70 FR 67 pgs. 18008-18012 - Metconazole; Notice of Filing a Pesticide Petition to Establish aTolerance for a Certain Pesticide Chemical in or on Food
Type: NOTICEVolume: 70Number: 67Pages: 18008 - 18012
Docket number: [OPP-2005-0016; FRL-7703-7]
FR document: [FR Doc. 05-7064 Filed 4-7-05; 8:45 am]
Agency: Environmental Protection Agency
Official PDF Version: PDF Version
ENVIRONMENTAL PROTECTION AGENCY
[OPP-2005-0016; FRL-7703-7]
Metconazole; Notice of Filing a Pesticide Petition to Establish aTolerance for a Certain Pesticide Chemical in or on Food
AGENCY:
Environmental Protection Agency (EPA).
ACTION:
Notice.
SUMMARY:
This notice announces the initial filing of apesticide petition proposing the establishment of regulations for residuesof a certain pesticide chemical in or on various foodcommodities.
DATES:
Comments, identified by docket identification(ID) number OPP-2005-0016, must be received on or before May 9, 2005.
ADDRESSES:
Comments may be submitted electronically, bymail, or through hand delivery/courier. Follow the detailed instructionsas provided in Unit I. of the SUPPLEMENTARYINFORMATION .
FOR FURTHER INFORMATION CONTACT:
Mary Waller,Registration Division (7505C), Office of Pesticide Programs, EnvironmentalProtection Agency, 1200 Pennsylvania Ave., NW., Washington, DC20460-0001; telephone number: (703) 308-9354; e-mail address: waller.mary@epa.gov .
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are anagricultural producer, food manufacturer, or pesticide manufacturer.Potentially affected entities may include, but are not limited to:
• Crop production (NAICS 111)
• Animal production (NAICS 112)
• Food manufacturing (NAICS 311)
• Pesticide manufacturing (NAICS 32532)
This listing is not intended to be exhaustive, but rather provides aguide for readers regarding entities likely to be affected by this action.Other types of entities not listed in this unit could also be affected. TheNorth American Industrial Classification System (NAICS) codes have beenprovided to assist you and others in determining whether this action mightapply to certain entities. If you have any questions regarding theapplicability of this action to a particular entity, consult the personlisted under FOR FURTHER INFORMATION CONTACT .
B. How Can I Get Copies of this Document and Other RelatedInformation?
1. Docket . EPA has established an official public docketfor this action under docket ID number OPP-2005-0016. Theofficial public docket consists of the documents specifically referenced inthis action, any public comments received, and other information related tothis action. Although a part of the official docket, the public docketdoes not include Confidential Business Information (CBI) or otherinformation whose disclosure is restricted by statute. The officialpublic docket is the collection of materials that is available for publicviewing at the Public Information and Records Integrity Branch (PIRIB), Rm.119, Crystal Mall #2, 1801 S. Bell St., Arlington, VA. This docketfacility is open from 8:30 a.m. to 4 p.m., Monday through Friday, excludinglegal holidays. The docket telephone number is (703) 305-5805.
2. Electronic access . You may access this Federal Register document electronically through the EPAInternet under the " Federal Register " listings at http://www.epa.gov/fedrgstr/ .
An electronic version of the public docket is available throughEPA's electronic public docket and comment system, EPA Dockets. You mayuse EPA Dockets at http://www.epa.gov/edocket/ to submit orview public comments, access the index listing of the contents of theofficial public docket, and to access those documents in the public docketthat are available electronically. Although not all docket materials may beavailable electronically, you may still access any of the publiclyavailable docket materials through the docket facility identified in UnitI.B.1. Once in the system, select "search," then key in theappropriate docket ID number.
Certain types of information will not be placed in the EPA Dockets.Information claimed as CBI and other information whose disclosure isrestricted by statute, which is not included in the official public docket,will not be available for public viewing in EPA's electronic public docket.EPA's policy is that copyrighted material will not be placed in EPA'selectronic public docket but will be available only in printed, paper formin the official public docket. To the extent feasible, publicly availabledocket materials will be made available in EPA's electronic public docket.When a document is selected from the index list in EPA Dockets, the systemwill identify whether the document is available for viewing in EPA'selectronic public docket. Although not all docket materials may beavailable electronically, you may still access any of the publiclyavailable docket materials through the docket facility identified in UnitI.B.1. EPA intends to work towards providing electronic access to all ofthe publicly available docket materials through EPA's electronic publicdocket.
