66 FR 225 pgs. 58477-58481 - Notice of Filing a Pesticide Petition to Establish a Tolerance fora Certain Pesticide Chemical in or on Food
Type: NOTICEVolume: 66Number: 225Pages: 58477 - 58481
Docket number: [PF-1042; FRL-6799-1]
FR document: [FR Doc. 01-28739 Filed 11-20-01; 8:45 am]
Agency: Environmental Protection Agency
Official PDF Version: PDF Version
ENVIRONMENTAL PROTECTION AGENCY
[PF-1042; FRL-6799-1]
Notice of Filing a Pesticide Petition to Establish a Tolerance fora Certain Pesticide Chemical in or on Food
AGENCY:
Environmental Protection Agency (EPA).
ACTION:
Notice.
SUMMARY:
This notice announces the initial filing of a pesticide petitionproposing the establishment of regulations for residues of a certain pesticide chemical in or onvarious food commodities.
DATES:
Comments, identified by docket control number PF-1042,must be received on or before Decmber 21, 2001.
ADDRESSES:
Comments may be submitted by mail, electronically, or inperson. 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 isimperative that you identify docket control number PF-1042 in the subject line on the firstpage of your response.
FOR FURTHER INFORMATION CONTACT:
By mail: Rita Kumar,Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency,1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (703) 308-8391;e-mail address: kumar.rita@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 orpesticide manufacturer. Potentially affected categories and entities may include, but are not limitedto:
| Categories | NAICS codes | Examples of 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 regardingentities likely to be affected by this action. Other types of entities not listed in the table could alsobe affected. The North American Industrial Classification System (NAICS) codes have beenprovided to assist you and others in determining whether or not this action might apply to certainentities. If you have questions regarding the applicability of this action to a particular entity, consultthe person listed under FOR FURTHER INFORMATION CONTACT .
B. How Can I Get Additional Information, Including Copies of this Document and OtherRelated Documents?
1. Electronically . You may obtain electronic copies of this document, and certainother related documents that might be available electronically, from the EPA Internet Home Pageat http://www.epa.gov/. To access this document, on the Home Page select "Laws andRegulations," "Regulations and Proposed Rules," and then look up the entry for this document under the " Federal Register -Environmental Documents." You can also go directlyto the Federal Register listings at http://www.epa.gov/fedrgstr/.
2. In person . The Agency has established an official record for this action underdocket control number PF-1042. The official record consists of the documents specificallyreferenced in this action, any public comments received during an applicable comment period, andother information related to this action, including any information claimed as confidential businessinformation (CBI). This official record includes the documents that are physically located in thedocket, as well as the documents that are referenced in those documents. The public version of theofficial record does not include any information claimed as CBI. The public version of the officialrecord, which includes printed, paper versions of any electronic comments submitted during anapplicable comment period, is available for inspection in the Public Information and RecordsIntegrity 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 PIRIBtelephone 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 properreceipt by EPA, it is imperative that you identify docket control number PF-1042 in thesubject line on the first page of your response.
1. By mail . Submit your comments to: Public Information and Records IntegrityBranch (PIRIB), Information Resources and Services Division (7502C), Office of PesticidePrograms (OPP), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington,DC 20460.
2. In person or by courier . Deliver your comments to: Public Information andRecords Integrity Branch (PIRIB), Information Resources and Services Division (7502C), Office ofPesticide Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 a.m. to 4 p.m., Mondaythrough 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 anyinformation electronically that you consider to be CBI. Avoid the use of special characters and anyform of encryption. Electronic submissions will be accepted in Wordperfect 6.1/8.0 or ASCII fileformat. All comments in electronic form must be identified by docket control numberPF-1042. Electronic comments may also be filed online at many Federal DepositoryLibraries.
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 claiminformation that you submit to EPA in response to this document as CBI by marking any part or allof that information as CBI. Information so marked will not be disclosed except in accordance withprocedures set forth in 40 CFR part 2. In addition to one complete version of the comment thatincludes any information claimed as CBI, a copy of the comment that does not contain theinformation claimed as CBI must be submitted for inclusion in the public version of the officialrecord. Information not marked confidential will be included in the public version of the officialrecord without prior notice. If you have any questions about CBI or the procedures for claiming CBI,please consult the person identified under FOR FURTHER INFORMATIONCONTACT .
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 youprovide.
