Pesticide, food, and feed additive petitions: FMC Corp.,

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Federal Register: September 8, 1999 (Volume 64, Number 173)NoticesPage 48829-48836From the Federal Register Online via GPO Access [wais.access.gpo.gov]

DOCID:fr08se99-62

ENVIRONMENTAL PROTECTION AGENCY

PF-888; FRL-6097-6Notice 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-888, must be received on or before October 8, 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-888 in the subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Linda Deluise, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 401 M St., SW., Washington, DC 20460; telephone number: (703) 305-5428; and e-mail address: deluise.linda@epa.gov.

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 be affected. The North American

[Page 48830]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-888. 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-888 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: ``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 5.1/ 6.1 or ASCII file format. All comments in electronic form must be identified by docket control number PF-888. Electronic comments may also be filedonline 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. 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.

II. What Action is the Agency Taking?

EPA has received pesticide petitions as follows proposing the establishment and/or amendment of regulations for residues of certain pesticide chemicals 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 these petitions contain 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 petitions. Additional data may be needed before EPA rules on the petitions.

List of Subjects

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

Dated: August 23, 1999.

James Jones,

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

[Page 48831]

1. FMC Corporation

PP 9F6037, 4F4399, and 4F3012

EPA has received pesticide petitions (PP 9F6037, 4F4399, and 4F3012) from FMC Corporation, 1735 Market Street, Philadelphia, PA 19103 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 zeta-cypermethrin (<plus-minus>-<greek-a>-cyano(3-phenoxyphenyl)methyl (<plus-minus>) cis, trans 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate) in or on the raw agricultural commodity sugar beets, roots at 0.05 parts per million (ppm), sugar beets, tops at 0.20 ppm; sugarcane at 0.60 ppm; corn, grain (field, seed and pop) at 0.05 ppm; green onions at 6.0 ppm; alfalfa seed at 0.5 ppm; alfalfa forage at 10.0 ppm; and alfalfa hay at 30.0 ppm; and corn, sweet (K+CWHR) at 0.1 ppm; corn, forage and corn, fodder at 30.0 ppm; poultry, meat at 0.05 ppm; poultry, meat byproducts at 0.05 ppm; poultry, fat at 0.05 ppm; eggs at 0.05 ppm; meat of cattle, goats, hogs, horses, and sheep at 0.3 ppm; fat of cattle, goats, hogs, horses, and sheep at 2.0 ppm; and milk, fat at 1.0 ppm (reflecting 0.2 ppm in whole milk). 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.

A. Residue Chemistry

1. Plant metabolism. The metabolism of cypermethrin in plants is adequately understood. Studies have been conducted to delineate the metabolism of radiolabelled cypermethrin in various crops all showing similar results. The residue of concern is the parent compound only.

2. Analytical method. There is a practical analytical method for detecting and measuring levels of cypermethrin 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 (Gas Chromatography with Electron Capture Detection (GC/ECD).

3. Magnitude of residues. Crop field trial residue data from studies conducted at the maximum label rates for sugar beets, sugarcane, corn (field, seed, pop and sweet), green and bulb onions, and alfalfa, show that the proposed zeta-cypermethrin tolerances on sugar beets, roots at 0.05 ppm; sugar beets, tops at 0.20 ppm; sugarcane at 0.60 ppm; corn, grain (field, seed and pop) at 0.05 ppm; green onions at 6.0 ppm; alfalfa seed at 0.5 ppm, alfalfa forage at 10.0 ppm, and alfalfa hay at 30.0 ppm; corn, sweet (K+CWHR) at 0.1 ppm, and corn, forage and corn, fodder at 30.0 ppm will not be exceeded when the zeta-cypermethrin products labeled for these uses are used as directed.

B. Toxicological Profile

1. Acute toxicity. For the purposes of assessing acute dietary risk, FMC has used the no observed adverse effect level (NOAEL) of 3.8 milligrams/kilograms/day (mg/kg/day) based on the NOAEL of 7.5 mg/kg/ day from the cypermethrin chronic feeding/oncogenicity study in rats and a correction factor of two to account for the differences in the percentage of the biologically active isomer. The lowest observed adverse effect level (LOAEL) of 50.0 mg/kg/day was based on neurological signs which were displayed during week one of the study. This acute dietary endpoint is used to determine acute dietary risks to all population subgroups.

2. Genotoxicity. The following genotoxicity tests were all negative: in vivo chromosomal aberration in rat bone marrow cells; in vitro cytogenic chromosome aberration; unscheduled DNA synthesis; CHO/ HGPTT mutagen assay; weakly mutagenic: gene mutation (Ames).

