[Federal Register Volume 63, Number 224 (Friday, November 20, 1998)]
[Notices]
[Pages 64484-64489]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-31066]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
[PF-836; FRL-6030-9]
Notice of Filing of Pesticide Petitions
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
-----------------------------------------------------------------------
[[Page 64485]]
SUMMARY: This notice announces the initial filing of pesticide
petitions proposing the establishment of regulations for residues of
certain pesticide chemicals in or on various food commodities.
DATES: Comments, identified by the docket control number PF-836, must
be received on or before December 21, 1998.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch, Information Resources and Services Division
(7502C), Office of Pesticides Programs, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments
to: Rm. 119, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
Comments and data may also be submitted electronically to: docket@epamail.epa.gov. Follow the instructions under ``SUPPLEMENTARY
INFORMATION.'' No confidential business information should be submitted
through e-mail.
Information submitted as a comment concerning this document may be
claimed confidential by marking any part or all of that information as
``Confidential Business Information'' (CBI). CBI should not be
submitted through e-mail. Information marked as CBI will not be
disclosed except in accordance with procedures set forth in 40 CFR part
2. A copy of the comment that does not contain CBI must be submitted
for inclusion in the public record. Information not marked confidential
may be disclosed publicly by EPA without prior notice. All written
comments will be available for public inspection in Rm. 1132 at the
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: The product manager listed in the
table below:
------------------------------------------------------------------------
Office location/
Product Manager telephone number Address
------------------------------------------------------------------------
Mark Dow PM-03................ Rm. 214, CM #2, 703- 1921 Jefferson
305-5533, e- Davis Hwy,
mail:[email protected] Arlington, VA
.epa.gov.
James Tompkins PM-25.......... Rm. 239, CM #2, 703- Do.
305-5697, e-
mail:tompkins.james@e.
------------------------------------------------------------------------
SUPPLEMENTARY INFORMATION: 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 petition. Additional data may be needed before EPA rules on the
petition.
The official record for this notice of filing, as well as the
public version, has been established for this notice of filing under
docket control number [PF-836] (including comments and data submitted
electronically as described below). A public version of this record,
including printed, paper versions of electronic comments, which does
not include any information claimed as CBI, is available for inspection
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal
holidays. The official record is located at the address in
``ADDRESSES'' at the beginning of this document.
Electronic comments can be sent directly to EPA at:
opp-docket@epamail.epa.gov
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption. Comments and data
will also be accepted on disks in Wordperfect 5.1 file format or ASCII
file format. All comments and data in electronic form must be
identified by the docket number (insert docket number) and appropriate
petition number. Electronic comments on notice may be filed online at
many Federal Depository Libraries.
List of Subjects
Environmental protection, Agricultural commodities, Food additives,
Feed additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: October 27, 1998.
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.
1. Bayer Corporation
PP 8F5023
EPA has received a pesticide petition (PP 8F5023) from Bayer
Corporation, 8400 Hawthorn Road, Kansas City, MO 64120, proposing
pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act,
21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance
for residues of cyfluthrin: [cyano[4-fluoro-3-phenoxyphenyl]-methyl-3-
[2,2-dichloroethenyl]-2,2-dimethyl-cyclopropanecarboxylate] in or on
the raw agricultural commodity soybean, bean at 0.03 parts per million
(ppm); soybean, forage at 8.0 ppm; soybean, hay at 4.0 ppm; field corn,
forage at 3.0 ppm; and field corn, fodder at 6.0 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.
A. Residue Chemistry
1. Plant metabolism. The metabolism of cyfluthrin in plants is
adequately understood. Studies have been conducted to delineate the
metabolism of radiolabeled cyfluthrin in various crops all showing
similar results. The residue of concern is cyfluthrin.
2. Analytical method. Adequate analytical methodology (gas/liquid
chromatography with an electron capture detector) is available for
enforcement purposes.
3. Magnitude of residues. Cyfluthrin is the active ingredient in
the registered end-use product Baythroid 2 Emulsifiable Pyrethroid
Insecticide, EPA Reg. No. 3125-351. Data to support the proposed
tolerances have been submitted to the Agency.
[[Page 64486]]
B. Toxicological Profile
1. Acute toxicity. There is a battery of acute toxicity studies for
cyfluthrin supporting an overall toxicity Category II for the active
ingredient.
2. Genotoxicty. Mutagenicity tests were conducted, including
several gene mutation assays (reverse mutation and recombination assays
in bacteria and a Chinese hamster ovary (CHO)/HGPRT assay); a
structural chromosome aberration assay (CHO/sister chromatid exchange
assay); and an unscheduled DNA synthesis assay in rat hepatocytes. All
tests were negative for genotoxicity.
