[Federal Register Volume 62, Number 95 (Friday, May 16, 1997)]
[Notices]
[Pages 27027-27033]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-12910]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-733; FRL-5717-6]
Notice of Filing of Pesticide Petitions
AGENCY: Environmental Protection Agency (EPA).
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-733, must
be received on or before June 16, 1997.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch, Information Resources and Services Division
(7506C), 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 by following
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: By mail: Jim Tompkins, Acting Product
Manager (PM) 25, Registration Division, (7505C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460. Office location and telephone number: Rm. 229, CM #2, 1921
Jefferson Davis Highway, Arlington, VA. 22202, (703) 305-5697; e-mail:
tompkins.jim@epamail.epa.gov.
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-733] (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.
[[Page 27028]]
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 file format or ASCII
file format. All comments and data in electronic form must be
identified by the docket number [PF-733] 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: May 8, 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 9F3804
BASF has submitted a pesticide petition (PP 9F3804) proposing
tolerances for residues of the pesticide, sethoxydim, [2-(1-
(ethoxyimino)butyl-5-[2-(ethylthio)propyl]-3-hydroxy-2-cyclohexen-1-
one] and its metabolites containing the 2-cyclohexen-1-one moiety
(calculated as the herbicide) in or on the raw agricultural
commodities, apricots, cherries (sweet and sour), nectarines, and
peaches, at 0.2 parts per million (ppm).
A. Residue Chemistry
1. Plant and animal metabolism. The qualitative nature of the
residues in plants and animals is adequately understood for the
purposes of registration. Metabolic pathways in apricots, cherries
(sweet and sour), nectarines, and peaches are similar. Analytical
methods for detecting levels of sethoxydim and its metabolites in or on
food with a limit of detection that allows monitoring of food with
residues at or above the levels set in these tolerances was submitted
to EPA.
2. Analytical method. The proposed analytical method involves
extraction, partition, and clean-up. Samples are then analyzed by gas
chromatography with sulfur-specific flame photometric detection. The
limit of quantitation is 0.05 ppm.
3. Magnitude of the residues. Peach samples from eleven trials in
six states (CA, GA, SC, NJ, WA, WV) were analyzed for residues of
sethoxydim and its metabolites. In none of the trials did the total
residue in treated samples exceed 0.10 ppm of sethoxydim equivalents.
Preharvest intervals (PHIs) ranged from 10 to 89 days with most samples
harvested at a 10 to 20 day PHI. The treatment program included
multiple applications at rates varying from 0.5 to 2.0 lb active
ingredient (a.i.)/acre. Most samples received three applications of 0.5
lb a.i./acre. BASF is proposing a tolerance of 0.2 ppm to account for
loss of residue during the first 30 days of frozen storage.
Sour cherry samples from six trials in five states (MI, PA, OR, UT,
WI) and sweet cherry samples from six trials in four states (WA, OR,
MI, CA) were analyzed for residues of sethoxydim and its metabolites.
In only one of the trials did the total residue in treated samples
exceed 0.10 ppm of sethoxydim equivalents. The maximum residue found in
this sample was only 0.13 ppm. PHIs ranged from 7 to 17 days with the
exception of one sweet cherry sample which had a PHI of 43 days. The
treatment program included multiple applications at rates varying from
0.3 or 0.5 lb a.i./acre. Most samples received two applications of 0.5
lb a.i./acre. BASF is proposing a tolerance of 0.2 ppm to account for
loss of residue during the first 30 days of frozen storage.
One apricot sample and one nectarine sample from separate trials in
California were analyzed for residues of sethoxydim and its
metabolites. The apricot sample showed a total residue of less than
0.10 ppm of sethoxydim equivalents. The nectarine sample contained a
total of 0.11 ppm of sethoxydim equivalents. The PHI was 17 days for
the apricot sample and 21 days for the nectarine sample. The treatment
program was two applications of 0.5 lb a.i./acre. BASF is proposing a
tolerance of 0.2 ppm to account for loss of residue during the first 30
days of frozen storage.
