[Federal Register Volume 62, Number 228 (Wednesday, November 26, 1997)]
[Rules and Regulations]
[Pages 63019-63027]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-31099]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Parts 180, 185 and 186
[OPP-300575; FRL-5754-6]
RIN 2070-AB78
Fenvalerate; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes tolerances for residues of
fenvalerate, including the S,S-enriched isomer esfenvalerate in or on
cottonseed at 0.2 parts per million (ppm). It also removes time
limitations for tolerances for residues of fenvalerate on the same
commodities that expire on November 15, 1997. DuPont Agricultural
Products requested this tolerance under the Federal Food, Drug and
Cosmetic Act (FFDCA), as amended by the Food Quality Protection Act of
1966 (Pub. L. 104-170). This tolerance was established under petition
number PP 7F2013.
DATES: This regulation is effective November 26, 1997. Objections and
requests for hearings must be received by EPA on or before January 26,
1998.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300575], 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 withthe Hearing Clerk identified by the docket
control number, [OPP-300575], must also be submitted to: Public
Information and Records Integrity Branch, Information Resources and
Services Division (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. In person,
bring a copy of objections and hearing requests to Rm. 1132, Crystal
Mall #2, 1921 Jefferson Davis Hwy., 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: [email protected]. Copies of objections and
hearing requests must be submitted as an ASCII file avoiding the use of
special characters and any form of encryption. Copies of objections and
hearing requests will also be accepted on disks in WordPerfect 5.1/6.1
file format or ASCII file format. All copies of objections and hearing
requests in electronic form must be identified by the docket control
number [OPP-300575]. 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: John Hebert, 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: CM #2, 1921 Jefferson Davis Hwy.,
Arlington, VA, (703) 308-3068, e-mail: [email protected].
Supplementary Information: On October 20, 1993 EPA established time
limited tolerances under Section 408 of the Federal Food Drug and
Cosmetic Act (FFDCA), 21 U.S.C. 346 a(d) and 348 for residues of
esfenvalerate on cottonseed. These tolerances expire on November 15,
1997. DuPont Agricultural Products, on September 15, 1997, requested
that the time limitation for tolerances established for residues of the
insecticide fenvalerate, including the S,S-enriched isomer
esfenvalerate in or on cottonseed at 0.2 parts per million (ppm) be
removed based on ecological and environmental effects data that they
had submitted as a condition of the registration. DuPont Agricultural
Products also submitted a summary of its petition as required under the
FFDCA as amended by the Food Quality Protection Act (FQPA) of 1996
(Pub. L. 104-170).
In the Federal Register of September 25, 1997 (62 FR 50337)(FRL
5748-2), EPA, issued a notice pursuant to section 408 of the Federal
Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(e) announcing the
filing of a pesticide petition (PP) for tolerance by DuPont
Agricultural Products, P.O. Box 80038, Wilmington, DE 19880-0038. This
notice included a summary of the petition prepared by DuPont
Agricultural Products. There were no comments received in response to
the notice of filing.
The basis for time limited tolerances that expire November 15, 1997
was given in the October 20, 1993 Federal Register (58 FR 54094). These
time-limited tolerances were predicated on the expiration of pesticide
product registrations that were made conditional due to lack of certain
ecological and
[[Page 63020]]
environmental effects data. The rationale for using time-limited
tolerances was to encourage pesticide manufacturers to comply with the
conditions of registration in a timely manner. There is no regulatory
requirement to make tolerances time-limited due to the conditional
status of a product registration under the Federal Insecticide,
Fungicide, Rodenticide Act (FIFRA) as amended. It is current EPA policy
to no longer establish time limitations on tolerance(s) with expiration
dates if none of the conditions of registration have any bearing on
human dietary risk. The current petition action meets that condition
and thus the expiration dates associated with specific crop tolerances
are being deleted.
The petition requested that 40 CFR 180.379 be amended by removing
the time limitation for a tolerance for residues of the pyrethroid
insecticide esfenvalerate, in or on: cottonseed at 0.2 parts per
million (ppm). Tolerances are based on the sum of all isomers of
fenvalerate. Fenvalerate is a racemic mixture of four isomers (about
25% each). This product was registered as Pydrin. However
since 1992, an S,S-isomer enriched formulation, Asana (esfenvalerate),
has been the only fenvalerate formulation sold in the U.S. for
agricultural use. Since the S,S-isomer is the insecticidally active
isomer, the use rate for Asana is four times lower than that
for Pydrin. A petition is pending (PP 4F4329), to convert
tolerances (still to be expressed as the sum of all isomers) based on
the use rates for Asana. Bridging residue studies have shown
Asana residues to be 3-4 times lower than Pydrin
residues.
I. Risk Assessment and Statutory Findings
New 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. 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. Second,
EPA examines exposure to the pesticide through the diet (e.g., food and
drinking water) and through exposures that occur as a result of
pesticide use in residential settings.
A. Toxicity
1. Threshold and non-threshold effects. For many animal 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 a study has 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 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. Thus, 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 acceptable by EPA. EPA generally uses the
RfD to evaluate the chronic risks posed by pesticide exposure. For
shorter term risks, EPA calculates a margin of exposure (MOE) by
dividing the estimated human exposure into the NOEL from the
appropriate animal study. Commonly, EPA finds MOEs lower than 100 to be
unacceptable. This 100-fold MOE is based on the same rationale as the
100-fold uncertainty factor.