3. Reproductive and developmental toxicity. An oral developmental
toxicity study in rats with a maternal and fetal no observed adverse
effect level (NOAEL) of 10 milligram/kilogram body weight/day (mg/kg/
bwt/day) highest dose tested (HDT).
An oral developmental toxicity study in rabbits with a maternal
NOAEL of 20 mg/kg/bwt/day and a maternal lowest effect level (LEL) of
60 mg/kg/bwt/day, based on decreased body weight gain and decreased
food consumption during the dosing period. A fetal NOAEL of 20 mg/kg/
bwt/day and a fetal LEL of 60 mg/kg/ bwt/day were also observed in this
study. The LEL was based on increased resorptions and increased
postimplantation loss.
A 3-generation reproduction study in rats with systemic toxicity
NOAELs of 7.5 and 2.5 mg/kg/bwt/day for parental animals and their
offspring, respectively. At higher dose levels (HDLs), the body weights
of parental animals and their offspring were reduced.
4. Subchronic toxicity. A subchronic toxicity feeding study using
rats demonstrated a NOAEL of 22.5 mg/kg/bwt/day, the HDT.
A 6 month toxicity feeding study in dogs established a NOAEL of 5
mg/kg/ bwt/day. The LEL was 15 mg/kg/bwt/day based on clinical signs
and reduced thymus weights.
5. Chronic toxicity. A 12 month chronic feeding study in dogs
established a NOAEL of 4 mg/kg/bwt/day. The LEL for this study is
established at 16 mg/kg/bwt/day, based on slight ataxia, increased
vomiting, diarrhea and decreased body weight.
A 24 month chronic feeding/carcinogenicity study in rats
demonstrated a NOAEL of 2.5 mg/kg/bwt/day and LEL of 6.2 mg/kg/bwt/day,
based on decreased body weights in males, decreased food consumption in
males, and inflammatory foci in the kidneys in females.
A 24 month carcinogenicity study in mice was conducted. Under the
conditions of the study there were no carcinogenic effects observed. A
24 month chronic feeding/carcinogenicity study in rats was conducted.
There were no carcinogenic effects observed under the conditions of the
study.
6. Animal metabolism. A metabolism study in rats showed that
cyfluthrin is rapidly absorbed and excreted, mostly as conjugated
metabolites in the urine, within 48 hours. An enterohepatic circulation
was observed.
7. Metabolite toxicology. No toxicology data have been required for
cyfluthrin metabolites. The residue of concern is cyfluthrin.
8. Endocrine disruption. There is no evidence of endocrine effects
in any of the studies conducted with cyfluthrin, thus, there is no
indication at this time that cyfluthrin causes endocrine effects.
C. Aggregate Exposure
1. Dietary exposure-- Food. Dietary exposure was estimated using
Novigen's Dietary Exposure Evaluation Model (DEEM) software; results
from field trial and processing studies; consumption data from the USDA
Continuing Surveys of Food Intake by Individuals (CSFIIs), conducted
from 1989 through 1992; and information on the percentages of crops
treated with cyfluthrin.
Cyfluthrin is currently registered for use in alfalfa, carrots,
citrus, cotton, peppers, radishes, sorghum, sunflower, sugarcane, sweet
corn, and tomatoes. In addition, it has an import tolerance for hops.
Various formulations are registered for use in food handling
establishments and in combination with another active ingredient, for
use in field corn, pop corn and sweet corn. For potential cyfluthrin
use on soybeans and field corn the impact on the exposure assessment
was examined.
Chronic dietary exposure estimates with the current label uses for
the overall U.S. population were 0.9% of the reference dose (RfD)
(0.008 mg/kg/ bwt/day). When soybeans, field corn and potatoes were
included the chronic dietary exposure estimates for the overall U.S.