For public commenters, it is important to note that EPA's policy isthat public comments, whether submitted electronically or in paper, will bemade available for public viewing in EPA's electronic public docket as EPAreceives them and without change, unless the comment contains copyrightedmaterial, CBI, or other information whose disclosure is restricted bystatute. When EPA identifies a comment containing copyrighted material,EPA will provide a reference to that material in the version of the commentthat is placed in EPA's electronic public docket. The entire printedcomment, including the copyrighted material, will be available in thepublic docket.
Public comments submitted on computer disks that are mailed ordelivered to the docket will be transferred to EPA's electronic publicdocket. Public comments that are mailed or delivered to the docket will bescanned and placed in EPA's electronic public docket. Where practical,physical objects will be photographed, and the photograph will be placed inEPA's electronic public docket along with a brief description written bythe docket staff.
C. How and to Whom Do I Submit Comments?
You may submit comments electronically, by mail, or through handdelivery/courier. To ensure proper receipt by EPA, identify theappropriate docket ID number in the subject line on the first page of yourcomment. Please ensure that your comments are submitted within thespecified comment period. Comments received after the close of the commentperiod will be marked "late." EPA is not required to considerthese late comments. If you wish to submit CBI or information that isotherwise protected by statute, please follow the instructions in Unit I.D.Do not use EPA Dockets or e-mail to submit CBI or information protected bystatute.
1. Electronically . If you submit an electroniccomment as prescribed in this unit, EPA recommends that you include yourname, mailing address, and an e-mail address or other contact informationin the body of your comment. Also include this contact information on theoutside of any disk or CD ROM you submit, and in any cover letteraccompanying the disk or CD ROM. This ensures that you can be identifiedas the submitter of the comment and allows EPA to contact you in case EPAcannot read your comment due to technical difficulties or needs furtherinformation on the substance of your comment. EPA's policy is that EPAwill not edit your comment, and any identifying or contact informationprovided in the body of a comment will be included as part of the commentthat is placed in the official public docket, and made available in EPA'selectronic public docket. If EPA cannot read your comment due to technicaldifficulties and cannot contact you for clarification, EPA may not be ableto consider your comment.
i. EPA Dockets . Your use of EPA's electronic publicdocket to submit comments to EPA electronically is EPA's preferred methodfor receiving comments. Go directly to EPA Dockets at http://www.epa.gov/edocket/ , and follow the online instructionsfor submitting comments. Once in the system, select "search,"and then key in docket ID number OPP-2005-0016. The system isan "anonymous access" system, which means EPA will not knowyour identity, e-mail address, or other contact information unless youprovide it in the body of your comment.
ii. E-mail . Comments may be sent by e-mail toopp-docket@epa.gov, Attention: Docket ID Number OPP-2005-0016.In contrast to EPA's electronic public docket, EPA's e-mail system is notan "anonymous access" system. If you send an e-mail commentdirectly to the docket without going through EPA's electronic publicdocket, EPA's e-mail system automatically captures your e-mail address.E-mail addresses that are automatically captured by EPA's e-mail system areincluded as part of the comment that is placed in the official publicdocket, and made available in EPA's electronic public docket.
iii. Disk or CD ROM . You may submit comments on adisk or CD ROM that you mail to the mailing address identified in UnitI.C.2. These electronic submissions will be accepted in WordPerfect orASCII file format. Avoid the use of special characters and any form ofencryption.
2. By mail . Send your comments to: PublicInformation and Records Integrity Branch (PIRIB) (7502C), Office ofPesticide Programs (OPP), Environmental Protection Agency, 1200Pennsylvania Ave., NW., Washington, DC 20460-0001, Attention: DocketID Number OPP-2005-0016.
3. By hand delivery or courier . Deliver yourcomments to: Public Information and Records Integrity Branch (PIRIB),Office of Pesticide Programs (OPP), Environmental Protection Agency, Rm.119, Crystal Mall #2, 1801 S. Bell St., Arlington, VA, Attention:Docket ID Number OPP-2005-0016. Such deliveries are onlyaccepted during the docket's normal hours of operation as identified inUnit I.B.1.