B. Toxicological Profile
1. Acute toxicity testing. Based on the available acute toxicity
data, sethoxydim does not pose any acute dietary risks. A summary of
the acute toxicity studies follows.
i. Acute oral toxicity, rat: Toxicity Category III;
LD50=3,125 mg/kg (male), 2,676 mg/kg (female).
ii. Acute dermal toxicity, rat: Toxicity Category III;
LD50>5,000 mg/kg (male and female).
iii. Acute inhalation toxicity, rat: Toxicity Category III;
LC50 (4-hour)=6.03 mg/L (male), 6.28 mg/L (female).
iv. Primary eye irritation, rabbit: Toxicity Category IV; no
irritation.
v. Primary dermal irritation, rabbit: Toxicity Category IV; no
irritation.
vi. Dermal sensitization, guinea pig: Waived because no
sensitization was seen in guinea pigs dosed with the end-use product
Poast (18 percent a.i.).
2. Subchronic toxicity testing. A summary of the subchronic
toxicity data follows.
A 21-day dermal study in rabbits with a no-observed-adverse-effect-
level (NOAEL) of >1,000 mg/kg/day (limit dose). The only dose-related
finding was slight epidermal hyperplasia at the dosing site in nearly
all males and females dosed at 1,000 mg/kg/day. This was probably an
adaptive response.
3. Chronic toxicity testing. A summary of the chronic toxicity
studies follows.
i. A 1-year feeding study with dogs fed diets containing 0, 8.86/
9.41, 17.5/19.9, and 110/129 milligrams (mg)/kilogram (kg)/day (males/
females) with a no-observed-effect-level (NOEL) of 8.86/9.41 mg/kg/day
(males/females) based on equivocal anemia in male dogs at the 17.5-mg/
kg/day dose level.
ii. A 2-year chronic feeding/carcinogenicity study with mice fed
diets containing 0, 40, 120, 360, and 1,080 ppm (equivalent to 0, 6,
18, 54, and 162 mg/kg/day) with a systemic NOEL of 120 ppm (18 mg/kg/
day) based on non-neoplastic liver lesions in male mice at the 360-ppm
(54 mg/kg/day) dose level. There were no carcinogenic effects observed
under the conditions of the study. The maximum tolerated dose (MTD) was
not achieved in female mice.
iii. A 2-year chronic feeding/carcinogenic study with rats fed
diets containing 0, 2, 6, and 18 mg/kg/day with a systemic NOEL greater
than or equal to 18 mg/kg/day (highest dose tested). There were no
carcinogenic effects observed under the conditions of the study. This
study was reviewed under current guidelines and was found to be
unacceptable because the doses
[[Page 27029]]
used were insufficient to induce a toxic response and an MTD was not
achieved.
iv. A second chronic feeding/carcinogenic study with rats fed diets
containing 0, 360, and 1,080 ppm (equivalent to 18.2/23.0, and 55.9/
71.8 mg/kg/day (males/females). The dose levels were too low to elicit
a toxic response in the test animals and failed to achieve an MTD or
define a lowest effect level (LEL). Slight decreases in body weight in
rats at the 1,080-ppm dose level, although not biologically
significant, support a free-standing no-observed-adverse-effect-level
(NOAEL) of 1,080 ppm (55.9/71.8 mg/kg/day (males/females)). There were
no carcinogenic effects observed under the conditions of the study.
v. In a rat metabolism study, excretion was extremely rapid and
tissue accumulation was negligible.
4. Developmental toxicity testing. A developmental toxicity study
in rats fed dosages of 0, 50, 180, 650, and 1,000 mg/kg/day with a
maternal NOAEL of 180 mg/kg/day and a maternal LEL of 650 mg/kg/day
(irregular gait, decreased activity, excessive salivation, and
anogenital staining); and a developmental NOAEL of 180 mg/kg/day, and a
developmental LEL of 650 mg/kg/day (21 to 22 percent decrease in fetal
weights, filamentous tail, and lack of tail due to the absence of
sacral and/or caudal vertebrae, and delayed ossification in the hyoids,
vertebral centrum and/or transverse processes, sternebrae and/or
metatarsals, and pubes).