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 tothis 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 amendmentof regulations for residues of a certain pesticide chemical in or on various food commodities undersection 408 of the Federal Food, Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a. EPA hasdetermined that this petition contains data or information regarding the elements set forth in section408(d)(2); however, EPA has not fully evaluated the sufficiency of the submitted data at this timeor whether the data support granting of the petition. Additional data may be needed before EPA ruleson the petition.
List of Subjects
Environmental protection, Agricultural commodities, Feed additives, Food additives, Pesticides and pests, Reporting and recordkeeping requirements.
Dated: October 24, 2001.
Peter Caulkins,
Acting Director, Registration Division, Office of Pesticide Programs.
Summary of Petition
The petitioner summary of the pesticide petition is printed below as required by section408(d)(3) of the FFDCA. The summary of the petition was prepared by the petitioner and representsthe view of the petitioner. EPA is publishing the petition summary verbatim without editing it inany way. The petition summary announces the availability of a description of the analytical methodsavailable to EPA for the detection and measurement of the pesticide chemical residues or anexplanation of why no such method is needed.
ISK Biosciences Corporation
6F4662, 6F4701, 6F4755, 6E4773, 5E4474
EPA has received pesticide petitions (6F4662, 6F4701, 6F4755, 6E4773, 5E4474) from ISKBiosciences Corporation, 7470 Auburn Road, Suite A, Concord, OH, 44077, proposing, pursuantto section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), toamend 40 CFR part 180 by establishing a tolerance for residues of the nematicide, fosthiazate,((RS)-S-sec-butyl O-ethyl 2-oxo-1,3-thiazolidin-3-ylphosphonothioate) and its metaboliteASC-67131 (BESoP, (RS)-S-sec-butyl O-ethyl N-2(methylsulfonyl)ethylphosphoramidothioate)] in or on the raw agricultural commodities tomatoes and peanuts at 0.02parts per million (ppm), potatoes at 0.03 ppm, and import tolerances on bananas and green coffee beans at 0.05parts per million (ppm). EPA has determined that the petitions contain data or information regardingthe elements set forth in section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated thesufficiency 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.
A. Residue Chemistry
1. Plant metabolism . Metabolism studies were conducted on tomatoes, potatoes,and peaches. Fosthiazate is extensively metabolized in plants by a combination of hydrolytic andoxidative processes that convert the parent to small polar fragments. Residues in mature edible plantparts consist of polar S-butyl group degradates and radioactivity that is reincorporated into plantnatural products from thiazolidinone ring carbon atoms. Analyses of leaf and stem tissuesestablished the identity of intermediate metabolites in the pathway.
2. Analytical method . A gas chromatographic analytical method using a flamephotoionization detector in the phosphorus mode has been validated for enforcement purposes. Thelimit of detection for both fosthiazate and its metabolite ASC-67131 is 0.01 ppm for all crops(tomatoes, potatoes, peanuts, bananas, green coffee beans and roasted coffee.) The limit of detectionfor both parent and metabolite in instant coffee is 0.05 ppm.
3. Magnitude of residues -i. Tomatoes . Theapplication rate of 4-6 lbs of the active ingredient per acre (a.i./acre) was applied andtomatoes harvested from 80-147 days after application in 6 of 15 test sites. No detectableresidues of either parent or the metabolite ASC-67131 were found (LOD = 0.01 ppm). The proposedmaximum label rate is 4.5 lb a.i./acre.
ii. Potatoes . The application rate of 4-6 lb of the a.i. was appliedand potatoes harvested from 82-179 days after application in 11 test sites. The maximumfosthiazate residue found was 0.02 ppm at 4 lb ai/acre and 0.07 ppm at 6 lb ai/acre, while nodetectable residues of the metabolite ASC-67131 were found. The proposed maximum label rateis 4.5 lb a.i./acre.
iii. Peanuts . The application rate of 4-6 lb of the a.i./acre was applied andpeanuts harvested from 99-175 days after application in 16 test sites. No detectable residuesof either parent or the metabolite ASC-67131 were found (LOD = 0.01 ppm) in either peanutnutmeat or hay. The proposed maximum label rate is 4.0 lb a.i./acre.
iv. Bananas . The maximum application rate of 2 grams of the active ingredient per mat was applied and bananas harvested from 0-126 days after application in6 of 15 test sites. The maximum fosthiazate residue found was 0.03 ppm, while no detectableresidues of the metabolite ASC-67131 were found.
v. Coffee . The maximum application rate of 2 grams of the activeingredient per plant was applied 60 days prior to harvest in eight test sites. The maximumfosthiazate residue found was 0.02 ppm, while no detectable residues of the metabolite ASC-67131were found. After a single application of fosthiazate at 10 grams per plant 31 days before harvest,roasted coffee beans and instant coffee were analyzed. No residues were found above the limit ofdetection of the method in the processed fractions.