D. How Should I Submit CBI to the Agency?
Do not submit information that you consider to be CBI electronicallythrough EPA's electronic public docket or by e-mail. You may claiminformation that you submit to EPA as CBI by marking any part or all ofthat information as CBI (if you submit CBI on disk or CD ROM, mark theoutside of the disk or CD ROM as CBI and then identify electronicallywithin the disk or CD ROM the specific information that is 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 that includes anyinformation claimed as CBI, a copy of the comment that does not contain theinformation claimed as CBI must be submitted for inclusion in the publicdocket and EPA's electronic public docket. If you submit the copy thatdoes not contain CBI on disk or CD ROM, mark the outside of the disk or CDROM clearly that it does not contain CBI. Information not marked as CBIwill be included in the public docket and EPA's electronic public docketwithout prior notice. If you have any questions about CBI or theprocedures for claiming CBI, please consult the person listed under FOR FURTHER INFORMATION CONTACT .
E. What Should I Consider as I Prepare My Comments for EPA?
You may find the following suggestions helpful for preparing yourcomments:
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 thatsupport your views.
4. If you estimate potential burden or costs, explain how you arrived atthe 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 IDnumber assigned to this action in the subject line on the first page ofyour response. You may also provide the name, date, and FederalRegister citation.
II. What Action is the Agency Taking?
EPA has received a pesticide petition as follows proposing theestablishment and/or amendment of regulations for residues of a certainpesticide chemical in or on various food commodities under section 408 ofthe Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a. EPA hasdetermined that this petition contains data or information regarding theelements set forth in FFDCA section 408(d)(2); however, EPA has not fullyevaluated the sufficiency of the submitted data at this time or whether thedata support granting of the petition. Additional data may be needed beforeEPA rules on the petition.
List of Subjects
Environmental protection, Agricultural commodities, Feed additives, Foodadditives, Pesticides and pests, Reporting and record keepingrequirements.
Dated: March 28, 2005.
Lois Rossi,
Director, Registration Division, Office of PesticidePrograms.
Summary of Petition
The petitioner summary of the pesticide petition is printed below asrequired by FFDCA section 408(d)(3). The summary of the petition wasprepared by the petitioner and represents the view of the petitioner. Thepetition summary announces the availability of a description of theanalytical methods available to EPA for the detection and measurement ofthe pesticide chemical residues or an explanation of why no such method isneeded.
Kureha Chemical Industry Co., Ltd
PP 9E5052
EPA has received a pesticide petition (PP 9E5052) from Kureha ChemicalIndustry Co., Ltd, c/o Company Agent, BASF Corporation, P.O. Box 13528,Research Triangle Park, NC, 27704-3528 proposing pursuant to section 408(d)of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. 346a(d), to amend 40CFR part 180 by establishing a tolerance for residues of metconazole in oron the raw agricultural commodity bananas at 0.05 parts per million. EPAhas determined that the petition contains data or information regarding theelements set forth in section 408(d)(2) of the FFDCA; however, EPA has notfully evaluated the sufficiency of the submitted data at this time orwhether the data supports granting of the petition. Additional data may beneeded before EPA rules on the petition.
A. Residue Chemistry
1. Plant metabolism . The qualitative nature of the residuesof metconazole in bananas is adequately understood. The metabolism ofmetconazole in bananas is characterized by a significant amount (greaterthan 85%) of unchanged parent compound. In addition to the parentcompound, many other minor residue components (each less than 2% of thetotal recovered radioactivity in the whole fruit) were detected.Metconazole is the only residue of toxicological concern in bananas.
2. Analytical method . A practical analytical method fordetecting and measuring the level of metconazole residues in whole bananasand banana pulp is submitted to EPA with this petition. Quantitation ofresidues of metconazole in bananas is by gas chromatography with anitrogen-phosphorus detector. This independently validated method isappropriate for the enforcement purposes of this petition.
3. Magnitude of residues . Residue field trials wereconducted in representative countries exporting the commodities of thispetition to the United States. Twelve field trials were conducted withbagged and unbagged bananas, with three sites located in each of fourcountries, Ecuador, Honduras, Costa Rica, and Mexico. The residue valuesreported from these field trials were all less than the proposed toleranceof 0.05 ppm for whole bananas. No processing study is included with thispetition as bananas have no processed commodities according to the EPAResidue Chemistry Test Guidelines.
