[Federal Register Volume 62, Number 209 (Wednesday, October 29, 1997)]
[Rules and Regulations]
[Pages 56082-56089]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-28641]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300567; FRL-5750-8]
RIN 2070-AB78
Avermectin; Pesticide Tolerances for Emergency Exemptions
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes a time-limited tolerance for the
combined residues of avermectin in or on basil. This action is in
response to an emergency exemption request under section 18 of the
Federal Insecticide, Fungicide, and Rodenticide Act permitting use of
the pesticide on basil. This regulation establishes a maximum
permissible level for residues of avermectin B1 and its
delta-8,9-isomer in this food commodity pursuant to section 408(l)(6)
of the Federal Food, Drug, and Cosmetic Act, as amended by the Food
Quality Protection Act of 1996. The tolerance will expire and is
revoked on September 30, 1998.
DATES: This regulation is effective October 29, 1997. Objections and
requests for hearings must be received by EPA on or before December 29,
1997.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300567], must be submitted to: Hearing
Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M St.,
SW., Washington, DC 20460. Fees accompanying objections and hearing
requests shall be labeled ``Tolerance Petition Fees'' and forwarded to:
EPA Headquarters Accounting Operations Branch, OPP (Tolerance Fees),
P.O. Box 360277M, Pittsburgh, PA 15251. A copy of any objections and
hearing requests filed with the Hearing Clerk identified by the docket
control number, [OPP-300567], 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-300567]. 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: Daniel Rosenblatt,
Registration Division (7505C), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.
Office location, telephone
[[Page 56083]]
number, and e-mail address: CM #2, 1921 Jefferson Davis Hwy.,
Arlington, VA, (703) 308-9375, e-mail: [email protected].
SUPPLEMENTARY INFORMATION: EPA, on its own initiative, pursuant to
section 408(e) and (l)(6) of the Federal Food, Drug, and Cosmetic Act
(FFDCA), 21 U.S.C. 346a(e) and (l)(6), is establishing a tolerance for
the combined residues of the miticide avermectin B1 and its
delta-8,9-isomer, in or on basil at 0.05 parts per million (ppm). This
tolerance will expire and is revoked on September 30, 1998. EPA will
publish a document in the Federal Register to remove the revoked
tolerance from the Code of Federal Regulations.
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. 301 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. These activities are described below and discussed in
greater detail in the final rule establishing the time-limited
tolerance associated with the emergency exemption for use of
propiconazole on sorghum (61 FR 58135, November 13, 1996)(FRL-5572-9).
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. . . .''
Section 18 of FIFRA authorizes EPA to exempt any Federal or State
agency from any provision of FIFRA, if EPA determines that ``emergency
conditions exist which require such exemption.'' This provision was not
amended by FQPA. EPA has established regulations governing such
emergency exemptions in 40 CFR part 166.
Section 408(l)(6) of the FFDCA requires EPA to establish a time-
limited tolerance or exemption from the requirement for a tolerance for
pesticide chemical residues in food that will result from the use of a
pesticide under an emergency exemption granted by EPA under section 18
of FIFRA. Such tolerances can be established without providing notice
or period for public comment.
Because decisions on section 18-related tolerances must proceed
before EPA reaches closure on several policy issues relating to
interpretation and implementation of the FQPA, EPA does not intend for
its actions on such tolerance to set binding precedents for the
application of section 408 and the new safety standard to other
tolerances and exemptions.
II. Emergency Exemption for Avermectin on Basil and FFDCA
Tolerances
Basil is a leafy herb that is produced for the fresh and dried
markets. California submitted information to EPA that indicates that
the leafminer (Liriomyza sp.) poses a significant threat to the
profitable production of basil. Basil affected by leafminer can be
rendered unmarketable because they feed on the plant's leaves and may
also make them susceptible to disease. California determined that the
conditions for a leafminer outbreak were favorable and invoked its
authorities under 40 CFR 166.40 to declare a crisis situation. After
considering the implications connected with the use of this pesticide
under a crisis situation, EPA is establishing this tolerance for the
use of avermectin on basil for control of leafminer in California.
As part of its assessment of this emergency exemption, EPA assessed
the potential risks presented by residues of avermectin in or on basil.
