[Federal Register Volume 64, Number 145 (Thursday, July 29, 1999)]
[Notices]
[Pages 41112-41116]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-19440]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-884; FRL-6095-6]


Notice of Filing a Pesticide Petition to Establish a Tolerance 
for Certain Pesticide Chemicals in or on Food

AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.

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SUMMARY: This notice announces the initial filing of a pesticide 
petition proposing the establishment of regulations for residues of 
certain pesticide chemicals in or on various food commodities.

DATES: Comments, identified by docket control number PF-884, must be 
received on or before August 30, 1999.

ADDRESSES: Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I.C. of the ``SUPPLEMENTARY INFORMATION'' section. To 
ensure proper receipt by EPA, it is imperative that you identify docket 
control number PF-884 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  By mail: Thomas Harris, Insecticide-
Rodenticide Branch, Registration Division (7505C), Office of Pesticide 
Programs, Environmental Protection Agency, 401 M St., SW., Washington, 
DC 20460; telephone number: (703) 308-9423; and e-mail address: 
[email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural 
producer, food manufacturer or pesticide manufacturer. Potentially 
affected categories and entities may include, but are not limited to:

 
------------------------------------------------------------------------
                                                          Examples of
           Categories                    NAICS            potentially
                                                       affected entities
------------------------------------------------------------------------
Industry                          111                 Crop production
 
                                  112                 Animal production
 
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------

    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in the table could also

[[Page 41113]]

be affected. The North American Industrial Classification System 
(NAICS) codes have been provided to assist you and others in 
determining whether or not this action might apply to certain entities. 
If you have questions regarding the applicability of this action to a 
particular entity, consult the person listed in the ``FOR FURTHER 
INFORMATION CONTACT'' section.

B. How Can I Get Additional Information, Including Copies of this 
Document and Other Related Documents?

    1. Electronically.. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations'' and then look up the entry for this document under the 
``Federal Register--Environmental Documents.'' You can also go directly 
to the Federal Register listings at http://www.epa.gov/fedrgstr/.
    2. In person. The Agency has established an official record for 
this action under docket control number PF-884. The official record 
consists of the documents specifically referenced in this action, any 
public comments received during an applicable comment period, and other 
information related to this action, including any information claimed 
as confidential business information (CBI). This official record 
includes the documents that are physically located in the docket, as 
well as the documents that are referenced in those documents. The 
public version of the official record does not include any information 
claimed as CBI. The public version of the official record, which 
includes printed, paper versions of any electronic comments submitted 
during an applicable comment period, is available for inspection in the 
Public Information and Records Integrity Branch (PIRIB), Rm. 119, 
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

    You may submit comments through the mail, in person, or 
electronically. To ensure proper receipt by EPA, it is imperative that 
you identify docket control number PF-884 in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs (OPP), Environmental Protection 
Agency, 401 M St., SW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by 
E-mail to: ``[email protected],'' or you can submit a computer disk as 
described above. Do not submit any information electronically that you 
consider to be CBI. Avoid the use of special characters and any form of 
encryption. Electronic submissions will be accepted in Wordperfect 5.1/
6.1 or ASCII file format. All comments in electronic form must be 
identified by docket control number PF-884. Electronic comments may 
also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

    Do not submit any information electronically that you consider to 
be CBI. You may claim information that you submit to EPA in response to 
this document as CBI 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. In addition to one complete 
version of the comment that includes any information claimed as CBI, a 
copy of the comment that does not contain the information claimed as 
CBI must be submitted for inclusion in the public version of the 
official record. Information not marked confidential will be included 
in the public version of the official record without prior notice. If 
you have any questions about CBI or the procedures for claiming CBI, 
please consult the person identified in the ``FOR FURTHER INFORMATION 
CONTACT'' section.