population were 0.8% of the RfD. For the most highly exposed population
subgroups, non-nursing infants (<1 year)="" and="" children="" 1="" to="" 6="" years="" of="" age,="" the="" exposure="" was="" estimated="" to="" be="" 1.9%="" of="" the="" rfd="" and="" 1.8%="" of="" the="" rfd="" respectively="" for="" current="" label="" uses="" and="" 1.7%="" of="" the="" rfd="" and="" 1.7%="" of="" the="" rfd="" respectively="" for="" label="" uses="" plus="" potatoes,="" soybeans,="" field="" corn.="" the="" apparent="" drop="" in="" the="" percentage="" of="" the="" rfd="" when="" these="" uses="" are="" added="" may="" be="" explained="" by="" the="" lower="" limit="" of="" detection="" of="" the="" field="" trial="" data="" for="" these="" crops="" as="" opposed="" to="" the="" food="" handling="" data.="" acute="" dietary="" exposures="" were="" estimated="" for="" the="" overall="" u.s.="" population,="" females="" 13="" years="" and="" older,="" children,="" ages="" 1-6,="" and="" 7-12="" years,="" infants,="" non-nursing="" and="" nursing.="" the="" exposure="" was="" compared="" to="" the="" noael="" of="" 20="" mg/kg/="" bwt/day="" to="" estimate="" the="" margin="" of="" exposures="" (moes).="" for="" the="" all="" the="" population="" subgroups="" studies="" the="" 95th="" and="" 99.9th="" percentile="" of="" exposure="" the="" moes="" were="" calculated="" to="" be="" over="" 18,000="" and="" 5,000="" respectively="" for="" all="" current="" label="" uses="" and="" 9,900="" and="" 3,800="" respectively="" for="" all="" label="" uses="" plus="" potatoes,="" field="" corn="" and="" soybeans.="" for="" women="" aged="" 13="" years="" and="" older="" the="" 95th,="" and="" 99.9th="" percentile="" of="" acute="" exposure="" the="" moes="" were="" calculated="" as="" 66,746="" and="" 18,390="" respectively="" for="" all="" current="" label="" uses="" and="" 33,704="" and="" 11,516="" respectively="" for="" label="" uses="" plus="" potatoes,="" field="" corn,="" and="" soybeans.="" lastly,="" for="" the="" potentially="" highest="" exposed="" population="" subgroups,="" non-nursing="" infants=""><1 year)="" and="" children="" ages="" 1-6="" years,="" the="" 95th,="" and="" 99.9th="" percentile="" of="" acute="" exposure="" to="" the="" moes="" were="" calculated="" at="" 53,356;="" 18,346="" and="" 5,179;="" 6,319="" respectively="" for="" all="" current="" label="" uses="" and="" 19,624;="" 9,964="" and="" 3802;="" 3943="" respectively="" for="" label="" uses="" plus="" potatoes,="" field="" corn,="" and="" soybeans.="" 2.="" drinking="" water.="" cyfluthrin="" is="" immobile="" in="" soil,="" therefore,="" will="" not="" leach="" into="" groundwater.="" additionally,="" due="" the="" insolubility="" and="" lipophilic="" nature="" of="" cyfluthrin,="" any="" residues="" in="" surface="" water="" will="" rapidly="" and="" tightly="" bind="" to="" soil="" particles="" and="" remain="" with="" sediment,="" therefore="" not="" contributing="" to="" potential="" dietary="" exposure="" from="" drinking="" water.="" 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="" 2="" meters="" are="" essentially="" zero=""><0.001 parts="" per="" billion="" (ppb).="" 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="" 52="" parts="" per="" trillion="" (ppt).="" concentration="" in="" actual="" drinking="" water="" would="" be="" much="" lower.="" based="" on="" these="" analyses,="" the="" contribution="" of="" water="" to="" the="" dietary="" risk="" estimate="" is="" negligible.="" 3.="" non-dietary="" exposure.="" non-occupational="" exposure="" to="" cyfluthrin="" may="" occur="" as="" a="" result="" of="" inhalation="" or="" contact="" from="" indoor="" residential,="" indoor="" commercial,="" and="" outdoor="" residential="" uses.="" pursuant="" to="" the="" requirements="" of="" federal="" insecticide,="" fungicide,="" and="" [[page="" 64487]]="" rodenticide="" act="" (fifra)="" as="" amended="" by="" the="" food="" quality="" protection="" act="" (fqpa)="" of="" 1996="" non-dietary="" and="" aggregate="" risk="" analyses="" for="" cyfluthrin="" were="" conducted.="" the="" analyses="" include="" evaluation="" of="" potential="" non-="" dietary="" acute="" application="" and="" post-application="" exposures.="" non-="" occupational,="" non-dietary="" exposure="" was="" assessed="" based="" on="" the="" assumption="" that="" a="" flea="" infestation="" control="" scenario="" represents="" a="" ``worst="" case''="" scenario.="" for="" the="" flea="" control="" infestation="" scenario="" indoor="" fogger,="" and="" professional="" residential="" turf="" same="" day="" treatments="" were="" included="" for="" cyfluthrin.