
[2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine], in or on food
commodities at 0.5 part per million (ppm).
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....''
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).
III. 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 and to
make a determination on aggregate exposure, consistent with section
408(b)(2), for a tolerance for residues of pyriproxyfen on all food
items in food handling establishments where food and food products are
held, processedand/or prepared at 0.1 ppm. EPA's assessment of
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 are
discussed in the following Table 1 as well as the no observed adverse
effect level (NOAEL) and the lowest observed adverse effect level
(LOAEL) from the toxicity studies reviewed.
[[Page 14854]]
Table 1.-- Subchronic, Chronic, and Other Toxicity
----------------------------------------------------------------------------------------------------------------
Guideline No. Study Type Results
----------------------------------------------------------------------------------------------------------------
870.3100 90-Day oral toxicity NOAEL = 23.49 mg/kg/day in males and 27.68
rodents mg/kg/day in females
LOAEL = 117.79 mg/kg/day in males and
141.28 mg/kg/day in females based on
higher mean total cholesterol and
phospholipids, decreased mean RBCs,
hematocrit and hemoglobin counts and
increased relative liver weight.
----------------------------------------------------------------------------------------------------------------
870.3150 90-Day oral toxicity in NOAEL = 100 mg/kg/day
dogs
LOAEL = 300 mg/kg/day based on increased
absolute and relative liver weight in
males and hepatocellular hypertrophy in
females. These findings were also observed
at 1000 mg/kg/day and may represent
adaptive changes at both 300 mg/kg/day and
the limit dose of 1000 mg/kg/day .
----------------------------------------------------------------------------------------------------------------
870.3200 21-Day dermal toxicity in NOAEL = >1,000 mg/kg/day for systemic
rats effects limit dose.
LOAEL = for systemic effects was not
established in this study. No dermal or
systemic toxicity at the limit dose.
----------------------------------------------------------------------------------------------------------------
870.3700a Prenatal developmental in Maternal NOAEL = 100 mg/kg/day
rats
LOAEL = 300 mg/kg/day based on increased
incidences in mortality and clinical signs
at 1,000 mg/kg/day with decreases in food
consumption, body weight, and body weight
gain together with increases in water
consumption at 300 and 1,000 mg/kg/day .
Developmental NOAEL = 300 mg/kg/day
LOAEL = 1,000 mg/kg/day based on increased
incidences of skeletal variations and
unspecified visceral variations at 1,000
mg/kg/day.
----------------------------------------------------------------------------------------------------------------
870.3700b Prenatal developmental in Maternal NOAEL = 100 mg/kg/day
rabbits
LOAEL = 300 mg/kg/day based on based on
premature delivery/abortions, soft stools,
emaciation, decreased activity and
bradypnea.
Developmental NOAEL = 300 mg/kg/day
LOAEL: only 4 litters examined at 1,000 mg/
kg/day [HDT] without effects.
----------------------------------------------------------------------------------------------------------------
870.3800 Reproduction and fertility Parental/Systemic NOAEL = 1,000 mg/kg/day
effects
LOAEL = 5,000 mg/kg/day based on based on
decreased body weight, weight gain and
food consumption in both sexes and both
generations. Increased liver weight in
both sexes of the F1 generation and liver
and kidney histopathology in F1 males.
Reproductive NOAEL = 5,000 ppm [HDT].
Offspring NOAEL = 1,000 ppm.
LOAEL = 5,000 ppm based on decreased pup
body weight on lactation days 14 and 21.
----------------------------------------------------------------------------------------------------------------
870.4100 Chronic toxicity dogs NOAEL = 100 mg/kg/day
LOAEL = 300 mg/kg/day based on based on
decreased weight gain, increased absolute
and relative liver weight, mild anemia,
increased cholesterol and triglycerides in
both sexes and slight anemia in males.
----------------------------------------------------------------------------------------------------------------
870.4200 Carcinogenicity mice NOAEL = 600 ppm
----------------------------------------------------------------------------------------------------------------
LOAEL = 3,000 ppm based on renal lesions in
both sexes. No statistically significant
increase in tumor incidence relative to
controls were observed in either sex at
any dose up to 3,000 ppm [HDT].
