[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