[Federal Register Volume 62, Number 56 (Monday, March 24, 1997)]
[Rules and Regulations]
[Pages 13833-13839]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: X97-20324]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180, 185 and 186
[OPP-300465; FRL-5597-7]
RIN No. 2070-AB78
Avermectin B1 and Its Delta-8,9-Isomer; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final Rule.
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SUMMARY: This document establishes time-limited tolerances for residues
of the insecticide avermectin and its delta-8,9-isomers in or on the
following raw agricultural commodities: cottonseed, citrus, dried hops,
potatoes, meat and meat byproducts, milk and processed food/feed
commodities. Merck Co., Inc. submitted a petition to EPA under the
Federal Food, Drug and Cosmetic Act as amended by the Food Quality
Protection Act of 1996 requesting the tolerances.
DATES: This regulation becomes effective March 24, 1997. The entries in
the table expire on September 1, 1999. Objections and requests for
hearings must be received by May 23, 1997.
ADDRESSES: Written objections and hearing requests identified by the
docket control number [OPP-300465/PP 7F3500; 8F3592; 5F4508; 4E4419 and
FAP 8H5660], may be submitted to: Hearing Clerk (1900), Environmental
Protection Agency, Rm. M3708, 401 M St. SW., Washington, DC 20460. A
copy of any objections and hearing requests filed with the Hearing
Clerk should be identified by the docket control number and submitted
to: Public Response and Program Resources Branch, Field Operations
Division (7506C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St. SW., Washington, DC 20460. In person,
bring copy of objections and hearing requests to Rm 1132, CM#2, 1921
Jefferson-Davis Hwy, Arlington, VA. Fees accompanying objections shall
be labeled ``Tolerance Petition Fees'' and forwarded to: EPA
Headquarters Accounting Operations Branch, OPP(Tolerance Fees), P.O.
Box 360277M, Pittsburgh, PA 15251. An electronic copy of objections and
hearing requests filed with the Hearing Clerk may be submitted to OPP
by sending electronic mail (e-mail) to: [email protected].
Copies of electronic objections and hearing requests must be
submitted as an ASCII file avoiding 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 5.1 file format
or ASCII file format. All copies of electronic objections and hearing
requests must be identified by the docket control number [OPP-300465/PP
7F3500; 8F3592; 5F4508; 4E4419 and FAP 8H5660]]. No Confidential
Business Information (CBI) should be submitted through e-mail. Copies
of electronic objections and hearing requests on this rule may be filed
online at many Federal Depository Libraries. Additional information on
electronic submission can be found below in this document.
FOR FURTHER INFORMATION CONTACT: By mail: George LaRocca, Product
Manager (PM) 13, Registration Division (7505C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St, SW., Washington,
DC 20460. Office location, telephone number and e-mail address: Rm.
204, CM #2, 1921 Jefferson-Davis Hwy, Arlington, VA 22202, (703) 305-
6100; e-mail: [email protected].
SUPPLEMENTARY INFORMATION: In the Federal Register dated May 8, 1996
(61 FR 20745), EPA proposed to renew time-limited tolerances for the
insecticide avermectin and its delta-8,9-isomer (avermectin) in or on
cottonseed at 0.005 parts per million (ppm); citrus, whole fruit, at
0.02 ppm; citrus oil, at 0.1 ppm; citrus dried pulp, at 0.1 ppm;
cattle, meat, at 0.02 ppm; cattle, meat byproducts, at 0.02 ppm;
cattle, fat, at 0.015 ppm; milk, at 0.005 ppm; and hops, dried, at 0.5
ppm. These tolerances were originally established in response to
pesticide petitions 7F3500, 8F3592, 4E4419, and food additive petition
8H5550 and have since expired. They were time-limited due to aquatic
pesticide exposure issues. The Agency was unable to publish a final
rule prior to the enactment of Food Quality Protection Act of 1996.
Because of new procedures under FQPA, Merck was required to submit a
new notice of filing requesting reissuance of these tolerances in
compliance with FQPA.
In the Federal Register dated December 10, 1996 (61 FR 65043), EPA
issued a notice of filing which announced that Merck had filed a
request to amend 40 CFR 180.449 by
[[Page 13834]]
reissuing the regulations that established tolerances for residues in
or on the raw agricultural commodities cottonseed at 0.005 ppm; citrus,
whole fruit at 0.02 ppm; citrus oil at 0.1 ppm; citrus dried pulp at
0.1 ppm; cattle, meat at 0.02 ppm; cattle, meat byproducts at 0.02 ppm;
cattle fat at 0.015 ppm; milk at 0.005 ppm and hops, dried at 0.5 ppm
and bring them into compliance with the FQPA. The notice contained a
summary of the petitions and conclusions and argument in support of the
petitioner's conclusion that the petition complied with FQPA. Also
included in the notice was a request to establish permanent tolerance
in/on the raw agricultural commodity potatoes at 0.005 ppm.
