[Federal Register Volume 63, Number 6 (Friday, January 9, 1998)]
[Notices]
[Pages 1456-1464]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-557]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-786; FRL-5762-6]
Notice of Filing of Pesticide Petitions
AGENCY: Environmental Protection Agency (EPA).
[[Page 1457]]
ACTION: Notice.
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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-786, must
be received on or before February 9, 1998.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch (7502C), Information Resources and Services
Division, Office of Pesticides Programs, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments
to: Rm. 1132, 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:
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Office location/
Product Manager telephone number Address
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Joanne Miller (PM 23)......... Rm. 237, CM #2, 703- 1921 Jefferson
305-6224, e-mail: Davis Hwy,
[email protected] Arlington, VA
.epa.gov.
Marion Johnson (PM 10)........ Rm. 217, CM #2, 703- Do.
305-6788, e-mail:
johnson.marion@epamai.
Cynthia Giles-Parker (PM 22).. Rm. 229, CM #2, 703- Do.
305-7740, e-mail:
parker.cynthia@epamai.
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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-786] (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. Comment and data
will also be accepted on disks in Wordperfect 5.1/6.1 or ASCII file
format. All comments and data in electronic form must be identified by
the docket control number [PF-786] and appropriate petition number.
Electronic comments on this 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: December 17, 1997.
James Jones,
Acting 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. BASF Corporation
PP 7F4881
EPA has received a pesticide petition (PP 7F4881) from BASF
Corporation, Agricultural Products, P.O. Box 13528, Research Triangle
Park, NC 27709, 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 Pridaben, [2 tert-
butyl-5(4-tert-butylbenzylthio)-4- chloropyridazin-3(2H)-one] in or on
the raw agricultural commodity. 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. BASF Corporation notes that metabolism in
plants is understood.
2. Analytical method. The proposed analytical method involves
extraction, partition, clean-up and detection of residues by gc/ecd.
3. Magnitude of residues. Eleven peach residue trials to determine
residues in peaches and nectarines were conducted in eight states.
Residues of pyridaben were measured by gc/ecd. The method of detection
had a limit of detection of 0.05 parts per million (ppm). Residues
ranged from <0.05 to="" 2.36.="" [[page="" 1458]]="" eight="" plum="" residue="" trials="" to="" determine="" residues="" in="" plums="" and="" prunes="" were="" conducted="" in="" four="" states.="" residues="" of="" pyridaben="" were="" measured="" by="" gc/ecd.="" the="" method="" of="" detection="" had="" a="" limit="" of="" detection="" of="" 0.05="" ppm.="" residues="" ranged="" from=""><0.05 to="" 0.683="" ppm.="" no="" residues="" trials="" were="" conducted="" to="" determine="" residues="" in="" cherries="" and="" apricots.="" only="" postharvest="" applications="" are="" requested.="" no="" residues="" will="" occur="" since="" pyridaben="" is="" not="" systemic="" and="" does="" not="" translocate.="" the="" limit="" of="" detection="" of="" 0.05="" ppm="" is="" proposed="" as="" the="" tolerance.="" fifteen="" grape="" residue="" trials="" were="" conducted="" in="" six="" states.="" residues="" of="" pyridaben="" were="" measured="" by="" gc/ecd.="" the="" method="" of="" detection="" had="" a="" limit="" of="" detection="" of="" 0.05="" ppm.="" residues="" ranged="" from="" 0.168="" to="" 1.38="" ppm.="" six="" pecan="" residue="" trials="" were="" conducted="" in="" four="" states="" to="" complete="" requirements="" for="" a="" group="" tolerance="" for="" nut="" crops.="" basf="" corporation="" was="" granted="" a="" tolerance="" of="" 0.05="" ppm="" for="" use="" on="" almonds.="" residues="" of="" pyridaben="" were="" measured="" by="" gc/ecd.="" the="" method="" of="" detection="" had="" a="" limit="" of="" detection="" of="" 0.05ppm.="" there="" were="" no="" residues="" above="" 0.05="" ppm.="" b.="" toxicological="" profile="" 1.="" acute="" toxicity--acute="" toxicity="" testing.="" i.="" acute="" oral="" toxicity="" (rat):="">50 = 1,100 mg/kg in males; 570 mg/kg in females.
Tox Category: III.
ii. Acute Oral Toxicity (mouse): LD50 = 424 mg/kg in
males; 383 mg/kg in females. Tox Category: II.
iii. Acute Dermal Toxicity (rat): LD50 = >2000 mg/kg in
males and females. Tox Category: III.
iv. Acute Inhalation Toxicity (rat): LC50 = 0.66 mg/l in
males; 0.62 mg/l in females. Tox Category: III.
v. Primary Eye Irritation (rabbit): Pyridaben is a slight ocular
irritant. Tox Category: III.
vi. Primary Dermal irritation (rabbit): Pyridaben is not a dermal
irritant. Tox Category: IV.
vii. Dermal Sensitization (guinea pig): Pyridaben is not a dermal
sensitizer.
viii. Acute Neurotoxicity (rat): Rats were dosed once with 0, 50,
100 and 200 milligram/kilogram (mg/kg). The No Observed Effect Level
(NOEL) for systemic toxicity was determined to be 50 mg/kg for both
males and females. The Lowest Observed Effect Level (LOEL) for systemic
effects was determined to be 100 mg/kg in both sexes based on decreased
food consumption, decreased body weight gain and increased clinical
signs. The LOEL for neurobehavioral effects was determined to be 200
mg/kg in males and >200 mg/kg in females.
2. Mutagenicity testing--Ames testing: Negative In vitro
cytogenicity (Chinese hamster lung cells): Negative In vivo
micronucleus assay (mouse): Negative DNA damage/repair (E. coli):
Negative.