870.4300 2-Year Chronic Feeding/ NOAEL = 35.1 mg/kg/day for females and >138
Oncogenicity rats mg/kg/day for males. LOAEL = 182.7 mg/kg/
day for females based on decrease of 16.9%
in body weight gain at 3,000 ppm. No
evidence of carcinogenic response.
----------------------------------------------------------------------------------------------------------------
870.5100 and 870.5265 Gene Mutation Assay(Ames Negative for induction of gene mutation
Test)/Reverse Mutation measured as the reversion to histidine
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.
----------------------------------------------------------------------------------------------------------------
870.5300 Gene Mutation Assay Negative for mutagenicity in Chinese
Mammalian Cells hamster V79 cells with and without
metabolic activation up to cytotoxic doses
[300 g/mL].
----------------------------------------------------------------------------------------------------------------
870.5380 Structural Chromosomal Nonclastogenic in Chinese hamster ovary
Aberration Assay In vivo cells both with and without S-9 activation
cytogenetics up to cytotoxic doses [300 g/mL].
----------------------------------------------------------------------------------------------------------------
[[Page 14855]]
870.5550 Other Genotoxicity Assays Did not induce an increase in unscheduled
(Unscheduled DNA DNA synthesis both with and without
Synthesis in HeLa cells) activation in HeLa cells exposed up to
insoluble doses ranging to 6.4 g/
mL [without activation] and 51.2 g/mL [with activation].
----------------------------------------------------------------------------------------------------------------
870.7485 Metabolism 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 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.
----------------------------------------------------------------------------------------------------------------
B. Toxicological Endpoints
The NOAEL from the toxicology study identified as appropriate for
use in risk assessment is used to estimate the toxicological level of
concern (LOC). However, the LOAEL is sometimes used for risk assessment
if no NOAEL was achieved in the toxicology study selected. An
uncertainty factor (UF) is applied to reflect uncertainties inherent in
the extrapolation from laboratory animal data to humans and in the
variations in sensitivity among members of the human population as well
as other unknowns. An UF of 100 is routinely used, 10X to account for
interspecies differences and 10X for intra species differences.
For dietary risk assessment (other than cancer) the Agency uses the
UF to calculate an acute or chronic reference dose (acute RfD or
chronic RfD) where the RfD is equal to the NOAEL divided by the
appropriate UF (RfD = NOAEL/UF). Where an additional safety factor is
retained due to concerns unique to the FQPA, this additional factor is
applied to the RfD by dividing the RfD by such additional factor. The
acute or chronic Population Adjusted Dose (aPAD or cPAD) is a
modification of the RfD to accommodate this type of FQPA Safety Factor.
For non-dietary risk assessments (other than cancer) the UF is used
to determine the LOC. For example, when 100 is the appropriate UF (10X
to account for interspecies differences and 10X for intraspecies
differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to
exposures (margin of exposure (MOE) = NOAEL/exposure) is calculated and
compared to the LOC.
The linear default risk methodology (Q*) is the primary method
currently used by the Agency to quantify carcinogenic risk. The Q*
approach assumes that any amount of exposure will lead to some degree
of cancer risk. A Q* is calculated and used to estimate risk which
represents a probability of occurrence of additional cancer cases
(e.g., risk is expressed as 1 x 10-\6\ or one in a
million). Under certain specific circumstances, MOE calculations will
be used for the carcinogenic risk assessment. In this non-linear
approach, a ``point of departure'' is identified below which
carcinogenic effects are not expected. The point of departure is
typically a NOAEL based on an endpoint related to cancer effects though
it may be a different value derived from the dose response curve. To
estimate risk, a ratio of the point of departure to exposure
(MOEcancer = point of departure/exposures) is calculated. A
summary of the toxicological endpoints for pyriproxyfen used for human
risk assessment is shown in the following Table 2:
Table 2.-- Summary of Toxicological Dose and Endpoints for pyriproxyfen for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
FQPA SF* and Level of
Exposure Scenario Dose Used in Risk Concern for Risk Study and Toxicological
Assessment, UF Assessment Effects
----------------------------------------------------------------------------------------------------------------
Acute Dietary general population Not Applicable Not Applicable There were no effects
including infants and children that could be
attributed to a single
exposure (dose) in
oral toxicity studies
including the
developmental toxicity
studies in rats and
rabbits.