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 MOE 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.
2. Differences in toxic effect due to exposure duration. The
toxicological effects of a pesticide can vary with different exposure
durations. EPA considers the entire toxicity data base, and based on
the effects seen for different durations and routes of exposure,
determines which risk assessments should be done to assure that the
public is adequately protected from any pesticide exposure scenario.
Both short and long durations of exposure are always considered.
Typically, risk assessments include ``acute,'' ``short-term,''
``intermediate term,'' and ``chronic'' risks. These assessments are
defined by the Agency as follows.
Acute risk, by the Agency's definition, results from 1-day
consumption of food and water, and reflects toxicity which could be
expressed following a single oral exposure to the pesticide residues.
High end exposure to food and water residues are typically assumed.
Short-term risk results from exposure to the pesticide for a period
of 1-7 days, and therefore overlaps with the acute risk assessment.
Historically, this risk assessment was intended to address primarily
dermal and inhalation exposure which could result, for example, from
residential pesticide applications. However, since enaction of FQPA,
this assessment has been expanded to include both dietary and non-
dietary sources of exposure, and will typically consider exposure from
food, water, and residential uses when reliable data are available. In
this assessment, risks from average food and water exposure, and high-
end residential exposure, are aggregated. High-end exposures from all 3
sources are not typically added because of the very low probability of
this occurring in most cases, and because the other conservative
assumptions built into the assessment assure adequate protection
[[Page 63021]]
of public health. However, for cases in which high-end exposure can
reasonably be expected from multiple sources (e.g. frequent and
widespread homeowner use in a specific geographical area), multiple
high-end risks will be aggregated and presented as part of the
comprehensive risk assessment/characterization. Since the toxicological
endpoint considered in this assessment reflects exposure over a period
of at least 7 days, an additional degree of conservatism is built into
the assessment; i.e., the risk assessment nominally covers 1-7 days
exposure, and the toxicological endpoint/NOEL is selected to be
adequate for at least 7 days of exposure. (Toxicity results at lower
levels when the dosing duration is increased.)
Intermediate-term risk results from exposure for 7 days to several
months. This assessment is handled in a manner similar to the short-
term risk assessment.
Chronic risk assessment describes risk which could result from
several months to a lifetime of exposure. For this assessment, risks
are aggregated considering average exposure from all sources for
representative population subgroups including infants and children.
B. Aggregate Exposure
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, residues in groundwater
or surface water that is consumed as drinking water, and other non-
occupational exposures through pesticide use in gardens, lawns, or
buildings (residential and other indoor 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. In evaluating food
exposures, EPA takes into account varying consumption patterns of major
identifiable subgroups of consumers, including infants and children.
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% 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 (anticipated residue data
and/or percent of crop treated data) which show, generally, that
pesticide residues in most foods when they are eaten are well below
established tolerances.
II. Aggregate Risk Assessment and Determination of Safety
Consistent with section 408(b)(2)(D), EPA has reviewed the
available scientific data and other relevant information in support of
this action, EPA has sufficient data to assess the hazards of
esfenvalerate and to make a determination on aggregate exposure,
consistent with section 408(b)(2), to remove the time limitation for a
tolerances for residues of esfenvalerate on cottonseed at 0.2 parts per
million (ppm). EPA's assessment of the dietary exposures and risks
associated with establishing the tolerance follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children. The nature of the toxic effects caused by esfenvalerate are
discussed below.
1. A battery of acute toxicity studies places technical
esfenvalerate in Toxicity category II for acute oral (LD50 =
87.2 mg/kg), Category III for acute dermal (LD50 > 2000 mg/
kg) and primary eye irritation, Category IV for primary skin
irritation. Esfenvalerate is a non-sensitizer. Acute inhalation on
technical grade active ingredient is waived due to negligible vapor
pressure. The Acute Delayed Neurotoxicity (Guideline 81-8) remains a
data gap.
2. In a 90-day feeding study, rats were administered 0, 4.7, 6.2,
7.8 or 18.7 mg/kg/day of esfenvalerate. The Lowest Observed Effect
Level (LOEL) is 18.7 mg/kg/day based on neurological dysfunction. The
NOEL is 7.8 mg/kg/day.
In another 90-day feeding study, rats were administered 0, 5, 15,
30 or 50 mg/kg/day of esfenvalerate. The LOEL is 15 mg/kg/day based on
neurological dysfunction. The NOEL is 5 mg/kg/day.
Esfenvalerate was administered to mice at dose levels of 0, 10.5,
30.5 or 106 mg/kg/day (male) and 0, 12.6, 36.8 or 113 mg/kg/day
(female). The LOEL for esfenvalerate is 106 mg/kg/day. The NOEL is 30.5
mg/kg/day.
3. In a chronic/onco feeding study (MRID 00082244, 00111888), rats
were administered 0.050, 0.25, 1.25 or 12.5 mg/kg/day of fenvalerate in
the diet for 2 years. The LOEL was 12.5 mg/kg/day. There
was no increase in tumors at 12.5 mg/kg/day. The NOEL was determined to
be 12.5 mg/kg/day (the Highest Dose Tested (HDT) in the 2 year study.)
