Pesticide, food, and feed additive petitions: Novartis Crop Protection, Inc.,

[Federal Register: April 7, 2000 (Volume 65, Number 68)]

[Notices]

[Page 18328-18332]

From the Federal Register Online via GPO Access [wais.access.gpo.gov]

[DOCID:fr07ap00-82]

ENVIRONMENTAL PROTECTION AGENCY

[PF-930; FRL-6499-4]

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.

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-930, must be received on or before May 8, 2000.

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.'' To ensure proper receipt by EPA, it is imperative that you identify docket control number PF-930 in the subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Thomas C. Harris, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (703) 308-9423; e- mail address: harris.thomas@epa.gov.

SUPPLEMENTARY INFORMATION:

1. General Information

   1. 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 Codes

      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 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 under ``FOR FURTHER INFORMATION CONTACT.''

   2. 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-930. 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.

   3. 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-930 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

         [[Page 18329]]

         (7502C), Office of Pesticide Programs (OPP), Environmental Protection Agency, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW., 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: ``opp-docket@epa.gov,'' 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 6.1/ 8.0 or ASCII file format. All comments in electronic form must be identified by docket control number PF-930. Electronic comments may also be filedonline at many Federal Depository Libraries.

   4. 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 under ``FOR FURTHER INFORMATION CONTACT.''

   5. 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. Make sure to submit your comments by the deadline in this notice.

      7. 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.

2. 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: March 28, 2000. James Jones, Director, Registration Division, Office of Pesticide Programs.

   Summary of Petition

   The petitioner summary of the pesticide petition is printed below as required by section 408(d)(3) of the FFDCA. The summary of the petition was prepared by the petitioner and represents the view of the petitioner. EPA is publishing the petition summary verbatim without editing it 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 residues or an explanation of why no such method is needed.

   Novartis Crop Protection, Inc.

   PP 9F5047

   EPA has received a pesticide petition (PP 9F5047) from Novartis Crop Protection, Inc., P.O. Box 18300, Greensboro, NC 27419 proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance for residues of abamectin (avermectin B1) and or its delta 8,9-isomer in or on the raw agricultural commodities plums at 0.01 parts per million (ppm), fruiting vegetables (except Cucurbits) group at 0.02 ppm, and leafy vegetables (except Brassica) group at 0.10 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 support granting of the petition. Additional data may be needed before EPA rules on the petition.

   1. Residue Chemistry

      1. Plant metabolism. The metabolism of abamectin in plants 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 B1aand a maximum of 20% avermectin B1band the delta 8,9-isomer of the B1aand of the B1bcomponents of the parent insecticide. Animal metabolism also has been studied but is not relevant to this petition, since the crops involved are not significant animal feed items. Under photolytic conditions in the laboratory and in the field, abamectin under goes 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 B1ais 6.5 hours.

      2. Analytical method. The analytical method involves homogenization, filtration, partition and cleanup with analysis by HPLC-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. Abamectin was applied to leaf lettuce and spinach in eleven trials in the following states: Colorado, California (4) sites; Florida, Texas, Arizona leaf lettuce; South Carolina spinach; New Jersey spinach; and New York leaf lettuce. Nine field trials were conducted in the principal

      [[Page 18330]]

      plum growing areas of the United States including California (6), Michigan (1), Oregon (1) and Washington (1). This data support the proposed tolerances of 0.01 ppm for residues of abamectin on plums and 0.10 ppm on leafy vegetables (except Brassica) group. Tolerances and residue data on tomatoes and peppers support the fruiting vegetable (except Cucurbits) group tolerance.

   2. Toxicological Profile

      1. Acute toxicity. The data base includes the following studies: A rat acute oral study with a LD50of 4.4 to 11.8 milligrams/ kilograms (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 LD50greater than 80 mg/kg; a rabbit acute dermal study with a LD50greater than 2,000 mg/kg; a rat acute inhalation study with a LC50greater than 5.73 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 no observed adverse effects level (NOAEL) of 1.0 mg/kg based upon emesis at 2.0 mg/kg.