A developmental toxicity study in rabbits fed doses of 0, 80, 160,
320, and 400 mg/kg/day with a maternal NOEL of 320 mg/kg/day and a
maternal LOEL of 400 mg/kg/day (37 percent reduction in body weight
gain without significant differences in group mean body weights and
decreased food consumption during dosing); and a developmental NOEL
greater than 400 mg/kg/day (highest dose tested).
5. Reproductive toxicity testing. A 2-generation reproduction study
with rats fed diets containing 0, 150, 600, and 3,000 ppm
(approximately 0, 7.5, 30, and 150 mg/kg/day) with no reproductive
effects observed under the conditions of the study.
6. Mutagenicity testing. Ames assays were negative for gene
mutation in Salmonella typhimurium strains TA98, TA100, TA1535, and TA
1537, with and without metabolic activity.
A Chinese hamster bone marrow cytogenetic assay was negative for
structural chromosomal aberrations at doses up to 5,000 mg/kg in
Chinese hamster bone marrow cells in vivo.
Recombinant assays and forward mutations tests in Bacillus
subtilis, Escherichia coli, and S. typhimurium were all negative for
genotoxic effects at concentrations of greater than or equal to 100
percent.
C. Threshold Effects
Based on the available chronic toxicity data, EPA has established
the Reference Dose (RfD) for sethoxydim at 0.09 mg/kg bw/day. The RfD
for sethoxydim is based on a 1-year feeding study in dogs with a
threshold NOEL of 8.86 mg/kg/day and an uncertainty factor of 100.
D. Non-Threshold Effects
A repeat chronic feeding/carcinogenicity study in rats was
submitted to EPA in November of 1995 and is awaiting review. The Agency
will reassess sethoxydim tolerances based on the outcome of the rat
chronic feeding/carcinogenicity study. In the interim, there is little
risk from establishment of the proposed tolerances since available
studies in rats and mice indicate no carcinogenic effects, there are
adequate data to establish a RfD, existing tolerances and the proposed
tolerances do not exceed the RfD, and the proposed tolerances utilize
less than 1 percent of the RfD. Thus, a cancer risk assessment is not
necessary.
E. Aggregate Exposure
1. Dietary exposure. For purposes of assessing the potential
dietary exposure, BASF has estimated aggregate exposure based on the
Theoretical Maximum Residue Contribution (TMRC) from the tolerances of
sethoxydim on: apricots at 0.2 ppm, cherries at 0.2 ppm, nectarines at
0.2 ppm, and peaches at 0.2 ppm. (The TMRC is a ``worst case'' estimate
of dietary exposure since it is assumed that 100 percent of all crops
for which tolerances are established are treated and that pesticide
residues are at the tolerance levels.) The TMRC from existing
tolerances for the overall US population is estimated at approximately
37 percent of the RfD. Dietary exposure to residues of sethoxydim in or
on food from these proposed tolerances increases the TMRC by less than
1 percent of the RfD for the overall US population. BASF estimates
indicate that dietary exposure will not exceed the RfD for any
population subgroup for which EPA has data [ref. Proposed Rule at 60 FR
13941 March 15, 1995]. This exposure assessment relies on very
conservative assumptions-100 percent of crops will contain sethoxydim
residues and those residues would be at the level of the tolerance-
which results in an overestimate of human exposure.
2. ``Other'' exposure. 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
available studies submitted to EPA for assessment of environmental
risk, BASF does not anticipate exposure to residues of sethoxydim in
drinking water. There is no established Maximum Concentration Level
(MCL) for residues of sethoxydim in drinking water under the Safe
Drinking Water Act (SDWA).