In doing so, EPA considered the new safety standard in FFDCA section
408(b)(2), and EPA decided that the necessary tolerance under FFDCA
section 408(l)(6) would be consistent with the new safety standard and
with FIFRA section 18. Consistent with the need to move quickly on the
emergency exemption in order to address an urgent non-routine situation
and to ensure that the resulting food is safe and lawful, EPA is
issuing this tolerance without notice and opportunity for public
comment under section 408(e), as provided in section 408(l)(6).
Although this tolerance will expire and is revoked on September 30,
1998, under FFDCA section 408(l)(5), residues of the pesticide not in
excess of the amounts specified in the tolerance remaining in or on
basil after that date will not be unlawful, provided the pesticide is
applied in a manner that was lawful under FIFRA. EPA will take action
to revoke this tolerance earlier if any experience with, scientific
data on, or other relevant information on this pesticide indicate that
the residues are not safe.
Because this tolerance is being approved under emergency conditions
EPA has not made any decisions about whether avermectin meets EPA's
registration requirements for use on basil or whether a permanent
tolerance for this use would be appropriate. Under these circumstances,
EPA does not believe that this tolerance serves as a basis for
registration of avermectin by a State for special local needs under
FIFRA section 24(c). Nor does this tolerance serve as the basis for any
State other than California to use this pesticide on this crop under
section 18 of FIFRA without following all provisions of section 18 as
identified in 40 CFR part 166. For additional information regarding the
emergency exemption for avermectin, contact the Agency's Registration
Division at the address provided above.
III. Risk Assessment and Statutory Findings
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
[[Page 56084]]
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% 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 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.
Percent of crop treated estimates are derived from federal and
private market survey data. Typically, a range of estimates are
supplied and the upper end of this range is assumed for the exposure
assessment. By using this upper end estimate of percent of crop
treated, the Agency is reasonably certain that exposure is not
understated for any significant subpopulation group. 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, to pesticide residues. For this
pesticide, the most highly exposed population subgroup (non-nursing
infants <1 year old) was not regionally based.
[[Page 56085]]
IV. 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
avermectin and to make a determination on aggregate exposure,
consistent with section 408(b)(2), for a time-limited tolerance for
combined residues of avermectin B1 and its delta-8,9-isomer
on basil at 0.05 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 avermectin
B1 and its delta-8,9-isomer are discussed below.
1. Acute toxicity. For acute dietary risk assessment, EPA
recommends use of a NOEL of 0.06 mg/kg/day from the developmental
toxicity study in mice. The effects observed at the Lowest Effect Level
(LEL) of 0.10 mg/kg/day involved cleft palate. For the purposes of this
action, an MOE of 300 is considered necessary to be adequately
protective for dietary (food only) exposure.
2. Short - and intermediate - term toxicity. For short- and
intermediate-term MOE calculations, EPA recommends use of the
developmental NOEL of 0.2 mg/kg/day from the oral developmental
toxicity study in mice. At the LEL of 0.4 mg/kg/day, there was an
increased incidence of cleft palate.
3. Chronic toxicity. EPA has established the RfD for avermectin at
0.0004 milligrams/kilogram/day (mg/kg/day). This RfD is based on a 2-
generation rat reproductive toxicity 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. The MF was used because of the severity 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 increased incidence of retinal rosettes
in F2b weanlings.
4. Carcinogenicity. Avermectin has been classified by EPA as a
Group E (``evidence of non-carcinogenicity for humans'') chemical.
Therefore, a cancer risk assessment is not needed.
B. Exposures and Risks
1. From food and feed uses. Tolerances have been established (40
CFR 180.449) for the combined residues of avermectin B1 and
its delta-8,9-isomer, in or on a variety of raw agricultural
commodities, ranging from 0.005 ppm in cottonseed to 0.05 ppm in
celery. Risk assessments were conducted by EPA to assess dietary
exposures and risks from avermectin B1 and its delta-8,9-
isomer as follows:
i. Acute exposure and risk. Acute dietary risk assessments are
performed for a food-use pesticide if a toxicological study has
indicated the possibility of an effect of concern occurring as a result
of a one day or single exposure. In a separate and earlier registration
action, the Agency required the development of more highly refined
residue and exposure information to support the pesticide. In response,
in October 1996, EPA received a Monte Carlo analysis for all uses of
avermectin at that time. Since that analysis was generated before this
section 18 action was submitted, EPA does not have information on acute
exposures for basil. Further, the Agency is not currently updating or
revising Monte Carlo analysis developed by registrants. Therefore, the
acute exposure assessment for this action does not include data
associated with the consumption of basil. In spite of the above
exception, data available to EPA suggest a high-end exposure estimate
of 0.000078 mg/kg/day for uses of avermectin. This results in a dietary
(food only) MOE of 769 for females 13 years and older, the population
subgroup of concern. In EPA's judgement, the addition of basil to acute
exposure and risk calculations would not produce acute risks (food
only) that exceed a level of concern.