      2. Genotoxicity. 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. 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 NOAEL was greater than 0.4 mg/kg/day (HDT). 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 (HDT). 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.

      6. Animal metabolism. Rats were given oral doses of 0.14 or 1.4 mg/ kg/day of abamectin or 1.4 mg/kg/day of the delta-8,9 isomer. Over 7 days, the percent 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 through 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 multi-generational 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.

   3. Aggregate Exposure

      Dietary exposure--i. Food. The acute dietary reference dose (RfD) is 0.0025 mg/kg/day from a 1-year dog study. The NOAEL is 0.25 mg/kg/ day, and the lowest observed adverse effect level (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 RfD used for the general population is 39.9% at the 99.9%. Children 1-6 years constitute the sub-population with the highest predicted exposure. The predicted percent RfD utilization for

      [[Page 18331]]

      this subgroup is 69.5% 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 RfD of 0.00012 mg/kg/ day for appropriate population dietary exposure analysis for abamectin in the most exposed population (non-nursing infants 1-year old) shows the percent RfD utilization to be only 20.0%. For the average U.S. population (48 contiguous states), dietary exposure for abamectin shows a minimal utilization of 9.4% of the RfD.

      ii. Drinking water. EPA modeling data (Generic Expected Environmental Concentration/Screening Concentration In Ground Water (GENEEC/SCIGROW)) indicated the worst case estimated environmental concentrations (EEC) of 0.485 ug/L avermectin for acute and 0.239 ug/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 ug/L for acute and 0.57 ug/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 run off from plant beds covered in plastic mulch and uncertainty on the amount of degradation of abamectin on black plastic compared to soil.

      Novartis believes the estimates of abamectin exposure in water derived from the PRZM-EXAMS model are overstated for several reasons. The PRZM-EXAMS model was designed to estimate exposure from ecological risk assessments and thus use 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.

      1. Surface water source drinking water generally comes from bodies of water that is substantially larger than a 1 hectare (2.5 acres) pond.

      2. 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.

      3. There is often at least some flow in a river or turnover in a reservoir or lake of water persistence to the pesticide near the drinking water facility is usually over estimated.

      4. 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.

      5. 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, this is the best available estimate of concentrations of abamectin in drinking water. Although the peak EEC of 0.88 ug/L slightly exceeds the acute DWLOC, 0.76 ug/L, considering the uncertain nature of the modeling estimate, Novartis does not expect aggregate acute exposure to avermectin will pose an unacceptable risk to human health.

      2. Non-dietary exposure. Avermectin's registered residential use include indoor crack/crevice and outdoor application to lawns. For lawn use, EPA conducted a risk assessment for adult applicators and post application exposure to avermectin using EPA's Draft SOP's for residential exposure assessments. The highest predicted exposure oral hand to mouth for children, resulted in a calculated margin of exposure 14,000. For children's post application exposure to avermectin from indoor crack/crevice products, valid exposure studies demonstrate there is no exposure and therefore no risk for indoor residential scenarios. Short-and intermediate-term risk for registered uses do not exceed EPA's level of concern. Chronic exposure and risk for the residential use is not expected. Short-and intermediate-term exposure and risk for the registered uses do not exceed EPA's level of concern.

   4. Cumulative Effects

      Section 408(b)(2)(D)(v) requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency considers ``available information'' concerning the cumulative effects of a particular pesticide residue and ``other substances that have a common mechanism of toxicity.'' EPA stated in the FR notice published on April 7, 1999, 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.

   5. 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% 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 neonatal 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 data base for abamectin is complete and that the developmental neurotoxicity study is a new and not yet initially required study. Additionally, there is 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

      [[Page 18332]]

      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 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 LD50in the adult rat and more than 20 times the LD50in the neonatal rat. The absence of 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.

   6. International Tolerances

      Codex has established an abamectin Maximum Residue Level of 0.02 ppm for peppers. The fruiting vegetable tolerance of 0.02 ppm for abamectin is harmonized with Codex.

      [FR Doc. 00-8263Filed4-6-00; 8:45 am]

      BILLING CODE 6560-50-F