="" deterministic="" (point="" values)="" were="" used="" to="" present="" a="" worse="" case="" upper-bound="" estimate="" of="" non-dietary="" exposure.="" the="" non-dietary="" exposure="" estimates="" were="" expressed="" as="" systemic="" absorbed="" doses="" for="" a="" summation="" of="" inhalation,="" dermal,="" and="" incidental="" ingestion="" exposures.="" these="" worst-case="" non-dietary="" exposures="" were="" aggregated="" with="" chronic="" dietary="" exposures="" to="" evaluate="" potential="" health="" risks="" that="" might="" be="" associated="" with="" cyfluthrin="" products.="" the="" chronic="" dietary="" exposures="" were="" expressed="" as="" an="" oral="" absorbed="" dose="" to="" combine="" with="" the="" non-dietary="" systemic="" absorbed="" doses="" for="" comparison="" to="" a="" systemic="" absorbed="" dose="" noael.="" results="" for="" each="" potential="" exposed="" subpopulation="" (of="" adults,="" children="" 1-6="" years,="" and="" infants=""><1 year)="" were="" compared="" to="" the="" systemic="" absorbed="" dose="" noael="" for="" cyfluthrin="" to="" provide="" estimates="" of="" moe.="" the="" large="" moes="" for="" cyfluthrin="" clearly="" demonstrate="" a="" substantial="" degree="" of="" safety.="" the="" total="" non-dietary="" moes="" are="" 3,800,="" 2,700,="" and="" 2,500="" for="" adults,="" children="" (1-6="" years),="" and="" infants=""><1 year),="" respectively.="" the="" aggregate="" moe="" for="" adults="" is="" approximately="" 3,700="" and="" the="" moes="" for="" infants="" and="" children="" exceed="" 2,400.="" the="" non-dietary="" methods="" used="" in="" the="" analyses="" can="" be="" characterized="" as="" highly="" conservative.="" this="" is="" due="" to="" the="" conservatism="" inherent="" in="" the="" calculation="" procedures="" and="" input="" assumptions.="" an="" example="" of="" this="" is="" the="" conservatism="" inherent="" in="" the="" jassercise="" methodology's="" over-="" representation="" of="" residential="" post-application="" exposures.="" it="" is="" important="" to="" acknowledge="" that="" these="" moes="" are="" likely="" to="" significantly="" underestimate="" actual="" moes="" due="" to="" a="" variety="" of="" conservative="" assumptions="" and="" biases="" inherent="" in="" the="" derivatization="" of="" exposure="" by="" this="" method.="" therefore,="" it="" can="" be="" concluded="" that="" large="" moes="" associated="" with="" potential="" non-dietary="" and="" aggregate="" exposures="" to="" cyfluthrin="" will="" result="" in="" little="" or="" no="" health="" risks="" to="" exposed="" persons.="" the="" aggregate="" risk="" analysis="" demonstrates="" compliance="" with="" the="" health-based="" requirements="" of="" the="" fqpa="" of="" 1996="" for="" the="" current="" label="" uses.="" the="" additional="" use="" of="" cyfluthrin="" on="" field="" corn="" and="" soybean="" crops="" will="" have="" no="" impact="" on="" the="" analysis="" for="" non-dietary="" exposure.="" d.="" cumulative="" effects="" bayer="" will="" submit="" information="" for="" epa="" to="" consider="" concerning="" potential="" cumulative="" effects="" of="" cyfluthrin="" consistent="" with="" the="" schedule="" established="" by="" epa="" at="" 62="" fr="" 42020="" (august="" 4,="" 1997)="" and="" other="" epa="" publications="" pursuant="" to="" the="" fqpa.="" e.="" safety="" determination="" 1.="" u.s.="" population.="" based="" on="" the="" exposure="" assessments="" described="" above="" and="" on="" the="" completeness="" and="" reliability="" of="" the="" toxicity="" data,="" it="" can="" be="" concluded="" that="" total="" aggregate="" exposure="" to="" cyfluthrin="" from="" all="" label="" uses="" plus="" soybeans="" and="" field="" corn="" will="" utilize="" less="" than="" 2%="" of="" the="" rfd="" for="" chronic="" dietary="" exposures="" and="" that="" moe="" in="" excess="" of="" 1,000="" exist="" for="" aggregate="" exposure="" to="" cyfluthrin="" for="" non-occupational="" exposure.="" epa="" generally="" has="" no="" concerns="" for="" exposures="" below="" 100%="" of="" the="" rfd,="" because="" the="" rfd="" represents="" the="" level="" at="" or="" below="" which="" daily="" aggregate="" exposure="" over="" a="" lifetime="" will="" not="" pose="" appreciable="" risks="" to="" human="" health.="" moe="" of="" 100="" or="" more="" (300="" for="" infants="" and="" children)="" also="" indicate="" an="" adequate="" degree="" of="" safety.="" thus,="" it="" can="" be="" concluded="" that="" there="" is="" a="" reasonable="" certainty="" that="" no="" harm="" will="" result="" from="" aggregate="" exposure="" to="" cyfluthrin="" residues.="" 2.="" infants="" and="" children.