The study is supplementary and does not satisfy the requirement for a
guideline series 83-5 combined chronic/carcinogenicity study in rats.
In a lifetime feeding study (MRID 00079877), rats were administered
0 or 50.0 mg/kg/day of fenvalerate in the diet. Spindle cell sarcomas
were produced in male rats only. The LOEL was 50.0 mg/kg/day based on
loss of weight and neurological effects. The NOEL was 12.5 mg/kg/day.
The conclusion that fenvalerate is associated with the production
of spindle cell sarcomas was later retracted by EPA. The study is
supplementary and does not satisfy the requirement for a guideline
series 83-5 combined chronic/ carcinogenicity study in rats. When taken
together with chronic/carcinogenicity feeding study (MRID's 00082244,
00111888) the guideline requirement for a 83-2a, cancer study in the
rat is satisfied.
4. In a 2-year feeding study mice were administered 0, 0, 1.5, 7.5,
38.0 or 187.5 mg/kg/day fenvalerate in the diet. The LOEL was 7.5 mg/
kg/day based on granulomatous changes (related to fenvalerate only, not
esfenvalerate). The NOEL was 1.5 mg/kg/day. This study satisfies the
requirement for combined chronic feeding carcinogenicity study in mice.
In an 18-month feeding study, mice 0, 15.0, 45.0, 150.0 or 450.0
mg/kg/day of fenvalerate in the diet. The LOEL is 45.0 mg/kg/day based
on granulomatous changes in the liver and spleen. The NOEL is 15.0 mg/
kg/day. No oncogenicity was observed. The study is supplementary and
does not satisfy the requirement for a guideline series 83-2b
carcinogenicity study in mice.
In a life span feeding study, mice were administered 0, 1.5, 4.5,
15.0 or 45.0 mg/kg/day of fenvalerate in the diet. The LOEL was
determined to be 15 mg/kg/day based on the granulomatous lesions
observed and on the change in hematological parameters. Fenvalerate was
determined not to be carcinogenic in the ddy strain of the mouse. The
NOEL was determined to be 3.48 mg/kg/day. The study is supplementary
and does not satisfy the requirement for a
[[Page 63022]]
guideline series 83-2b carcinogenicity study in mice.
5. In a 21-day probe for a 1 year feeding study 2 male and 2 female
beagles were administered 0, 2.80, 6.40 or 9.38 mg/kg/day in males and
0, 2.25, 7.37 or 8.50 mg/kg/day of esfenvalerate. The LOEL was
determined to be 6.40 mg/kg/day based on nervous system involvement and
decreases in body weight and food consumption. The NOEL is 2.25 mg/kg/
day.
In a 1-year feeding study, 6 male and 6 female beagles/group were
administered 0, 0.68, 1.36 or 5.29 mg/kg/day esfenvalerate. The LOEL
was determined to be 6.40 mg/kg/day based on nervous system involvement
and decreases in body weight and food consumption. The NOEL was
determined to be 5.29 mg/kg/day. These studies are acceptable and
satisfies the requirement for a guideline series 83-1b chronic feeding
study in dogs.
6. Esfenvalerate was administered to female rats at doses of 0,
2.5, 5.0, 10.0 or 20.0 mg/kg/day from gestation days 6 through 15
(pilot study doses were 1.0, 2.0, 3.0, 4.0, 5.0 and 20 mg/kg/day). The
LOEL is 2.5 mg/kg/day based on behavioral/Central Nervous System
clinical signs. The NOEL for maternal toxicity is 2.0 mg/kg/day (from
the pilot study). There was no evidence of developmental toxicity at
any dose. The NOEL is 20 mg/kg/day, the highest dose tested.
Esfenvalerate was administered to rabbits at doses of 0, 3.0, 10.0
or 20.0 mg/kg/day from gestation days 7 through 19 (pilot study doses
were 0, 2.0, 3.0, 4.0, 4.5, 5.0 or 20.0 mg/kg/day). The LOEL is 3.0 mg/
kg/day based on behavioral/CNs clinical signs. The NOEL is 2.0 mg/kg/
day (from the pilot study). There was no evidence of developmental
toxicity at any dose. The LOEL is greater than 20.0 mg/kg/day. The NOEL
is equal to or greater than 20.0 mg/kg/day, the highest dose tested.
7. In a 2-generation reproduction toxicity study in rats
esfenvalerate was administered to rats at dose levels of 0, 3.75, 5.0,
17.5 and 35.0/17.5 mg/kg/day. The LOEL for parental toxicity is 3.75
mg/kg/day based on decreases in mean body weights of F1
females and an increased incidence of skin lesions. The NOEL could not
be determined. The LOEL for reproductive toxicity is 5.0 mg/kg/day
based on decreases in F1 pup weights on day 21 of lactation;
decreases in litter size and F2 pup weights and an increased
incidence of subcutaneous hemorrhage. The NOEL is 3.75 mg/kg/day.