B. Toxicological Profile
1. Acute toxicity . Results of the acute toxicity testing are described below.
| Oral toxicity to rats (suspended in corn oil) | LD 50 is 73 mg/kg bwt (males) 57 mg/kg bwt (females) |
| Oral toxicity to rats (solution in water) | LD 50 is 49 mg/kg bwt (males) 28 mg/kg bwt (females) |
| Dermal toxicity to rats | LD 50 is 2,372 mg/kg bwt (males) 853 mg/kg bwt (females) |
| Inhalation toxicity to rats (4-hour) exposure | LC 50 is 0.83 milligrams per Liter (mg/L) (males) 0.56 mg/L (females) |
| Dermal irritation, rabbits | No irritation |
| Eye irritation, rabbits no wash | Irritation reversible in 1 week, mortality |
| Eye irritation, rabbits with wash | Irritation, reversible in 1 week, no mortality |
| Skin sensitization Magnusson-Klingman | Positive |
| Acute delayed neurotoxicity: hen | Negative |
| Acute cholinesterase no observed adverse effect level (NOAEL): rat | No inhibition of cholinesterase activity at 4 mg/kg bwt in erythrocyte or brain |
| Acute neurotoxicity: rat | NOEL for functional observation battery, motor activity andneuropathology:10 mg/kg bwt |
2. Genotoxicty . A battery of tests has been conducted to assess the genotoxicpotential of technical fosthiazate. Assays conducted included in vitro genemutation tests in bacteria and mammalian cell systems, a chromosomal aberration test in mammaliancells, a DNA repair test in bacteria and an in vivo micronucleus test in mice.Technical fosthiazate did not elicit a genotoxic response in any of the studies conducted.
3. Reproductive and developmental toxicity . In a developmental study with ratsat 0, 3, 5, and 10 mg/kg bwt/day the NOAEL for maternal toxicity based on the maternal body weightreduction was 5 mg/kg bwt/day. The NOAEL for developmental effects was 10 mg/kg bw/day.Technical fosthiazate did not cause developmental toxicity in rats.
A developmental study with rabbits was conducted at dosages 0, 0.5, 1.0, 1.5 or 2.0mg/kg bwt/day. The NOAEL for maternal effects in this study was 2.0 mg/kg bwt/day. This dosagewas considered very close to a maternally toxic dose because, in the preliminary study, maternallethality was observed at 5 mg/kg bwt/day and there were isolated incidences of maternal animals inextremis at 2.0 and 2.5 mg/kg bwt/day. The NOAEL for developmental effects was considered 2.0mg/kg bwt/day. Technical fosthiazate was not teratogenic in rabbits.
In a two generation reproduction study, technical fosthiazate was administered via thediet at concentrations of 0, 3.2, 10.7, 32.2 or 107.2 ppm to CD rats. The group receiving 107.2 ppmwas terminated at weaning of the F0 generation due to poor survival of offspring. In the firstgeneration, there was a statistically significant increase in the length of gestation at 107.2 ppm. Thedifference was not significant at any other dosage or in the second generation. Viability indices andbody weight gain of F1 offspring were reduced at 32.2 ppm and higher. These effects wereparticularly marked at 107.2 ppm. No effects on pup viability were observed in the secondgeneration. The dietary concentration of 10.7 ppm which was equivalent to 0.86 mg/kg bwt/day wasthe NOAEL for the effects on pup survivability and pup body weightobserved in this study.
4. Subchronic toxicity . In a 13-week feeding study in rats with arecovery phase, Sprague-Dawley rats received technical fosthiazate via the diet at concentrations of0, 1.07, 10.7, 53.6 or 429 ppm for 13 weeks. The NOAEL for the study was 10.7 ppm technicalfosthiazate in the diet based on inhibition of brain cholinesterase activity and adrenal effects. Theeffects were reversible.
In a 13-week study, beagle dogs received technical fosthiazate at dosages of 0,0.054, 0.11, 0.54, or 5.4 mg/kg bwt/day daily. The NOAEL for adrenal effects and cholinesteraseinhibition in the erythrocyte and brain, was 0.54 mg/kg bwt/day.