="" in="" assessing="" the="" potential="" for="" additional="" sensitivity="" of="" infants="" and="" children="" to="" residues="" of="" cyfluthrin,="" the="" data="" from="" developmental="" studies="" in="" both="" rat="" and="" rabbit="" and="" a="" 2-generation="" reproduction="" study="" in="" the="" rat="" can="" be="" considered.="" the="" developmental="" toxicity="" studies="" evaluate="" any="" potential="" adverse="" effects="" on="" the="" developing="" animal="" resulting="" from="" pesticide="" exposure="" of="" the="" mother="" during="" prenatal="" development.="" the="" reproduction="" study="" evaluates="" any="" effects="" from="" exposure="" to="" the="" pesticide="" on="" the="" reproductive="" capability="" of="" mating="" animals="" through="" 2-generations,="" as="" well="" as="" any="" observed="" systemic="" toxicity.="" the="" toxicology="" data="" which="" support="" these="" uses="" of="" cyfluthrin="" include:="" i.="" a="" rat="" oral="" developmental="" toxicity="" study="" in="" which="" maternal="" and="" fetal="" noaels="" of="" 10="" mg/kg/bwt/day="" hdt="" were="" observed.="" ii.="" an="" oral="" developmental="" toxicity="" study="" in="" which="" rabbits="" had="" a="" maternal="" noael="" of="" 20="" mg/kg/bwt/day="" and="" a="" maternal="" lel="" of="" 60="" mg/kg/bwt/="" day,="" based="" on="" decreased="" body="" weight="" gain="" and="" decreased="" food="" consumption="" during="" the="" dosing="" period.="" a="" fetal="" noael="" of="" 20="" mg/kg/bwt/day="" and="" a="" fetal="" lel="" of="" 60="" mg/kg/bwt/day="" were="" also="" observed="" in="" this="" study.="" the="" lel="" was="" based="" on="" increased="" resorptions="" and="" increased="" postimplantation="" loss.="" iii.="" an="" oral="" developmental="" toxicity="" study="" performed="" with="" beta-="" cyfluthrin,="" the="" resolved="" isomer="" mixture="" of="" cyfluthrin,="" has="" been="" submitted="" to="" the="" agency="" and="" is="" currently="" under="" review.="" iv.="" a="" developmental="" toxicity="" study="" in="" rats="" exposed="" via="" inhalation="" to="" liquid="" aerosols="" of="" cyfluthrin="" revealed="" developmental="" toxicity,="" but="" only="" in="" the="" presence="" of="" maternal="" toxicity.="" the="" developmental="" noael="" was="" 0.46="" mg/m3="" on="" the="" basis="" of="" reduced="" placental="" and="" fetal="" weights,="" and="" delayed="" ossification.="" the="" noael="" for="" overt="" maternal="" toxicity="" was=""><0.46 mg/m3,="" the="" lowest="" dose="" tested="" (ldt).="" in="" a="" rat="" 3-generation="" reproduction="" study,="" systemic="" toxicity="" noaels="" of="" 7.5="" and="" 2.5="" mg/kg/bwt/day="" for="" parental="" animals="" and="" their="" offspring,="" respectively,="" were="" observed.="" at="" higher="" dose="" levels,="" the="" body="" weights="" of="" parental="" animals="" and="" their="" offspring="" were="" reduced.="" another="" multiple-="" generation="" reproduction="" study="" in="" rats="" has="" been="" submitted="" to="" the="" agency="" and="" is="" currently="" under="" review.="" to="" assess="" acute="" dietary="" exposure="" and="" determine="" a="" moe="" for="" the="" overall="" u.s.="" population="" and="" certain="" subgroups,="" the="" agency="" has="" used="" the="" rabbit="" developmental="" toxicity="" study="" which="" had="" a="" maternal="" noael="" of="" 20="" mg/kg/bwt/day.="" because="" the="" toxicological="" endpoint="" is="" one="" of="" developmental="" toxicity,="" the="" population="" group="" of="" concern="" for="" this="" analysis="" was="" women="" aged="" 13="" and="" above.="" this="" subgroup="" most="" closely="" approximates="" women="" of="" child-bearing="" age.="" the="" moe="" is="" calculated="" as="" the="" ratio="" of="" the="" noael="" to="" the="" exposure.="" the="" agency="" calculated="" the="" moe="" to="" be="" over="" 600.="" generally,="" moe's="" greater="" than="" 100="" for="" data="" derived="" from="" animal="" studies="" are="" regarded="" as="" showing="" no="" appreciable="" risk.="" ffdca="" section="" 408="" provides="" that="" epa="" may="" apply="" an="" additional="" safety="" factor="" for="" infants="" and="" children.="" the="" additional="" safety="" factor="" may="" be="" used="" when="" pre-="" and="" post-natal="" threshold="" effects="" were="" observed="" in="" studies="" or="" to="" account="" for="" incompleteness="" of="" the="" toxicity="" database.="" the="" results="" of="" the="" 3-generation="" study="" in="" rats="" provided="" evidence="" suggesting="" that,="" with="" respect="" to="" effects="" of="" cyfluthrin="" on="" body="" weight,="" pups="" were="" more="" sensitive="" than="" adult="" rats.