8. In a reverse gene mutation assay in bacteria, S. typhimurium and
Escherichia coli were exposed to fenvalerate in DMSO at concentrations
of 15, 50, 150, 500, 1,500, or 5,000 g/plate in the presence
and absence of mammalian metabolic activation (S9-mix). There was no
evidence of induced mutant colonies over background.
In a mammalian cell gene mutation assay at the HGPRT locus, Chinese
hamster V79 cells cultured in vitro were exposed to fenvalerate in DMSO
at concentrations of 12.6, 42, 126, 420 g/ml in the presence
of mammalian metabolic activation (S9-mix) and at concentrations of
4.2, 12.6, 42, 126 g/ml in the absence of S9-mix. There was no
evidence of induced mutant colonies over background. In Chinese hamster
lung fibroblasts (V79 cells) forward gene mutation assay the test was
negative up to cytotoxic and/or precipitating levels (126 g/ml
in the absence of metabolic activation -S9; 420 g/ml in the
presence of metabolic activation +S9).
In a mammalian cell cytogenetics chromosomal aberration assay CHO-
K1 cell cultures were exposed to fenvalerate in DMSO at concentrations
of 4.2 g/ml, 8.4 g/ml, 21 g/ml, 42
g/ml respectively without exogenous metabolic activation (S9-
mix) and at concentrations of 21 g/ml, 42 g/ml, 84
g/ml, 210 g/ml respectively with S9-mix. There was no
evidence of a significant induction of chromosomal aberrations or
polyploid cells over background.
A mouse micronucleus assay was negative in male ICR mice up to the
HDT (150 mg/kg) administered by intraperitoneal injection. Since there
appears to be no sex specific difference in the toxicity of
Esfenvalerate, the use of males only is justifiable. No overt toxicity
was observed, but suggestive evidence of bone marrow cytotoxicity was
seen 48 hours post-administration at the highest dose level tested.
Other genetic toxicology studies submitted on racemic Fenvalerate
indicate that the mixture containing equal parts of the four
stereoisomers is not mutagenic in bacteria. The racemic mixture was
also negative in a mouse host mediated assay and in a mouse dominant
lethal assay.
9. The following studies are considered data gaps in the toxicology
data base: general metabolism, 21 day dermal, dermal penetration and
acute, subchronic and developmental mammalian neurotoxicity. These
studies will be required under a special data call in letter pursuant
to Section 3 (c)(2)(B) of FIFRA. Although these data are lacking EPA
has sufficient toxicity data base to support these tolerances and these
additional studies are not expected to significantly change its risk
assessment.
B. Toxicological Endpoints
1. Acute toxicity. EPA has established an NOEL of 2.0 mg/kg/day
through the dietary route in rat and rabbit developmental studies. This
NOEL is based on behavioral and central nervous system clinical signs.
A MOE of 100 is required.
2. Short - and intermediate - term toxicity. To assess risk from
(nonfood) short and intermediate term dermal exposure, EPA has
established a NOEL of 2.0 mg/kg/day from the rat and rabbit
developmental studies. No dermal penetration/absorption study is
available and the NOEL incorporates a 25% dermal absorption based on
the weight-of-evidence available for structurally related pyrethroids.
This NOEL is based on behavioral and central nervous system clinical
signs. For exposure via inhalation the Agency used an oral NOEL of 2.0
mg/kg/day and assumed 100% absorption (based on the 2 mg/kg/day used
for the dermal risk assessment since no appropriate inhalation toxicity
studies are available).
3. Chronic toxicity. EPA has established the RfD for esvenvalerate
at 0.02 mg/kg/day. This RfD is based on a NOEL of 2.0 mg/kg/day through
the dietary exposure route in developmental study in rat. The NOEL is
based on behavioral changes and clinical signs of neurotoxicity. This
RfD is based on an uncertainty factor of 100.
4. Carcinogenicity. Esfenvalerate is classified as a Group E. There
is no evidence of carcinogenicity in either rats or mice.
C. Exposures and Risks
1. From food and feed uses. Tolerances have been established (40
CFR 180.379) for the residues of fenvalerate, in or on a variety of raw
agricultural commodities.
EPA notes that the acute dietary risk assessments used Monte Carlo
modeling (in accordance with Tier 3 of EPA June 1996 ``Acute Dietary
Exposure Assessment'' guidance document) incorporating anticipated
residues and percent of crop treated refinements. Field trial data and
FDA monitoring data were used to generate anticipated residues or
residue distribution for Monte Carlo analyses. Chronic dietary risk
assessments used anticipated residues and percent crop treated
refinements. Risk assessments were conducted by EPA to assess dietary
exposures and risks from esfenvalerate as follows:
i. Acute exposure and risk. Acute dietary risk assessments are
performed for a food-use pesticide if a toxicological
[[Page 63023]]
study has indicated the possibility of an effect of concern occurring
as a result of a one day or single exposure. The NOEL used for the
acute dietary exposure was 2.0 mg/kg/day. Potential acute exposures
from food commodities were estimated using a Tier 3 acute dietary risk
assessment (Monte Carlo Analysis). The MOE's (99.9th percentile) for
the US population based on an acute dietary exposure of 0.011717 mg/kg/
day are 171. For children 1-6 years old (most highly exposed
population) the MOE's based on an acute dietary exposure of 0.019445
mg/kg/day are 103. The Agency has no cause for concern if total acute
exposure calculated for the 99.9th percentile yields an MOE of 100 or
larger.
ii. Chronic exposure and risk. Potential chronic exposures were
estimated using NOVIGEN's DEEM (Dietary Exposure Evaluation Model). The
RfD used for the chronic dietary analysis is 0.02 mg/kg/day. Using
tolerance values and anticipated residues discussed above the risk
assessment resulted in use of 1.9% of the RfD for the general US
population and 4.6% of the RfD for children 1-6 years.