ii. Chronic exposure and risk. As part of this action, EPA reviewed
information that establishes chronic dietary exposure estimates for
avermectin. This chronic dietary (food only) risk assessment used
anticipated residue refinement for commodities with tolerances for
avermectin, but did not incorporate any refinement for percent of crop
treated (default of 100% was assumed). Therefore, the resulting
exposure estimates should be viewed as partially refined; further
refinement for percent of crop treated would result in lower dietary
exposure estimates. The existing avermectin tolerances plus the
proposed tolerances associated with the section 18 use of the chemical
result in an Anticipated Residue Contribution that ranges from 5% of
the RfD for the U.S. Population to 12% of the RfD for non-nursing
infants less than a year old.
2. From drinking water. In examining aggregate exposure, FQPA
directs EPA to consider available information concerning exposures from
the pesticide residues in food and all other non-occupational
exposures. The primary non-food sources of exposure the Agency looks at
include drinking water (whether from ground or surface water), and
exposure through pesticide use in gardens, lawns, or buildings
(residential and other indoor uses). Based on data available to EPA,
avermectin is moderately persistent and not very mobile. It is not
likely to be found extensively in ground water, but could be found in
surface water. Under anaerobic conditions in the absence of light,
avermectin does not degrade. No Health Advisories or Maximum
Contaminant Levels for avermectin in drinking water have been
established.
Because the Agency lacks sufficient water-related exposure data to
complete a comprehensive drinking water risk assessment for many
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. The Agency 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
aggregate risk contributed by consumption of contaminated water. While
EPA has not yet pinpointed the appropriate bounding figure for exposure
from contaminated water, the ranges the Agency is continuing to examine
are all below the level that would cause avermectin to exceed the RfD
if the tolerance being considered in this document were granted. The
Agency has therefore concluded that the potential exposures associated
with avermectin in water, even at the higher levels the Agency is
considering as a conservative upper bound, would not prevent the Agency
from determining that there is a reasonable certainty of no harm if the
tolerance is granted.
3. From non-dietary exposure. Avermectin is currently registered
for use on the following residential non-food sites: ornamental crops
(herbaceous and woody), turf, households (indoor and outdoor), and
[[Page 56086]]
non-food areas of food handling establishments.
i. Chronic exposure and risk. Given the uses for avermectin, a
chronic non-dietary exposure scenario would not be expected.
ii. Short- and intermediate-term exposure and risk. EPA assessed
indoor residential risk characterization data to evaluate short- and
intermediate-term exposure and risk. Based on the assumptions for
exposure total oral, dermal, and respiratory estimated absorbed daily
exposure could total .00023 mg/kg/day. This correlates to a total
short- and intermediate-term indoor residential MOE of 870 for the U.S.
population.
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 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.
C. Aggregate Risks and Determination of Safety for U.S. Population
1. Acute risk. The population subgroup of concern is females 13
years and older. The MOE for this subgroup from food exposures is 769.
Despite the potential for exposures to avermectin from drinking water,
EPA does not expect the acute aggregate risk to exceed levels of
concern.
2. Chronic risk. Using the ARC exposure assumptions described
above, EPA has concluded that aggregate exposure to avermectin from
food will utilize 5% of the RfD for the U.S. population. The major
identifiable subgroup with the highest aggregate exposure is non-
nursing infants <1 year 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. Based on the
nature of the residential uses, a chronic scenario would not be
expected. Despite the potential for exposure to avermectin in drinking
water and from non-dietary, non-occupational exposure, EPA does not
expect the aggregate exposure to exceed 100% of the RfD. EPA concludes
that there is a reasonable certainty that no harm will result from
aggregate exposure to avermectin residues.
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.
As referenced above, for short- and intermediate-term exposures,
EPA assessed information that addresses this topic in relation to human
exposure associated with residential use through oral, dermal, and
respiratory exposures. The anticipated MOE was 803 for the U.S.
population. EPA considers this MOE to be adequately protective.
D. Aggregate Cancer Risk for U.S. Population
Avermectin has been classified as a Group E ``evidence of non-
carcinogenicity for humans'' chemical by EPA. Therefore, a cancer risk
assessment is not needed.