3. Reproductive and developmental toxicity. No evidence of additional sensitivity to young rats was observed following prenatal or postnatal exposure to zeta-cypermethrin.

i. A 2-generation reproductive toxicity study with zeta- cypermethrin in rats demonstrated a NOAEL of 7.0 mg/kg/day and a LOAEL of 27.0 mg/kg/day for parental/systemic toxicity based on body weight, organ weight, and clinical signs. There were no adverse effects in reproductive performance. The NOAEL for reproductive toxicity was considered to be > 45.0 mg/kg/day, the highest dose tested.

ii. A developmental study with zeta-cypermethrin in rats demonstrated a maternal NOAEL of 12.5 mg/kg/day and a LOAEL of 25 mg/ kg/day based on decreased maternal body weight gain, food consumption and clinical signs. There were no signs of developmental toxicity at 35.0 mg/kg/day, the highest dose level tested.

iii. A developmental study with cypermethrin in rabbits demonstrated a maternal NOAEL of 100 mg/kg/day and a LOAEL of 450 mg/ kg/day based on decreased body weight gain. There were no signs of developmental toxicity at 700 mg/kg/day, the highest dose level tested.

4. Subchronic toxicity. Short- and intermediate-term toxicity. The NOAEL of 3.8 mg/kg/day based on the NOAEL 7.5 mg/kg/day from the cypermethrin chronic feeding/oncogenicity study in rats and a correction factor of two to account for the biologically active isomer would also be used for short- and intermediate-term MOE calculations (as well as acute, discussed in (1) above). The LOAEL of 50.0 mg/kg/day was based on neurological signs which were displayed during week one of the study.

5. Chronic toxicity-- i. The reference dose (RfD) of 0.0125 mg/kg/ day for zeta-cypermethrin is based on a NOAEL of 2.5 mg/kg/day from a cypermethrin rat reproduction study and an uncertainty factor of 200 (used to account for the differences in the percentage of the biologically active isomer). The endpoint effect of concern was based on consistent decreased body weight gain in both sexes at the LOAEL of 7.5 mg/kg/day.

ii. Cypermethrin is classified as a Group C Chemical (possible human carcinogen with limited evidence of carcinogenicity in animals) based upon limited evidence for carcinogenicity in female mice; assignment of a Q* has not been recommended.

6. Animal metabolism. The metabolism of cypermethrin in animals is adequately understood. Cypermethrin has been shown to be rapidly absorbed, distributed, and excreted in rats when administered orally. Cypermethrin is metabolized by hydrolysis and oxidation.

7. Metabolite toxicology. The Agency has previously determined that the metabolites of cypermethrin are not of toxicological concern and need not be included in the tolerance expression.

8. Endocrine disruption. No special studies investigating potential estrogenic or other endocrine effects of cypermethrin have been conducted. However, no evidence of such effects were reported in the standard battery of required toxicology studies which have been completed and found acceptable. Based on these studies, there is no evidence to suggest that cypermethrin has an adverse effect on the endocrine system.

C. Aggregate Exposure

1. Dietary exposure-- i. Food. Permanent tolerances, in support of registrations, currently exist for residues of zeta-cypermethrin on cottonseed; pecans; lettuce, head; onions, bulb; and cabbage and livestock commodities of cattle, goats, hogs, horses, and sheep (along with the associated meat and milk tolerances). For the purposes of

[Page 48832]assessing the potential dietary exposure for these existing and the subject proposed tolerances, FMC has utilized available information on anticipated residues, monitoring data and percent crop treated (PCT) as follows:

ii. Acute exposure and risk. Acute dietary exposure risk assessments are performed for a food-use pesticide if a toxicological study has indicated the possibility of an effect of concern occurring as a result of a 1-day or single exposure. For the purposes of assessing acute dietary risk for zeta-cypermethrin, FMC has used the NOAEL of 3.8 mg/kg/day based on the NOAEL of 7.5 mg/kg/day from the cypermethrin chronic feeding/oncogenicity study in rats and a correction factor of two to account for the differences in the percentage of the biologically active isomer. The LOAEL of 50.0 mg/kg/ day was based on neurological signs which were displayed during week one of this study. This acute dietary endpoint is used to determine acute dietary risks to all population subgroups. Available information on anticipated residues, monitoring data and PCT was incorporated into a Tier 3 analysis, using Monte Carlo modeling for commodities that may be consumed in a single serving. These assessments show that the margins of exposure (MOE) are significantly greater than the EPA standard of 100 for all subpopulations. The 95th percentile of exposure for the overall U. S. population was estimated to be 0.001934 mg/kg/day (MOE of 1964); 99th percentile 0.003844 mg/kg/day (MOE of 988); and 99.9th percentile 0.012574 mg/kg/day (MOE of 302). The 95th percentile of exposure for all infants < 1 year old was estimated to be 0.002195 mg/kg/day (MOE of 1730); 99th percentile 0.004976 mg/kg/day (MOE of 763); and 99.9th percentile 0.016942 mg/kg/day (MOE of 224). The 95th percentile of exposure for nursing infants < 1 year old was estimated to be 0.001090 mg/kg/day (MOE of 3484); 99th percentile 0.002516 mg/kg/ day (MOE of 1510); and 99.9th percentile 0.004140 mg/kg/day (MOE of 917). The 95th percentile of exposure for non-nursing infants < 1 year old was estimated to be 0.002288 mg/kg/day (MOE of 1660); 99th percentile 0.006164 mg/kg/day (MOE of 616); and 99.9th percentile 0.018741 mg/kg/day (MOE of 202). The 95th percentile of exposure for children 1 to 6 years old (the most highly exposed population subgroup) and children 7 to 12 years old was estimated to be, respectively, 0.002993 mg/kg/day (MOE of 1269) and 0.002286 mg/kg/day (MOE of 1662); 99th percentile 0.005234 mg/kg/day (MOE of 725) and 0.004178 (MOE of 909); and 99.9th percentile 0.034965 mg/kg/day (MOE of 108) and 0.014545 (MOE of 261). The 95th percentile of exposure for females (13+/nursing) was estimated to be 0.001448 mg/kg/day (MOE of 2623); 99th percentile 0.003594 mg/kg/day (MOE of 1057); and 99.9th percentile 0.011663 mg/kg/day (MOE of 325). Therefore, FMC concludes that the acute dietary risk of zeta-cypermethrin, as estimated by the dietary risk assessment, does not appear to be of concern.