E. What Should I Consider as I Prepare My Comments for EPA?

    You may find the following suggestions helpful for preparing your 
comments:
     1. Explain your views as clearly as possible.
     2. Describe any assumptions that you used.
     3. Provide copies of any technical information and/or data you 
used that support your views.
    4. If you estimate potential burden or costs, explain how you 
arrived at the estimate that you provide.
     5. Provide specific examples to illustrate your concerns.
     6. Offer alternative ways to improve the rule or collection 
activity.
    7. Make sure to submit your comments by the deadline in this 
notice.
    8. To ensure proper receipt by EPA, be sure to identify the docket 
control number assigned to this action in the subject line on the first 
page of your response. You may also provide the name, date, and Federal 
Register citation.

II. What Action is the Agency Taking?

     EPA has received a pesticide petition as follows proposing the 
establishment and/or amendment of regulations for residues of certain 
pesticide chemical in or on various food commodities under section 408 
of the Federal Food, Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a. 
EPA has determined that this petition contains data or information 
regarding the elements set forth in section 408(d)(2); however, EPA has 
not fully evaluated the sufficiency of the submitted data at this time 
or whether the data supports granting of the petition. Additional data 
may be needed before EPA rules on the petition.

List of Subjects

    Environmental protection, Agricultural commodities, Feed additives, 
Food additives, Pesticides and pests, Reporting and recordkeeping 
requirements.

    Dated: July 23, 1999.

Donald R. Stubbs,

Acting Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Petitioner summaries of the pesticide petitions are printed below 
as required by section 408(d)(3) of the FFDCA. The summaries of the 
petitions were prepared by the petitioners and represent the views of 
the petitioners. EPA is publishing the petition summaries verbatim 
without editing them in any way. The petition summary announces the 
availability of a description of the analytical methods available to 
EPA for the detection and measurement of the pesticide chemical

[[Page 41114]]

residues or an explanation of why no such method is needed.

Novartis Crop Protection, Inc.

    1. EPA has received a request from Novartis Crop Protection, Inc., 
PO Box 18300, Greensboro, NC 27419 referencing pesticide petitions PP 
8F3592, 7F3500, 4E4419 and 5F4508, proposing pursuant to section 408(d) 
of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. 346a(d), to amend 
40 CFR 180.449 by establishing permanent tolerances for residues of 
abamectin (avermectin B1) and its delta 8,9-isomers in or on 
the agricultural commodities cattle, fat at 0.015 parts per 
million(ppm); cattle, meat byproducts at 0.02 ppm; cattle, meat at 0.02 
ppm; citrus, dried pulp at 0.10 ppm; citrus, oil at 0.10 ppm; citrus, 
whole fruit at 0.02 ppm; cottonseed at 0.005 ppm; cotton gin by-
products at 0.15 ppm; hops, dried at 0.20 ppm; milk at 0.005 ppm; and 
potatoes at 0.005 ppm. EPA has determined that the petition contains 
data or information regarding the elements set forth in section 
408(d)(2) of the FFDCA; however, EPA has not fully evaluated the 
sufficiency of the submitted data at this time or whether the data 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.
    The subject tolerances, except for cotton gin by-products, were 
established as time-limited tolerances with an expiration date of 
September 1, 1999 (62 FR 13833-13839, March 24, 1997) (FRL-5597-7). 
Three issues identified in the referenced Federal Register document 
were the cause of the subject tolerances only being extended as time-
limited tolerances. The three issues (cotton gin by-product residue 
data, review of the Monte Carlo dietary risk assessment, indoor 
residential risk assessment) are now resolved. The present petition 
proposes that these time-limited tolerances be converted to permanent 
tolerances.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of abamectin in plants and 
animals is adequately understood and the residues of concern include 
the parent insecticide, abamectin or avermectin B1 (which is 
a mixture of a minimum of 80% avermectin B1a and a maximum 
of 20% avermectin B1b) and the delta 8,9-isomer of the 
B1a and of the B1b components of the parent 
insecticide. Under photolytic conditions in the laboratory and in the 
field, abamectin undergoes isomerization around the 8,9-double bond to 
produce small amounts of the delta-8,9 isomer. The photo-oxidative 
half-life of the delta-8,9 isomer is 4.5 hours and that of avermectin 
B1a is 6.5 hours.
    2. Analytical method. The analytical method involves 
homogenization, filtration, partition and cleanup with analysis by high 
performance liquid chromatography fluorescence detection. The methods 
are sufficiently sensitive to detect residues at or above the 
tolerances proposed. All methods have undergone independent laboratory 
validation as required by PR Notice 88-5.
    3. Magnitude of residues. Data to support the new and proposed 
conversion of the present time-limited tolerances to full tolerances 
with no expiration date have been previously submitted under Pesticide 
Petitions PP 7F3500, 8F3592, 4E4419, 5F4508, 5E4566, and Food Additive 
Petition 8H5550.