Based on review of new residue data for dried hops (PP 5E4566), EPA
concluded that 0.2 ppm, rather than 0.05 ppm, is the more appropriate
tolerance level and therefore the subject petition is amended
accordingly.
There were no comments received in response to the notices of
filing.
I. Background and Statutory Authority
The Food Quality Protection Act of 1996 (FQPA) (Pub. L. 104-170)
was signed into law August 3, 1996. FQPA amends both the Federal Food,
Drug, and Cosmetic Act (FFDCA), 21 U.S.C. et seq., and the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA), 7 U.S.C. 136 et
seq. The FQPA amendments went into effect immediately. Among other
things, FQPA amends FFDCA to bring all EPA pesticide tolerance-setting
activities under a new section 408 with a new safety standard and new
procedures.
New section 408(b)(2)(A)(i) allows EPA to establish a tolerance
(the legal limit for a pesticide chemical residue in or on a food) only
if EPA determines that the tolerance is safe. Section 408(b)(2)(A)(ii)
defines safe to mean that there is a reasonable certainty that no harm
will result for 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, 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 aggregated exposure to
the pesticide chemical. Section 408 (b)(2)(D) specified factors EPA is
to consider in establishing a tolerance. Section 408 (b)(3) requires
EPA to determine that there is a practical method for detecting and
measuring levels of the pesticide chemical residue in or on food and
that the tolerance be set at a level at or above the limit of detection
of the designated method. Section 408 (b)(4) requires EPA to determine
whether a maximum residue level has been established for the pesticide
chemical by the Codex Alimentarius Commission. If so, and EPA does not
propose to adopt that level, EPA must publish for public comment a
notice explaining the reasons for departing from the Codex level.
II. Risk Assessment and Statutory Findings
EPA performs a number of analyses to determine the risks from
aggregated exposure to pesticide residues. First, EPA determines the
toxicity of pesticides based primarily on toxicological studies using
laboratory animals. These studies may address adverse health effects,
including (but not limited to) reproductive effects, developmental
toxicity, toxicity to the nervous system, and carcinogenicity. For many
of these studies, a dose response relationship can be determined, which
provides a dose that causes adverse effects (threshold effects) and
doses causing no observed effects (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 aggregated exposure over a lifetime will not pose an
appreciable risk 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.
Lifetime feeding studies in two species of laboratory animals are
conducted to screen pesticides for cancer effects. When evidence of
increased cancer is noted in these studies, the Agency conducts a
weight of the evidence review of all relevant toxicological data
including short term and mutagenicity studies and structure activity
relationship. Once a pesticide has been classified as a potential human
carcinogen, different types of risk assessments (e.g., linear low dose
extrapolations or margin of exposure (MOE) calculations based on the
appropriate NOEL) will be carried out based on the nature of the
carcinogenic response and the Agency's knowledge of its mode of action.
In examining aggregated exposure, FQPA requires that EPA take into
account available and reliable information concerning exposure from the
pesticide residue in the food in question, residues in other foods for
which there are tolerances, and other non-occupational exposures, such
as where residues leach into groundwater or surface water that is
consumed as drinking water. 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 residues level. The Theoretical Maximum
Residue Contribution (TMRC) is an estimate of the level of residues
consumed daily if each food item contained pesticide residues equal to
the tolerance. The TMRC is a worst case estimate since it is based on
the assumptions that food contains pesticide residues at the tolerance
level and that 100 percent of the crop is treated by pesticides that
have established tolerances. If the TMRC exceeds the RfD or poses a
lifetime cancer risk that is greater than approximately one in a
million, EPA attempts to derive a more accurate exposure estimate for
the pesticide by evaluating additional types of information
(anticipated residue data and/or percent crop treated data) which show,
generally, that pesticide residues in most foods when they are eaten
are well below established tolerances.