iii. Chronic exposure and risk. The RfD of 0.0125 mg/kg/day for zeta-cypermethrin is based on a NOAEL of 2.5 mg/kg/day from a cypermethrin rat reproduction study and an uncertainty factor of 200 (used to account for the differences in the percentage of the biologically active isomer). The endpoint effect of concern was based on consistent decreased body weight gain in both sexes at the LOAEL of 7.5 mg/kg/day. A chronic dietary exposure/risk assessment has been performed for zeta-cypermethrin using the above RfD. Available information on anticipated residues, monitoring data and PCT 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 ARC is estimated to be 0.000379 mg/kg body weight (bwt)/day and utilizes 3.0% of the RfD for the overall U. S. population. The ARC for nursing infants (<1 year) and non-nursing infants (< 1 year) is estimated to be 0.000104 mg/kg bwt/day and 0.000509 mg/kg bwt/day and utilizes 0.8% and 4.1% of the RfD, respectively. The ARC for children 1-6 years old (subgroup most highly exposed) and children 7-12 years old is estimated to be 0.000904 mg/kg bwt/day and 0.000544 mg/kg bwt/day and utilizes 7.2% and 4.4% of the RfD, respectively. The ARC for females (13+/ nursing) is estimated to be 0.000365 mg/kg bwt/day and utilizes 2.9% of the RfD. Generally speaking, the EPA has no cause for concern if the total dietary exposure from residues for uses for which there are published and proposed tolerances is less than 100% of the RfD. Therefore, FMC concludes that the chronic dietary risk of zeta- cypermethrin, as estimated by the dietary risk assessment, does not appear to be of concern.

iv. Drinking water. Laboratory and field data have demonstrated that cypermethrin is immobile in soil and will not leach into ground water. Other data show that cypermethrin is virtually insoluble in water and extremely lipophilic. As a result, FMC concludes that residues reaching surface waters from field runoff will quickly adsorb to sediment particles and be partitioned from the water column. Further, a screening evaluation of leaching potential of a typical pyrethroid was conducted using EPA's Pesticide Root Zone Model (PRZM3). Based on this screening assessment, the potential concentrations of a pyrethroid in ground water at depths of 1 and 2 meters are essentially zero (<0.001 parts per billion). Surface water concentrations for pyrethroids were estimated using PRZM3 and Exposure Analysis Modeling System (EXAMS) using standard EPA cotton runoff and Mississippi pond scenarios. The maximum concentration predicted in the simulated pond was 0.052 parts per billion. Concentrations in actual drinking water would be much lower than the levels predicted in the hypothetical, small, stagnant farm pond model since drinking water derived from surface water would normally be treated before consumption. Based on these analyses, the contribution of water to the dietary risk estimate is negligible. Therefore, FMC concludes that together these data indicate that residues are not expected to occur in drinking water.

2. Non-dietary exposure. Zeta-cypermethrin is registered for agricultural crop applications only, therefore non-dietary exposure assessments are not warranted.

D. Cumulative Effects

In consideration of potential cumulative effects of cypermethrin and other substances that may have a common mechanism of toxicity, to our knowledge there are currently no available data or other reliable information indicating that any toxic effects produced by cypermethrin would be cumulative with those of other chemical compounds; thus only the potential risks of cypermethrin have been considered in this assessment of its aggregate exposure. FMC intends to submit information for the EPA to consider concerning potential cumulative effects of cypermethrin consistent with the schedule established by EPA in the Federal Register of August 4, 1997 (62 FR 42020) (FRL-5734-6) and other EPA publications pursuant to the Food Quality Protection Act.