B. Toxicological Profile
A complete, valid and reliable database of mammalian and genetictoxicology studies supports the proposed tolerance for metconazole onbananas. Two geometric isomers of metconazole exist, with the fungicidalactivity being associated primarily with the cis isomer. The technicalmaterial that is manufactured for use on bananas is a mixture of cis andtrans isomers in an 85 to 15 ratio (85:15). Toxicology studies submittedin support of this petition were conducted on the technical materialcomposed of either the 85:15 isomer mixture (AC 900768) or a more purified(greater than 95%) sample of the cis isomer (WL 136184).
1. Acute toxicity . AC 900768 technical is considered to beslightly toxic (Toxicity Category III) to the rat by the oral route ofexposure. In an acute oral study in rats, the LD 50 value ofAC 900768 technical was 727 milligrams per kilogram of body weight (mg/kgb.w.) for males and 595 mg/kg b.w. for females. The oral LD 50 for combined sexes was 660 mg/kg b.w. An oral LD 50 study in rats conducted with WL 136184 technical alsosupports the classification of metconazole as slightly toxic by the oralroute of exposure. The oral LD 50 values of WL 136184technical were 1,626 mg/kg b.w. for males and 1,312 mg/kg b.w. for females,with an LD 50 value for combined sexes of 1,459 mg/kg b.w.Since this petition is for an import tolerance, anticipated exposure isonly via the oral route. As such, oral toxicity data sufficiently assessrisk of acute exposure.
2. Genotoxicty . AC 900768 technical (the 85:15 isomermixture) and WL 136184 technical (greater than 95% cis isomer) were testedin an extensive battery of in vitro and in vivo genotoxicity assays measuring several different endpoints of potentialgenotoxicity. Collective results from these studies indicate thatmetconazole does not pose a genotoxic risk, and therefore, is not likely tobe a genotoxic carcinogen.
3. Reproductive and developmental toxicity . Developmentaltoxicity studies in rats conducted with AC 900768 technical and WL 136184technical showed no evidence of teratogenic effects in fetuses, and noevidence of developmental toxicity in the absence of maternal toxicity.Thus, metconazole is neither a selective developmental toxicant nor ateratogen in the rat. In the rat developmental toxicity study with AC900768 technical, the no-observable-adverse-effect-level (NOAEL) formaternal toxicity was 12 mg/kg b.w./day, based on decreased body weightgain at 30 mg/kg b.w./day, the next highest dose tested, and the NOAEL fordevelopmental toxicity was also 12 mg/kg b.w./day, based on decreased fetalbody weights and an increased incidence of skeletal ossification variationsat 30 mg/kg b.w./day. In the rat developmental toxicity study conductedwith WL 136184 technical, the NOAEL for maternal toxicity was 24 mg/kgb.w./day based on decreased body weight gain at 60 mg/kg b.w./day, thehighest dose tested, and the NOAEL for developmental toxicity was also 24mg/kg b.w./day, based on an increase in the total number of resorptions,reductions in fetal body weights and an increased incidence of skeletalossification variations at 60 mg/kg b.w./day.
Results from a developmental toxicity study in rabbits with AC 900768also indicated no evidence of teratogenicity or developmental toxicity inthe absence of maternal toxicity. Thus, metconazole technical is neither aselective developmental toxicant nor a teratogen in the rabbit. In thisrabbit developmental study, the NOAEL for maternal toxicity was 20 mg/kgb.w./day based on decreased food consumption and body weight gain,reductions in hemoglobin, hematocrit and corpuscular volume, increases inplatelet counts and alkaline phosphatase activity, and increased absoluteand relative liver weights at 40 mg/kg b.w./day (the highest dose tested).The NOAEL for developmental toxicity was also 20 mg/kg b.w./day, based onan increase in the total number and mean number of resorptions anddecreased fetal body weight at 40 mg/kg b.w./day.