BASF has not estimated non-occupational exposure for sethoxydim.
Sethoxydim is labeled for use by homeowners on and around the following
use sites: flowers, evergreens, shrubs, trees, fruits, vegetables,
ornamental groundcovers, and bedding plants. Hence, the potential for
non-occupational exposure to the general population exists. However,
these use sites do not appreciably increase exposure. Protective
clothing requirements, including the use of gloves, adequately protect
homeowners when applying the product. The product may only be applied
through hose-end sprayers or tank sprayers as a 0.14 percent solution.
Sethoxydim is not a volatile compound so inhalation exposure during and
after application would be negligible. Dermal exposure would be minimal
in light of the protective clothing and the low application rate. Post-
treatment (re-entry) exposure would be negligible for these use sites
as contact with treated surfaces would be low. Dietary risks from
treated food crops are already adequately regulated by the established
tolerances. The additional usesapricots, cherries, nectarines, and
peacheswill not increase the non-occupational exposure appreciably, if
at all. The potential for non-occupational exposure to the general
population is, thus, insignificant.
F. Cumulative Exposure
BASF also considered the potential for cumulative effects of
sethoxydim and other substances that have a common mechanism of
toxicity. BASF is aware of one other active ingredient which is
structurally similar, clethodim. However BASF believes that
consideration of a common mechanism of toxicity is not appropriate at
this time. BASF does not have any reliable information to indicate that
toxic effects produced by sethoxydim would be cumulative with clethodim
or any other chemical; thus BASF is considering
[[Page 27030]]
only the potential risks of sethoxydim in its exposure assessment.
G. Safety Determination
1. U.S. population. Reference Dose (RfD), using the conservative
exposure assumptions described above, BASF has estimated that aggregate
exposure to sethoxydim will utilize <38 percent="" of="" the="" rfd="" for="" the="" us="" population.="" epa="" generally="" has="" no="" concern="" for="" exposures="" below="" 100="" percent="" 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="" sethoxydim,="" including="" all="" anticipated="" dietary="" exposure="" and="" all="" other="" non-="" occupational="" exposures.="" 2.="" infants="" and="" children.="" developmental="" toxicity="" was="" observed="" in="" a="" developmental="" toxicity="" study="" using="" rats="" but="" was="" not="" seen="" in="" a="" developmental="" toxicity="" study="" using="" rabbits.="" in="" the="" developmental="" toxicity="" study="" in="" rats="" a="" maternal="" noael="" of="" 180="" mg/kg/day="" and="" a="" maternal="" lel="" of="" 650="" mg/kg/day="" (irregular="" gait,="" decreased="" activity,="" excessive="" salivation,="" and="" anogenital="" staining)="" was="" determined.="" a="" developmental="" noael="" of="" 180="" mg/kg/day="" and="" a="" developmental="" lel="" of="" 650="" mg/kg/day="" (21="" to="" 22="" percent="" decrease="" in="" fetal="" weights,="" filamentous="" tail="" and="" lack="" of="" tail="" due="" to="" the="" absence="" of="" sacral="" and/or="" caudal="" vertebrae,="" and="" delayed="" ossification="" in="" the="" hyoids,="" vertebral="" centrum="" and/or="" transverse="" processes,="" sternebrae="" and/or="" metatarsals,="" and="" pubes).