E. Safety Determination

1. U.S. population. Based on a complete and reliable toxicology data base, the RfD for zeta-cypermethrin is 0.0125 mg/kg/day, based on a NOAEL of

[Page 48833]2.5 mg/kg/day and a LOAEL of 7.5 mg/kg/day from the cypermethrin rat reproduction study and an uncertainty factor of 200. Available information on anticipated residues, monitoring data and PCT was incorporated into an analysis to estimate the ARC for 26 population subgroups. The ARC is generally considered a more realistic estimate than an estimate based on tolerance level residues. The ARC is estimated to be 0.000379 mg/kg body weight (bwt)/day and utilizes 3.0% of the RfD for the overall U. S. population. The ARC for nursing infants (<1 year) and non-nursing infants (<1 year) is estimated to be 0.000104 mg/kg bwt/day and 0.000509 mg/kg bwt/day and utilizes 0.8% and 4.1% of the RfD, respectively. The ARC for children 1-6 years old (subgroup most highly exposed) and children 7-12 years old are estimated to be 0.000904 mg/kg bwt/day and 0.000544 mg/kg bwt/day and utilizes 7.2% and 4.4% of the RfD, respectively. The ARC for females (13+/nursing) is estimated to be 0.000365 mg/kg bwt/day and utilizes 2.9% of the RfD. Generally speaking, the EPA has no cause for concern if the total dietary exposure from residues for uses for which there are published and proposed tolerances is less than 100% of the RfD. Therefore, FMC concludes that the chronic dietary risk of zeta- cypermethrin, as estimated by the aggregate risk assessment, does not appear to be of concern.

The 95th percentile of exposure for the overall U. S. population was estimated to be 0.001934 mg/kg/day (MOE of 1964); 99th percentile 0.003844 mg/kg/day (MOE of 988); and 99.9th percentile 0.012574 mg/kg/ day (MOE of 302). The 95th percentile of exposure for all infants < 1 year old was estimated to be 0.002195 mg/kg/day (MOE of 1730); 99th percentile 0.004976 mg/kg/day (MOE of 763); and 99.9th percentile 0.016942 mg/kg/day (MOE of 224). The 95th percentile of exposure for nursing infants < 1 year old was estimated to be 0.001090 mg/kg/day (MOE of 3484); 99th percentile 0.002516 mg/kg/day (MOE of 1510); and 99.9th percentile 0.004140 mg/kg/day (MOE of 917). The 95th percentile of exposure for non-nursing infants < 1 year old was estimated to be 0.002288 mg/kg/day (MOE of 1660); 99th percentile 0.006164 mg/kg/day (MOE of 616); and 99.9th percentile 0.018741 mg/kg/day (MOE of 202). The 95th percentile of exposure for children 1 to 6 years old (the most highly exposed population subgroup) and children 7 to 12 years old was estimated to be, respectively, 0.002993 mg/kg/day (MOE of 1269) and 0.002286 mg/kg/day (MOE of 1662); 99th percentile 0.005234 mg/kg/day (MOE of 725) and 0.004178 (MOE of 909); and 99.9th percentile 0.034965 mg/kg/day (MOE of 108) and 0.014545 (MOE of 261). The 95th percentile of exposure for females (13+/nursing) was estimated to be 0.001448 mg/ kg/day (MOE of 2623); 99th percentile 0.003594 mg/kg/day (MOE of 1057); and 99.9th percentile 0.011663 mg/kg/day (MOE of 325). Therefore, FMC concludes that there is reasonable certainty that no harm will result from acute exposure to zeta-cypermethrin.

2. Infants and children-- i. General. In assessing the potential for additional sensitivity of infants and children to residues of zeta- cypermethrin, FMC considered data from developmental toxicity studies in the rat and rabbit, and a 2-generation reproductive study in the rat. The data demonstrated no indication of increased sensitivity of rats to zeta-cypermethrin or rabbits to cypermethrin in utero and/or postnatal exposure to zeta-cypermethrin or cypermethrin. The developmental toxicity studies are designed to evaluate adverse effects on the developing organism resulting from pesticide exposure during prenatal development to one or both parents. Reproduction studies provide information relating to effects from exposure to the pesticide on the reproductive capability of mating animals and data on systemic toxicity. FFDCA section 408 provides that EPA may apply an additional margin of safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the data base.

ii. Developmental toxicity studies. In the prenatal developmental toxicity studies in rats and rabbits, there was no evidence of developmental toxicity at the highest doses tested (35.0 mg/kg/day in rats and 700 mg/kg/day in rabbits). Decreased body weight gain was observed at the maternal LOAEL in each study; the maternal NOAEL was established at 12.5 mg/kg/day in rats and 100 mg/kg/day in rabbits.

iii. Reproductive toxicity study. In the 2-generation reproduction study in rats, offspring toxicity (body weight) and parental toxicity (body weight, organ weight, and clinical signs) was observed at 27.0 mg/kg/day and greater. The parental systemic NOAEL was 7.0 mg/kg/day and the parental systemic LOAEL was 27.0 mg/kg/day. There were no developmental (pup) or reproductive effects up to 45.0 mg/kg/day, highest dose tested.