A 2-generation reproductive toxicity study in rats conducted with WL136184 technical (greater than 95% cis isomer) is submitted in support ofthis tolerance petition. The results of the two-generation reproductionstudy with WL 136184 technical are sufficiently conservative for evaluatingthe potential reproductive toxicity of the 85:15 isomer mixture ofmetconazole technical. The results from the reproductive toxicity studywith WL 136184 technical support a NOAEL for parental toxicity of 8 mg/kgb.w./day, based on increased ovarian weight and increased gestation lengthat the next highest dose tested (32 mg/kg b.w./day). The NOAEL for growthand development of the offspring is also 8 mg/kg b.w./day, based onreductions in live litter size for F 2 litters at 32 mg/kgb.w./day. The NOAEL for reproductive performance and fertility was 48mg/kg b.w./day (the highest dose tested).
Results of the pilot and definitive reproduction studies anddevelopmental toxicity studies conducted with AC 900768 technical and/or WL136184 technical show no increased sensitivity to developing offspring ascompared to parental animals, as comparable NOAELs were obtained forparental toxicity and growth and development of offspring.
4. Subchronic toxicity . Short-term (28-day) dietarytoxicity studies in rats were conducted with AC 900768 and WL 136184technical materials. In the 28-day study with AC 900768, the NOAEL was 100ppm (approximately 9.6 mg/kg b.w./day), based on reductions in body weight,body weight gain, food consumption, and hemoglobin concentration for males,as well as increased absolute and relative liver weights, and increasedincidences of hepatic fatty vacuolation and parenchymal hypertrophy formales and females at 1,000 ppm (the next highest concentration tested).Similar results were observed in the study conducted with WL 136184technical. Based on these results, the NOAEL for WL 136184 is 300 ppm(approximately 28.5 mg/kg b.w./day), supported by decreased body weightsand body weight gains and increased incidences of hepatic fatty vacuolationfor males and females, increased absolute and adjusted liver weights forfemales, and decreased food consumption for males at 1,000 ppm (the nexthighest concentration tested).
In a 28-day dietary study in dogs conducted with AC 900768 technical(85:15 isomer mixture), the NOAEL was a dietary concentration of 1,000 ppm(approximately 38.6 mg/kg b.w./day), based on decreased food consumption,body weight losses, increased alkaline phosphatase activity, increasedspleen and liver weights, and urinalysis changes for males and females, andincreased absolute and relative thyroid gland weights for females at 7,000ppm, the highest concentration tested.
Subchronic (90-day) dietary studies in rats were conducted with AC900768 technical and WL 136184 technical. In the study conducted with AC900768, the NOAEL was 100 ppm (approximately 6.8 mg/kg b.w./day) based onhepatic fatty vacuolation in males at 300 ppm, the next highestconcentration tested. The NOAEL from the study conducted with WL 136184technical was 450 ppm (approximately 30.9 mg/kg b.w./day) based ondecreased food consumption, body weights, and body weight gains, clinicalchemistry changes, increased absolute and adjusted liver weights, andhistopathological changes in the liver and/or stomach for males andfemales, and decreased red blood cell parameters for females at 1,350 ppm,the highest concentration tested.
In a 90-day dietary study in mice conducted with AC 900768, theNOAEL was 30 ppm (approximately 5.5 mg/kg b.w./day), based on increasedaspartate and alanine aminotransferase activities in males, increasedabsolute and relative weights of the liver and spleen of females, andincreased incidences of hepatocelluar vacuolation and hypertrophy for malesand females at 300 ppm, the next highest concentration tested.
A 90-day dietary study in beagle dogs with AC 900768 technical supportsa NOAEL of 60 ppm (approximately 2.5 mg/kg b.w./day) based on decreasedbody weight gain and food consumption for females, and a slight increase inreticulocyte count for males at 600 ppm, the next highest concentrationtested.
5. Chronic toxicity . Findings similar to those observed inthe short-term subchronic studies were also apparent in the long-termdietary toxicity studies conducted in rats, dogs and mice. Long-term(104-weeks) administration of AC 900768 (85:15 isomer mixture) to ratssupported a NOAEL for systemic toxicity of 100 ppm (approximately 4.8 mg/kgb.w./day), based on increased adjusted liver weight, and increasedincidences of hepatocellular lipid vacuolation and centrilobularhypertrophy at interim sacrifice for males at 300 ppm, the next highestconcentration tested. In a one-year dietary study in beagle dogs, theNOAEL was 300 ppm (approximately 11.1 mg/kg b.w./day), based on decreasedbody weight gain for males during weeks 1 to 13 and increased alkalinephosphatase activity for males and females at 1,000 ppm, the next highestconcentration tested.