----------------------------------------------------------------------------------------------------------------
Chronic Dietary all populations NOAEL = 35.1 mg/kg/day; FQPA SF = 1; cPAD = Combined/chronic
UF = 100; Chronic RfD 0.35/1 = 0.35 mg/kg/ toxicity - rat: LOAEL
= 0.35 mg/kg/day day = 182.7 mg/kg/day
based on decreased
weight gain in female
rats.
----------------------------------------------------------------------------------------------------------------
Long-Term Dermal (several months to NOAEL= 35.1 mg/kg/day LOC for MOE = 100 Combined/chronic
lifetime) (Residential) toxicity - rat: LOAEL
= 182.7 mg/kg/day
based on decreased
weight gain in female
rats.
----------------------------------------------------------------------------------------------------------------
Long-Term Inhalation (several months NOAEL= 35.1 mg/kg/day LOC for MOE = 100 Combined/chronic
to lifetime) (Residential) toxicity - rat: LOAEL
= 182.7 mg/kg/day
based on decreased
weight gain in female
rats.
----------------------------------------------------------------------------------------------------------------
[[Page 14856]]
Cancer (oral, dermal, inhalation) ``Group E'' human Not Applicable There is no evidence of
carcinogen carcinogenic
potential. Therefore,
a cancer risk
assessment is not
required.
----------------------------------------------------------------------------------------------------------------
\*\ The reference to the FQPA Safety Factor refers to any additional safety factor retained due to concerns
unique to the FQPA.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. Tolerances have been
established (40 CFR 180.510 (a) for the residues of pyriproxyfen, in or
on the following raw agricultural commodities: pome fruits (crop group
11) (0.2 ppm), citrus fruits (crop group 10) (0.3 ppm), fruiting
vegetables (except cucurbits) (crop group 8) (0.2 ppm), tree nuts (crop
group 14) (0.02 ppm), cotton seed (0.05 ppm), cotton gin byproducts
(2.0 ppm), almond hulls (2.0 ppm), citrus oil (20 ppm), and citrus
pulp, dried (2.0 ppm). In todays action tolerances will be established
for the residues of pyriproxyfen in or on all foods at 0.10 ppm as a
result of the proposed use of pyriproxyfen in food handling
establishments. Risk assessments were conducted by EPA to assess
dietary exposures from pyriproxyfen in food as follows:
i. Acute exposure. 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 one day
or single exposure. An acute dose and endpoint was not selected for any
population subgroup for pyriproxyfen. No effects that could be
attributed to a single exposure (dose) were observed in oral toxicity
studies including the developmental toxicity studies in rats and
rabbits. A dose and endpoint were not identified for acute dietary risk
assessment; therefore, the Agency concludes that there is a reasonable
certainty of no harm from acute dietary exposure.
ii. Chronic exposure. In conducting this chronic dietary risk
assessment the Dietary Exposure Evaluation Model (DEEM)
analysis evaluated the individual food consumption as reported by
respondents in the USDA 1989-1992 nationwide Continuing Surveys of Food
Intake by Individuals (CSFII) and accumulated exposure to the chemical
for each commodity. A conservative analysis was conducted using
published and recommended tolerance level residues and 100% crop
treated assumptions for all commodities. No anticipated residues or
percent crop treated estimates were used. The residue levels of all
food commodities, except those with existing tolerances, were set at
0.1 ppm. For commodities with tolerances greater than 0.1 ppm, existing
tolerance level residues were employed. The cPAD for all population
subgroups is 0.35 mg/kg/day. For chronic dietary risk estimates, HED's
level of concern is for exposures >100% cPAD. Dietary exposure
estimates for the U.S. population and other representative subgroups
are presented in the following table 3:
Table 3.--Summary of Results from Chronic DEEM Analysis of Pyriproxyfen
------------------------------------------------------------------------
Exposure
Subgroups (mg/kg/ %cPAD
day)
------------------------------------------------------------------------
U.S. Population (48 states) 0.003258 0.9
------------------------------------------------------------------------
All infants (< 1 year) 0.005538 1.6
------------------------------------------------------------------------
Children (1-6 years) 0.008956 2.6
------------------------------------------------------------------------
Children (7-12 years) 0.005229 1.5
------------------------------------------------------------------------
Females 13-50 yrs 0.002323 0.7
------------------------------------------------------------------------
Males 13-19 yrs 0.003158 0.9
------------------------------------------------------------------------
Males 20+ yrs 0.002228 0.6
------------------------------------------------------------------------
Seniors 55+ 0.002233 0.6
------------------------------------------------------------------------
The population subgroups listed include those subgroups having
sufficient numbers of survey respondents in the CSFII food consumption
survey to be considered statistically reliable. The results show that
chronic dietary exposure to pyriproxyfen residues from all existing and
proposed uses do not exceed HED's level of concern of 100% cPAD.