="" since="" developmental="" effects="" were="" observed="" only="" at="" doses="" where="" maternal="" toxicity="" was="" noted,="" the="" developmental="" effects="" observed="" are="" believed="" to="" be="" secondary="" effects="" resulting="" from="" maternal="" stress.="" 3.="" reproductive="" toxicity.="" a="" 2-generation="" reproduction="" study="" with="" rats="" fed="" diets="" containing="" 0,="" 150,="" 600,="" and="" 3,000="" ppm="" (approximately="" 0,="" 7.5,="" 30,="" and="" 150="" mg/kg/day)="" produced="" no="" reproductive="" effects="" during="" the="" course="" of="" the="" study.="" although="" the="" dose="" levels="" were="" insufficient="" to="" elicit="" a="" toxic="" response,="" the="" agency="" has="" considered="" this="" study="" usable="" for="" regulatory="" purposes="" and="" has="" established="" a="" free-standing="" noel="" of="" 3,000="" ppm="" (approximately="" 150="" mg/kg/day)="" [ref.="" proposed="" rule="" at="" 60="" fr="" 13941].="" 4.="" reference="" dose.="" based="" on="" the="" demonstrated="" lack="" of="" significant="" developmental="" or="" reproductive="" toxicity="" basf="" believes="" that="" the="" rfd="" used="" to="" assess="" safety="" to="" children="" should="" be="" the="" same="" as="" that="" for="" the="" general="" population,="" 0.09="" mg/kg/day.="" using="" the="" conservative="" exposure="" assumptions="" described="" above,="" basf="" has="" concluded="" that="" the="" most="" sensitive="" child="" population="" is="" that="" of="" children="" ages="" 1="" to="" 6.="" basf="" calculates="" the="" exposure="" to="" this="" group="" to="" be=""><75 percent="" of="" the="" rfd="" for="" all="" uses="" (including="" those="" proposed="" in="" this="" document).="" the="" proposed="" tolerances="" in="" apricots,="" cherries,="" nectarines,="" and="" peaches="" represent="" an="" exposure="" to="" this="" group="" of=""><1 percent="" of="" the="" rfd.="" 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="" sethoxydim,="" including="" all="" anticipated="" dietary="" exposure="" and="" all="" other="" non-occupational="" exposures.="" h.="" other="" considerations="" the="" nature="" of="" the="" residue="" is="" adequately="" understood,="" and="" practical="" and="" adequate="" analytical="" methods="" are="" available="" for="" enforcement="" purposes.="" enforcement="" methods="" for="" sethoxydim="" are="" listed="" in="" the="" pesticide="" analytical="" manual,="" vol.="" ii="" (pam="" ii).="" enforcement="" methods="" have="" also="" been="" submitted="" to="" the="" food="" and="" drug="" administration="" for="" publication="" in="" pam="" ii.="" there="" is="" no="" reasonable="" expectation="" that="" secondary="" residues="" will="" occur="" in="" milk,="" eggs="" or="" meat="" of="" livestock="" and="" poultry="" from="" the="" proposed="" uses="" of="" sethoxydim="" on="" apricots,="" cherries,="" nectarines,="" and="" peaches;="" there="" are="" no="" livestock="" feed="" items="" associated="" with="" these="" commodities.="" i.="" international="" tolerances="" a="" maximum="" residue="" level="" has="" not="" been="" established="" for="" sethoxydim="" in="" apricots,="" cherries="" (sweet="" and="" sour),="" peaches,="" and="" nectarines="" by="" the="" codex="" alimentarius="" commission.="" 2.="" monsanto="" company="" pp="" 8f2128="" monsanto="" company="" has="" submitted="" pesticide="" petition="" (pp="" 8f2128)="" proposing="" the="" establishment="" of="" tolerances="" for="" residues="" of="" the="" herbicide="" triallate="" (s-2,3,3,="" trichloroallyl="" diisopropyl="" thiocarbamate)="" and="" its="" metabolite="" 2,3,3,-trichloro-2-propene="" sulfonic="" acid="" (tscpa)="" expressed="" as="" the="" parent="" equivalent,="" in="" on="" on="" the="" raw="" agricultural="" commodities="" sugarbeet="" roots="" at="" 0.1="" ppm="" and="" sugarbeet="" foliage="" at="" 0.5="" ppm.