B. Toxicological Profile

    1. Acute toxicity. The database includes the following studies: A 
rat acute oral study with a LD50 of 4.4 to 11.8 milligrams/
kilogram (mg/kg) (males) and 10.9 to 14.9 mg/kg (females). An acute 
oral toxicity in the CF-1 mouse with the delta 8,9-isomer has 
LD50 greater than 80 mg/kg. A rabbit acute dermal study with 
a LD50 > 2,000 mg/kg. A rat acute inhalation study with a 
LC50 > 5.73 milligrams/liter (mg/L). A primary eye 
irritation study in rabbits which showed irritation. A primary dermal 
irritation study in rabbits which showed no irritation. A primary 
dermal sensitization study in guinea pigs which showed no skin 
sensitization potential. An acute oral toxicity study in monkeys with a 
no observed adverse effects level (NOAEL) of 1.0 mg/kg based upon 
emesis at 2.0 mg/kg.
    2. Genotoxicty. The Ames assays conducted with and without 
metabolic activation were both negative. 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 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. There are also 
many studies and a great deal of clinical and follow-up experience with 
regard to ivermectin, a closely similar human and animal drug.
    3. Reproductive and developmental toxicity. The following 
reproductive and developmental tixocity studies were conducted:
    i. A 2-generation study in rats with a NOAEL of 0.12 mg/kg/day in 
pups based upon retinal folds, decreased body weight, and mortality. 
The NOAELs for systemic and reproductive toxicity were 0.4 mg/kg/day. 
In the 2-generation reproduction study in rats with the delta 8,9-
isomer, the NOAEL was 0.4 mg/kg/day and the lowest observed adverse 
effect level (LOAEL) was greater than 0.4 mg/kg/day (the highest dose 
tested).
    ii. An oral teratology study in the CF-1 mouse with a maternal 
NOAEL of 0.05 mg/kg/day based upon decreased body weights and tremors. 
The fetal NOAEL was 0.20 mg/kg/day based upon cleft palates. An oral 
teratology study with the delta 8,9-isomer in CF-1 mice with a maternal 
NOAEL of 0.10 mg/kg/day based upon decreased body weights. The fetal 
NOAEL was 0.06 mg/kg/day based upon cleft palate. An oral teratology 
study in rabbits with a maternal NOAEL of 1.0 mg/kg/day based upon 
decreased body weights and tremors. The fetal NOAEL was 1.0 mg/kg/day 
based upon clubbed feet. An oral teratology study in rats with a 
maternal and fetal NOAEL at 1.6 mg/kg/day, the highest dose tested. An 
oral teratology study with the delta 8,9-isomer with a maternal NOAEL 
in CF-1 mice that expressed P-glycoprotein greater than 1.5 mg/kg/day, 
the highest and only dose tested. No cleft palates were observed in 
fetuses that expressed normal levels of P-glycoprotein, but fetuses 
with low or no levels of P-glycoprotein had increased incidence of 
cleft palates.
    4. Subchronic toxicity. A rat 8-week feeding study with a NOAEL of 
1.4 mg/kg/day based upon tremors. A rat 14-week oral toxicity study 
with a NOAEL of 0.4 mg/kg/day, the highest dose tested. A dog 12-week 
feeding study with a NOAEL of 0.5 mg/kg/day based upon mydriasis. A dog 
18-week oral study with a NOAEL of 0.25 mg/kg/day based upon mortality. 
A CD-1 mouse 84-day feeding study with a NOAEL of 4 mg/kg/day based 
upon decreased body weights.
    5. Chronic toxicity. A rat 53-week oncogenicity feeding study, 
negative for oncogenicity, with a NOAEL of 1.5 mg/kg/day based upon 
tremors. A CD-1 mouse 94-week oncogenicity feeding study, negative for 
oncogenicity, with a NOAEL of 4 mg/kg/day based upon decreased body 
weights. A dog 53-week chronic feeding study, negative for 
oncogenicity, with a NOAEL of 0.25 mg/kg/day based upon mydriasis.