Refinement of residue estimates using %CT corrections and anticipated
residue estimates would result in even lower residue estimates.
2. Dietary exposure from drinking water. The Agency uses the
Generic Estimated Environmental Concentration (GENEEC) or the Pesticide
Root Zone/Exposure Analysis Modeling System (PRZM/EXAMS) to estimate
pesticide concentrations in surface water and SCI-GROW, which predicts
pesticide concentrations in groundwater. In general, EPA will use
GENEEC (a tier 1 model) before using PRZM/EXAMS (a tier 2 model) for a
screening-level assessment for surface water. The GENEEC model is a
subset of the PRZM/EXAMS model that uses a specific high-end runoff
scenario for pesticides. GENEEC incorporates a farm pond scenario,
while PRZM/EXAMS incorporate an index reservoir environment in place of
the previous pond scenario. The PRZM/EXAMS model includes a percent
crop area factor as an adjustment to account for the maximum percent
crop coverage within a watershed or drainage basin.
None of these models include consideration of the impact processing
(mixing, dilution, or treatment) of raw water for distribution as
drinking water would likely have on the removal of pesticides from the
source water. The primary use of these models by the Agency at this
stage is to provide a coarse screen for sorting out pesticides for
which it is highly unlikely that drinking water concentrations would
ever exceed human health levels of concern.
Since the models used are considered to be screening tools in the
risk assessment process, the Agency does not use estimated
environmental concentrations (EECs) from these models to quantify
drinking water exposure and risk as a %RfD or %PAD. Instead drinking
water levels of comparison (DWLOCs) are calculated and used as a point
of comparison against the model estimates of a pesticide's
concentration in water. DWLOCs are theoretical upper limits on a
pesticide's concentration in drinking water in light of total aggregate
exposure to a pesticide in food, and from residential uses. Since
DWLOCs address total aggregate exposure to pyriproxyfen they are
further discussed in the aggregate risk sections below.
[[Page 14857]]
Based on the PRZM/EXAMS and SCI-GROW models the estimated
environmental concentrations (EECs) of pyriproxyfen for acute exposures
are estimated to be 0.11 parts per billion (ppb) for surface water and
0.006 ppb for ground water. The EECs for chronic exposures are
estimated to be 0.11 ppb for surface water and 0.006 ppb for ground
water.
3. From non-dietary exposure. The term ``residential exposure'' is
used in this document to refer to non-occupational, non-dietary
exposure (e.g., for lawn and garden pest control, indoor pest control,
termiticides, and flea and tick control on pets).
Pyriproxyfen is currently registered for use in residential non-
dietary sites for flea and tick control. Formulations include contact
sprays, emulsifiable concentrates, and impregnated materials (pet
collars). 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 instructs
to change the collar once a year), and 1% of the active ingredient is
available for dermal and inhalation exposure per day (assumption from
Draft HED Standard Operating Procedures (SOPs) for Residential Exposure
Assessments, 18-DEC-1997). The assessment also assumes an absorption
rate of 100%. This is a conservative assumption since the dermal
absorption was estimated to be 10% (HED Hazard Identification
Assessment Review Committee, 24-OCT-1997). The following Table 4 shows
residential exposure and risk Assessment for homeowner use of pet
collars:
Table 4.--Residential Exposure and Risk Assessment for Homeowner Use of
Pet Collars
------------------------------------------------------------------------
Average
Potential
Application Dose Chronic
Population Subgroup Rate\1\ mg/ Rate\2\ Term
day (mg/kg/ MOE\3\
day)
------------------------------------------------------------------------
Children 0.58 0.00058 61,000
------------------------------------------------------------------------
Adults 0.58 0.000081 430,000
------------------------------------------------------------------------
\1\Product label: Reg. No. 2382-149 (0.5% pyriproxyfen, ovisterilant pet
collar). Application rate = 42 gm collar x 0.5% a.i./collar x
1,000 mg/1 gm x 1/365 days. Collar to be replaced once a year.