3. Reproductive and developmental toxicity-- i. Developmental
toxicity testing (rat). Sprague Dawley rats were dosed with 0, 2.5,
5.7, 13 and 30 mg/kg/day pyridaben in the diet from days 6 through 15
of gestation. The Maternal NOEL was determined to be 4.7 mg/kg/day and
the maternal LOEL was determined to be 13 mg/kg/day based on decreased
body weight gain, and decreased food consumption during the dosing
period. The developmental NOEL was determined to be 13 mg/kg/day and
the developmental LOEL was determined to be 30 mg/kg/day based on
decreased fetal body weight and an increase in incomplete ossification
in selected bones.
ii. Developmental toxicity (rabbit). New Zealand white rabbits were
dosed with 0, 1.5, 5, and 15 mg/kg/day pyridaben in the diet from days
6 through 19 of gestation. The Maternal NOEL was determined to be 5 mg/
kg/day and the maternal LOEL was determined to be 15 mg/kg/day based on
decreased body weight gain, and decreased food consumption during the
dosing period. The developmental NOEL was determined to be >15 mg/kg/
day and the developmental LOEL was determined to be >15 mg/kg/day.
iii. Developmental toxicity (rabbit). Himalayan rabbits were dosed,
by dermal application, with 0, 70, 170 and 450 mg/kg/day pyridaben from
days 6 through 19 of gestation. The Maternal systemic NOEL was
determined to be 70 mg/kg/day and the maternal LOEL was determined to
be 170 mg/kg/day based on decreased body weight gain, and decreased
food consumption during the dosing period. The developmental NOEL was
determined to be 170 mg/kg/day and the LOEL determined to be 450 mg/kg/
day based on decreased ossification of the skull.
iv. Reproductive toxicity testing, multigeneration reproduction
(rat). CD rats were dosed with 0, 10, 28 and 80 ppm pyridaben in the
diet. The Parental/Systemic NOEL was determined to be 28 ppm in both
sexes (equivalent to 2.20 mg/kg/day in males and 2.41 mg/kg/day in
females). The Parental/Systemic LOEL was determined to be 80 ppm
(equivalent to 6.31 mg/kg/day in males and 7.82 mg/kg/day in females)
based on decreased body weight, decreased body weight gain and
decreased food efficiency. The reproductive NOEL and LOEL were both
determined to be >80 ppm in males and females.
4. Subchronic toxicity-- i. A 21-day dermal (rat). Rats were
repeatedly dosed with pyridaben at 0, 30. 100, 300 and 1,000 mg/kg/day
for 21 days. The NOEL was determined to be 100 mg/kg/day and the LOEL
300 mg/kg/day based on decreased body weight gain in females.
ii. A 90-day rodent (rat). CD rats were dosed with pyridaben at 0,
30, 65, 155 and 350 ppm in the diet for 13 weeks. The NOEL was
determined to be 65 ppm (4.94 mg/kg/day) for males and 30 ppm (2.64 mg/
kg/day) in females. The LOEL for males was determined to be 155 ppm
(11.55 mg/kg/day) based on reduced body weight gain, reduced food
consumption, reduced food efficiency, and altered clinical pathology
parameters. The LOEL for females was determined to be 65 ppm (5.53 mg/
kg/day) based on reduced body weight gain and reduced food efficiency.
iii. A 90-day non-rodent (dog). Beagle dogs were dosed with
pyridaben at 0, 0.5, 1,4, and 16 mg/kg/day in the diet for 13 weeks.
The NOEL was determined to be 1 mg/kg/day and the LOEL determined to be
4 mg/kg/day based on reduced body weight gain and an increase in
clinical signs in both sexes.
iv. A 90-day neurotoxicity (rat). Rats were dosed with pyridaben at
0, 30, 100, and 350 ppm in the diet for 13 weeks. The systemic NOEL was
determined to be 100 ppm (equivalent to 8.5 mg/kg/day in males and 9.3
mg/kg/day in females). The systemic LOEL was determined to be 350 ppm
(equivalent to 28.8 mg/kg/day in males and 31.1 mg/kg/day in females)
based on decreased body weight gain, decreased food consumption and
decreased food efficiency. No neuropathological effects were noted in
the study.
5. Chronic toxicity-- i. A 1-year non-rodent (dog). Two studies
were run. In the first, beagle dogs were dosed with pyridaben at 0, 1,
4, 16 and 32 mg/kg/day in the diet for 1-year. In the second, beagle
dogs were dosed with pyridaben at 0 and 0.5 mg/kg/day in the diet for
1-year. The NOEL was determined to be <0.5 ppm="" and="" loel="" determined="" to="" be="" 0.5="" mg/kg/day="" based="" on="" increased="" clinical="" signs="" and="" decreased="" body="" weight="" gain="" in="" both="" sexes.="" ii.="" combined="" rodent="" chronic="" toxicity/carcinogenicity="" (rat).="" wistar="" rats="" were="" fed="" 0,="" 4,="" 10,="" 28="" and="" 80="" ppm="" pyridaben="" in="" the="" diet="" to="" assess="" carcinogenicity="" and="" 0,="" 4,="" 10,="" 28="" and="" 120="" ppm="" in="" the="" diet="" to="" assess="" chronic="" toxicity="" for="" 104="" weeks.="" the="" noel="" was="" determined="" to="" be="" 28="" ppm="" in="" both="" sexes="" (equivalent="" to="" 1.13="" mg/kg/day="" in="" males="" and="" 1.46="" mg/kg/day="" in="" females).="" the="" loel="" was="" determined="" [[page="" 1459]]="" to="" be="" 120="" ppm="" in="" both="" sexes="" (equivalent="" to="" 5.0="" mg/kg/day="" in="" males="" and="" 6.52="" mg/kg/day="" in="" females)="" based="" on="" decreased="" body="" weight="" gain="" in="" both="" sexes="" and="" decreased="" alt="" levels="" in="" males.="" pyridaben="" was="" not="" carcinogenic="" under="" the="" conditions="" of="" the="" test.="" iii.="" carcinogenicity="" in="" the="" rodent="" (mouse).="" cd-1="" mice="" were="" fed="" 0,="" 2.5,="" 8.0,="" 25="" and="" 80="" ppm="" pyridaben="" in="" the="" diet="" for="" 78="" weeks.="" the="" noel="" was="" determined="" to="" be="" 25="" ppm="" in="" both="" sexes="" (equivalent="" to="" 2.78="" mg/kg/day="" in="" both="" sexes).="" the="" loel="" was="" determined="" to="" be="" 80="" ppm="" in="" both="" sexes="" (equivalent="" to="" 8.88="" mg/kg/day="" in="" males="" and="" 9.74="" mg/kg/day="" in="" females)="" based="" on="" decreased="" body="" weight="" gain,="" decreased="" food="" efficiency="" and="" changes="" in="" organ="" weights="" and="" histopathology.="" pyridaben="" was="" not="" carcinogenic="" under="" the="" conditions="" of="" the="" test.="" 6.="" animal="" metabolism.="" basf="" corporation="" notes="" that="" metabolism="" in="" animals="" is="" understood.="" 7.="" threshold="" effects.="" based="" on="" the="" available="" chronic="" toxicity="" data,="" epa="" has="" established="" the="" reference="" dose="" (rfd)="" for="" pyridaben="" at="" 0.005="" mg/="" kg/day.