="" a.="" toxicological="" profile="" monsanto="" has="" submitted="" numerous="" toxicology="" studies="" in="" support="" of="" triallate.="" the="" following="" are="" summaries="" of="" key="" toxicology="" studies.="" 1.="" several="" acute="" toxicology="" studies="" place="" technical="" triallate="" in="" acute="" toxicity="" category="" iii="" for="" acute="" oral="" and="" dermal="" toxicity,="" primary="" eye="" and="" dermal="" irritation,="" and="" in="" toxicity="" category="" iv="" for="" acute="" inhalation="" toxicity.="" triallate="" is="" not="" a="" skin="" sensitizer.="" the="" noel="" for="" acute="" oral="" toxicity="" in="" rats="" is="" 50="" mg/kg="" with="" a="" loel="" of="" 100="" mg/kg="" based="" on="" flat-footed="" appearance="" of="" the="" hindlimbs="" observed="" at="" the="" 100="" mg/kg="" dose="" level.="" 2.="" a="" more="" thorough="" acute="" neurotoxicity="" study="" in="" rats="" was="" conducted="" in="" which="" the="" observers="" were="" unaware="" of="" treatment="" level.="" in="" this="" acute="" neurotoxicity="" study="" rats="" were="" administered="" gavage="" dosage="" levels="" of="" 0,="" 60,="" 300,="" or="" 600="" mg/kg.="" the="" loel="" and="" noel="" of="" this="" study="" was="" determined="" to="" be="" 300="" mg/kg="" and="" 60="" mg/kg,="" respectively.="" the="" loel="" was="" based="" on="" a="" transient="" decrease="" in="" motor="" activity="" detected="" at="" the="" time="" of="" peak="" effect="" (7="" hr,="" postdosing).="" no="" gross="" pathological="" findings="" were="" present;="" neurohistopathological="" examinations="" did="" not="" reveal="" any="" treatment-="" related="" lesions="" in="" either="" the="" central="" or="" peripheral="" nervous="" systems.="" abnormal="" behavioral="" effects="" were="" detected="" at="" the="" 600="" mg/kg="" dose="" but="" not="" at="" any="" of="" the="" lower="" dose="" levels.="" 3.="" a="" subchronic="" neurotoxicity="" study="" in="" rats="" exposed="" for="" 13-weeks="" through="" the="" diet="" to="" 0,="" 100,="" 500="" or="" 2,000="" ppm="" triallate="" (0,6.38,="" 32.9,="" or="" 128.8="" mg/kg/day,="" males,="" respectively;="" 0,="" 8.14,="" 38.9,="" or="" 146.6,="" females,="" respectively).the="" loel="" for="" systemic="" toxicity="" and="" neurotoxicity="" was="" 500="" ppm="" (mg/kg/day:="" 32.9,="" males;="" 38.9,="" females);="" the="" noel="" was="" 100="" ppm="" (mg/kg/day:="" 6.38,="" males;="" 8.14,="" females).="" the="" loel="" was="" based="" on="" treatment-related="" lesions="" in="" the="" spinal="" cord="" and="" peripheral="" nervous="" systems.="" abnormal="" behavioral="" effects="" were="" detected="" at="" the="" 2,000="" ppm="" level="" but="" not="" at="" any="" of="" the="" lower="" dose="" levels.="" 4.="" a="" 2-year="" feeding="" study="" with="" dogs="" fed="" dosage="" levels="" of="" 0,="" 1.275,="" 4.25="" and="" 12.75="" milligrams/kilograms/day="" (mg/kg/day)="" with="" a="" no-observed="" effect="" level="" (noel)="" of="" 1.275="" mg/kg/day="" and="" a="" lel="" of="" 4.25="" mg/kg/day="" based="" on="" increased="" liver="" weight,="" elevated="" serum="" alkaline="" phosphate="" values,="" and="" increased="" hemosiderin="" deposition.