\2\Potential Dose Rate (PDR) = Application rate x fraction of ai
available for exposure (1%) x absorption rate(100%) x 1/(10 or
71.8 kg bw for children or adults, respectively) (Draft HED Standard
Operating Procedures (SOPs) for Residential Exposure Assessments, 18-
DEC-1997).
\3\Dermal and Inhalation NOAEL = 35.1 mg/kg/day; MOE = NOAEL/Exposure;
Adequate MOE = 100.
The estimated chronic term MOE is 61,000 for children, and 430,000 for
adults. The risk estimates indicate that potential risks from pet
collar uses do not exceed HED's level of concern (MOEs < 100).
4. Cumulative exposure to substances with a 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. Safety Factor for Infants and Children
1. Safety factor for infants and children--i. In general. 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 prenatal and postnatal toxicity and the completeness of the
data base on toxicity and exposure 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.
ii. Prenatal and postnatal 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.
iii. Conclusion. The 10X safety factor to protect infants and
children was reduced to 1x because (1) the toxicology data base is
complete; (2) there is no indication of increased susceptibility of
rats or rabbit fetuses to in utero and/or postnatal exposure in the
developmental and reproductive toxicity studies; (3) a developmental
neurotoxicity study is not required; (4) food exposure estimates are
unrefined (assuming tolerance level residues and 100% CT) and likely
result in an overestimate of the actual dietary exposure; (5) EFED
models are used for ground and surface source drinking water exposure
assessments resulting in conservative estimates of actual dietary
exposures; and (6) the Draft Standard Operating Procedures for
Residential Exposure Assessments have been used as the basis for all
calculations which normally rely on one or more upper-percentile
assumptions and are considered to be protective.
E. Aggregate Risks and Determination of Safety
To estimate total aggregate exposure to a pesticide from food,
drinking water, and residential uses, the Agency calculates DWLOCs
which are used as a point of comparison against the model estimates of
a pesticide's concentration in water (EECs). DWLOC values are not
regulatory standards for drinking water. DWLOCs are theoretical upper
limits on a pesticide's concentration in drinking water in light of
total aggregate exposure to a pesticide in food and residential uses.
In calculating a DWLOC, the Agency determines how much of the
acceptable exposure (i.e., the PAD) is
[[Page 14858]]
available for exposure through drinking water [e.g., allowable chronic
water exposure (mg/kg/day) = cPAD - (average food + residential
exposure)]. This allowable exposure through drinking water is used to
calculate a DWLOC.
A DWLOC will vary depending on the toxic endpoint, drinking water
consumption, and body weights. Default body weights and consumption
values as used by the USEPA Office of Water are used to calculate
DWLOCs: 2L/70 kg (adult male), 2L/60 kg (adult female), and 1L/10 kg
(child). Default body weights and drinking water consumption values
vary on an individual basis. This variation will be taken into account
in more refined screening-level and quantitative drinking water
exposure assessments. Different populations will have different DWLOCs.
Generally, a DWLOC is calculated for each type of risk assessment used:
acute, short-term, intermediate-term, chronic, and cancer.
When EECs for surface water and groundwater are less than the
calculated DWLOCs, OPP concludes with reasonable certainty that
exposures to the pesticide 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. Because OPP considers the aggregate risk resulting from
multiple exposure pathways associated with a pesticide's uses, levels
of comparison in drinking water may vary as those uses change. If new
uses are added in the future, OPP will reassess the potential impacts
of residues of the pesticide in drinking water as a part of the
aggregate risk assessment process.
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 maximum percentage of the
cPAD that will be utilized by dietary (food) exposure to residues of
pyriproxyfen is 2.6% percent for children (1-6 years). Chronic
residential exposure to pyriproxyfen from pet collars is estimated to
increase total pyriproxyfen exposure to infants and children only
marginally. Despite the potential for exposure to pyriproxyfen in
drinking water, EPA does not expect the aggregate exposure to exceed
100% of the cPAD.
EPA bases this determination on a comparison of estimated
concentrations of pyriproxyfen in surface and ground water to
calculated drinking water levels of comparison. 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
comparison 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.