Section 408(b)(2)(E) authorizes EPA to consider available data and
information on the anticipated residue levels of pesticide residues in
food and the actual levels of pesticide chemicals that have been
measured in food. If EPA relies on such information, EPA must require
that data be provided five years after the tolerance is established,
modified, or left in effect, demonstrating that the levels in food are
not above the levels anticipated. Following the initial data
submission, EPA is authorized to require similar data on a time frame
it deems appropriate. Section 408(b)(2)(F) allows the Agency to use
data on the actual percent of crop treated when establishing a
tolerance only where the Agency can make the following findings: (1)
that the data used are reliable and provide a valid basis for showing
the percentage of food derived from a crop that is likely to contain
residues; (2) that the exposure estimate does not underestimate the
exposure for any significant subpopulation and; (3) where data on
regional pesticide use and food consumption are available, that the
exposure estimate does not understate exposure for any regional
population. In addition, the Agency must provide for periodic
evaluation of any estimates used.
The percent of crop treated estimates for esfenvalerate were
derived from federal and market survey data. EPA considers these data
reliable. A range of estimates are supplied by this data and the upper
end of this range was used for the exposure assessment. By using this
upper end estimate of percent crop treated, the Agency is reasonable
certain that exposure is not underestimated for any significant
subpopulation. Further, regional consumption information is taken into
account through EPA's computer-based model for evaluating the exposure
of significant subpopulations including several regional groups. Review
of this regional data allows the Agency to be reasonably certain that
no regional population is exposed to residue levels higher than those
estimated by the Agency. To meet the requirement for data on
anticipated residues, EPA will issue a Data Call-In (DCI) notice
pursuant to FFDCA section 408(f) requiring submission of data on
anticipated residues in conjunction with approval of the registration
under the FIFRA.
2. From drinking water. Esfenvalerate is immobile in soil and will
not leach into groundwater. Additionally, due to their insolubility and
lipophilic nature, any residues in surface water will rapidly and
tightly bind to soil particles and remain with sediment. A screening
evaluation of leaching potential of a typical potential of a typical
pyrethroid was conducted using EPA's Pesticide Root Zone Model (PRZM1).
Based on this screening assessment, the potential concentrations of a
pyrethroid in ground water at depths of 1 and 2 meters are essentially
zero (much less than 0.001 parts per billion). Therefore, EPA concludes
that residues are not expected to occur in drinking water.
i. Acute exposure and risk. Acute drinking water exposure is
estimated for the US population to be 0.000039 mg/kg/day with an MOE of
51,743. For Non-nursing infants less than 1 year old the exposure is
0.000074 with and MOE of 27,042.
ii. Chronic exposure and risk. Chronic drinking water exposure is
estimated for the US population to be 0.000001 mg/kg/day and for the
non-nursing infants 0.000005 mg/kg/day. Zero percent of the RfD is
occupied by both population groups.
3. From non-dietary exposure. Esfenvalerate is registered for non-
crop uses including spray treatments in and around commercial and
residential areas, treatments for control of ectoparasites on pets,
home care products including foggers, pressurized sprays, crack and
crevice treatments, lawn and garden sprays, and pet and pet bedding
sprays. For the non-agricultural products, the very low amounts of
active ingredient they contain, combined with the low vapor pressure
(1.5 x 10-9 mm Mercury at 25 deg. C.) and low dermal
penetration, would result in minimal inhalation and dermal exposure.
Individual non-dietary risk exposure analyses were conducted using
a flea infestation scenario that included pet spray, carpet and room
treatment, and lawn care, respectively.
Short- and intermediate-term exposure and risk. The total aggregate
non-dietary exposure including lawn, carpet, and pet uses (mg/kg/day)
are: 0.000023 for adults; 0.00129 for children aged 1-6 years; and
0.00138 for infants less than one year old.
It can be concluded that the potential non-dietary exposure for
esfenvalerate are associated with substantial margins of safety.
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.'' The Agency believes that ``available
information'' in this context might include not only toxicity,
chemistry, and exposure data, but also scientific policies and
methodologies for understanding common mechanisms of toxicity and
conducting cumulative risk assessments. For most pesticides, although
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 with any other substances, EPA does not at this
time have the methodologies to resolve the complex scientific issues
concerning common mechanism of toxicity in a meaningful way. EPA has
begun a pilot process to study this issue further through the
examination of particular classes of pesticides. The Agency hopes that
the results of this pilot process will increase the Agency's scientific
understanding of this question such that EPA will be able to develop
and apply scientific principles for better determining which chemicals
have a common mechanism of toxicity and evaluating the cumulative
effects of such chemicals. The Agency anticipates, however, that even
as its understanding of the science of common mechanisms increases,
decisions on specific classes of chemicals will be heavily dependent on
chemical specific data, much of which may not be presently available.