="" the="" rfd="" for="" pyridaben="" is="" based="" on="" a="" 1-year="" feeding="" study="" in="" dogs="" with="" a="" threshold="" lowest-observed="" effect="" level="" (loel)="" of="" 0.5="" mg/kg/="" day="" based="" on="" increased="" clinical="" signs="" and="" decreased="" body="" weight="" gain="" in="" both="" sexes="" and="" an="" uncertainty="" factor="" of="" 100.="" 8.="" non-threshold="" effects.="" using="" its="" guidelines="" for="" carcinogenic="" risk="" assessment,="" epa="" has="" classified="" pyridaben="" as="" group="" ``e''="" for="" carcinogenicity="" (no="" evidence="" of="" carcinogenicity)="" based="" on="" the="" results="" of="" carcinogenicity="" studies="" in="" two="" species.="" there="" was="" no="" evidence="" of="" carcinogenicity="" in="" an="" 18-month="" feeding="" study="" in="" mice="" and="" a="" 2-year="" feeding="" study="" in="" rats="" at="" the="" dosage="" levels="" tested.="" the="" doses="" tested="" were="" adequate="" for="" identifying="" a="" cancer="" risk.="" thus,="" a="" cancer="" risk="" assessment="" is="" not="" necessary.="" c.="" aggregate="" exposure="" 1.="" dietary="" exposure--i.="" food.="" since="" pyridaben="" is="" regulated="" based="" upon="" non-carcinogenic="" chronic="" toxicity,="" basf="" conducted="" a="" dres="" analysis="" based="" on="" anticipated="" residue="" levels="" determined="" by="" the="" tolerance="" support="" branch="" of="" hed.="" the="" anticipated="" residue="" levels="" were="" derived="" from="" the="" average="" residue="" levels="" from="" field="" trials="" conducted="" at="" the="" maximum="" proposed="" use="" rate="" and="" minimum="" pre-harvest="" interval,="" and="" a="" correction="" factor="" of="" 2.3="" to="" account="" for="" all="" organosoluble="" residues="" as="" determined="" by="" epa="" hed.="" this="" analysis="" demonstrates="" that="" the="" exposure="" to="" non-nursing="" infants=""><1 year,="" the="" most="" sensitive="" sub-population="" is="" approximately="" 128.6%="" of="" the="" rfd="" and="" to="" the="" general="" population="" exposure="" is="" approximately="" 18.6%.="" assuming="" a="" conservative="" pyridaben="" market="" share="" of="" 65%="" of="" all="" crop="" uses,="" then="" the="" most="" sensitive="" sub-population="" is="" approximately="" 83.8%="" of="" the="" rfd="" and="" to="" the="" general="" population="" exposure="" is="" approximately="" 12.1%.="" ii.="" drinking="" water.="" other="" potential="" sources="" of="" exposure="" of="" the="" general="" population="" to="" residues="" of="" pesticides="" are="" residues="" in="" drinking="" water="" and="" exposure="" from="" non-occupational="" sources.="" based="" on="" the="" studies="" submitted="" to="" epa="" for="" assessment="" of="" environmental="" risk,="" basf="" does="" not="" anticipate="" exposure="" to="" residues="" of="" pyridaben="" in="" drinking="" water.="" there="" is="" no="" established="" maximum="" concentration="" level="" for="" residues="" of="" pyridaben="" in="" drinking="" water="" under="" the="" safe="" drinking="" water="" act.="" basf="" has="" not="" estimated="" non-occupational="" exposure="" for="" pyridaben="" since="" the="" current="" registration="" for="" pyridaben="" is="" limited="" to="" commercial="" greenhouse="" use="" for="" non-food="" ornamental="" plants="" and="" the="" only="" other="" use="" will="" be="" for="" commercial="" apple/pear="" and="" citrus="" production="" the="" potential="" for="" non-="" occupational="" exposure="" to="" the="" general="" population="" is="" considered="" to="" be="" insignificant.="" d.="" cumulative="" effects="" basf="" also="" considered="" the="" potential="" for="" cumulative="" effects="" of="" pyridaben="" and="" other="" substances="" that="" have="" a="" common="" mechanism="" of="" toxicity.="" basf="" has="" concluded="" that="" consideration="" of="" a="" common="" mechanism="" of="" toxicity="" is="" not="" appropriate="" at="" this="" time="" since="" there="" is="" no="" reliable="" information="" to="" indicate="" that="" toxic="" effects="" produced="" by="" pyridaben="" would="" be="" cumulative="" with="" those="" of="" any="" other="" chemical="" compounds.="" e.="" safety="" determination="" 1.="" u.s.="" population.="" reference="" dose="" (rfd),="" using="" the="" exposure="" assumptions="" described="" in="" section="" iii,="" above,="" basf="" concludes="" that="" aggregate="" exposure="" to="" pyridaben="" will="" utilize="" approximately="" 12.1%="" the="" rfd="" for="" the="" u.s.="" population.="" epa="" generally="" has="" no="" concern="" for="" exposures="" below="" 100%="" of="" the="" rfd.="" therefore,="" based="" on="" the="" completeness="" and="" reliability="" of="" the="" toxicity="" data="" and="" the="" conservative="" exposure="" assessment,="" basf="" concludes="" that="" there="" is="" a="" reasonable="" certainty="" that="" no="" harm="" will="" result="" from="" aggregate="" exposure="" to="" residues="" of="" pyridaben,="" including="" all="" anticipated="" dietary="" exposure="" and="" all="" other="" non-="" occupational="" exposures.="" 2.="" infants="" and="" children.="" developmental="" toxicity="" (delayed="" ossification)="" was="" observed="" in="" developmental="" toxicity="" studies="" using="" rats="" and="" rabbits.="" the="" no-observed="" effect="" level's="" (noel's)="" for="" developmental="" effects="" were="" established="" at="" 13="" mg/kg/day="" in="" the="" rat="" study="" and="" 15="" mg/kg/="" day="" in="" the="" rabbit="" study.="" the="" developmental="" effect="" observed="" in="" these="" studies="" is="" believed="" to="" be="" a="" secondary="" effect="" resulting="" from="" maternal="" stress="" (decreased="" body="" weight="" gain="" and="" food="" consumption).="" in="" a="" 2-generation="" reproduction="" study="" in="" rats,="" pups="" from="" the="" high="" dose="" group,="" which="" were="" fed="" diets="" containing="" 80="" ppm="" (equivalent="" to="" 6.31="" and="" 7.82="" mg/kg/day="" in="" male="" and="" females,="" respectively)="" gained="" less="" weight="" beginning="" on="" lactation="" day="" 14.="" parental="" systemic="" toxicity="" including="" decreased="" body="" weights,="" body="" weight="" gains="" and="" food="" efficiency="" in="" males,="" and="" slightly="" decreased="" body="" weights="" and="" body="" weight="" gains="" in="" females="" during="" lactation="" was="" also="" observed="" in="" the="" high="" dose="" group.