The following table 5 summarizes the quantitative aspects of the
aggregate risk assessment for chronic exposure to pyriproxyfen. For
chronic exposure to pyriproxyfen in surface and ground water, the
DWLOCs are 12,000 g/L for U.S. population and 3,400
g/L for children (1-6 years). Estimated average concentrations
of pyriproxyfen in surface and ground water are 0.11 ppb and 0.006 ppb,
respectively. The estimated average concentrations of pyriproxyfen in
surface and ground water are less than EPA'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, EPA concludes that there is a reasonable certainty that
no harm will result to any population subgroup from chronic aggregate
exposure to pyriproxyfen residues.
Table 5.--Aggregate Risk Assessment for Chronic Exposure to Pyriproxyfen
------------------------------------------------------------------------
cPAD Surface Ground
mg/ Exposure Water Water Chronic
Population Subgroup kg/ mg/kg/ EEC EEC DWLOC
day day (ppb) (ppb) (ppb)
------------------------------------------------------------------------
U.S. population - all 0.35 0.003258 0.11 0.006 12000
seasons
------------------------------------------------------------------------
All Infants (<1 year) 0.35 0.005538 0.11 0.006 3400
------------------------------------------------------------------------
Children (1-6 years) 0.35 0.008956 0.11 0.006 3,400
------------------------------------------------------------------------
Children (7-12 years) 0.35 0.005229 0.11 0.006 3,400
------------------------------------------------------------------------
Females (13-50 years) 0.35 0.002323 0.11 0.006 10,000
------------------------------------------------------------------------
Males (13-19 years) 0.35 0.003158 0.11 0.006 12,000
------------------------------------------------------------------------
Males (20+ years) 0.35 0.002228 0.11 0.006 12,000
------------------------------------------------------------------------
Seniors (55+) 0.35 0.002233 0.11 0.006 12,000
------------------------------------------------------------------------
3. Short-term risk. Pyriproxyfen is not expected to pose a short-
term risk due to the lack of significant toxicological effects
observed.
4. Intermediate-term risk. Pyriproxyfen is not expected to pose an
intermediate-term risk due to the lack of significant toxicological
effects observed.
5. Aggregate cancer risk for U.S. population. Pyriproxyfen is
classified as Category E: not carcinogenic in two acceptable animal
studies and is, therefore, not expected to pose a cancer risk to
humans.
6. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the general population, and to infants and children from aggregate
exposure to pyriproxyfen residues.
[[Page 14859]]
IV. Other Considerations
A. Analytical Enforcement Methodology
Previously, the Agency successfully validated gas chromatography
(GC) methods for pyriproxyfen on cotton seed and on pome fruits, citrus
fruits, fruiting vegetables, and tree nuts. Biological Test Center
(BTC) conducted an Independent Laboratory Validation (ILV) of the
proposed enforcement method for tolerances of pyriproxyfen on four
representative foods using high performance liquid chromatography
(HPLC) with ultraviolet (UV) detection. Sugar, flour, lettuce and
butter were selected to represent high sugar content foods, dry foods,
high water content foods, and fatty foods, respectively. The limit of
quantitation (LOQ) was 0.1 ppm for all foods except butter, which was
0.5 ppm. Sugar, flour, and lettuce samples were fortified at 0.1 and
0.5 ppm. Average recoveries ranged from 89% to 97% for these food
samples. Butter was fortified at 0.5 and 2.4 ppm and gave an average
recovery of 68%. Some modifications to the analytical method were
necessary for the butter samples. With incorporation of these
modifications, EPA considers the ILV of the pyriproxyfen
(Nylar) analytical method for food commodities to be
successful.
Agency validation of the HPLC method on flour, candy, lettuce, and
butter, and of the GC method on liver was requested and completed. EPA
concludes these methods are adequate as analytical enforcement methods
pending revision of the methods as requested by the Agency laboratory.
Valent submitted data from a study performed by Corning Hazleton
Inc. describing the testing of pyriproxyfen through the Food and Drug
Administration (FDA) Multiresidue Methods Protocols A, C, D, E, and F
found in the Pesticide Analytical Manual Volume I (PAM I), Appendix II.
This study was previously reviewed in a memo dated 06-MAY-1997.