Consistent with sections 408(b)(2)(C) and (D), EPA has reviewed the
available scientific data and other relevant information in support of
this action. EPA has also assessed the toxicology data base for
avermectin and its delta-8,9-isomers in its evaluation of applications
for registration on cotton, citrus, hops, and potatoes. EPA has
sufficient data to assess the hazards of avermectin and its delta-8,9-
isomers and to make a determination on aggregate exposure, consistent
with section 408(b)(2), for granting time-limited tolerances for
residues of avermectin
[[Page 13835]]
and its delta-8,9-isomers on cottonseed at 0.005 ppm; citrus, whole
fruit at 0.02 ppm; citrus oil at 0.1 ppm; citrus dried pulp at 0.1 ppm;
cattle, meat at 0.02 ppm; cattle, meat byproducts at 0.02 ppm; cattle
fat at 0.015 ppm; milk at 0.005 ppm, potatoes at 0.005 ppm and hops at
0.2 ppm.
The data submitted in the petitions and other relevant material
have been evaluated. The toxicology data listed below were considered
in support of these tolerances.
A. Toxicology Data Base
1. Acute studies. A battery of acute toxicity studies placing
technical avermectin in Toxicity Categories I and III.
2. Subchronic studies. i. A rat 8-week feeding study with a NOEL of
1.4 milligrams per kilograms per day (mg/kg/day) based upon tremors.
ii. A rat 14-week oral toxicity study with a NOEL of 0.4 mg/kg/day,
the highest dose tested.
iii. A dog 12-week feeding study with a NOEL of 0.5 mg/kg/day based
upon mydriasis.
iv. A dog 18-week oral study with a NOEL of 0.25 mg/kg/day based
upon mortality.
v. A CD-1 mouse 84-day feeding study with a NOEL of 4 mg/kg/day
based upon decreased body weights.
3. Chronic studies. i. A rat 105-week oncogenicity feeding study,
negative for oncogenicity with dose levels up to and including 2.0 mg/
kg/day, the highest dose tested (HDT), with a NOEL of 1.5 mg/kg/day
based upon tremors.
ii. A CD-1 mouse 94-week oncogenicity feeding study, negative for
oncogenicity at dose levels up to and including 8 mg/kg/day (HDT), with
a NOEL of 4 mg/kg/day based upon decreased body weights.
iii. A dog 53-week chronic feeding study, with a NOEL of 0.25 mg/
kg/day based upon mydriasis.
4. Developmental toxicity studies. i. An oral teratology study in
the CF-1 mouse with a maternal NOEL of 0.05 mg/kg/day based upon
decreased body weights and tremors. The fetal NOEL was 0.20 mg/kg/day
based upon cleft palates.
ii. An oral teratology study with the delta 8,9-isomer in CF-1 mice
with a maternal NOEL of 0.10 mg/kg/day based upon decreased body
weights. The fetal NOEL was 0.06 mg/kg/day based upon cleft palate.
iii. An oral teratology study in rabbits with a maternal NOEL of
1.0 mg/kg/day based upon decreased body weights and tremors at the
lowest observed effect level (LOEL) of 2.0 mg/kg/day. The fetal NOEL
was 1.0 mg/kg/day based upon clubbed feet and delayed ossification of
sternebrae, metacarpels and phalanges at the lowest effect level (LEL)
of 2.0 mg/kg/day.
iv. An oral teratology study in rats with a maternal and fetal NOEL
at 1.6 mg/kg/day (HDT).
5. Reproductive effects study. i. A 2-generation study in rats with
a NOEL of 0.12 mg/kg/day in pups based upon retinal folds, decreased
body weight, and mortality at the LEL of 0.4 mg/kg/day. The NOELs for
systemic and reproductive toxicity were 0.4 mg/kg/day (HDT).
6. Mutagenicity studies. i. The Ames assays conducted with and
without metabolic activation were both negative.
ii. The V-79 mammalian cell mutagenesis assays conducted with and
without metabolic activation did not produce mutations. In an alkaline
elution/rat hepatocyte assay, abamectin was found to induce single
strand DNA breaks without significant toxicity in rat hepatocytes
treated in vitro at doses greater than 0.2 millimole (mM). This in
vitro dose of 0.2 mM is biologically unobtainable in vivo, due to the
toxicity of the compound. However, at these potentially lethal doses,
in vivo treatment did not induce DNA single strand breaks in
hepatocytes. In the mouse bone marrow assay, abamectin was not found to
induce chromosomal damage.
B. Toxicological Profile
1. Dietary risks--i. Acute toxicity. Because of the developmental
effects seen in animal studies, EPA used the mouse developmental
toxicity study (with a pup NOEL of 0.06 mg/kg/day for developmental
toxicity for the delta-8,9-isomer) to assess acute dietary exposure and
determine a MOE for the overall U.S. population and certain subgroups.