iv. Prenatal and postnatal sensitivity. There was no evidence of developmental toxicity in the studies at the highest doses tested in the rat (35.0 mg/kg/day) or in the rabbit (700 mg/kg/day). Therefore, there is no evidence of a special dietary risk (either acute or chronic) for infants and children which would require an additional safety factor.

v. Postnatal. Based on the absence of pup toxicity up to dose levels which produced toxicity in the parental animals, there is no evidence of special postnatal sensitivity to infants and children in the rat reproduction study.

vi. Conclusion. Based on the above, FMC concludes that reliable data support use of the standard 100-fold uncertainty factor, and that an additional uncertainty factor is not needed to protect the safety of infants and children. As stated above, aggregate exposure assessments utilized significantly less than 1% of the RfD for either the entire U. S. population or any of the 26 population subgroups including infants and children. Therefore, it may be concluded that there is reasonable certainty that no harm will result to infants and children from aggregate exposure to cypermethrin residues.

F. International Tolerances

There are no Codex, Canadian, or Mexican residue limits for residues of zeta-cypermethrin in or on sugar beets, sugarcane, corn (field, seed, pop and sweet), green and bulb onions, and alfalfa.

2. FMC Corporation

PP 9F6040

EPA has received a pesticide petition (PP 9F6040) from FMC Corporation, 1735 Market Street, Philadelphia, PA 19103 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 zeta-cypermethrin (<plus-minus>-<greek-a>- cyano(3-phenoxyphenyl)methyl (<plus-minus>) cis, trans 3-(2,2- dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate) in or on the raw agricultural commodity rice, grain at 1.2 ppm; rice, straw at 2.0 ppm; and rice, hulls at 16.0 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.

[Page 48834]A. Residue Chemistry

1. Plant metabolism. The metabolism of cypermethrin in plants is adequately understood. Studies have been conducted to delineate the metabolism of radiolabelled cypermethrin in various crops all showing similar results. The residue of concern is the parent compound only.

2. Analytical method. There is a practical analytical method for detecting and measuring levels of cypermethrin 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 (Gas Chromatography with Electron Capture Detection (GC/ECD).

3. Magnitude of residues. Crop field trial residue data from studies conducted at the maximum label rates for rice grain show that the proposed zeta-cypermethrin tolerances on rice, grain at 1.2 ppm, rice, straw at 2.0 ppm and rice, hulls at 16.0 ppm will not be exceeded when the zeta-cypermethrin products labeled for these uses are used as directed.

B. Toxicological Profile

1. Acute toxicity. For the purposes of assessing acute dietary risk, FMC has used the NOAEL of 3.8 mg/kg/day based on the NOAEL of 7.5 mg/kg/day from the cypermethrin chronic feeding/oncogenicity study in rats and a correction factor of two to account for the differences in the percentage of the biologically active isomer. The LOAEL) of 50.0 mg/kg/day was based on neurological signs which were displayed during week one of the study. This acute dietary endpoint is used to determine acute dietary risks to all population subgroups.

2. Genotoxicity. The following genotoxicity tests were all negative: in vivo chromosomal aberration in rat bone marrow cells; in vitro cytogenic chromosome aberration; unscheduled DNA synthesis; CHO/ HGPTT mutagen assay; weakly mutagenic: gene mutation (Ames).

3. Reproductive and developmental toxicity. No evidence of additional sensitivity to young rats was observed following prenatal or postnatal exposure to zeta-cypermethrin.

i. A 2-generation reproductive toxicity study with zeta- cypermethrin in rats demonstrated a NOAEL of 7.0 mg/kg/day and a LOAEL of 27.0 mg/kg/day for parental/systemic toxicity based on body weight, organ weight, and clinical signs. There were no adverse effects in reproductive performance. The NOAEL for reproductive toxicity was considered to be > 45.0 mg/kg/day, the highest dose tested.

ii. A developmental study with zeta-cypermethrin in rats demonstrated a maternal NOAEL of 12.5 mg/kg/day and a LOAEL of 25 mg/ kg/day based on decreased maternal body weight gain, food consumption and clinical signs. There were no signs of developmental toxicity at 35.0 mg/kg/day, the highest dose level tested.

iii. A developmental study with cypermethrin in rabbits demonstrated a maternal NOAEL of 100 mg/kg/day and a LOAEL of 450 mg/ kg/day based on decreased body weight gain. There were no signs of developmental toxicity at 700 mg/kg/day, the highest dose level tested.

4. Subchronic toxicity. Short- and intermediate-term toxicity. The NOAEL of 3.8 mg/kg/day based on the NOAEL 7.5 mg/kg/day from the cypermethrin chronic feeding/oncogenicity study in rats and a correction factor of two to account for the biologically active isomer would also be used for short- and intermediate-term MOE calculations (as well as acute, discussed in (1) above). The LOAEL of 50.0 mg/kg/day was based on neurological signs which were displayed during week one of the study.