Although at present the Agency does not know how to apply the
information in its files concerning common mechanism issues to most
risk
[[Page 63024]]
assessments, there are pesticides as to which the common mechanism
issues can be resolved. These pesticides include pesticides that are
toxicologically dissimilar to existing chemical substances (in which
case the Agency can conclude that it is unlikely that a pesticide
shares a common mechanism of activity with other substances) and
pesticides that produce a common toxic metabolite (in which case common
mechanism of activity will be assumed).
Although esfenvalerate is similar to other members of the synthetic
pyrethroid class of insecticides, EPA does not have, at this time,
available data to determine whether esfenvalerate has a common method
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, esfenvalerate 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 esfenvalerate has a common
mechanism of toxicity with other substances.
D. Aggregate Risks and Determination of Safety for U.S. Population
1. Acute risk. The acute aggregate risk assessment takes into
account exposure from food and drinking water. The potential acute
exposure from food and drinking water to the overall US population
provides an acute dietary exposure of 0.011756 mg/kg/day with an MOE of
170. This acute dietary exposure estimate is considered conservative,
using anticipated residue values and percent crop-treated data in
conjunction with Monte Carlo analysis.
2. Chronic risk. Using the ARC exposure assumptions described
above, EPA has concluded that aggregate exposure to esfenvalerate from
food and drinking water will utilize 1.9% of the RfD for the U.S.
population based on a dietary exposure of 0.000377 mg/kg/day. The major
identifiable subgroup with the highest aggregate exposure are children
1 - 6 years old (discussed below). EPA generally has no concern for
exposures below 100% of the RfD because the Rfd represents the level at
or below which daily aggregate dietary exposure over a lifetime will
not pose appreciable risks to human health.
3. Short- and intermediate-term risk. Short- and intermediate-term
aggregate exposure takes into account chronic dietary food and water
(considered to be a background exposure level) plus indoor and outdoor
residential exposure. The potential short- and intermediate-term
aggregate risk for the U.S. population is an exposure of 0.0082 mg/kg/
day with an MOE of 244.
EPA concludes that there is reasonable certainty that no harm will
result from aggregate exposure to esfenvalerate residues.
E. Aggregate Cancer Risk for U.S. Population
Esfenvalerate is classified as a Group E carcinogen - no evidence
of carcinogenicity in rats or mice. Therefore, a carcinogenicity risk
analysis is not required.
F. Aggregate Risks and Determination of Safety for Infants and Children
1. Safety factor for infants and children.--i. In general. In
assessing the potential for additional sensitivity of infants and
children to residues of esfenvalerate, EPA considered data from
developmental toxicity studies in the rat and rabbit and a two-
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 one or both parents. Reproduction studies provide information
relating to effects from exposure to the pesticide on the reproductive
capability of mating animals and data on systemic toxicity.
FFDCA section 408 provides that EPA shall apply an additional
tenfold margin of safety for infants and children in the case of
threshold effects to account for pre-and post-natal toxicity and the
completeness of the database unless EPA determines that a different
margin of safety will be safe for infants and children. Margins of
safety are incorporated into EPA risk assessments either directly
through use of a MOE analysis or through using uncertainty (safety)
factors in calculating a dose level that poses no appreciable risk to
humans. EPA believes that reliable data support using the standard MOE
and uncertainty factor (usually 100 for combined inter- and intra-
species variability) and not the additional tenfold MOE/uncertainty
factor when EPA has a complete data base under existing guidelines and
when the severity of the effect in infants or children or the potency
or unusual toxic properties of a compound do not raise concerns
regarding the adequacy of the standard MOE/safety factor.
ii. Developmental toxicity studies. In both prenatal developmental
toxicity studies in rats and rabbits, there is no evidence of
developmental toxicity at a dose up to 20 mg/kg/day. Maternal clinical
neurotoxicity (based on behavioral and central nervous system clinical
signs) was observed at a dose as low as 2.5 or 3.0 mg/kg/day for rats
and rabbits respectively. The maternal NOEL was 2.0 mg/kg/day.
iii. Reproductive toxicity study. In the two-generation
reproduction study in rats, offspring toxicity was observed only at
dietary levels which were also found to be toxic to parental animals.
The LOEL was 5.1 mg/kg/day based on decrease in mean body weights of
females and increased incidence of dermal lesions. The NOEL for
parental systemic toxicity was not determined. Effects on the
offspring, including decreased pup weights in both generations during
early and/or late lactation, decreased litter size, and increased
incidence of subcutaneous hemorrhage, were observed at dietary levels
of 6.70 mg/kg/day and above, with a NOEL of 5.1 mg/kg/day.
iv. Pre- and post-natal sensitivity. There is no evidence of
additional sensitivity to young rats or rabbits following pre- or
postnatal exposure to esfenvalerate.
v. Conclusion. Based on the above, EPA concludes that reliable data
support use of the standard 100-fold uncertainty factor, and that an
additional uncertainty factor is not needed to protect the safety of
infants and children.