="" the="" results="" of="" this="" study="" indicate="" that="" the="" loss="" in="" weight="" gain="" in="" pups="" from="" the="" high="" dose="" group="" was="" affected="" by="" nursing.="" no="" clear="" scientific="" consensus="" yet="" exists="" to="" define="" the="" most="" appropriate="" endpoints="" for="" assessing="" risk="" in="" children.="" however,="" in="" consideration="" of="" the="" data="" that="" show="" both="" developmental="" and="" reproductive="" toxicity="" were="" effects="" secondary="" to="" parental="" toxicity,="" basf="" believes="" that="" the="" established="" reference="" dose="" (rfd)="" of="" 0.005="" mg/kg/day="" is="" the="" most="" conservative="" approach="" for="" assessing="" risk="" in="" children.="" using="" the="" exposure="" assumptions="" described="" in="" section="" 5,="" above,="" basf="" has="" concluded="" that="" the="" percent="" of="" the="" rfd,="" when="" adjusted="" for="" a="" conservative="" market="" share="" of="" 65%,="" that="" will="" be="" utilized="" by="" aggregate="" exposure="" to="" residues="" of="" pyridaben="" from="" the="" proposed="" use="" in="" citrus,="" apples,="" pears,="" almonds,="" peaches,="" plums,="" and="" grapes="" is="" approximately="" 83.8%="" for="" non-nursing="" infants="">< 1="" year),="" the="" most="" sensitive="" sub-population.="" based="" on="" the="" completeness="" and="" reliability="" of="" the="" toxicity="" data="" and="" the="" conservative="" exposure="" assessment,="" basf="" concludes="" that="" there="" is="" a="" reasonable="" certainty="" that="" no="" harm="" will="" result="" to="" infants="" and="" children="" from="" aggregate="" exposure="" to="" the="" residues="" of="" pyridaben,="" including="" all="" anticipated="" dietary="" exposure="" and="" all="" other="" non-occupational="" exposures.="" f.="" other="" considerations="" the="" qualitative="" nature="" of="" the="" residues="" in="" plants="" and="" animals="" is="" adequately="" understood.="" residues="" of="" the="" parent="" molecule,="" pyridaben="" are="" the="" only="" residues="" of="" concern.="" residues="" of="" pyridaben="" do="" not="" concentrate="" in="" the="" processed="" commodities="" apple="" and="" citrus="" juice.="" there="" is="" a="" practical="" analytical="" method="" for="" detecting="" and="" measuring="" levels="" of="" pyridaben="" in="" or="" on="" food="" with="" [[page="" 1460]]="" a="" limit="" of="" detection="" that="" allows="" monitoring="" of="" food="" with="" residues="" at="" or="" above="" the="" levels="" set="" in="" these="" tolerances.="" endocrine="" effects.="" no="" specific="" tests="" have="" been="" conducted="" with="" pyridaben="" to="" determine="" whether="" the="" chemical="" may="" have="" an="" effect="" in="" humans="" that="" is="" similar="" to="" an="" effect="" produced="" by="" a="" naturally="" occurring="" estrogen="" or="" other="" endocrine="" effects.="" however,="" there="" were="" no="" significant="" findings="" in="" other="" relevant="" toxicity="" studies,="" i.e.,="" teratology="" and="" multi-generation="" reproductive="" studies,="" which="" would="" suggest="" that="" pyridaben="" produces="" endocrine="" related="" effects.="" g.="" international="" tolerances="" a="" maximum="" residue="" level="" has="" not="" been="" established="" for="" pyridaben="" by="" the="" codex="" alimentarius="" commission.="" (pm="" 10)="" 2.="" gmja="" specialties="" pp="" 7g4891="" epa="" has="" received="" a="" pesticide="" petition="" (pp="" 7g4891)="" from="" gmja="" specialties,="" 1001="" 13th="" avenue="" east,="" bradenton,="" fl="" 34208,="" 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="" pt807-hcl="" in="" or="" on="" the="" raw="" agricultural="" commodity="" oranges="" at="" 0.01="" ppm.="" the="" proposed="" analytical="" method="" is="" extracting="" pt807-hcl="" from="" whole="" oranges,="" juice,="" and="" dried="" pulp="" using="" organic="" solvents="" has="" been="" validated.="" extracted="" pt807-hcl="" residues="" are="" analyzed="" using="" high="" performance="" liquid="" chromatography="" (hplc)="" with="" a="" uv="" detector.="" the="" limit="" of="" quantitation="" (loq)="" of="" the="" method="" is="" 0.01="" part="" per="" million="" (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="" plant="" metabolism.="" the="" metabolism="" of="" pt807-hcl="" in="" plants="" and="" animals="" is="" understood.="" in="" plants="" (oranges),="" unchanged="" parent="" is="" the="" only="" residue="" identified="" in="" fruit.="" valencia="" orange="" trees="" were="" treated="" with="">14C PT807-HCl at a nominal rate of 1,000 ppm (approximately
60x the maximum recommended application rate). Fruit from the previous
season's crop present on the tree at the time of application was
harvested 50 days after treatment (DAT) and mature fruit (not present
on the tree at application) was harvested 370 DAT. Total radioactive
residue (TRR) levels were 0.538 ppm in 50 DAT orange samples and were
0.051 ppm in 370 DAT orange samples. Most of the radioactivity was
present on the peel (88.63% TRR or 0.475 ppm in the 50 DAT fruit, and
64.19% TRR or 0.033 ppm in the 370 DAT fruit). Unchanged parent PT807-
HCl was detected in 50 DAT mature fruit using organic solvents has been
validated. Extracted PT807-HCl residues are analyzed using HPLC with a
UV detector. The LOQ of the method is 0.01 ppm.
B. Toxicological Profile
1. Acute toxicity. A battery of acute toxicity studies has been
conducted and the results indicate that PT807-HCl exhibits low acute
oral, dermal, and inhalation toxicity. PT807-HCl also has low potential
as a skin or eye irritant and is not a skin sensitizer.
2. Genotoxicity. The genotoxic potential of PT807-HCl has been
assessed in an Ames Salmonella assay, a CHO HGPRT gene mutation assay,
a mouse micronucleus assay, and an in vitro CHO assay for chromosomal
aberrations. The in vitro chromosomal aberration assay was positive
with and without metabolic activation; however, all of the remaining
assays were negative, indicating very low genotoxic potential of PT807
weakened by the negative finding in an in vivo study (mouse
micronucleus) measuring a similar endpoint.
3. Reproductive and developmental toxicity. A 2-generation
reproductive toxicity study of PT807-HCl is ongoing.