E. 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 avermectin, 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 maternal pesticide exposure during gestation.
Reproduction studies provide information relating to effects from
exposure to the pesticide on the reproductive capability of mating
animals and data on systemic toxicity.
FFDCA section 408 provides that EPA shall apply an additional
tenfold margin of safety for infants and children in the case of
threshold effects to account for pre-and post-natal toxicity and the
completeness of the database unless EPA determines that a different
margin of safety will be safe for infants and children. Margins of
safety are incorporated into EPA risk assessments either directly
through use of a 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 100-
fold safety factor (usually 100 for combined inter- and intra-species
variability) and not the additional tenfold safety 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 safety factor.
ii. Developmental toxicity studies. In the mouse developmental
toxicity analysis, the maternal (systemic) NOEL was 0.05 mg/kg/day
based on mortality
[[Page 56087]]
at the Lowest-observed effect level (LOEL) of 0.075 mg/kg/day. The
developmental (fetal) NOEL was 0.2 mg/kg/day based on cleft palate at
the LOEL of 0.4 mg/kg/day. The Delta-8,9-Isomer was also tested for
developmental toxicity in the mouse. In the mouse developmental study
for the isomer, the maternal (systemic) NOEL was 0.10 mg/kg/day, based
on mortality at the LOEL of 0.20 mg/kg/day. The developmental (fetal)
NOEL was 0.06 mg/kg/day, based on cleft palate at the LOEL of 0.10 mg/
kg/day.
In the rat developmental study, the maternal (systemic) NOEL was
greater than or equal to 1.6 mg/kg/day. The developmental (fetal) NOEL
was 1.6 mg/kg/day. In the rabbit developmental study, the maternal
(systemic) NOEL was 1.0 mg/kg/day, based on decreased body weight and
decreased food and water consumption at the LOEL of 2.0 mg/kg/day. The
developmental (fetal) NOEL was 1.0 mg/kg/day, based on clubbed foot,
and delayed ossification of sternebrae, metacarpals, and phalanges at
the LOEL of 2.0 mg/kg/day.
iii. Reproductive toxicity study. In the 2-generation rat
reproductive toxicity study, the maternal (systemic) NOEL was 0.4 mg/
kg/day highest dose tested (HDT). The developmental (pup) NOEL was 1.2
mg/kg/day, based on decreased viability indices, decreased pup body
weight, and retinal fold in weanlings at the LOEL of 0.4 mg/kg/day. The
reproductive (pup) NOEL was 0.4 mg/kg/day (HDT).
iv. Pre- and post-natal sensitivity. Both the delta-8,9-isomer of
avermectin and avermectin per se exhibit cleft palate in CF1 mouse
developmental studies. The NOEL for cleft plate for the delta-8,9-
isomer is 0.06 mg/kg/day with the LOEL at 0.10 mg/kg/day. For
avermectin per se, the NOEL for cleft palate is 0.2 mg/kg/day with the
LOEL at 0.4 mg/kg/day. Therefore, pre-natal sensitivity to the
regulated residue for avermectin is demonstrated when considering these
developmental findings in the CF1 Mouse. An additional 3-fold
uncertainty factor has been added to account for these developmental
findings.
An acute dietary risk assessment is needed based on the results of
the developmental study in mice with the delta-8,9-isomer. This risk
assessment will evaluate acute dietary risk to females 13 years and
older. For the purpose of the section 18, an MOE of 300 is considered
necessary to be adequately protective for dietary (food only) exposure.
To evaluate the pre-natal risks, the acute dietary MOE calculations
for females 13 years and older has been conducted using the lowest NOEL
for all developmental studies for cleft palate (0.06 mg/kg/day).
The results of the rat reproduction study required that a Modifying
Factor of 3 be added to the usual uncertainty factor of 100 used for
the RfD. EPA used this Modifying Factor in developing this analysis.
Typically, the Agency uses a modifying factor of 10 when no study is
available and uses a modifying factor of 3 when a study exists which
shows effects in the fetus before they appear in the parent.
2. Acute risk. The acute dietary MOE for females 13 years and older
(accounts for both maternal and fetal exposure) is 769. This MOE
calculation is based on the developmental NOEL in mice of 0.06 mg/kg/
day. This estimate is based on Monte Carlo modeling incorporating
anticipated residue and percent of crop treated refinement. In EPA's
judgement, the large acute dietary MOE provides assurance that there is
a reasonable certainty of no harm for females 13 years and older and
the pre-natal development of infants.