[[Page 41115]]

    6. Animal metabolism. Rats were given oral doses of 0.14 or 1.4 
milligrams/kilogram of bodyweight (mg/kg bw) per day of abamectin or 
1.4 mg/kg bw per day of the delta-8,9 isomer. Over 7 days, the 
percentages excreted in urine were 0.3-1% of the administered dose of 
abamectin and 0.4% of the dose of the isomer. The animals eliminated 
69-82% of the dose of abamectin and 94% of the dose of isomer in feces. 
In rats, goats and cattle, unchanged parent compound accounted for up 
to 50% of the total radioactive residues in tissues. The 24-
hydroxymethyl derivative of abamectin was found in rats, goats and 
cattle treated with the compound and in rats treated with the delta-8,9 
isomer, and the 3'-O-demethyl derivative was found in rats and cattle 
administered abamectin and in rats administered the isomer.
    7. Metabolite toxicology. There are no metabolites of concern based 
on a differential metabolism between plants and animals. The potential 
hazard of the 24-hydroxymethyl or the 3'-O-demethyl animal metabolites 
was evaluated in thorough toxicology studies with abamectin, photolytic 
break-down product, the delta 8,9-isomer.
    8. Endocrine disruption.There is no evidence that abamectin is an 
endocrine disrupter. Evaluation of the rat multigenerational study 
demonstrated no effect on the time to mating or on the mating and 
fertility indices, suggesting no effects on the estrous cycle, on 
mating behavior, or on male or female fertility at doses up to 0.4 mg/
kg/day, the highest dose tested. Furthermore, the range finding study 
demonstrated no adverse effect on female fertility at doses up to 1.5 
mg/kg/day, the highest dose tested. Similarly, chronic and subchronic 
toxicity studies in mice, rats, and dogs did not demonstrate any 
evidence of toxicity to the male or female reproductive tract, or to 
the thyroid or pituitary (based upon organ weights and gross and 
histopathologic examination). In the developmental studies, the pattern 
of toxicity observed does not seem suggestive of any endocrine effect. 
Finally, experience with ivermectin in breeding animals, including 
sperm evaluations in multiple species, shows no adverse effects 
suggestive of endocrine disruption.