Since the toxicological endpoints pertain to developmental toxicity,
the risk assessment evaluated acute dietary risk to females 13+ years
old, the subgroup which most closely approximates women of child
bearing ages. For purposes of these time-limited tolerances, an MOE of
300 is considered necessary to be adequately protective for dietary
exposure.
(Note: EPA notes that the petitioner has used a NOEL of 0.05 mg/
kg/day in its assessment. EPA currently considers the appropriate
NOEL to be 0.06 mg/kg/day; therefore the petitioner's MOE values
have been corrected to reflect this higher NOEL.)
ii. Chronic risk. Based on the available chronic toxicity data, EPA
has established the Reference Dose (RfD) for avermectin and its delta-
8,9-isomer at 0.0004 mg/kg/day based on a 2-generation rat reproduction
study with a NOEL of 0.12 mg/kg/day and an uncertainty factor of 300.
In addition to the uncertainty factor of 100 for inter-and intra-
species variations, a modifying factor (MF) of 3 was used for a total
uncertainty factor of 300. The MF was used because of the effects (pup
deaths) and the steep dose-response curve. At the LEL of 0.40 mg/kg/
day, there was decreased pup body weight and viability during lactation
as well as an increase of incidence of retinal rosettes in F2b
weanlings.
iii. Carcinogenicity. Using EPA Guidelines for Carcinogen Risk
Assessment published September 24, 1986 (51 FR 3392), EPA has
classified avermectin as Group ``E'' for carcinogenicity (no evidence
of carcinogenicity) based on the results of a carcinogenicity studies
in two species. Infants and Children: EPA has concluded that avermectin
and related compounds induce developmental toxicity in several species.
To assess the potential for additional sensitivity of infants and
children to residues of avermectin, EPA used the rat 2-generation
reproduction study NOEL of 0.12 mg/kg/day based upon toxicity observed
in nursing pups and the mouse oral teratology study NOEL of 0.06 mg/kg/
day based upon cleft palate in developing fetuses.
2. Non-dietary risks-- i. Short-and intermediate term occupational
or residential dermal or inhalation risks. EPA used the developmental
NOEL of 0.2 mg/kg/day from the oral developmental toxicity study of CF-
1 mice. At the LEL of 0.4 mg/kg/day, there was an increased incidence
of cleft palate.
ii. Chronic occupational or residential risk. For chronic MOE
calculations, EPA used the developmental NOEL of 0.12 mg/kg/day from a
2-generation rat reproduction study. At a LEL of 0.4 mg/kg/day, there
was increased pup deaths during lactation decreased pup body weight and
increased incidence of retinal rosettes.
iii. Dermal absorption. EPA used a value of 1% based on a monkey
dermal absorption study.
C. Aggregate Exposure
1. From food and feed uses. The primary source for human exposure
to avermectin will be from ingestion of both raw and processed
agricultural commodities proposed in the December 10, 1996 Notice of
Filing cited above and from the commodities in 40 CFR 180.449, 185.300
and 186.300.
Any secondary residues occurring in cattle meat, meat byproduct,
milk and fat from the addition of the feed items potato culls and
processed potato waste
[[Page 13836]]
will be covered by the existing tolerances for these commodities. There
is no reasonable expectation of finite residues in poultry and swine,
therefore no tolerances are necessary at this time. Although data
indicates avermectin residues accumulate in some rotational crops at
levels up to 10 to 12 ppb, the residue was due to polar degradates that
are of little toxicological concern. Thus, it is unlikely that residues
will accumulate in rotational crops.
The dietary risk assessment will be reevaluated with respect to
secondary residues in ruminant tissues and milk upon submission and
review of field trail data for cotton gin-byproducts.
2. From potable (drinking) water use. There is no established
Maximum Concentration Level for residues of avermectin in drinking
water. No Health Advisory Levels for avermectin in drinking water have
been established. Because the Agency lacks specific water related
exposure data for most pesticides, EPA has commenced and nearly
completed a process to identify a reasonable yet conservative bounding
figure for the potential contribution of water related exposure to the
aggregate risk posed by a pesticide. In developing the bounding figure,
EPA estimated residue levels in water for a number of specific
pesticides using various data sources. EPA then applied the estimated
residue levels, in conjunction with appropriate toxicological endpoints
(RfD's or acute dietary NOEL's) and assumptions about body weight and
consumption, to calculate, for each pesticide, the increment of
aggregated risk contributed by consumption of contaminated water. This
analysis can be found in the Special Record for the FQPA. While EPA has
not yet pinpointed the appropriate bounding figure for consumption of
contaminated water, the ranges EPA is continuing to examine are all
below the level that would cause avermectin to exceed the RfD, if the
tolerances being considered in this document are granted. EPA has
therefore concluded that the potential exposure associated with
avermectin in water, even at the higher levels EPA is considering as a
conservative upper bound, would not prevent EPA from determining that
there is a reasonable certainty of no harm if the proposed tolerances
are granted.