="" the="" rfd="" for="" triallate="" is="" 0.013="" mg/kg/day="" based="" on="" the="" noel="" of="" 1.275="" mg/kg/day="" and="" an="" uncertainty="" factor="" of="" 100="" for="" intra-="" and="" inter-species="" variation.="" cholinesterase="" activity="" in="" plasma,="" erythrocytes="" and="" brain="" was="" not="" inhibited="" after="" 1.5,="" 3,="" 6,="" 12,="" 18="" and="" 24="" months="" of="" exposure.="" 5.="" a="" second="" chronic="" dog="" study="" was="" conducted="" in="" which="" dogs="" were="" administered="" gelatin="" capsules="" containing="" doses="" of="" 0,="" 0.5,="" 2.5,="" or="" 15="" mg="" triallate/kg/day="" for="" 1-year.="" the="" lel="" based="" on="" an="" increase="" in="" serum="" alkaline="" [[page="" 27031]]="" phosphatase="" level="" was="" 15="" mg/kg/day="" and="" the="" noel="" was="" 2.5="" mg/kg/day.="" 6.="" a="" 2-year="" chronic="" feeding/="" carcinogenicity="" study="" in="" b6c3f1="" mice="" fed="" dosage="" levels="" of="" 0,="" 3,="" 9,="" or="" 37.5="" mg/kg/day="" resulted="" in="" a="" statistically="" significant="" increased="" incidence="" of="" hepatocellular="" carcinomas="" in="" males="" at="" 37.5="" mg/kg/day="" and="" a="" positive="" trend="" and="" a="" borderline="" significant="" increase="" in="" females="" at="" 37.5="" mg/kg/day.="" for="" chronic="" toxicity,="" the="" noel="" was="" 3="" mg/kg/day="" and="" the="" lel="" was="" 9="" mg/kg/day.="" the="" lel="" was="" based="" on="" increases="" in="" liver="" weights;="" the="" incidence="" of="" altered="" hepatic="" foci="" of="" the="" liver;="" splenic="" hematopoiesis="" and="" blood="" glucose="" levels="" in="" males="" at="" 60="" and="" 250="" ppm.="" 7.="" a="" 2-year="" chronic="" feeding/carcinogenicity="" study="" in="" male="" and="" female="" rats="" fed="" dose="" levels="" of="" 0,="" 0.5,="" 2.5,="" and="" 12.5="" mg/kg/day="" resulted="" in="" an="" increased="" incidence="" in="" renal="" tubular="" cell="" adenoma="" above="" historical="" control="" levels.="" although="" no="" absolute="" pair-wise="" statistical="" significance="" was="" found,="" renal="" tubular="" cell="" adenoma="" is="" considered="" a="" rare="" tumor="" type="" making="" this="" finding="" biologically="" significant.="" for="" chronic="" toxicity,="" the="" noel="" was="" 2.5="" mg/kg/day="" and="" the="" lel="" was="" 12.5="" mg/kg/day.="" the="" lel="" was="" based="" on="" decreased="" survival="" in="" high-dose="" males="" and="" females,="" decreased="" mean="" body="" weight="" in="" high-dose="" males,="" and="" increased="" adrenal="" weights="" in="" high-dose="" males.="" 8.="" a="" chronic/oncogenicity="" study="" of="" triallate="" was="" also="" conducted="" in="" hamsters="" at="" 50,="" 300,="" or="" 2,000="" ppm="" for="" 79="" (females)="" or="" 95="" (males)="" weeks.="" the="" objective="" of="" this="" study="" was="" to="" see="" if="" triallate="" induces="" melanotic="" changes="" (nodular="" aggregated="" of="" melanocyte,="" possibly="" premalignant)="" in="" skin="" of="" hamsters="" similar="" to="" those="" induced="" by="" diallate,="" a="" compound="" structurally="" similar="" to="" triallate.="" there="" were="" no="" increases="" in="" either="" non-neoplastic="" or="" neoplastic="" lesions="" in="" any="" organs.="" for="" chronic="" toxicity,="" the="" noel="" was="" 300="" ppm="" and="" lel="" was="" 2,000="" ppm="" based="" on="" a="" decrease="" in="" body="" weight="" gain="" and="" corresponding="" decrease="" in="" food="" consumption="" by="" males="" fed="" the="" 2,000="" ppm="" diet="" during="" the="" first="" 13="" weeks="" of="" the="" study="" but="" not="" thereafter.