="" thus,="" the="" agency="" determined="" that="" an="" additional="" 3-fold="" uncertainty="" factor="" (uf)="" should="" be="" used="" in="" risk="" assessments="" to="" ensure="" adequate="" protection="" of="" infants="" and="" children.="" [[page="" 64488]]="" generally,="" the="" epa="" considers="" moe="" of="" at="" least="" 100="" to="" indicate="" an="" adequate="" degree="" of="" safety.="" with="" an="" additional="" 3x="" uf,="" this="" would="" be="" 300="" for="" infants="" and="" children.="" using="" the="" exposure="" assessments="" described="" above="" and="" based="" on="" the="" described="" toxicity="" data="" aggregate="" exposure="" to="" infants="" and="" children="" indicate="" a="" margin="" of="" exposure="" in="" excess="" of="" 3,800.="" thus,="" it="" can="" be="" concluded="" that="" there="" is="" a="" reasonable="" certainty="" that="" no="" harm="" will="" result="" to="" infants="" and="" children="" from="" aggregate="" exposure="" to="" cyfluthrin="" residues.="" f.="" conclusions="" the="" available="" data="" indicate="" that="" there="" is="" reasonable="" certainty="" of="" no="" harm="" from="" the="" aggregate="" exposure="" from="" all="" currently="" registered="" uses="" of="" cyfluthrin="" plus="" potatoes,="" field="" corn="" and="" soybeans.="" g.="" international="" tolerances="" there="" are="" no="" codex="" maximum="" residue="" levels="" (mrls)="" currently="" established="" for="" residues="" of="" cyfluthrin="" on="" soybean="" commodities.="" there="" is="" a="" codex="" mrls="" for="" maize="" of="" 0.05="" ppm.="" 2.="" dow="" agrosciences="" pp="" 6f4784,="" pp="" 7f4856="" epa="" has="" received="" pesticide="" petitions="" (pp="" 6f4784="" and="" pp="" 7f4856)="" from="" dow="" agrosciences,="" 9330="" zionsville="" road,="" indianapolis,="" in="" 46268-1054,="" proposing="" pursuant="" to="" section="" 408(d)="" of="" the="" federal="" food,="" drug,="" and="" cosmetic="" act,="" 21="" u.s.c.="" 346a(d),="" to="" amend="" 40="" cfr="" part="" 180="" by="" establishing="" a="" tolerance="" for="" residues="" of="" the="" herbicide="" diclosulam="" (n-="" (2,6-dichlorophenyl)-5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-c]pyrimidine-="" 2-sulfonamide)="" in="" or="" on="" the="" raw="" agricultural="" commodities="" soybean="" and="" peanut="" at="" 0.02="" parts="" per="" million="" (ppm).="" epa="" has="" determined="" that="" the="" petitions="" contain="" 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="" petitions.="" a.="" residue="" chemistry="" 1.="" plant="" metabolism.="" nature="" of="" residue="" studies="" demonstrated="" that="" residues="" of="" diclosulam="" would="" not="" be="" expected="" to="" accumulate="" to="" significant="" levels="" in="" soybeans="" or="" peanuts="" grown="" on="" soil="" treated="" with="" diclosulam,="" and="" that="" it="" was="" appropriate="" to="" base="" the="" magnitude="" of="" total="" terminal="" residues="" and="" proposed="" tolerances="" only="" on="" residues="" of="" the="" parent="" compound,="" diclosulam.="" 2.="" analytical="" method.="" analytical="" method="" is="" available="" for="" the="" determination="" of="" diclosulam="" in="" soybeans="" and="" peanuts="" at="" a="" limit="" of="" quantitation="" (loq)="" of="" 0.01="" ppm="" that="" is="" suitable="" for="" the="" enforcement="" of="" the="" proposed="" tolerance="" of="" 0.02="" ppm.="" 3.="" magnitude="" of="" residues.="" no="" detectable="" residues="" of="" diclosulam="" are="" expected="" to="" result="" from="" soil="" applications="" to="" fields="" intended="" for="" soybeans="" or="" peanuts="" under="" the="" proposed="" maximum="" label="" conditions.="" on="" the="" basis="" of="" the="" limit="" of="" detection="" (lod)="" of="" 0.003="" ppm="" for="" diclosulam="" in="" the="" analytical="" method,="" a="" tolerance="" of="" 0.02="" ppm="" is="" proposed="" for="" soybeans="" and="" peanuts.="" soybeans="" and="" peanuts="" treated="" with="" 3="" times="" the="" maximum="" label="" rates="" also="" resulted="" in="" no="" detectable="" residues="" of="" diclosulam="" in="" the="" soybean="" and="" peanuts="" or="" processed="" meal="" and="" oils.="" thus,="" no="" tolerances="" are="" being="" proposed="" for="" diclosulam="" in="" any="" processed="" products.="" b.="" toxicological="" profile="" 1.="" acute="" toxicity--diclosulam="" acute="" toxicity="" is="" low.="" the="" acute="" oral="">50 in the rat is >5,000 milligrams/kilogram (mg/kg) in
both males and females and the acute dermal LD50 in the
rabbit is >2,000 mg/kg. The inhalation LC50 in the rat is
>5.04 mg/l of air. Diclosulam produced no indications of dermal
irritation in rabbits or sensitization in the guinea pig, and only very
slight transient eye irritation in the rabbit following acute exposure.