3. From non-dietary uses. Avermectin is registered for various uses
including use on ornamentals (herbaceous and woody), household
dwellings (indoor and outdoor), and non-food areas of food handling
establishments. The exposure from these uses are expected to be oral,
dermal and respiratory in nature. Based on the nature of the outdoor
residential uses (spot treatment), EPA has concluded that residential
exposure resulting from outdoor uses will not be significant. Likewise,
based upon the nature of the indoor and outdoor residential uses, EPA
has concluded that a chronic residential exposure study is not
necessary. The indoor residential exposure assessment to determine risk
from exposure to children and adults was based on a California EPA
(Medical Toxicology and Worker Health and Safety Branches) review of an
avermectin residential exposure study.
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 assessments, there are pesticides as to which the common mechanism
issues can be resolved. These pesticides include pesticides that are
toxicologically and structurally 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).
EPA does not have, at this time, available data to determine
whether avermectin 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,
avermectin 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 avermectin has a common mechanism of toxicity
with other substances.
D. Safety Determinations
1. U.S. population and non-nursing infants. A chronic dietary
exposure/risk assessment was conducted for avermectin using a RfD of
0.0004 mg/kg/day based on a NOEL of 0.12 mg/kg/day from a 2-year
generation rat reproduction study and an uncertainty factor of 300.
Available information on anticipated residues and 100% crop treated was
incorporated into the analysis to estimate the Anticipated Residue
Contribution (ARC). The ARC is generally considered a more realistic
estimate than an estimate based on tolerance-level residues. The
cumulative total of established and proposed uses will result in
exposure estimates of 0.000020 mg/kg/day for the overall U.S.
population and utilize 5% of the RfD. For the most highly exposed
population subgroup, non-nursing infants less than 1 year old, the ARC
for established and current uses is estimated at 0.00043 mg/kg/day
utilizing 11% of RfD. EPA generally has no concern for exposure below
100% of the RfD because the RfD represents the level at or below which
daily aggregated dietary exposure over a life time will not pose an
appreciable risk to human health. EPA therefore concludes that there is
reasonable certainty that no harm will result from dietary exposure to
avermectin residues.
Due to developmental toxicity concerns, an acute dietary exposure/
risk assessment for these tolerances and pending tolerances have been
performed. The acute dietary risk assessment used Monte Carlo modeling
incorporating anticipated residues and percent of crop treated
refinement. The subgroup of concern in this analysis is
[[Page 13837]]
women aged 13 and above which is the subgroup most closely
approximating women of child bearing age. At the calculated high-end
exposure of 0.00078 mg/kg/day, the acute dietary MOE is 769 for females
13+ years old. Based on these results, EPA has no acute dietary
concerns since EPA considers an MOE of greater than 300 adequately
protective.
EPA notes that the acute dietary risk assessment 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. For the purpose of
these time limited tolerances, EPA concludes that this analysis is
adequate to assess acute dietary exposure, but prior to establishment
of permanent tolerances a full review of this analysis will be
required.
Section 408 (b)(2)(E) requires that, if EPA relies upon anticipated
residue levels in setting a tolerance, EPA must require that data be
submitted 5 years after approval of the tolerance on whether the
anticipated residue level remains accurate. Because this tolerance is
limited to approximately 2 1/2 years, data are not being required at
this time.
2. Infants and children. FFDCA section 408 provides that EPA shall
apply an additional tenfold margin of exposure (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 exposure (safety) will be safe
for infants and children. Margins of exposure (safety) are often
referred to as uncertainty (safety) factors. EPA believes that reliable
data support using the standard margin of exposure (usually 100x for
combined inter-and intra-species variability) and not the additional
tenfold margin of exposure when EPA has a complete data base under
existing guidelines and when the severity of the effect in infants and
children, and the potency or unusual toxic properties of a compound do
not raise concerns regarding the adequacy of the standard margin of
exposure.