4. Analytical method. An analytical method capable of extracting
PT807-HCl from whole oranges, juice, and dried pulp using organic
solvents has been validated. Extracted PT807-HCl residues are analyzed
using high performance liquid chromatography (HPLC) with a UV detector.
The limit of quantitation (LOQ) of the method is 0.01 ppm.
5. Magnitude of residues. Seventeen field trials were conducted
using various varieties of oranges in California (4 trials), Florida
(12 trials), and Texas (1 trial). Two of the trials (1 in California
and 1 in Florida) were decline studies with sampling intervals of 0, 7,
14, 30, and 60 days after application. For all other trials, oranges
were harvested at the earliest possible time for normal commercial
harvest after a single application with PT807-HCl at the maximum
recommended application rate (6 g a.i./A). At some of the test sites
(depending on the variety of oranges), the previous season's crops was
present on the tree at application for these trials, oranges were
collected 0 to 68 days after treatment (DAT). In all other trials,
fruit were not present on the trees at applications and mature oranges
were collected at normal harvest (197 to 359 DAT). Samples were
analyzed for residues of PT807-HCl by HPLC with UV detection. Residues
of PT807-HCl were nondetectable (<0.01 ppm)="" in="" all="" treated="" and="" control="" samples.="" a="" processing="" study="" was="" conducted="" using="" oranges="" treated="" at="" 5x="" the="" maximum="" application="" rate="" in="" california.="" the="" harvested="" oranges="" were="" from="" the="" previous="" season's="" crop="" and="" were="" on="" the="" tree="" at="" the="" time="" of="" application.="" therefore="" the="" application="" represents="" the="" maximum="" possible="" residues.="" no="" detectable="" residues="" were="" measured="" in="" whole="" oranges,="" juice,="" or="" oil.="" residues="" of="" pt807-hcl="" were="" detectable="" in="" dried="" pulp="" at="" 0.015="" and="" 0.017="" ppm="" (average="" 0.016="" ppm).="" correcting="" the="" measured="" residues="" for="" the="" exaggerated="" application="" rate,="" no="" detectable="" residues="" are="" likely="" in="" any="" processed="" product="" of="" oranges.="" residues="" of="" pt807-hcl="" were="" determined="" to="" be="" stable="" in="" whole="" orange="" fruit,="" oil,="" juice,="" and="" dried="" pulp="" stored="" frozen="" up="" to="" 113="" days.="" 6.="" subchronic="" toxicity.="" subchronic="" toxicity="" studies="" have="" been="" conducted="" with="" pt807-hcl="" in="" mice,="" rats,="" and="" dogs.="" in="" dietary="" studies="" in="" rats="" and="" dogs,="" the="" most="" notable="" findings="" include="" decreased="" food="" consumption="" and="" a="" consequent="" decrease="" in="" bodyweight="" gain.(resulting="" primarily="" from="" poor="" palatability="" of="" the="" test="" material).="" dogs="" also="" showed="" a="" trend="" toward="" anemia,="" and="" males="" showed="" arrested="" or="" delayed="" sexual="" maturation="" at="" the="" high="" dose="" (equivalent="" to="" approximately="" 222="" mg/="" kg/day).="" marked="" weight="" loss="" and="" decreased="" weight="" gain="" was="" observed="" at="" this="" dose="" and="" this="" dose="" level="" is="" considered="" to="" have="" exceeded="" a="" mtd.="" rats="" dosed="" by="" gavage="" showed="" signs="" of="" neurotoxic="" effects="" (tremors,="" incoordination,="" changes="" in="" activity)="" at="" doses="" 3--="" mg/kg/day.="" in="" mice="" treatment-related="" decreased="" food="" consumption="" and="" body="" weight="" gain="" were="" seen="" in="" males="" at="" 7,000="" (hdt).="" no="" treatment-related="" toxicity="" was="" evident="" at="" dietary="" doses="" up="" to="" 3,500="" ppm="" (479="" and="" 635="" mg/kg/day="" for="" males="" and="" females,="" respectively).="" 7.="" chronic="" toxicity.="" chronic="" toxicity="" studies="" of="" pt807-hcl="" in="" rats="" and="" doges="" are="" currently="" ongoing.="" 8.="" animal="" metabolism.="">14CPT807-HCl was extensively
metabolized and readily eliminated in the urine and feces following
oral administration to a lactating goat. The efficient elimination
processes resulted in negligible to modest retention of radioactive
residues in milk and tissues (<0.2 %="" of="" the="" administered="" dose).="" no="" residues="" of="" unchanged="" parent="" were="" identified="" in="" tissues="" or="" milk.="" the="" rapid="" elimination="" of="" the="" pt807-hcl="" and="" its="" metabolites="" [[page="" 1461]]="" coupled="" with="" the="" highly="" exaggerated="" dose="" (approximately="" 3,600x="" the="" dietary="" burden)="" clearly="" indicates="" that="" no="" detectable="" residues="" of="" pt807-="" hcl="" will="" accumulate="" in="" milk="" and="" tissues.="" 9.="" metabolite="" toxicology.="" the="" metabolism="" of="" pt807-hcl="" in="" oranges="" has="" been="" determined.="" the="" only="" significant="" metabolite="" is="" unchanged="" parent.="" no="" detectable="" residues="" of="" pt807-hcl="" are="" anticipated="" in="" oranges="" treated="" at="" the="" recommended="" application="" rate.="" c.="" aggregate="" exposure="" 1.="" dietary="" exposure.="" there="" are="" no="" anticipated="" dietary="" exposures="" to="" pt807-hcl="" outside="" of="" those="" requested="" in="" this="" temporary="" tolerance="" petition.="" the="" chronic="" dietary="" exposure="" from="" the="" consumption="" of="" oranges="" and="" its="" processed="" products="" treated="" with="" pt807-hcl="" is="" very="" low.="" the="" exposure="" is="" only="" 5.0="" %="" of="" the="" rfd="" (0.00063="" mg/kg/day)="" for="" the="" most="" highly="" exposed="" sub-population,="" children="" 1="" to="" 6="" years="" old.="" the="" dietary="" exposure="" is="" only="" 1.7%="" of="" the="" rfd="" (0.00021="" mg/kg/day)="" for="" the="" u.s.="" population.="" 2.="" food.="" the="" proposed="" temporary="" tolerance="" of="" 0.01="" ppm="" was="" used="" for="" the="" residue="" level="" to="" calculate="" the="" dietary="" exposure="" from="" residues="" of="" pt807-hcl="" in="" or="" on="" oranges.="" based="" on="" the="" processing="" study,="" there="" is="" no="" anticipated="" concentration="" of="" residues="" of="" pt807-hcl="" in="" processed="" products="" of="" oranges,="" therefore,="" the="" proposed="" temporary="" tolerance="" level="" for="" whole="" oranges="" was="" also="" used="" for="" the="" processed="" commodities.="" for="" the="" purpose="" of="" calculating="" a="" worst-case="" estimate,="" it="" was="" assumed="" that="" 100%="" of="" the="" oranges="" and="" their="" processed="" products="" were="" treated="" with="" pt807-="" hcl.="" 3.="" drinking="" water.="" based="" on="" the="" results="" of="" the="" geneec="" model,="" the="" 56-day="" chronic="" eec="" (calculated="" from="" the="" lowest="">oc value
measured for PT807-HCl) is 0.315 g/L. Using the standard
drinking water consumption scenarios of 2 liters per day for a 70-kg
adult and 1 liter per day for a 10 kg child, the calculated consumption
of PT807-HCl in drinking is 0.009 g/kg/day for an adult and
0.032 g/kg/day for a child. These consumption values
correspond to 0.7% of the RfD for adults and 2.6% of the RfD for
children. As discussed above, drinking water concentrations calculated
by the GENEEC procedure represent very conservative screening level
assessments of drinking water exposure. Finally, the above drinking
water calculations use the water concentration calculated from the
lowest Koc value measured for PT807-HCl. Three of four soils
tested gave Koc values that are more than 10-fold higher,
leading to correspondingly lower calculated water concentrations.