5. Chronic toxicity-- i. The RfD of 0.0125 mg/kg/day for zeta- cypermethrin is based on a NOAEL of 2.5 mg/kg/day from a cypermethrin rat reproduction study and an uncertainty factor of 200 (used to account for the differences in the percentage of the biologically active isomer). The endpoint effect of concern was based on consistent decreased body weight gain in both sexes at the LOAEL of 7.5 mg/kg/day.

ii. Cypermethrin is classified as a Group C Chemical (possible human carcinogen with limited evidence of carcinogenicity in animals) based upon limited evidence for carcinogenicity in female mice; assignment of a Q* has not been recommended.

6. Animal metabolism. The metabolism of cypermethrin in animals is adequately understood. Cypermethrin has been shown to be rapidly absorbed, distributed, and excreted in rats when administered orally. Cypermethrin is metabolized by hydrolysis and oxidation.

7. Metabolite toxicology. The Agency has previously determined that the metabolites of cypermethrin are not of toxicological concern and need not be included in the tolerance expression.

8. Endocrine disruption. No special studies investigating potential estrogenic or other endocrine effects of cypermethrin have been conducted. However, no evidence of such effects were reported in the standard battery of required toxicology studies which have been completed and found acceptable. Based on these studies, there is no evidence to suggest that cypermethrin has an adverse effect on the endocrine system.

C. Aggregate Exposure

1. Dietary exposure-- i. Food. Permanent tolerances, in support of registrations, currently exist for residues of zeta-cypermethrin on cottonseed; pecans; lettuce, head; onions, bulb; and cabbage and livestock commodities of cattle, goats, hogs, horses, and sheep (and their associated meat and milk tolerances). For the purposes of assessing the potential dietary exposure for these existing and the subject proposed tolerances, FMC has utilized available information on anticipated residues, monitoring data and PCT as follows:

ii. Acute exposure and risk. Acute dietary exposure risk assessments are performed for a food-use pesticide if a toxicological study has indicated the possibility of an effect of concern occurring as a result of a 1-day or single exposure. For the purposes of assessing acute dietary risk for zeta-cypermethrin, FMC has used the NOAEL of 3.8 mg/kg/day based on the NOAEL of 7.5 mg/kg/day from the cypermethrin chronic feeding/oncogenicity study in rats and a correction factor of two to account for the differences in the percentage of the biologically active isomer. The LOAEL of 50.0 mg/kg/ day was based on neurological signs which were displayed during week one of this study. This acute dietary endpoint is used to determine acute dietary risks to all population subgroups. Available information on anticipated residues, monitoring data and PCT was incorporated into a Tier 3 analysis, using Monte Carlo modeling for commodities that may be consumed in a single serving. These assessments show that the margins of exposure (MOE) are significantly greater than the EPA standard of 100 for all subpopulations. The 95th percentile of exposure for the overall U. S. population was estimated to be 0.001049 mg/kg/day (MOE of 3622); 99th percentile 0.003166 mg/kg/day (MOE of 1200); and 99.9th percentile 0.012313 mg/kg/day (MOE of 308). The 95th percentile of exposure for all infants < 1 year old was estimated to be 0.000610 mg/kg/day (MOE of 6229); 99th percentile 0.001955 mg/kg/day (MOE of 1943); and 99.9th percentile 0.019362 mg/kg/day (MOE of 196). The 95th percentile of exposure for nursing infants < 1 year old was estimated to be 0.000283 mg/kg/day (MOE of 13418); 99th percentile 0.001141 mg/ kg/day

[Page 48835](MOE of 3330); and 99.9th percentile 0.002424 mg/kg/day (MOE of 1567). The 95th percentile of exposure for non-nursing infants < 1 year old was estimated to be 0.000657 mg/kg/day (MOE of 5784); 99th percentile 0.007700 mg/kg/day (MOE of 493); and 99.9th percentile 0.019395 mg/kg/ day (MOE of 195). The 95th percentile of exposure for children 1 to 6 years old (the most highly exposed population subgroup) and children 7 to 12 years old was estimated to be, respectively, 0.001184 mg/kg/day (MOE of 3208) and 0.001177 mg/kg/day (MOE of 3227); 99th percentile 0.003894 mg/kg/day (MOE of 975) and 0.003337 (MOE of 1138); and 99.9th percentile 0.034204 mg/kg/day (MOE of 111) and 0.013940 (MOE of 272). The 95th percentile of exposure for females (13+/nursing) was estimated to be 0.001070 mg/kg/day (MOE of 3549); 99th percentile 0.003318 mg/kg/ day (MOE of 1145); and 99.9th percentile 0.011127 mg/kg/day (MOE of 341). Therefore, FMC concludes that the acute dietary risk of zeta- cypermethrin, as estimated by the dietary risk assessment, does not appear to be of concern.