A 90-day dietary neurotoxicity study in rats was conducted at doses of 0, 0.07,0.56 and 2.4 mg/kg bwt/day and of 0, 0.08, 0.57 and 2.5 mg/kg bwt/day to males and females,respectively. In spite of lower cholinesterase levels, no clinical signs of cholinesterase inhibition,no differences in the functional observational battery, in mean forelimb and hind limb gripstrengths, mean foot-spread, mean motor activity values or neuropathology were observed in theanimals administered 2.5 mg/kg bwt/day of technical fosthiazate via the diet. The NOAEL forinhibition of cholinesterase activity in the brain was 0.56 mg/kg bwt/day.
In a 21-day dermal toxicity study in rats, at dosages of 0, 0.5, 2.5, 25, or 250mg/kg bwt/day by occluded dermal application for 21 days, the NOAEL in terms of cholinesteraseinhibition in the brain was 2.5 mg/kg bwt/day.
5. Chronic toxicity . In a 2-year feeding study in rats, technicalfosthiazate was administered to CD rats at dietary concentrations of 0, 1.07, 10.7, 53.6, or 214 ppm.Treatment did not change the incidence of any neoplasm. The NOAEL for the study which was basedon adrenal effects and cholinesterase inhibition in the brain, was 10.7 ppm in the diet which wasequivalent to 0.41 mg/kg bwt/day.
In the mouse oncogenicity study, technical fosthiazate was administered for a period of102 weeks to CD-1 mice at concentrations of 0, 10.7, 32.2, 107, or 322 ppm. There was noevidence of oncogenic potential. The NOAEL of technical fosthiazate in CD-1 mice wasconsidered to be 32.2 ppm which was equivalent to 3.32 mg/kg bwt/day.
A 12-month oral chronic toxicity study was conducted in beagle dogs at doselevels of 0, 0.05, 0.1, 0.5 and 5.0 mg/kg bwt/day. No treatment-related change in brain cholinesteraseactivity was noted. The NOAEL which was based upon adrenal effects was 0.5 mg/kg bwt/day.
Comparison of the toxicology data from subchronic (90 days exposure) and chronicstudies showed no major differences in effects or in effect levels. Therefore, a single reference dose(RfD) for subchronic and chronic exposure is proposed.
6. RfD . Fosthiazate is nonteratogenic, nononcogenic, and nonmutagenic and there is noevidence of bioaccumulation. Inhibition of cholinesterase activity is considered the primarytreatment-related effect from fosthiazate. Although cholinesterase activity was measured in plasma,erythrocytes and brain in the toxicity studies with fosthiazate, the values from the brain areconsidered the most relevant for assessing adverse effects. For cholinesterase activity, only data forinhibition of activity in the brain will therefore be included in the selection of a NOAEL for the RfD.In addition to inhibition of cholinesterase activity, fosthiazate treatment was associated with othereffects.
The lowest NOAEL value was 0.41 mg/kg bwt/day for the inhibition of brain cholinesteraseactivity from the 2-year feeding study in rats. In that study, rats were fed a constant dietaryconcentration of fosthiazate. The NOAEL for inhibition of brain cholinesterase activity was 10.7 ppmin the diet for both males and females. Since relative food consumption is a little lower in malesthan females, the compound consumption was a little lower in males. Since females have beenshown to be more sensitive to the effects of fosthiazate than males, and NOAEL wereobserved in the female group fed a diet containing 10.7 ppm which gave a dose of 0.54 mg/kg bwt/day, the conclusion could be made that 0.54 mg/kg bwt/day would be an appropriate NOAEL. Themore conservative value of 0.41 mg/kg bwt/day will be proposed to add to the certainty of no adverseeffects. The standard safety factor of 100 will be applied to the conservative NOAEL of 0.41 mg/kg bwt/day to give a proposed RfD of 0.0041 mg/kg bwt/day.
7. Animal metabolism . Fosthiazate is extensively metabolized in rats by acombination of hydrolytic and oxidative processes that rapidly convert the parent molecule to smallfragments, including CO 2 . The carbon atoms of the thiazolidinone ring appear to bereincorporated into tissues based on the levels found in carcasses at termination. Extensiveconjugation via the glutathione pathway appears to occur.