In a 104-week carcinogenicity study in rats conducted with AC 900768,the NOAEL for carcinogenicity was 1,000 ppm (approximately 50 mg/kgb.w./day), the highest concentration tested. In this study the NOAEL forchronic systemic toxicity was 100 ppm (approximately 5.6 mg/kg b.w./day),based on increased incidences of centrilobular hypertrophy and pigmentdisposition in the liver, and increased incidences of cortical vacuolationin the adrenal in males at 300 ppm, the next highest concentrationtested.
A 91-week carcinogenicity study in mice with AC 900768 supports a NOAELfor non-neoplastic effects of 30 ppm (approximately 4.8 mg/kg b.w./day),based on increased white blood cell count for males, increased aspartateand alanine aminotransferase activities and increased absolute and adjustedliver weight for females, and microscopic changes in the liver, spleen andadrenal gland for males and females at 300 ppm (the next highestconcentration tested). The NOAEL for carcinogenicity was 300 ppm(approximately 48.3 mg/kg b.w./day) based on increased incidences ofhepatocellular adenomas in males and females and hepatocellular carcinomasin females at 1,000 ppm, the highest concentration tested. The increasedincidences of hepatic adenomas and carcinomas at the highest concentrationtested are considered to occur through promotional and non-genotoxicsecondary mechanisms following toxicity and induction of mixed functionoxidase in mice. Consequently, metconazole is not likely to be oncogenicin humans at the insignificant levels of exposure resulting from its use asa fungicide.
AC 900768 technical and WL 136184 technical are not genotoxiccarcinogens, as supported by a battery of in vitro and in vivo mutagenicity tests, which cover all major geneticendpoints.
6. Animal metabolism . The rat metabolism studies indicatethat the qualitative nature of the residues of metconazole in animals isadequately understood. In studies conducted with radiolabeled AC 900768(85:15 isomer mixture) or radiolabeled WL 136184 (greater than 95% cisisomer) radioactivity was rapidly eliminated in urine and feces with 48hours of dosing. Biliary excretion was shown to be a prominent route ofelimination. At both high and low doses of AC 900768, male rats generallyexcreted statistically significantly lower amounts of radioactivity in theurine, and greater amounts of radioactivity in the feces, compared tofemales. The pattern of metabolites detected was similar at high and lowdoses, and little or no parent compound was found in the feces or urine.Five days following oral dosing of AC 900768 at the higher level, lowlevels of radioactivity were detected in the majority of tissues analyzed;however higher concentrations of radioactivity were found in the adrenalglands, gastro-intestinal tract and liver. A comparison of radioactivitylevels in the adrenal glands following oral administration of low and highdoses indicates that uptake in the adrenal may be saturable. No differencesin tissue levels were noted between males and females. Hen and goatmetabolism studies are not required, because bananas are not used assignificant feedstuff for poultry or cattle.
7. Metabolite toxicology . The metabolite CL 382390 wasidentified in the banana metabolism study at levels of less than 0.02 ppmor less than 2% of the total radioactive residue in whole bananas. Thisspecific monohydroxylated metabolite was not confirmed in the ratmetabolism studies; however, other monohydroxylated metabolites, includingits stereo isomer were identified. In addition, CL 382390 was shown tohave a low order of acute toxicity via the oral route with an LD 50 value of greater than 5,000 mg/kg b.w. Another metabolitenot identified in the rat metabolism studies, triazolylalanine, was foundin the triazole-3,5-14C CL 900768 treated banana at less than 0.02 ppm orless than 2% of the total radioactive residue in whole bananas.Triazolylalanine has been shown to have a low order of acute toxicity bythe oral route with an oral LD 50 value of greater than 5,000mg/kg [WHO/FAO Joint Meeting on Pesticide Residues (JMPR) review, 1989].Thus, the parent metconazole is considered to be the only toxicologicallysignificant residue in bananas.
8. Endocrine disruption . Collective organ weight data andhistopathological findings from the two-generation rat reproductive study,as well as from the subchronic and chronic toxicity studies in threedifferent animal species, demonstrate no apparent estrogenic effects ortreatment-related effects of metconazole on the endocrine system.