iii. Chronic exposure and risk. The RfD of 0.0125 mg/kg/day for zeta-cypermethrin is based on a NOAEL of 2.5 mg/kg/day from a cypermethrin rat reproduction study and an uncertainty factor of 200 (used to account for the differences in the percentage of the biologically active isomer). The endpoint effect of concern was based on consistent decreased body weight gain in both sexes at the LOAEL of 7.5 mg/kg/day. A chronic dietary exposure/risk assessment has been performed for zeta-cypermethrin using the above RfD. Available information on anticipated residues, monitoring data and PCT was incorporated into the analysis to estimate the ARC. The ARC is generally considered a more realistic estimate than an estimate based on tolerance level residues. The ARC is estimated to be 0.000158 mg/kg body weight (bwt)/day and utilizes 1.3% of the RfD for the overall U. S. population. The ARC for non-nursing infants (<1 year) and nursing infants (<1 year) is estimated to be 0.000212 mg/kg/day and 0.000032 mg/kg/day and utilizes 1.7% and 0.3% of the RfD, respectively. The ARC for children 1-6 years old (subgroup most highly exposed) and children 7-12 years old is estimated to be 0.000268 mg/kg bwt/day and 0.000168 mg/kg bwt/day and utilizes 2.1% and 1.3% of the RfD, respectively. The ARC for females (13+/nursing) is estimated to be 0.000170 mg/kg bwt/day and utilizes 1.4% of the RfD. Generally speaking, the EPA has no cause for concern if the total dietary exposure from residues for uses for which there are published and proposed tolerances is less than 100% of the RfD. Therefore, FMC concludes that the chronic dietary risk of zeta-cypermethrin, as estimated by the dietary risk assessment, does not appear to be of concern.

vi. Drinking water. Laboratory and field data have demonstrated that cypermethrin is immobile in soil and will not leach into ground water. Other data show that cypermethrin is virtually insoluble in water and extremely lipophilic. As a result, FMC concludes that residues reaching surface waters from field runoff will quickly adsorb to sediment particles and be partitioned from the water column. Further, a screening evaluation of leaching potential of a typical pyrethroid was conducted using EPA's Pesticide Root Zone Model (PRZM3). Based on this screening assessment, the potential concentrations of a pyrethroid in ground water at depths of 1 and 2 meters are essentially zero (<0.001 parts per billion). Surface water concentrations for pyrethroids were estimated using PRZM3 and Exposure Analysis Modeling System (EXAMS) using standard EPA cotton runoff and Mississippi pond scenarios. The maximum concentration predicted in the simulated pond was 0.052 ppb. Concentrations in actual drinking water would be much lower than the levels predicted in the hypothetical, small, stagnant farm pond model since drinking water derived from surface water would normally be treated before consumption. Based on these analyses, the contribution of water to the dietary risk estimate is negligible. Therefore, FMC concludes that together these data indicate that residues are not expected to occur in drinking water.

2. Non-dietary exposure. Zeta-cypermethrin is registered for agricultural crop applications only, therefore non-dietary exposure assessments are not warranted.

D. Cumulative Effects

In consideration of potential cumulative effects of cypermethrin and other substances that may have a common mechanism of toxicity, to our knowledge there are currently no available data or other reliable information indicating that any toxic effects produced by cypermethrin would be cumulative with those of other chemical compounds; thus only the potential risks of cypermethrin have been considered in this assessment of its aggregate exposure. FMC intends to submit information for the EPA to consider concerning potential cumulative effects of cypermethrin consistent with the schedule established by EPA in Federal Register August 4, 1997 (62 FR 42020) and other EPA publications pursuant to the Food Quality Protection Act.

E. Safety Determination

1. U.S. population. Based on a complete and reliable toxicology data base, the RfD for zeta-cypermethrin is 0.0125 mg/kg/day, based on a NOAEL of 2.5 mg/kg/day and a LOAEL of 7.5 mg/kg/day from the cypermethrin rat reproduction study and an uncertainty factor of 200. Available information on anticipated residues, monitoring data and PCT was incorporated into an analysis to estimate the ARC for 26 population subgroups. The ARC is generally considered a more realistic estimate than an estimate based on tolerance level residues. The ARC is estimated to be 0.000158 mg/kg body weight (bwt)/day and utilizes 1.3% of the RfD for the overall U. S. population. The ARC for non-nursing infants (<1 year) and nursing infants (<1 year) is estimated to be 0.000212 mg/kg/day and 0.000032 mg/kg/day and utilizes 1.7% and 0.3% of the RfD, respectively. The ARC for children 1-6 years old (subgroup most highly exposed) and children 7-12 years old is estimated to be 0.000268 mg/kg bwt/day and 0.000168 mg/kg bwt/day and utilizes 2.1% and 1.3% of the RfD, respectively. The ARC for females (13+/nursing) is estimated to be 0.000170 mg/kg bwt/day and utilizes 1.4% of the RfD. Generally speaking, the EPA has no cause for concern if the total dietary exposure from residues for uses for which there are published and proposed tolerances is less than 100% of the RfD. Therefore, FMC concludes that the chronic dietary risk of zeta-cypermethrin, as estimated by the aggregate risk assessment, does not appear to be of concern.