Pyriproxyfen was recovered from fortified apple and cotton samples
through protocols A, C, D, E, and F. The metabolite PYPAC was tested
with protocols A, B, C, and D. The multiresidue methods will serve as
confirmatory methods for residues of pyriproxyfen. The multiresidue
recovery data were sent to the FDA for inclusion in PAM I.
The methods may be requested from: Calvin Furlow, PRRIB, IRSD
(7502C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW, Washington, DC 20460; telephone number:
(703) 305-5229; e-mail address: [email protected].
B. International Residue Limits
There are no CODEX, Canadian, or Mexican tolerances for
pyriproxyfen residues in or on any food items or raw agricultural
commodities (RACs). Maximum residue limits (MRLs) have been proposed
for cotton seed, citrus, meat, and edible offal; however, there is no
certainty these proposed levels will become official. Therefore,
international harmonization is not an issue at this time.
C. Conditions
As a condition of the registration a revised analytical method for
foods must be submitted.
V. Conclusion
Therefore, a tolerance is established for residues of pyriproxyfen
[2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy]pyridine], in or on all foods
at 0.10 ppm.
VI. Objections and Hearing Requests
Under section 408(g) of the FFDCA, as amended by the FQPA, any
person may file an objection to any aspect of this regulation and may
also request a hearing on those objections. The EPA procedural
regulations which govern the submission of objections and requests for
hearings appear in 40 CFR part 178. Although the procedures in those
regulations require some modification to reflect the amendments made to
the FFDCA by the FQPA of 1996, EPA will continue to use those
procedures, with appropriate adjustments, until the necessary
modifications can be made. The new section 408(g) provides essentially
the same process for persons to ``object'' to a regulation for an
exemption from the requirement of a tolerance issued by EPA under new
section 408(d), as was provided in the old FFDCA sections 408 and 409.
However, the period for filing objections is now 60 days, rather than
30 days.
A. What Do I Need to Do to File an Objection or Request a Hearing?
You must file your objection or request a hearing on this
regulation in accordance with the instructions provided in this unit
and in 40 CFR part 178. To ensure proper receipt by EPA, you must
identify docket control number OPP-301103 in the subject line on the
first page of your submission. All requests must be in writing, and
must be mailed or delivered to the Hearing Clerk on or before May 14,
2001.
1. Filing the request. Your objection must specify the specific
provisions in the regulation that you object to, and the grounds for
the objections (40 CFR 178.25). If a hearing is requested, the
objections must include a statement of the factual issue(s) on which a
hearing is requested, the requestor's contentions on such issues, and a
summary of any evidence relied upon by the objector (40 CFR 178.27).
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.
Mail your written request to: Office of the Hearing Clerk (1900),
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460. You may also deliver your request to the Office
of the Hearing Clerk in Rm. C400, Waterside Mall, 401 M St., SW.,
Washington, DC 20460. The Office of the Hearing Clerk is open from 8
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
telephone number for the Office of the Hearing Clerk is (202) 260-4865.
2. Tolerance fee payment. If you file an objection or request a
hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or
request a waiver of that fee pursuant to 40 CFR 180.33(m). You must
mail the fee to: EPA Headquarters Accounting Operations Branch, Office
of Pesticide Programs, P.O. Box 360277M, Pittsburgh, PA 15251. Please
identify the fee submission by labeling it ``Tolerance Petition Fees.''
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 the waiver of these fees, you may contact James
Tompkins by phone at (703) 305-5697, by e-mail at [email protected],
or by mailing a request for information to Mr. Tompkins at Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
If you would like to request a waiver of the tolerance objection
fees, you must mail your request for such a waiver to: James Hollins,
Information Resources and Services Division (7502C), Office of
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460.
[[Page 14860]]
3. Copies for the Docket. In addition to filing an objection or
hearing request with the Hearing Clerk as described in Unit VI.A., you
should also send a copy of your request to the PIRIB for its inclusion
in the official record that is described in Unit I.B.2. Mail your
copies, identified by docket control number OPP-301103, to: Public
Information and Records Integrity Branch, Information Resources and
Services Division (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
In person or by courier, bring a copy to the location of the PIRIB
described in Unit I.B.2. You may also send an electronic copy of your
request via e-mail to: [email protected]. Please use an ASCII file
format and avoid the use of special characters and any form of
encryption. Copies of electronic objections and hearing requests will
also be accepted on disks in WordPerfect 6.1/8.0 or ASCII file format.