2. Acute risk. The potential acute exposure from food and drinking
water to the most sensitive population subgroup, children 1-6 years old
is 0.019477 mg/kg/day with an MOE of 103. The Agency has no cause for
concern if total acute exposure calculated for the 99.9th percentile
yields a MOE of 100 or larger.
3. Chronic risk. Using the conservative exposure assumptions
described above, EPA has concluded that aggregate exposure to
esfenvalerate from food and drinking water will utilize 4.6% of the RfD
for children 1-6 years old, the most sensitive population subgroup
based on a dietary exposure of 0.000912 mg/kg/day. EPA generally has no
concern for exposures below 100% of the RfD because the RfD represents
the level at or below which daily aggregate dietary exposure over a
lifetime will not pose appreciable risks to human health.
4. Short- or intermediate-term risk. EPA has concluded that
potential short- or intermediate -term aggregate exposure of
esfenvalerate from chronic dietary food and water (considered to be a
background exposure level) plus indoor and outdoor residential exposure
to children (1-6 years old) is 0.0113 mg/kg/day with an MOE of 177. For
infants
[[Page 63025]]
(less than 1 year old) the exposure is 0.0098 mg/kg/day with an MOE of
204.
EPA concludes that there is a reasonable certainty that no harm
will result to infants and children from aggregate exposure to
esfenvalerate residues.
5. Special docket. The complete acute and chronic exposure analyses
(including dietary, non-dietary, drinking water, and residential
exposure, and analysis of exposure to infants and children) used for
risk assessment purposes can be found in the Special Docket for the
FQPA under the title ``Risk Assessment for Extension of Tolerances for
Synthetic Pyrethroids.'' Further explanation regarding EPA's decision
regarding the additional safety factor can also be found in the Special
Docket.
G. Endocrine Disrupter Effects
EPA is required to develop a screening program to determine whether
certain substances (including all pesticides and inerts) ``may have an
effect in humans that is similar to an effect produced by a naturally
occurring estrogen, or such other endocrine effect...'' The Agency is
currently working with interested stakeholders, including other
government agencies, public interest groups, industry and research
scientists in developing a screening and testing program and a priority
setting scheme to implement this program. Congress has allowed 3 years
from the passage of FQPA (August 3, 1999) to implement this program. At
that time, EPA may require further testing of this active ingredient
and end use products for endocrine disrupter effects.
III. Other Considerations
A. Metabolism in Plants and Animals
The nature of the residue in plants and animals is adequately
defined. EPA has concluded that the qualitative nature of the residue
is the same for both fenvalerate and esfenvalerate. The residue to be
regulated is fenvalerate: the S,S; R,S; S,R; and R,R isomers.
B. Analytical Enforcement Methodology
There is a practical analytical method utilizing electron-capture
gas chromatography with nitrogen phosphorous detection available for
enforcement with a limit of detection that allows monitoring food with
residues at or above tolerance levels. The limit of detection for
updated method is the same as that of the current PAM II, which is 0.01
ppm.
C. Magnitude of Residues
Tolerances are based on the sum of all isomers of fenvalerate.
Fenvalerate is a racemic mixture of four isomers (about 25% each). This
product was registered as Pydrin . However since 1992, an S,S-isomer
enriched formulation, Asana (esfenvalerate), has been the
only fenvalerate formulation sold in the U.S. for agricultural use.
since the S,S-isomer is the insecticidally active isomer, the use rate
for Asanais four times lower than that for Pydrin.
A petition is pending (PP 4F4329), to convert tolerances (still to be
expressed as the sum of all isomers) based on the use rates for
Asana. Bridging residue studies have shown
Asanaresidues to be 3-4 times lower than Pydrin
residues.
EPA has established a tolerance of 0.2 ppm for fenvalerate on
cottonseed. Magnitude of residue and processing studies support this
tolerance.
D. International Residue Limits
Codex maximum residue levels (MRL's) have been established for
residues of fenvalerate on a number of crops that also have U.S.
tolerances. The Codex MRL for fenvalerate on cottonseed is in harmony
with the U.S. tolerance.
As indicated in the Notice of Filing, there are small differences
between the section 408 tolerances and the Codex MRL values for
specific commodities. These differences could be caused by differences
in methods to establish tolerances, calculate animal feed dietary
exposure, and as a result of different agricultural practices. EPA will
specifically address these differences when the pesticides are
reregistered and the tolerances made permanent.
IV. Conclusion
Therefore, the tolerances are established for residues of
fenvalerate in cottonseed at 0.2 ppm.
V. 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
new section 408(e) and (l)(6) as was provided in the old section 408
and in section 4-. However, the period for filing objections is 60
days, rather than 30 days. EPA currently has procedural regulations
which govern the submission of objections and hearing requests. These
regulations will require some modification to reflect the new law.
However, until those modifications can be made, EPA will continue to
use those procedural regulations with appropriate adjustments to
reflect the new law.
Any person may, by January 26, 1998 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 may be disclosed publicly
by EPA without prior notice.