In assessing the potential for additional sensitivity of infants
and children to residues of avermectin, EPA considered data from
developmental toxicity studies in the rat, mouse and rabbit and a 2-
year generation reproduction study in the rat. The developmental
toxicity studies are designed to evaluate adverse effects on the
developing organism resulting from pesticide exposure during prenatal
development to the mothers. Reproduction studies provide information
relating to effects from exposure to the pesticide on the reproductive
capability of mating animals and data on systemic toxicity.
3. Prenatal effects. The developmental and maternal NOELs for
avermectin in rats are both > 1.6 mg/kg/day, highest dose tested. For
rabbits, the developmental and maternal NOELs and LOELs are both 1.0
and 2.0 mg/kg/day, respectively. These studies suggest that avermectin
does not exhibit any special prenatal sensitivity. However, both
avermectin and its delta-8,9-isomer exhibit cleft palate in the CF-1
mouse developmental studies. For avermectin and its delta,-8,9-isomer,
the NOEL for cleft palate is 0.2 mg/kg/day with the LOEL at 0.4 mg/kg/
day and NOEL 0.06 mg/kg/day with the LOEL at 0.10 mg/kg/day,
respectively. Therefore, prenatal sensitivity to the regulated residue
for avermectin is demonstrated when considering these effects in the
CF-1 mouse. To evaluate the prenatal risk, the acute dietary MOE
calculation for women 13+ years old has been conducted, resulting in a
MOE of 769, which is considered adequate to protect prenatal exposure.
4. Post-natal effects. Post-natal effects were determined by a 2-
year generation rat reproduction study with a NOEL of 0.12 mg/kg/day
and LOEL of 0.4 mg/kg/day, where effects in the pups included death,
decreased body weight and retinal folds. In contrast, the NOEL for
parental toxicity is 0.4 mg/kg/day. This suggests post-natal
sensitivity for infants and children. However, with respect to the
post-natal sensitivity for the delta-8,9-isomer, a 1-generation rat
reproduction study at doses up to 0.4 mg/kg/day did not produce any
parental or pup toxicity. The established RfD is 0.0004 mg/kg/day based
on the 2-year generation rat reproduction study with a NOEL of 0.12 mg/
kg/day and an uncertainty factor of 300. The post-natal sensitivity for
infants and children has been considered by employing a 300-fold
uncertainty factor in the calculation of the RfD. The highest
calculated aggregate percentage of the RfD is 11% for non-nursing
infants. At this level, risk to infants and children due to post-natal
exposure do not raise concerns.
Therefore, EPA concludes the reliable data support use of a 300-
fold safety factor, which incorporates an additional modifying factor
(MF) for the effect and dose response curve, and thus no additional
safety factor is not needed to protect the safety of infants and
children. (EPA notes that the petitioner, in their Notice of Filing,
indicated that some of the studies EPA used in its risk assessments are
not appropriate for assessing the risk potential of avermectin and/or
overstate the risk and that an additional MF is unnecessary and
submitted additional data in this regard. EPA has not yet completed its
review of these data, but will take it into account in later
reassessment of the tolerances.)
E. Aggregate Risk Assessment
1. Acute risk assessment. The acute aggregate risk assessment takes
into account exposure from food only. As indicated above, although EPA
has not identified a water exposure figure based upon available
environmental data, avermectin is not expected to be mobile in soil or
water environments and poses relatively little threat to drinking
water. The combined exposure to avermectin from food and residential
uses is considered in the short-and intermediate-term risk assessment.
An acute dietary MOE of greater than 300 would not be of concern to
EPA. As indicated earlier, the MOE for females 13+ years was calculated
to be 769. Under any bounding assumption EPA is considering for
exposure from drinking water, this MOE would not be significantly
reduced. Therefore, EPA has no acute aggregate concern due to exposure
to avermectin through food and drinking water.
2. Short-and intermediate risk assessment. The short-and
intermediate term aggregate risk takes into account exposure from
chronic dietary food and indoor/outdoor residential exposure. Based on
the nature of the outdoor residential uses (spot treatment),
residential outdoor exposure for avermectin is insignificant. The
residential indoor exposure was based on the California EPA review of
an indoor residential exposure study. A total indoor MOE of 800 was
calculated for short-and intermediate-term risk, taking into account
and residential exposures. For the most highly exposed population
subgroup (non-nursing infants less than 1 year old), an aggregate
short-and intermediate-term MOE of 733 was calculated. Under any
bounding assumption EPA is considering for exposure from drinking
water, this MOE would not be significantly reduced. As indicated
earlier, an MOE of greater than 300 would not be of concern to EPA,
therefore current uses of avermectin is below the level of concern.