4. Non-dietary exposure. There are currently no registered uses for
PT807-HCl, and therefore, there is no anticipated non-occupational
exposure to the chemical.
D. Cumulative Effects
GMJA Specialities is not aware of any currently registered products
that are structurally similar to PT-807-HCl or that would be likely to
share a common mechanism of action. Therefore, no cumulative exposures
are considered in the PT807-HCl dietary risk assessment.
E. Safety Determination
1. U.S. population. The chronic dietary exposure from the
consumption of oranges and its processed products treated with PT807-
HCl is very low. The exposure is only 5.0 % of the RfD (0.00063 mg/kg/
day) for the most highly exposed sub-population, children 1 to 6 years
old. The dietary exposure is only 1.7% of the RfD (0.00021 mg/kg/day)
for the U.S. population.
2. Infants and children. The reference dose is conservatively
calculated using a very high (10,000-fold ) safety factor for children.
Based on currently available data, PT807-HCl does not present a unique
hazard to infants or children and there is no evidence that children
are likely to be more sensitive to the toxic effects of PT807-HCl. A 2-
generation reproductive toxicity study with PT807-HCl in rats is
currently ongoing. PT807-HCl showed evidence of developmental effects
in rats only at a severely maternally toxic dose level. No evidence of
developmental toxicity was seen in rabbits.
F. International Tolerances
There are no Codex Alimentarius Commission (Codex Maximum Residue
Levels (MRLs) for PT807-HCl. (PM 22)
3. Rohm & Haas Company
PP 3F4229
EPA has received a pesticide petition (PP 3F4229) from Rohm & Haas
Company, Philadelphia, PA, 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 oxyfluorfen in or
on the raw agricultural commodities peanut meat, meal, vine, hay, crude
oil, soap stock, and refined oil at 0.05 ppm and peanut hulls at 0.10
ppm. The proposed analytical method involves extraction from the raw
agricultural commodity with methanol or acetonitrite. Extracts are
refluxed in presence of NaOH and Al to reduce and or hydrolyze residues
to 4-(2-chloro-4-(trifluoromethyl)-phenoxy)-2-ethoxybenzenenamine. The
derivatives are partitioned into hexane and heptafluorobutyryl
derivatives prepared. Following Florisel cleanup, residues are
determined by electron capture GLC. 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 and animal metabolism. The chemical identities of
potential plant residues resulting from the use of oxyfluorfen have
been elucidated. The principal residue in plants is parent oxyflurofen.
The chemical identities of potential animal residues resulting from
consumption of oxyfluorfen-treated crops have been elucidated. Parent
oxyfluorfen is the principal residue in animal tissues. Oxyfluorfen
residues do not transfer to milk (concentration <0.01 ppm="" at="" 10x="" dose).="" residues="" also="" do="" not="" appreciably="" transfer="" to="" cow="" muscle,="" liver="" and="" kidney="" (highest="" level="" 0.011="" ppm="" at="" 10x="" dose).="" residues="" are="" present="" in="" cow="" fat="" at="" low="" levels="" (less="" than="" 0.01="" at="" 1x="" dose).="" residues="" in="" eggs="" and="" hen="" liver="" are="" 0.02="" ppm="" or="" less="" on="" average="" at="" a="" 1x="" dose,="" and="" less="" than="" 0.01="" ppm="" in="" muscle="" at="" the="" 1x="" dose.="" residues="" approach="" 0.2="" ppm="" in="" hen="" fat="" at="" the="" 1x="" dose.="" 2.="" analytical="" method.="" there="" is="" a="" practical="" analytical="" method="" for="" detecting="" and="" measuring="" levels="" of="" oxyfluorfen="" in="" or="" on="" food="" with="" a="" limit="" of="" detection="" that="" allows="" monitoring="" of="" food="" with="" residues="" at="" or="" above="" the="" levels="" in="" these="" proposed="" tolerances.="" epa="" has="" provided="" information="" on="" this="" method="" to="" fda.="" the="" method="" is="" available="" to="" anyone="" who="" is="" interested="" in="" pesticide="" residue="" enforcement="" from:="" by="" mail,="" calvin="" furlow,="" public="" response="" and="" program="" resources="" branch,="" field="" operations="" division="" (7502c),="" office="" of="" pesticide="" programs,="" environmental="" protection="" agency,="" 401="" m="" st.,="" sw.,="" washington,="" dc="" 20460.="" office="" location="" and="" telephone="" number:="" crystal="" mall="" #2,="" rm.="" 1132,="" 1921="" jefferson="" davis="" highway,="" arlington,="" virginia,="" 703-305-5805.="" 3.="" magnitude="" of="" the="" residues.="" residue="" studies="" have="" been="" conducted="" in="" accordance="" with="" the="" geographic="" distribution="" mandated="" by="" the="" epa="" for="" peanuts.="" oxyfluorfen="" residues="" were="" not="" detectable="" in="" nutmeat="" [ndr="">80 mg/kg/day (NOEL 20
mg/kg/ day) in a rat 2-generation reproduction study.
4. Subchronic and chronic toxicity. Adverse effects on the liver
marked the LOEL in all three chronic toxicity studies with NOELs of
2.5, 2.0, and 0.3 mg/kg/day seen in the dog, rat, and mouse studies
respectively. A statistically significant positive dose-related trend
for liver adenomas and carcinomas was observed in the chronic mouse
study and oxyfluorfen is classified as a Group C chemical by EPA. A
reference dose of 0.003 mg/kg/day and a Q1* of 0.128 (mg/kg/
day) -1 has been set by the Agency.