End use formulations of diclosulam have similar low acute toxicity
profiles.
2. Genotoxicty. In a battery of short-term in vitro genotoxicity
tests (Ames, CHO/HGPRT, chromosomal aberration) and an in vivo
cytogenetic assay, diclosulam was negative.
3. Reproductive and developmental toxicity. Diclosulam exhibited no
effects on reproduction or fetal development. No effects on
reproduction or fetal development in a multigeneration reproduction
study in rats and no effects on reproductive performance or neonatal
survival were seen at the highest dose tested (HDT) (limit test at
1,000 milligrams/kilogram/day (mg/kg/day). In a developmental toxicity
study in rabbits, the maternal no observed adverse effect level (NOAEL)
was 65 mg/kg/day and the developmental NOAEL was at least 650 mg/kg/
day.
4. Subchronic toxicity. Thirteen-week dietary toxicity studies in
rats, mice and dogs were conducted. The primary target organs
identified in these studies were the kidneys (rat), and the liver (rat,
mouse and dog). In the rat 13-week study the NOAELs were 50 mg/kg/day
in the male and 100 mg/kg/day in the female, based on liver
histopathologic evaluation in males and decreased body weights in
females. In the mouse, the NOAEL was 100 mg/kg/day based upon
hepatocellular hypertrophy. An NOAEL of 5 mg/kg/day was established in
the dog based upon centrilobular hepatocellular hypertrophy at 25 mg/
kg/day. In a 21-day repeated dermal application study in rabbits,
diclosulam when given at a dose of 1,000 mg/kg/day produced no signs of
dermal irritation or systemic toxicity.
5. Chronic toxicity. In a 2-year combined chronic toxicity/
oncogenicity study in the rat, the NOAEL for chronic toxicity was 5 mg/
kg/day based upon kidney effects characterized as slight, subtle
alteration in kidney tubular morphology, mostly within the
corticomedullary junction which likely represented more a physiologic
adaptation than a pathological change indicative of a toxic injury.
There was no evidence of an oncogenic response. In a 2-year dietary
feeding study in B6C3F1 mice conducted at 50, 100, 250 and 500 mg/kg/
day, 50 mg/kg/day was considered the NOAEL in males and the NOAEL in
females based upon histologic changes in the kidney. The lesion noted
in male mice was a reduced vacuolation of the kidney tubular epithelium
at all dose levels. Decreased absolute and relative kidney weights were
seen at 100 mg/kg/day and above. In female mice, focal dilation with
hyperplasia of the lining epithelium of the renal cortical tubules was
seen at 100 mg/kg/day and above. There was no evidence of an oncogenic
response. In a 1-year chronic toxicity study in dogs, the NOAEL was
considered 25 mg/kg/day, the HDT. Measurable toxicity was anticipated
based on the results of the 13-week study in dogs; however, the only
treatment related effects were slight elevations in serum alkaline
phosphatase and creatinine levels at 25 mg/kg/day, which were
considered within the normal limits of variability in dogs.
6. Animal metabolism. Metabolism studies conducted on diclosulam
indicated over 80% of a single or repeated dose of 5 mg/kg was
absorbed, while at 500 mg/kg/day, there was incomplete absorption of
diclosulam, with only 15-20% of the dose absorbed. Urinary elimination
was rapid with half-lives of approximately 7-12 hours. Sex dependent
differences in disposition of the 5 mg/kg dose were traced to more
efficient elimination of unchanged diclosulam in the female versus male
kidney but are of no known toxicologic significance. Due to its rapid
elimination, diclosulam has little potential to accumulate upon
repeated administration.