Do not include any CBI in your electronic copy. You may also submit an
electronic copy of your request at many Federal Depository Libraries.
B. When Will the Agency Grant a Request for a Hearing?
A request for a hearing will be granted if the Administrator
determines that the material submitted shows the following: There is a
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 issue(s) in the manner sought
by the requestor would be adequate to justify the action requested (40
CFR 178.32).
VII. Regulatory Assessment Requirements
This final rule establishes a tolerance under FFDCA section 408(d)
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) (Public Law 104-4). Nor
does it require any special considerations under Executive Order 12898,
entitled Federal Actions to Address Environmental Justice in Minority
Populations and Low-Income Populations (59 FR 7629, February 16, 1994);
or OMB review or any Agency action under Executive Order 13045,
entitled Protection of Children from Environmental Health Risks and
Safety Risks (62 FR 19885, April 23, 1997). This action does not
involve any technical standards that would require Agency consideration
of voluntary consensus standards pursuant to section 12(d) of the
National Technology Transfer and Advancement Act of 1995 (NTTAA),
Public Law 104-113, section 12(d) (15 U.S.C. 272 note). Since
tolerances and exemptions that are established on the basis of a
petition under FFDCA section 408(d), such as the tolerance 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. In addition, the Agency has determined that this
action will not have a substantial direct effect on States, on the
relationship between the national government and the States, or on the
distribution of power and responsibilities among the various levels of
government, as specified in Executive Order 13132, entitled Federalism
(64 FR 43255, August 10, 1999). Executive Order 13132 requires EPA to
develop an accountable process to ensure ``meaningful and timely input
by State and local officials in the development of regulatory policies
that have federalism implications.'' ``Policies that have federalism
implications'' is defined in the Executive Order to include regulations
that have ``substantial direct effects on the States, on the
relationship between the national government and the States, or on the
distribution of power and responsibilities among the various levels of
government.'' This final rule directly regulates growers, food
processors, food handlers and food retailers, not States. This action
does not alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of FFDCA section 408(n)(4).
For these same reasons, the Agency has determined that this rule
does not have any ``tribal implications'' as described in Executive
Order 13175, entitled Consultation and Coordination with Indian Tribal
Governments (65 FR 67249, November 6, 2000). Executive Order 13175,
requires EPA to develop an accountable process to ensure ``meaningful
and timely input by tribal officials in the development of regulatory
policies that have tribal implications.'' ``Policies that have tribal
implications'' is defined in the Executive Order to include regulations
that have ``substantial direct effects on one or more Indian tribes, on
the relationship between the Federal government and the Indian tribes,
or on the distribution of power and responsibilities between the
Federal government and Indian tribes.'' This rule will not have
substantial direct effects on tribal governments, on the relationship
between the Federal government and Indian tribes, or on the
distribution of power and responsibilities between the Federal
government and Indian tribes, as specified in Executive Order 13175.
Thus, Executive Order 13175 does 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 to 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 this final rule in the Federal Register. This final
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: February 28, 2001.
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), 346(a) and 371.
2. Section 180.510(a) is amended by designating the text following
the heading ``General'' as paragraph (a)(1), and by adding paragraph
(a)(2) to read as follows:
[[Page 14861]]
Sec. 180.510 Pyriproxyfen; tolerances for residues.
(a) General. (1) * * *
(2) A tolerance of 0.10 parts per million is established for all
foods as a result of the proposed use of NYLAR in food handling
establishments where food and food products are held, prepared,
processed or served. Application is limited to space, general surface,
spot, and/or crack and crevice treatment in food handling
establishments where food and food products are held, processed,
prepared and served. Space and general surface application may be used
only when the facility is not in operation provided exposed food is
covered or removed from the area being treated prior to application.
Spot, and/or crack and crevice treatment may be used while the facility
is in operation provided exposed food is covered or removed from the
area being treated prior to application. Food contact surfaces should
be thoroughly washed with an effective cleaning compound and rinced
with potable water after use of the product. To assure safe use of this
additive, its label and labeling shall conform to that registered with
the U.S. Environmental Protection Agency, and shall be used in
accordance with such label and labeling.
* * * * *
[FR Doc. 01-6330 Filed 3-13-01; 8:45 am]
BILLING CODE 6560-50-S