5. Animal metabolism. Animal metabolism studies have been conducted
on farm animals using laying hens and lactating goats and in a
laboratory animal (rat). These studies were reviewed and accepted by
the Agency. EPA has concluded that the metabolism of oxyfluorfen in
animals is adequately understood.
C. Aggregate Exposure
1. Food. To determine chronic (using the RfD) and cancer (using the
Q1* approach) risks, refined dietary exposure estimates
using percent of crop treated and anticipated residues were utilized
for registered uses of oxyfluorfen with established tolerances on the
following food and/or animal feed items: dates, figs, guava, loquats,
olives, papaya, persimmon, pomegranate, plantains, kiwi, cocoa butter,
coffee, artichokes, taro-roots and greens, garlic, shallots,
cauliflower, bok-choy, and other Chinese variety cole crops, dry beans,
crabapples, quince, blackberry, raspberry, Brazil nut, cashew,
chestnuts, hazelnuts, hickory nuts, macadamias, pecans, horseradish,
peppermint, spearmint, pistachio nuts, cotton, cherries, nectarines,
plums, prunes, almonds, walnuts, bananas, broccoli, cabbage, apricots,
nutmeat, milk, onions, soybeans, apples, pears, peaches, grapes, and
corn. Actual residues are expected to be quite low because the majority
of the use patterns direct sprays onto weeds or soil and away from the
crop. There are long preharvest intervals for sprays which are directly
applied to crops.
Acute dietary exposure (food only) was calculated using the TMRC
(worst case) assumptions.
2. Drinking water. The Agency has reviewed environmental fate data
which indicate that oxyfluorfen is persistent but nonmobile. There is
no established Maximum Concentration Level (MCL) for residues of
oxyfluorfen in drinking water. No health advisory levels for
oxyfluorfen in drinking water have been established. As noted in
``Pesticides in Groundwater Database'' EPA 734-12-92-001, September
1992, 188 wells were monitored in Texas in 1987 and 1988. No detectable
residues of oxyfluorfen were found in any of the samples.
While EPA has not yet pinpointed the appropriate bounding figure
for consumption of contaminated water, the ranges the Agency is
continuing to examine are all below the level that would cause
oxyfluorfen to exceed the RfD if the tolerance being considered in this
document were granted. In addition, chronic exposure to oxyfluorfen
residues resulting from potential water exposure would not increase the
total cancer risk so that it exceeds the Agency's level of concern. The
potential exposures associated with oxyfluorfen in water, even at the
higher levels the Agency is considering as a conservative upper bound
for RfD exposure considerations, would not prevent the Agency from
determining that there is a reasonable certainty of no harm if the
tolerance is granted.
Despite the potential for acute exposure to oxyfluorfen in drinking
water, it is not expected that the aggregate acute exposure will exceed
the Agency's level of concern if the tolerance being considered in this
document were granted. The potential acute term exposures associated
with oxyfluorfen in water, even at the higher levels the Agency is
considering as a conservative upper bound, would not prevent the Agency
from determining that there is a reasonable certainty of no harm if the
tolerance is granted.
3. Non-dietary exposure. Oxyfluorfen is registered for outdoor
residential use. Acceptable, reliable data are not currently available
with which to assess acute risk. However, based on the available
residential exposure data and the best professional judgment of
scientists who have worked with the available occupational exposure
data, 5% of the risk for outdoor residential uses is a reasonable,
protective default assumption for this pesticide. Chronic exposure to
oxyfluorfen residues resulting from potential outdoor residential
exposure would not increase the total chronic or cancer risks so that
they exceed the Agency's level of concern.
Theoretically, it is also possible that a residential, or other
non-dietary, exposure could be combined with the acute total dietary
exposure from food and water. However, the Agency does not believe that
aggregating multiple exposure to large amounts of pesticide residues in
the residential environment via multiple products and routes for a one-
day exposure is a reasonably probable event. It is highly unlikely
that, in one day, an individual would have multiple high-end exposures
to the same pesticide by treating their lawn and garden, treating their
house via crack and crevice application, swimming in a pool, and be
maximally exposed in the food and water consumed.
D. Cumulative Effects
EPA does not have, at this time, available data to determine
whether oxyfluorfen has a common mechanism of toxicity with other
substances or how to include this pesticide in a cumulative risk
assessment. Unlike other pesticides for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity,
oxyfluorfen does not appear to produce a toxic metabolite produced by
other substances. For the purposes of this tolerance action, therefore,
EPA has not assumed that oxyfluorfen has a common mechanism of toxicity
with other substances.
E. Endocrine Effects
The toxicity studies required by EPA for the registration of
pesticides measure numerous endpoints with sufficient sensitivity to
detect potential endocrine-modulating activity. No effects have been
identified in subchronic, chronic, reproductive, or developmental
toxicity studies to indicate any endocrine-modulating activity by
oxyfluorfen.
[[Page 1463]]
More importantly, the multi-generation reproduction study in rodents is
a complex study design which measures a broad range of endpoints in the
reproductive system and in developing offspring that are sensitive to
alterations by chemical agents. Oxyfluorfen has been tested in two
separate multi-generation studies and each time the results
demonstrated that oxyfluorfen is not a reproductive toxin.
F. Safety Determination
1. U.S. population-- i. Chronic RfD and cancer risk. Using the
refined dietary exposure assumptions described above and taking into
account the completeness and reliability of the toxicity data, it is
concluded that aggregate dietary exposure (food only) to oxyfluorfen
will utilize 0.04% of the RfD for the general United States population.
EPA has no concern generally 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. Despite the potential for exposure to oxyfluorfen in
drinking water and from the 5% default-level contribution from non-
dietary, nonoccupational exposure, it is not expected the aggregate
exposure will exceed 100% of the RfD. As noted above, oxyfluorfen has
been classified as a Group C chemical by the Agency based on liver
adenomas and carcinomas in the 20-month mouse feeding study. The Agency
recommends using the Q1* approach to assess cancer risk. A
value of 0.067 (mg/kg/day)-1 is recommended.