8. Metabolite toxicology . Comparison of the metabolism of fosthiazate by plantsand in animals indicates that a number of the identified metabolites are common to both plants andanimals but metabolism in plants is more extensive than in animals. There are, however, nometabolites of toxicological concern in plants that do not appear in animal studies.
9. Endocrine disruption . Although subtle histological changes were observedin the ovary and adrenals which are organs with endocrine function, there were no treatment-relatedeffects associated with fosthiazate treatment which are indicative of an effect on endocrine function.Since the histological changes in the adrenals and ovaries were observed only at dosages which alsoinhibited cholinesterase activity, it is considered possible that the changes were physiologicaladaptions secondary to inhibition of cholinesterase activity. There were no other effects observedin the subchronic or chronic studies, such as changes to the uterus or mammary tissue or changes inurine production which might indicate a change in physiology related to the ovarian or adrenalchanges.
In the reproduction study with fosthiazate, fertility and gestation indices were unaffectedby fosthiazate even when administered at dietary concentrations which would result in severeinhibition of cholinesterase activity. At those high dietary concentrations (107.2 ppm) the onlytreatment-related difference in reproductive effect was a statistically significant increase in lengthof gestation. It is considered that the effect on gestation could have been secondary to maternaltoxicity. The difference was not significant at any other dosage in the first or second generation.
From the reproduction study, reproductive capacity was unaffected by treatment; ovarianeffects were not observed; and adrenal effects were observed only in groups administered 107.2 ppm.
The conclusion can be drawn that no effects on the endocrine system would be expectedbelow the threshold for cholinesterase inhibition. Therefore, a NOAEL set for cholinesteraseinhibition should also cover any other effects.
C. Aggregate Exposure
1. Dietary exposure -i. Food . For purposes of assessingthe potential dietary exposure, EPA initially estimates exposure using the tolerance (i.e., 0.02 ppmon tomatoes and peanuts, 0.03 ppm on potatoes, 0.05 ppm on bananas and whole green coffee beans)as a worst case scenario. The potential exposure is obtained by multiplying the tolerance levelresidues by the consumption data which estimates the amount of treated products consumed byvarious population subgroups. In chronic analyses, the average consumption for all individuals ina population subgroup is used, while in acute analyses only consumers of treated commodities areincluded. While both potato and peanut fractions are fed to animals, metabolism studies show thatresidues are incorporated into natural products, and thus there is no exposure to residues oftoxicological concern through secondary residues in meat, milk and eggs.
ii. Drinking water . The potential for residues of fosthiazate to occur in tapwater, non-tap water, and water in commercially prepared food was also evaluated. Four fielddissipation studies were conducted with fosthiazate in California, Georgia, North Carolina andWashington (Doc. # 3931-95-EF-000). These studies clearly demonstrate thatfosthiazate and its degradates do not leach under field conditions, and that the DT90 of the parentcompound ranged from 48-92 days. It is therefore reasonable to conclude that the potentialfor fosthiazate to contaminate ground water is extremely low. As fosthiazate will be incorporatedinto the soil after application, no significant runoff or spray drift is expected. Therefore,contamination of surface water is highly unlikely. Additionally for bananas and coffee, the proposedtolerance of fosthiazate is for import commodities only. Due to these factors, residues of fosthiazateare not expected in drinking water.
2. Non-dietary exposure . Since there are no domestic uses (home/garden) forfosthiazate, there are no non-occupational exposures.
D. Cumulative Effects
Fosthiazate is an organophosphate, with the most sensitive indicator of toxicity being inhibitionof cholinesterase after both short- and long-term administration. While the exact mechanism for thiseffect may or may not be identical to other organophosphates, in the case of the present petitions, thiseffect is considered to be insignificant. This is due primarily to the extremely low exposure to theU.S. population from the proposed uses of fosthiazate. The incremental increase in exposure toorganophosphates from the addition of fosthiazate is extremely small. For example, the highestexposed population subgroups from chronic exposure to residues in/on tomatoes, potatoes andpeanuts are children 1-6 yrs with an estimated chronic exposure of 0.000132 mg/kg bwt/day,which represents 3.2% of the RfD. The highest exposed population subgroup from chronic exposureto residues in/on bananas is non-nursing infants 1 year old with an estimated chronic exposure of0.000045 mg/kg bwt/day, which represents 1.1% of the RfD. The highest exposed populationsubgroup from chronic exposure to residues in/on coffee are seniors (55+), females (20+) and males(20+) with 0.000002 mg/kg bwt/day, which represents an insignificant portion of the RfD. When allcrops, are included in the assessment estimated chronic exposure for children 1-6 yrsincreases to 0.000173 mg/kg bwt/day, which represents 4.2% of the RfD. This is particularly relevantin that this assessment assumed tolerance level residues for all crops (0.02 ppm for tomatoes andpeanuts, 0.03 ppm for potatoes and 0.05 ppm for bananas and coffee). Indeed, when anticipatedresidues are used estimated exposure is less than 2% of the RfD for all population groups.