For the purposes of these time-limited tolerances, EPA has
concluded that the California EPA assessment is adequate to estimate
residential exposure from registered non-dietary uses of avermectin but
prior to establishment of
[[Page 13838]]
permanent tolerances, a full review of the indoor residential risk
assessment will be required.
3. Chronic risk assessment. The aggregated chronic risk is equal to
the sum of the chronic risk from food, drinking water, and indoor and
outdoor residential exposures. For avermectin, the residential uses are
not of the type that would be expected to produce a long-term exposure.
Therefore, residential exposure was aggregated with dietary exposure
only in the short-and intermediate-term risk assessment. The aggregated
chronic risk (food only) is 5% of the RfD for the U.S. population and
11% of the RfD for the population subgroup non-nursing infants less
than 1 year old. Under any bounding assumptions EPA is considering for
exposure from drinking water, exposure to avermectin would not exceed
the RfD. EPA therefore concludes that there is reasonable certainty
that no harm will result to consumers, including infants and children
from aggregate exposure to avermectin residues.
F. Other Considerations
1. Endocrine effects. No evidence of effects on the endocrine
systems of mammals were reported in the toxicology studies described
above. There is no evidence at this time that avermectin causes
endocrine effects.
2. Metabolism and nature of residues. The metabolism of avermectin
and nature of residues in plants and animals is adequately understood
for the purpose of these tolerances. The residues of concern are
avermectin B1 and its delta-8,9-isomer.
3. International tolerances. There are no Codex maximum residue
levels established for residues of avermectin on citrus, cotton, potato
and hop commodities.
4. Analytical method. There is a practical analytical method for
detecting and measuring the levels of avermectin and its delta-8,9-
isomer in or on food with a limit of detection that allows monitoring
of food with residues at or above the levels set in these tolerances
(high performance liquid chromatography with fluorescence detection,
with crop specific clean up methods). EPA has provided information on
this method to the Food and Drug Administration. The method is
available to anyone who is interested in pesticide residue enforcement
from: Calvin Furlow, Public Response and Program Resources Branch, 401
M St. SW., Washington, DC 20460. Office location and telephone number:
CM #2, Rm 1128, 1921 Jefferson Davis Highway, Arlington, VA, 703-305-
5805.
III. Summary of Findings
Tolerances are time-limited to allow for development and review of
residue field trials on cotton gin byproducts and to complete full
review of the Monte Carlo acute dietary and indoor residential risk
assessments. These tolerances will expire and be revoked without any
further action by EPA (other than publishing a notice in the Federal
Register so that the CFR can be corrected) on September 1, 1999
Residues remaining in or on the above RAC's after expiration of
these tolerances will not be considered actionable if the pesticide is
legally applied during the term and in accordance with the provisions
of the conditional registrations.
EPA concludes that the proposed time-limited tolerances will be
safe. Therefore it is proposed that the tolerances be established as
set forth below.
IV. 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 (1)(6) as was provided in the old section 408
and in section 409. However, the period of filing objections is 60
days, rather than 30 days. EPA currently has procedural regulations
which governs the submission of objections and hearing requests. These
regulation will require some modification to reflect the new law.
However, until these modifications can be made, EPA will continue to
use those procedural regulations with appropriate adjustments to
reflect the new law.
Any person may by May 23, 1997, file written objections to any
aspect of this regulation and may also request a hearing on those
objections. Objections and hearing requests must be filed with the
Hearing Clerk, at the address given above (40 CFR 178.20). A copy of
the objections and/or hearing requests filed with the Hearing Clerk
should be submitted to the OPP docket for this rulemaking. The
objections submitted must specify the provisions of the regulation
deemed objectionable and the grounds for the objections (40 CFR
178.25). Each objection must be accompanied by the fee prescribed by 40
CFR 180.33(i). If a hearing is requested, the objections must include a
statement of the factual 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 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 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
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 Confidential Business
Information (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 with prior notice.
V. Public Docket
A record has been established for this rulemaking under docket
number [OPP-300465/PP 7F3500; 8F3592; 5F4508; 4E4419 and FAP 8H5660]. A
public version of this record, which does not include any information
claimed as CBI, is available for inspection form 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 Response and Program Resources
Branch, Field Operations Division (7506C), Office of Pesticide
Programs, Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, Va.
The official record for this rulemaking, as well as the public
version, as described above, is kept in paper form. Accordingly, in the
event there are objections and hearing requests, EPA will transfer any
copies of the 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. The official rulemaking
record is the paper record maintained at the address in ``ADDRESSEE''
at the beginning of this document.