The 95th percentile of exposure for the overall U. S. population was estimated to be 0.001049 mg/kg/day (MOE of 3622); 99th percentile 0.003166 mg/kg/day (MOE of 1200); and 99.9th percentile 0.012313 mg/kg/ day (MOE of 308). The 95th percentile of exposure for all infants < 1 year old was estimated to be 0.000610 mg/kg/day (MOE of 6229); 99th percentile 0.001955 mg/kg/day (MOE of 1943); and 99.9th percentile 0.019362 mg/kg/day (MOE of 196). The 95th percentile of exposure for nursing infants < 1 year old was estimated to be 0.000283 mg/kg/day (MOE of 13418); 99th percentile 0.001141 mg/kg/day (MOE of 3330); and 99.9th percentile 0.002424 mg/kg/day (MOE of 1567). The 95th percentile of

[Page 48836]exposure for non-nursing infants < 1 year old was estimated to be 0.000657 mg/kg/day (MOE of 5784); 99th percentile 0.007700 mg/kg/day (MOE of 493); and 99.9th percentile 0.019395 mg/kg/day (MOE of 195). The 95th percentile of exposure for children 1 to 6 years old (the most highly exposed population subgroup) and children 7 to 12 years old was estimated to be, respectively, 0.001184 mg/kg/day (MOE of 3208) and 0.001177 mg/kg/day (MOE of 3227); 99th percentile 0.003894 mg/kg/day (MOE of 975) and 0.003337 (MOE of 1138); and 99.9th percentile 0.034204 mg/kg/day (MOE of 111) and 0.013940 (MOE of 272). The 95th percentile of exposure for females (13+/nursing) was estimated to be 0.001070 mg/ kg/day (MOE of 3549); 99th percentile 0.003318 mg/kg/day (MOE of 1145); and 99.9th percentile 0.011127 mg/kg/day (MOE of 341). Therefore, FMC concludes that there is reasonable certainty that no harm will result from acute exposure to zeta-cypermethrin.

2. Infants and children-- i. General. In assessing the potential for additional sensitivity of infants and children to residues of zeta- cypermethrin, FMC considered data from developmental toxicity studies in the rat and rabbit, and a 2-generation reproductive study in the rat. The data demonstrated no indication of increased sensitivity of rats to zeta-cypermethrin or rabbits to cypermethrin in utero and/or postnatal exposure to zeta-cypermethrin or cypermethrin. The developmental toxicity studies are designed to evaluate adverse effects on the developing organism resulting from pesticide exposure during prenatal development to one or both parents. Reproduction studies provide information relating to effects from exposure to the pesticide on the reproductive capability of mating animals and data on systemic toxicity. FFDCA section 408 provides that EPA may apply an additional margin of safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the data base.

ii. Developmental toxicity studies. In the prenatal developmental toxicity studies in rats and rabbits, there was no evidence of developmental toxicity at the highest doses tested (35.0 mg/kg/day in rats and 700 mg/kg/day in rabbits). Decreased body weight gain was observed at the maternal LOAEL in each study; the maternal NOAEL was established at 12.5 mg/kg/day in rats and 100 mg/kg/day in rabbits.

iii. Reproductive toxicity study. In the 2-generation reproduction study in rats, offspring toxicity (body weight) and parental toxicity (body weight, organ weight, and clinical signs) was observed at 27.0 mg/kg/day and greater. The parental systemic NOAEL was 7.0 mg/kg/day and the parental systemic LOAEL was 27.0 mg/kg/day. There were no developmental (pup) or reproductive effects up to 45.0 mg/kg/day, highest dose tested.

iv. Prenatal and postnatal sensitivity. There was no evidence of developmental toxicity in the studies at the highest doses tested in the rat (35.0 mg/kg/day) or in the rabbit (700 mg/kg/day). Therefore, there is no evidence of a special dietary risk (either acute or chronic) for infants and children which would require an additional safety factor.

v. Postnatal. Based on the absence of pup toxicity up to dose levels which produced toxicity in the parental animals, there is no evidence of special postnatal sensitivity to infants and children in the rat reproduction study.

vi. Conclusion. Based on the above, FMC concludes that reliable data support use of the standard 100-fold uncertainty factor, and that an additional uncertainty factor is not needed to protect the safety of infants and children. As stated above, aggregate exposure assessments utilized significantly less than 1% of the RfD for either the entire U. S. population or any of the 26 population subgroups including infants and children. Therefore, it may be concluded that there is reasonable certainty that no harm will result to infants and children from aggregate exposure to cypermethrin residues.

F. International Tolerances

There are no Codex, Canadian, or Mexican residue limits for residues of zeta-cypermethrin in or on rice grain, straw or hulls.

FR Doc. 99-23198Filed9-7-99; 8:45 amBILLING CODE 6560-50-F

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