A similar situation applies to acute exposure (and risk) from the proposed uses. Fortomatoes, potatoes and peanuts, the highest exposed subgroup is all infants 1 year old, with an acuteexposure of 0.000479 mg/kg bwt/day at the 95th percentile for consumers only. This results in aMOE of 8,300, which exceeds the traditional level considered to provide adequate protection bynearly two orders of magnitude. When residues on bananas and coffee beans are included in theassessment, children 1-6 yrs have an estimated acute exposure at the 95th percentile of 0.000588mg/kg bwt/day, which results in an MOE of 6,800. Again, when anticipated residues, as calculatedfor acute exposure (i.e., the highest field trial residue), are used in the assessment for all the proposedcrops, the highest exposure is only 0.000456 mg/kg bwt/day at the 95th percentile, with an MOE of8,700 for all infants (consumers only). Indeed MOE's at the 99.9th percentile of exposure are farhigher than generally is considered to be safe by the agency for all population subgroups.
E. Safety Determination
1. U.S. population . Using the conservative exposure assumptions and theproposed RfD and acute NOEL described above, dietary exposure was calculated.
As discussed above, even under the "worst-case" chronic exposurescenario, a very small portion of the RfD was used. When anticipated residues for tomatoes, potatoesand peanuts are used in the chronic dietary exposure assessment, the estimated exposure is 0.000068mg/kg bwt/day, for the total U.S. population (or 1.7% of the RfD). When bananas and coffee beansare included in the assessment, the estimated exposure is 0.000083 mg/kg bwt/day for the total U.S.population (or 2.0% of the RfD).
The acute exposure estimates clearly indicate that exposures provide adequate MOEs atthe 95th percentile of exposure. The U.S. population has an estimated 95th percentile exposurevalue of 0.000246 mg/kg bwt/day, equivalent to an MOE of 16,000 for tomatoes, potatoes andpeanuts. When bananas and coffee are included in the assessment, the estimated 95th percentileexposure for the total U.S. population is 0.000279 mg/kg bwt/day, which results in an MOE of14,000. These values are more than 2 orders of magnitude higher than a level considered to provideadequate protection. The exposure estimate for fosthiazate when highest field trial residue is usedis 0.000187 mg/kg bwt/day, representing an MOE of 21,000, including all crops. Therefore, sincethere are no other avenues of exposure (see aggregate exposure section of this document) ISKBiosciences Corporation concludes that there is a reasonable certainty that no harm will result fromaggregate exposure to fosthiazate residues from use on tomatoes, potatoes, peanuts, bananas andcoffee.
2. Infants and children . In assessing the potential for additional sensitivity ofinfants and children to residues of fosthiazate, data from developmental toxicity studies and otherappropriate studies are considered. ISK Biosciences Corporation calculates that children 1-6(the highest exposed subgroup) have an estimated chronic dietary exposure of 0.000132 mg/kgbwt/day, which represents only 3.2% of the RfD using worst case assumptions. When bananas andcoffee beans are included, these estimates are 0.000173 mg/kg bwt/day and 4.2% of the RfD forchildren 1-6. When anticipated residues are used in calculating chronic dietary exposure,only 1.1% of the RfD is consumed for this population subgroup and 1.3% of the RfD after bananasand coffee are included in the assessment. Acute exposure estimates similarly show no concern asall infants 1 year of age (the highest exposed subgroup) have MOEs of 8,300 even when usingworst case assumptions. When bananas and coffee are included in the assessment, children1-6 years (the highest exposed subgroup) have an MOE of 6,800. Therefore, since there areno other avenues of exposure other than dietary, there is reasonable certainty that no harm will resultto infants and children from aggregate exposure to fosthiazate from use on tomatoes, potatoes,peanuts, bananas and coffee.
F. International Tolerances
There are no Codex maximum residue levels established for residues of fosthiazate.
[FR Doc. 01-28739 Filed 11-20-01; 8:45 am]
BILLING CODE 6560-50-S