[[Page 64489]]
7. Metabolite toxicology. The residue of concern for tolerance
setting purposes is the parent material (diclosulam). Thus, there is no
need to address metabolite toxicity.
C. Aggregate Exposure
1. Dietary exposure--Food. For Purposes of assessing the potential
dietary exposure from use of diclosulam on soybeans and peanuts, a
conservative estimate of aggregate exposure is determined by
Theoretical Maximum Residue Contribution (TMRC) assuming that 100% of
the soybeans and peanuts have a residue of diclosulam at the proposed
tolerance level of 0.02 ppm. This results in an extremely conservative
estimate of exposure for diclosulam, because no residues are expected
in these commodities at the proposed maximum label rate. The potential
dietary exposure is obtained by multiplying the tolerance residue level
on soybeans and peanuts (0.02 ppm) by the consumption data which
estimates the amount of soybean and peanut products consumed by various
population subgroups. The maximum potential average daily dose (ADD) of
diclosulam values determined for various populations are clearly
significant overestimates compared with actual exposure. When ADDs are
compared to the Reference Dose (RfD), which uses the lowest NOAEL of 5
mg/kg/day from the 2-year rat chronic toxicity study and an uncertainty
factor of 100, the ADD for all U.S. consumers including the highest
exposed group, non-nursing infants under 1-year old, would
theoretically be exposed to about 0.1% of the RfD.
2. Drinking water. Another potential source of dietary exposure are
residues in drinking water. Based upon the available field dissipation
and field run off studies conducted with diclosulam there is little
potential for exposure to diclosulam in drinking water to cause any
human health concern.
D. Cumulative Effects
There is no reliable information to indicate that diclosulam has a
common mechanism of toxicity with any other chemical compound or that
potential toxic effects of diclosulam would be cumulative with those of
any other pesticide chemical. Thus Dow AgroSciences believes it is
appropriate to consider only the potential risks of diclosulam in its
exposure assessment.
E. Safety Determination
1. U.S. population. Using the conservative exposure assumptions
described above, and based on the completeness and reliability of the
toxicity data, Dow AgroSciences has concluded that aggregate exposure
to diclosulam potentially can utilize about 0.1% of the RfD for non-
nursing infants under 1-year old, theoretically the most exposed
population. EPA generally has no concern for exposures below 100% of
the RfD because the RfD represents the level at or below which daily
aggregate dietary exposure over a lifetime will not pose appreciable
risks to human health. Therefore, Dow AgroSciences concludes that there
is a reasonable certainty that no harm will result from aggregate
exposure to diclosulam residues in on soybeans and peanuts and its
processed products.
The complete toxicology profile for diclosulam shows no evidence of
physiological effects characteristic of the disruption of the hormone
estrogen. Based upon this observation, diclosulam does not meet the
criteria for an estrogenic compound.
2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of diclosulam, data
from developmental toxicity studies in rats and rabbits and a
multigeneration reproduction study in the rat are considered. 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 and potential systemic toxicity of
mating animals and on various parameters associated with the well-being
of offspring.
FFDCA section 408 provides that EPA may apply an additional safety
factor for infants and children in the case of threshold effects to
account for pre- and post-natal toxicity and the completeness of the
data base. Based on the current toxicological data requirements, the
data base for diclosulam relative to pre- and post-natal effects for
children is complete. Further, for diclosulam, the NOAEL in the chronic
feeding study which was used to calculate the RfD (5 mg/kg/day) is
already lower than the NOAELs from the developmental studies in rats
and rabbits by a factor of more than 200-fold.
Concerning the reproduction study in rats, there were no effects on
reproduction or fetal development, even at a dose over 100 times the
NOAEL used to establish the RfD. Therefore, Dow AgroSciences concludes
that an additional uncertainty factor is not needed and that the RfD at
0.05 mg/kg/day is appropriate for assessing risk to infants and
children.
Using the conservative exposure assumptions previously described,
the percent RfD utilized by the aggregate (diet, and drinking water)
exposure to residues of diclosulam on soybeans and peanuts is 0.000051
mg/kg/day for non-nursing infants under 1-year old, theoretically the
most exposed population subgroup. Thus, based on the completeness and
reliability of the toxicity data and the conservative exposure
assessment, Dow AgroSciences concludes that there is a reasonable
certainty that no harm will result to infants and children from
aggregate exposure to diclosulam on soybeans and peanuts.
F. International Tolerances
There are no Codex maximum residue levels established for residues
of diclosulam on soybeans, peanuts or any other food or feed crop.
[FR Doc. 98-31066 Filed 11-19-98; 8:45 am]
BILLING CODE 6560-50-F