C. Aggregate Exposure

    1. Dietary exposure--i. Food. The acute dietary Reference Dose 
(aRfD) is 0.0025 mg/kg/day from a 1-year dog study. The NOAEL is 0.25 
mg/kg/day, and the LOAEL is 0.50 mg/kg/day based on mydriasis (pupil 
dilation) which was observed after 1 week of dosing. An uncertainty 
factor of 100 to account for interspecies extrapolation (10x) and 
intraspecies variability (10x) was recommended. EPA has also retained 
the 10X safety factor for infants and children resulting in an aRfD of 
0.00025 mg/kg for appropriate populations. EPA has determined that the 
studies conducted with the CF-1 mouse are not relevant to human safety 
assessment. A Monte Carlo acute dietary exposure analysis predicted the 
percent population adjusted dose (PAD) used for the general population 
is 35% at the 99.9 percentile. Children 1-6 years old constitute the 
sub-population with the highest predicted exposure. The predicted 
percent PAD utilization for this subgroup is 70% for 99.9% of the 
individuals.
    EPA has established the RfD for abamectin at 0.0012 mg/kg/day from 
a 2-generation reproduction study in rats. The developmental NOAEL is 
0.12 mg/kg/day, and the developmental LOAEL is 0.40 mg/kg/day based on 
decreased pup body weight and viability during lactation, and increased 
incidence of retinal rosettes in F2b weanlings. An uncertainty factor 
of 100 to account for interspecies extrapolation (10x) and intraspecies 
variability (10x) was recommended. EPA has also retained the 10X safety 
factor for infants and children resulting in an aRfD of 0.00012 mg/kg/
day for appropriate populations dietary exposure analysis for abamectin 
in the most exposed population (non-nursing infants <1 year old) shows 
the percent PAD utilization to be only 19%. For average U.S. 
populations (48 states), dietary exposure for abamectin shows a minimal 
utilization of 7% of the PAD.
    ii. Drinking water. EPA modeling data (Generic expected 
environmental concentration/Screening concentration In Ground Water 
indicated worst case estimated environmental concentrations (EEC) of 
0.485 micrograms/liter (g/L) avermectin for acute and 0.239 
g/L for chronic exposure, both in surface water from the same 
use of abamectin on strawberries (the maximum use rate on the label). 
Refined modeling data Pesticide Root Zone Model-Exposure Analysis 
Modeling System (PRZM--EXAM) indicate a worst case EEC of 0.88 
g/L for acute and 0.57 g/L for chronic, both 
calculated for an abamectin use on strawberries grown on black plastic 
mulch. EPA noted and Novartis agrees that the certainty of the 
concentrations estimated for strawberries is low, due to uncertainty on 
the amount of runoff from plant beds covered in plastic mulch and 
uncertainty on the amount of degradation of abamectin on black plastic 
compared to soil.
    EPA and Novartis believe the estimates of abamectin exposure in 
water derived from the PRZM-EXAMS model are significantly overstated 
for several reasons. The PRZM-EXAMS model was designed to estimate 
exposure from ecological risk assessments and thus uses a scenario of a 
body of water approximating the size of a 1 hectare (2.5 acres) pond. 
This tends to overstate drinking water exposure levels for the 
following reasons. First, surface water source drinking water generally 
comes from bodies of water that are substantially larger than a 1 
hectare (2.5 acres) pond. Second, the modeled scenario also assumes 
that essentially the whole basin receives an application of the 
pesticide. Yet in virtually all cases, basins large enough to support a 
drinking water facility will contain a substantial fraction of the area 
which does not receive pesticide. Third, there is often at least some 
flow (in a river) or turnover (in a reservoir or lake) of the water so 
the persistence of the pesticide near the drinking water facility is 
usually overestimated. Fourth, even assuming a reservoir is directly 
adjacent to an agricultural field, the agricultural field may not be 
used to grow a crop on which the pesticide in question is registered 
for use. Fifth, the PRZM-EXAMS modeled scenario does not take into 
account reductions in residue loading due to applications of less than 
the maximum application rate or no treatment of the crop at all 
(percent crop treated data). Although there is a high degree of 
uncertainty to this analysis, these are the best available estimates of 
concentrations of abamectin in drinking water. Although the peak EEC of 
0.88 g/L slightly exceeds the acute drinking water level of 
concern, 0.76 g/L, considering the uncertain nature of the 
modeling estimate, EPA does not expect aggregate acute exposure to 
avermectin will pose an unacceptable risk to human health.
    2. Non-dietary exposure. Avermectin's registered residential uses 
include indoor crack/crevice and outdoor application to lawns. For lawn 
uses, EPA conducted a risk assessment for adult applicators and 
postapplication exposure to avermectin using the EPA's Draft SOPs for 
Residential Exposure Assessments. The highest predicted exposure, oral 
hand to mouth for children, resulted in a calculated margin of exposure 
of 14,000. For children's postapplication exposure to avermectin from 
indoor crack/crevice products, valid exposure studies demonstrate there 
is no exposure and therefore no risk for indoor residential

[[Page 41116]]

scenarios. Chronic exposures for the residential uses are not expected. 
Short-and intermediate-term risk for the registered uses do not exceed 
EPA's level of concern.