C. Aggregate Exposure
1. Dietary exposure . The potential dietary exposure tometconazole has been calculated from the proposed tolerance for bananas.The very conservative chronic dietary exposure estimates for this cropassumes that 100 percent of all bananas were treated with metconazole andthat all treated bananas contain metconazole residues at the tolerancelevel of 0.05 ppm.
2. Food . Using the assumptions discussed above, theTheoretical Maximum Residue Concentration (TMRC) values of metconazole werecalculated for the U.S. general population and subgroups. Based on theproposed tolerance, the TMRC values for each group are:
• 0.0000142 mg/kg b.w./day for the general population;
• 0.0000461 mg/kg b.w./day for all infants;
• 0.0000473 mg/kg b.w./day for non-nursing infants;
• 0.0000407 mg/kg b.w./day for children 1 to 6 years of age;and
• 0.0000156 mg/kg b.w./day for children 7 to 12 years ofage.
Potential exposure to residues of metconazole in food will be restrictedto intake of bananas, dried bananas, and banana nectar.
3. Drinking water . The tolerance proposed in this petitionis for a raw agricultural commodity imported into the United States. Thereare no approved uses for metconazole in the United States; therefore, thepotential exposure to metconazole in drinking water is not relevant to thispetition.
4. Non-dietary exposure . This petition is for a toleranceon an imported commodity. There is no approved use of metconazole in theUnited States. and none is being sought; therefore, the potential fornon-dietary exposure to metconazole is not pertinent to this petition.
D. Cumulative Effects
Metconazole is a member of the triazole class of fungicides. Othermembers of this class are registered for use in the United States.Although metconazole and other triazoles may have similar fungicidal modesof action, there are no available data to determine whether metconazole hasa common mechanism of mammalian toxicity with other triazoles orinformation on how to include this pesticide in a cumulative riskassessment. Therefore, for the purposes of this tolerance petition noassumption has been made with regard to cumulative exposure with othercompounds having a common mode of action.
E. Safety Determination
1. U.S. population . The Reference Dose (RfD) represents thelevel at or below which daily aggregate exposure over a lifetime will notpose appreciable risks to human health. The chronic toxicity studies inrats and mice are the most appropriate studies to assess chronic dietaryrisk. These studies support a NOAEL of 4.8 mg/kg b.w./day, as the mostsensitive dose for the estimation of the RfD for metconazole in humans.Based on the presence of a complete database for reproductive anddevelopmental toxicity, and in the absence of teratogenicity or selectivedevelopmental toxicity, the use of a 100-fold safety factor is warrantedfor this compound. Applying a safety factor of 100 to this NOAEL resultsin the RfD of 0.048 mg/kg b.w./day. The chronic dietary exposure of0.0000142 mg/kg b.w./day for the general U.S. population will utilize only0.03% of the RfD of 0.048 mg/kg b.w./day. EPA generally has no concern forexposures below 100% of the RfD. The complete and reliable toxicity dataand the conservative chronic dietary exposure assumptions support theconclusion that there is a "reasonable certainty of no harm"from potential dietary exposure to residues of metconazole in bananas.
2. Infants and children . The conservative dietary exposureestimates previously presented will utilize 0.1 percent of the RfD for allinfants and as well as for the non-nursing infant group, which is the mosthighly exposed population subgroup. The chronic dietary exposures forchildren 1 to 6 years of age will utilize only 0.08% of the RfD, while forchildren ages 7 to 12 the estimated exposure will utilize only 0.03% of theRfD. Results from the two-generation reproduction study in rats with WL136184 (greater than 95% cis isomer) and the developmental toxicity studieswith AC 900768 in rats and rabbits indicate no increased sensitivity todeveloping offspring when compared to parental toxicity. For both the ratand rabbit developmental toxicity studies, embryotoxicity was only observedat maternally toxic doses. These results indicate that metconazole isneither a selective developmental toxicant nor a teratogen in either therat or rabbit. Therefore, an additional safety factor is not warranted,and the RfD of 0.048 mg/kg b.w./day, which utilizes a 100-fold safetyfactor is appropriate to ensure a reasonable certainty of no harm toinfants and children.
F. International Tolerances
There are no Codex maximum residue levels established or proposed forresidues of metconazole in bananas.
[FR Doc. 05-7064 Filed 4-7-05; 8:45 am]
BILLING CODE 6560-50-S