VI. Regulatory Assessment Requirements
Under Executive Order 12866 (58 FR 51735, October 4, 1993), this
action is not a ``significant regulatory action'' and, since this
action does not impose any information collection requirements as
defined by the Paperwork Reduction Act, 44 U.S.C. 3501 et seq., it is
not
[[Page 13839]]
subject to review by the Office of Management and Budget. In addition,
this action does not impose any enforceable duty or contain any
unfunded mandate as described in the Unfunded Mandates Reform Act of
1995 (Pub. L. 104-4), or require prior consultation with State
officials as specified by Executive Order 12875 (58 FR 58093, October
28, 1993), or special considerations as required by Executive Order
12898 (59 FR 7629, February 16, 1994).
Because tolerances established on the basis of a petition under
section 408(d) of FFDCA do not require issuance of a proposed rule, the
regulatory flexibility analysis requirements of the Regulatory
Flexibility Act (RFA), 5 U.S.C. 604(a), do not apply. Prior to the
recent amendment of the FFDCA, EPA had treated such rulemaking as
subject to the RFA; however, the amendments to the FFDCA clarify that
no proposal is required for such rulemakings and hence that the RFA is
inapplicable. Nonetheless, the Agency has previously assessed whether
establishing tolerances or exemptions from tolerance, raising tolerance
levels, or expanding exemptions adversely impact small entities and
concluded, as a generic matter, that there is no adverse impact. (46 FR
24950) (May 4, 1981).
Pursuant to 5 U.S.C. 801(a)(1)(A) of the Small Business Regulatory
Enforcement Fairness Act of 1996 (Title II of Pub. L. 104-121, 110
Stat. 847), EPA submitted a report containing this rule and other
required information to the U.S. Senate, the U.S. House of
Representatives and the Comptroller General of the General Accounting
Office prior to publication of the rule in today's Federal Register.
This rule is not a major rule as defined by 5 U.S.C. 804(2).
List of Subjects
40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
40 CFR Part 185
Environmental protection, Food additives, Pesticides and pests.
40 CFR Part 186
Environmental protection, Animal feeds, Pesticides and pests.
Dated: March 14, 1997.
Penelope A. Fenner-Crisp,
Acting Director, Office of Pesticide Programs.
Therefore, 40 CFR Chapter I is amended as follows:
1. In part 180:
PART 180--[AMENDED]
a. The authority citation of part 180 continues to read:
Authority: 21 U.S.C. 346a and 371.
b. In Sec. 180.449 by revising paragraph (a) to read as follows:
Sec. 180.449 Avermectin B1 and its delta-8,9-isomer; tolerances
for residues.
(a) Tolerances are established for the combined residues of the
insecticide avermectin (a mixture of avermectins containing greater
that or equal to 80% avermectin B1a(5-O-dimethyl avermectin
A1a) and less than or equal to 20% avermectin b(5-O-demethyl-25-
de(1-methylpropyl)-25-(1-methylethyl) avermectin A1a)) and its
delta-8, 9-isomer in or on the following commodities:
------------------------------------------------------------------------
Parts per
Commodity million Expiration/Revocation Date
------------------------------------------------------------------------
Cattle, fat.................. 0.015 ppm September 1, 1999
Cattle, mbyp................. 0.02 ppm September 1, 1999
Cattle, meat................. 0.02 ppm September 1, 1999
Citrus, dried pulp........... 0.10 ppm September 1, 1999
Citrus, oil.................. 0.10 ppm September 1, 1999
Citrus, whole fruit.......... 0.02 ppm September 1, 1999
Cottonseed................... 0.005 ppm September 1, 1999
Hops, dried.................. 0.2 ppm September 1, 1999
Milk......................... 0.005 ppm September 1, 1999
Potatoes..................... 0.005 ppm September 1, 1999
------------------------------------------------------------------------
* * * * *
2. In part 185:
PART 185--[AMENDED]
a. The authority citation for part 185 is revised to read as
follows:
Authority: 21 U.S.C. 348.
Sec. 185.300 [Removed]
b. By removing Sec. 185.300 in its entirety.
3. In part 186:
PART 186--[AMENDED]
a. The authority citation for part 186 is revised to read as
follows:
Authority: 21 U.S.C. 348.
Sec. 186.300 [Removed]
b. By removing Sec. 186.300 in its entirety.
[FR 97-7352 Filed 3-21-97; 8:45 am]
BILLING CODE 6560-50-F