3. Chronic risk. Using the conservative exposure assumptions
described above, EPA has concluded that aggregate exposure to
avermectin from food will utilize 12% of the RfD for non-nursing
infants less than a year old and 8% of the RfD for children 1-6 years
old. 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. Based on the nature of the residential uses, a chronic
scenario would not be expected. Despite the potential for exposure to
avermectin in drinking water and from non-dietary, non-occupational
exposure, EPA does not expect the aggregate exposure to exceed 100% of
the RfD. EPA concludes that there is a reasonable certainty that no
harm will result to infants and children from aggregate exposure to
avermectin residues.
4. Short- or intermediate-term risk. The anticipated MOEs for
short- and intermediate-term exposures for infants and children do not
pose a level of concern. The calculated MOEs range from 716 for non-
nursing infants to 787 for children 7-12 years old.
V. Other Considerations
A. Metabolism In Plants and Animals
The nature of the residue in plants and animals is adequately
understood. As cited at 40 CFR 180.449, the regulable residues are
avermectin B1 and its delta-8,9-isomer.
B. Analytical Enforcement Methodology
Merck Method 10001, rev. 2, a high pressure liquid chromatography
(HPLC)-fluorescence method, may be used to enforce the tolerance
expression. This method has been submitted to FDA for publication in
PAM Volume II.
C. Magnitude of Residues
Residues of avermectin B1 and its delta 8,9-isomer are
not expected to exceed 0.05 ppm on basil as a result of this section 18
use. Secondary residues are not expected in animal commodities as no
feed items are associated with this use.
D. International Residue Limits
No Codex MRLs have been established for avermectin residues on
basil.
VI. Conclusion
Therefore, the tolerance is established for combined residues of
avermectin B1 and its delta-8,9-isomer in basil at 0.05 ppm.
VII. 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 409. However, the period for filing objections is 60
days, rather than 30 days. EPA currently has procedural regulations
which govern the submission of objections and hearing requests. These
regulations will require some modification to reflect the new law.
However, until those modifications can be made, EPA will continue to
use those procedural regulations with appropriate adjustments to
reflect the new law.
Any person may, by December 29, 1997, file written objections to
any aspect of this regulation and may also request a hearing on those
objections. Objections and hearing requests must be filed with the
Hearing Clerk, at the address given above (40 CFR 178.20). A copy of
the objections and/or hearing requests filed with the Hearing Clerk
should be submitted to the OPP docket for this rulemaking. The
objections submitted must specify the provisions of the regulation
deemed objectionable and the grounds for the objections (40 CFR
178.25). Each objection must be accompanied by the fee prescribed by 40
CFR 180.33(i). If a hearing is requested, the objections must include a
statement of the factual issues on which a hearing is requested, the
requestor's contentions on such issues, and a summary of any evidence
relied upon
[[Page 56088]]
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.
VIII. Public Record and Electronic Submissions
EPA has established a record for this rulemaking under docket
control number [OPP-300567] (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, Information Resources and Services Division (7502C),
Office of Pesticide Programs, Environmental Protection Agency, Crystal
Mall #2, 1921 Jefferson Davis Hwy., 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.
IX. Regulatory Assessment Requirements
This final rule establishes a time-limited tolerance under FFDCA
section 408(l)(6). 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 under FFDCA section 408 (1)(6), such as the tolerance in
this final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601et
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 acations published on May 4, 1981 (46 FR
24950), and was provided to the Chief Counsel for Advocacy of the Small
Business Administration.
X. 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 in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: October 22, 1997.
James Jones,
Acting Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
PART 180 -- [AMENDED]
1. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 346a and 371.
2. Section 180.449 is amended in paragraph (b) by alphabetically
adding a commodity to the table to read as follows:
Sec. 180.449 Avermectin B1 and its delta-8,9-isomer;
tolerances for residues.
* * * * *
(b) * * *
------------------------------------------------------------------------
Expiration/
Commodity Parts per million revocation date
------------------------------------------------------------------------
Basil........................... 0.05 ppm 9/30/98
* * * * * * *
------------------------------------------------------------------------
[[Page 56089]]
* * * * *
[FR Doc. 97-28641 Filed 10-28-97; 8:45 am]
BILLING CODE 6560-50-F