D. Cumulative Effects

    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 EPA stated in an FR notice 
published on April 7, 1999 (64 FR 16843-16850) (FRL-6070-6) that it 
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.

E. Safety Determination

    1. U.S. population. Using the exposure assumptions described above 
and based on the completeness and reliability of the toxicity data 
base, Novartis has calculated aggregate exposure levels for this 
chemical. The calculations show that chronic exposure is below 100 
percent of the RfD and the predicted acute exposure is below 100% of 
the acute RfD for all subpopulations. Novartis concludes that there is 
a reasonable certainty that no harm will result from aggregate exposure 
to abamectin residues.
    2. Infants and children. The FQPA authorizes the employment of an 
additional safety factor of up to 10X to guard against the possibility 
of prenatal or postnatal toxicity, or to account for an incomplete data 
base on toxicity or exposure. EPA has chosen to retain the FQPA 10X 
safety factor for abamectin based on several reasons including evidence 
of neurotoxicity, susceptibility of neo-natal rat pups, similarity to 
ivermectin, lack of a developmental neurotoxicity study, and concern 
for exposure to infants and children.
    It is the opinion of Novartis that a 3X safety factor is more 
appropriate for abamectin at this time. EPA has evaluated abamectin 
repeatedly since its introduction in 1985 and has found repeatedly that 
the level of dietary exposure is sufficiently low to provide ample 
margins of safety to guard against any potential adverse effects of 
abamectin. In addition, valid exposure studies demonstrate there is no 
exposure via indoor applications of abamectin products. Novartis states 
that the database for abamectin is complete and that the developmental 
neurotoxicity study is a new and not yet initially required study. 
Additionally, there is much more information regarding human risk 
potential than is the case with most pesticides, because of the 
widespread animal-drug and human-drug uses of ivermectin, the closely 
related analog of abamectin.
    It is the opinion of Novartis that the use of a full 10X safety 
factor to address risks to infants and children is not necessary. The 
established chronic endpoint for abamectin in the neonatal rat is 
overly conservative. Similar endpoints for ivermectin are not used by 
the Food and Drug Administration to support the allowable daily intake 
for ivermectin residues in food from treated animals. No evidence of 
toxicity was observed in neonatal rhesus monkeys after 14 days of 
repeated administration of 0.1 mg/kg/day (highest dose tested) and in 
juvenile rhesus monkeys after repeated administration of 1.0 mg/kg/day 
(highest dose tested). The comparative data on abamectin and ivermectin 
in primates also clearly demonstrate the dose response for exposure to 
either compound is much less steep than that seen in the neonatal rat. 
Single doses as high as 24 mg/kg of either abamectin or ivermectin in 
rhesus monkeys did not result in mortality; however, this dose was more 
than two times the LD50 in the adult rat and more than 20 
times the LD50 in the neonatal rat. The absence of a steep 
dose-response curve in primates provides a further margin of safety 
regarding the probability of toxicity occurring in infants or children 
exposed to avermectin compounds. The significant human clinical 
experience and widespread animal drug uses of ivermectin without 
systemically toxic, developmental, or postnatal effects supports the 
safety of abamectin to infants and children.

F. International Tolerances

     The Codex residue definition for MRLs is consistent with that of 
the United States. Codex MRLs for abamectin include cattle fat 0.1 mg/
kg; cattle kidney 0.05 mg/kg; cattle liver 0.1 mg/kg; citrus fruits 
0.01 mg/kg; cottonseed 0.01 mg/kg; hops, dry 0.1 mg/kg; cattle milk 
0.005 mg/kg; goat milk at 0.005 mg/kg; and potato 0.01 mg/kg.

[FR Doc. 99-19440 Filed 7-28-99; 8:45 am]
BILLING CODE 6560-50-F