The refined dietary assumptions for existing oxyfluorfen tolerances
plus those proposed for peanuts result in an Anticipated Residue
Contribution (ARC) that is equivalent to a risk of 8.0 x
10-8 (food only). Actual residues are expected to be quite
low because the majority of the use patterns direct sprays onto weeds
and away from the crop and there are long preharvest intervals for
sprays which are directly applied to crops. Environmental fate data
indicate that oxyfluorfen strongly adheres to soil, does not leach into
groundwater and has not been detected in sampled groundwater. Based on
this information, occurrence of oxyfluorfen in drinking water is
unlikely. Outdoor residential uses of oxyfluorfen are limited and
exposure is expected to be low. Oxyfluorfen is toxic to lawn grasses
and certain ornamental plants, and use is generally limited to spot
treatments for nonselective weed control. Chronic exposure to
oxyfluorfen residues resulting from potential residential and/or water
exposure would not increase the total cancer risk so that it exceeds
the Agency's level of concern. There is a reasonable certainty that no
harm will result from chronic aggregate exposure to oxyfluorfen
residues.
ii. Acute risk. The acute dietary exposure endpoint of concern for
oxyfluorfen is fused sternebrae in developing pups which was observed
in the rabbit developmental study. The population subgroup of concern
is females 13+ years old (women of childbearing age). For this
subgroup, the calculated MOE at the high end exposure is greater than
5,000. The Agency considers dietary (food) MOEs of greater than 100 to
be acceptable for oxyfluorfen. Acute dietary exposure (food only) was
calculated using the TMRC (worst case) assumptions.
In the absence of data for drinking water exposure, the ranges of
exposure being considered by the Agency for consumption of contaminated
water will be reserved for drinking water. The aggregate MOE level of
concern for dietary plus the addition of upperbound estimates for
drinking water is not likely to raise the MOE level of concern above
150. Despite the potential for acute exposure to oxyfluorfen in
drinking water, it is not expected that the aggregate exposure will
exceed the Agency's level of concern if the tolerance being considered
in this document were granted. It is therefore concluded that the
potential acute exposure associated with oxyfluorfen in water, even at
the higher levels the Agency is considering as a conservative upper
bound, would not prevent the Agency from determining that there is a
reasonable certainty of no harm if the tolerance is granted.
2. Infants and Children. The toxicology database is complete for
oxyfluorfen relative to prenatal and postnatal toxicity. In the
developmental toxicity study in rabbits, at the maternally toxic dose
of 30 mg/kg/day, there were developmental anomalies (fused sternebrae)
in the fetuses which demonstrated that prenatal toxicity should be
evaluated by an acute dietary risk estimate. The acute dietary MOE for
pregnant women 13+ years old is greater than 5,000 based on a
developmental NOEL of 10 mg/kg/day. This MOE is much higher than the
minimal acceptable MOE (100 for dietary-food only) and suggests that
prenatal developmental risks to infants and children from exposure to
oxyfluorfen dietary residues is not a concern. Additionally, the rabbit
developmental NOEL of 10 mg/kg/day is 33 times greater than the NOEL of
0.3 mg/kg/day used to calculate the RfD. In the developmental toxicity
study in rats, both the developmental and maternal NOEL and LOEL of 18
and 183 mg/kg/day, respectively, occurred at the same dose levels and
demonstrates that there is no special sensitivity in infants and
children exposed to oxyfluorfen. Although the developmental findings in
the rat were severe effects, the developmental NOEL of 18 mg/kg/day is
greater than the rabbit developmental NOEL of 10 mg/kg/day used to
calculate acute dietary MOEs. Therefore, the acute dietary risk
estimates calculated from the rabbit developmental NOEL are lower than
acute dietary MOEs which could be calculated for the more severe
effects occurring in rats above the NOEL of 18 mg/kg/day. By basing the
acute dietary MOEs on the NOEL in the most sensitive species (rabbit),
pregnant women are protected against both types of prenatal toxicity
effects as seen in the rat and rabbit developmental toxicity studies.
Therefore, there are no significant prenatal toxicity concerns for
infants and children due to the high MOE for pregnant women 13+ years
old. In the 2-generation reproductive toxicity study in rats used to
assess the postnatal toxicity potential of infants and children, the
NOEL and LOEL of 20 mg/kg/day and 80 mg/kg/day, respectively, for
developmental/reproductive and systemic toxicity demonstrated that
there are no pup toxicity effects in the absence of parental toxicity
(NOEL and LOEL are the same for pups and parental animals). Therefore,
there are no special postnatal sensitivities in infants and children
which can be attributed to the findings of the 2-generation
reproductive toxicity study in rats. Additionally, the developmental/
reproductive NOEL of 20/mg/kg/day [which is the NOEL for decreased
litter size at birth as well as decreased pup body weight] and the
parental systemic NOEL of 20 mg/kg/day is 66 times greater than the
NOEL of 0.3 mg/kg/day used to calculate the RfD.
Based on the above, EPA concludes that reliable data support use of
the standard hundredfold margin of exposure/uncertainty factor and that
an additional margin/factor is not needed to protect the safety of
infants and children.
i. Chronic risk. Using the refined exposure assumptions described
above and taking into account the completeness and reliability of the
toxicity data, it is concluded that aggregate dietary exposure to
oxyfluorfen will utilize 0.05% of the RfD for infants and 0.08% of the
RfD for children. EPA generally has no concern for exposures below 100%
of the RfD because the RfD represents the level at
[[Page 1464]]
or below which daily aggregate dietary exposure over a lifetime will
not pose appreciable risks to human health. Despite the potential for
exposure to oxyfluorfen in drinking water and from non-dietary,
nonoccupational exposure, the chronic aggregate exposure is not
expected to exceed 100% of the RfD. There is a reasonable certainty
that no harm will result to infants and children from chronic aggregate
exposure to oxyfluorfen residues.
ii. Acute risk. As mentioned above, the acute dietary exposure
endpoint of concern for oxyfluorfen is fused sternebrae in developing
pups which was observed in the rabbit developmental study. The
population subgroup of concern is females 13+ years old (women of
childbearing age). For this subgroup, the calculated MOE at the high
end exposure is greater than 5,000. The Agency considers dietary (food)
MOEs of greater than 100 to be acceptable for oxyfluorfen. Acute
dietary exposure (food only) was calculated using the TMRC (worst case)
assumptions.
In the absence of data for drinking water exposure, the ranges of
exposure being considered by the Agency for consumption of contaminated
water will be reserved for drinking water. Based on the ranges under
consideration, the aggregate MOE level of concern for dietary plus the
addition of drinking water is not likely to raise the MOE above the
Agency's level of concern. The large MOE calculated for this use of
oxyfluorfen provides assurance that there is a reasonable certainty of
no harm for infants and children.
G. International Tolerances
There are no Codex Alimentarius Commission (CODEX) maximum residue
levels (MRL's) established for residue of oxyfluorfen in or on raw
agricultural commodities. (PM 23)
[FR Doc. 98-557 Filed 1-8-98; 8:45 am]
BILLING CODE 6560-50-F