VI. Public Record and Electronic Submissions
EPA has established a record for this rulemaking under docket
control number [OPP-300575] (including any comments and data submitted
electronically). A public version of this record, including printed,
paper versions of electronic comments, which does not include any
information claimed as CBI, is available for inspection from 8:30 a.m.
to 4 p.m., Monday through Friday, excluding legal holidays. The public
record is located in Room 1132 of the Public Information and Records
Integrity Branch,
[[Page 63026]]
Information Resources and Services division (7502C), Office of
Pesticide Programs, Environmental Protection Agency, Crystal Mall #2,
1921 Jefferson Davis Highway, Arlington, VA.
Electronic comments may 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.
The official record for this rulemaking, as well as the public
version, as described above will be kept in paper form. Accordingly,
EPA will transfer any copies of objections and hearing requests
received electronically into printed, paper form as they are received
and will place the paper copies in the official rulemaking record which
will also include all comments submitted directly in writing. The
official rulemaking record is the paper record maintained at the
Virginia address in ``ADDRESSES'' at the beginning of this document.
VII. Regulatory Assessment Requirements
This final rule removes time limitations for 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) (Pub. L. 104-4). Nor does it require any prior consultation as
specified by Executive Order 12875, entitled Enhancing the
Intergovernmental Partnership (58 FR 58093, October 28, 1993), or
special considerations as required by Executive Order 12898, entitled
Federal Actions to Address Environmental Justice in Minority
Populations and Low-Income Populations (59 FR 7629, February 16, 1994),
or require OMB review in accordance with Executive Order 13045,
entitled Protection of Children from Environmental Health Risks and
safety Risks (62 FR 19885, April 23, 1997).
In addition, since these tolerances and exemptions that are
established on the basis of a petition under FFDCA section 408(d), such
as the tolerance/exemption in this final rule, do not require the
issuance of a proposed rule, the requirements of the Regulatory
Flexibility Act (RFA) (5 U.S.C. 601 et seq.) do not apply.
Nevertheless, the Agency has previously assessed whether establishing
tolerances, exemptions from tolerances, raising tolerance levels or
expanding exemptions might adversely impact small entities and
concluded, as a generic matter, that there is no adverse economic
impact. The factual basis for the Agency's generic certification for
tolerance actions published on May 4, 1981 (46 FR 24950) and was
provided to the Chief counsel for Advocacy of the Small Business
Administration.
VIII. Submission to Congress and the General Accounting Office
Under 5 U.S.C. 801(a)(1)(A), as added by the Small Business
Regulatory Enforcement Fairness Act of 1996, the Agency has 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 this rule in
today's Federal Register. This is not a ``major rule'' as defined by 5
U.S.C. 804(2).
List of Subjects
40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and record
keeping requirements.
40 CFR Part 185
Environmental protection, Food and additives, Pesticides and pest.
40 CFR Part 186
Environmental protection, Animal feeds, Pesticides and pest.
Dated: November 14, 1997.
James Jones,
Acting Director, Registration Divisision, Office of Pesticide Programs.
Therefore, 40 CFR Chapter I is amended as follows:
PART 180 -- [AMENDED]
1. In part 180:
a. The authority citation for part 180 continues to read as
follows:
Authority : 21 U.S.C. 346a and 371.
b. Section 180.379 is amended as follows:
i. By adding a heading to paragraph (a), designating the text
following the heading as paragraph (a)(1) and by revising the entry for
cottonseed in the table to newly designated paragraph (a)(1).
ii. By redesignating paragraph (b) as paragraph (c).
iii. By adding a paragraph heading to newly designated paragraph
(c).
iv. By adding and reserving new paragraph (b) and (d) with
paragraph headings.
The additions and amendments to Sec. 180.379 read as follows:
Sec. 180.379 Cyano-(3-phenoxyphenyl)methyl-4-chloro--(1-
methylethyl) benzeneacetate; tolerances for residues.
(a) General. (1) Tolerances are established for residues of the
insecticide Cyano-(3-phenoxyphenyl)methyl-4-chloro--(1-
methylethyl) benzeneacetate in or on the following raw agricultural
commodities:
------------------------------------------------------------------------
Commodity Parts per million
------------------------------------------------------------------------
* * * * *
cottonseed................................ 0.2
* * * * *
------------------------------------------------------------------------
* * * * *
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. * * *
(d) Indirect or inadvertent residues. [Reserved]
PART 185 -- [AMENDED]
2. In part 185:
a. The authority citation for part 185 continues to read as
follows:
Authority : 21 U.S.C. 346a and 348.
Sec. 185.1300 [Removed]
b. Section 185.1300 is amended by transferring paragraph (a)
introductory text, (a)(1), (a)(2), (a)(3), and (a)(4) to Sec. 180.379
and redesignating them as paragraphs (a)(2), (a)(2)(i), (a)(2)(ii),
(a)(2)(iii) and (a)(2)(iv); the remainder of Sec. 185.1300 is removed.
PART 186 -- [AMENDED]
3. In part 186:
a. The authority citation for part 186 continues to read as
follows:
Authority : 21 U.S.C. 342, 348 and 701.
[[Page 63027]]
Sec. 186.1300 [Removed]
b. Section 186.1300 is amended by transferring the text to
Sec. 180.379 and redesignating it as paragraph (a)(3) and Sec. 186.1300
is removed.
[FR Doc. 97-31099 Filed 11-25-97; 8:45 am]
BILLING CODE 6560-50-F