="" 9.="" a="" 2-generation="" reproduction="" study="" with="" rats="" fed="" dose="" levels="" of="" 0,="" 50,="" 150="" or="" 600="" ppm="" resulted="" in="" a="" reproductive="" noel="" of="" 150="" ppm="" and="" a="" lel="" of="" 600="" ppm.="" treatment-related="" reproductive="" effects="" were:="" reduced="" pregnancy="" rates;="" shortened="" gestation="" period;="" increased="" neonate="" mortality="" in="" the="" f2b="" litter;="" reduced="" pup="" weights="" at="" birth="" in="" the="" f2b="" litter;="" and="" reduced="" pup="" weights="" in="" late="" lactation="" in="" all="" litters.="" these="" effects="" were="" only="" observed="" in="" rats="" treated="" with="" the="" highest="" dose="" level="" which="" also="" caused="" maternal="" toxicity="" was="" manifested="" by="" an="" increase="" in="" mortality,="" decrease="" in="" body="" weight,="" increase="" in="" chronic="" nephritis,="" and="" head="" bobbing="" and="" circling.="" for="" maternal="" toxicity,="" the="" lel="" was="" 600="" ppm="" and="" noel="" was="" 150="" ppm.="" 10.="" a="" developmental="" toxicity="" study="" in="" rats="" fed="" dose="" levels="" of="" 0,="" 10,="" 30,="" or="" 90="" mg/kg/day="" during="" gestation="" days="" 6-21="" resulted="" in="" a="" developmental="" toxicity="" noel="" greater="" than="" 90="" mg/kg/day.="" for="" fetotoxicity,="" the="" lel="" was="" 90="" mg/kg/day="" and="" the="" noel="" was="" 30="" mg/kg/day="" based="" on="" reduced="" body="" weight,="" reduced="" ossification="" of="" the="" skull,="" and="" malaligned="" sternebrae.="" for="" maternal="" toxicity,="" the="" lel="" was="" 90="" mg/kg/day="" and="" the="" noel="" was="" 30="" mg/kg/day="" based="" on="" reduction="" in="" maternal="" body="" weight.="" the="" teratogenic="" noel="" was=""> 90 mg/kg/day.
11. A developmental toxicity study in rabbits fed doses of 0, 5,
15, and 45 mg/kg/day on gestation days 6 through 28 resulted in a
developmental toxicity NOEL greater than 45 mg/kg/day. For
fetotoxicity, the LEL was 15 mg/kg/day and the NOEL was 5 mg/kg/day
based on an increase in fused sternebrae, increased number of bent
hyoid arch bones, as well as decreased body weight. The NOEL was >45
mg/kg/day for teratogenicity.
12. Numerous mutagenicity assays have been conducted with triallate
resulting in mixed results. Triallate gave a positive response for base
pair conversions in Salmonella strains TA100 and TA1535 with and
without activation and negative results without activation in Ames
assays. Triallate was positive for mitotic recombination in
Saccharomyces cerevisiae strain D3 but was negative for gene conversion
in strain D4. The mouse lymphoma gene mutation assay produced both
positive results for forward mutations at the TK+/- locus
with and without activation and negative results at this locus.
Triallate was nonmutagenic in a dominant lethal test with mice given a
single intraperitoneal injection; this study however, was considered
inadequate by current test guideline/standards. Triallate did not
induce gene mutations (HGPRT) locus) in Chinese hamster ovary cells
(CHO) with and without metabolic activation. It gave a positive
response for sister chromatid exchanges (SCEs) in CHO cells both with
and without metabolic activation. Triallate did not induce unscheduled
DNA synthesis in rat hepatocytes. In an in vivo cytogenetic assay, no
mutagenic response was seen in the bone marrow cells of hamsters.
Overall, triallate is genotoxic in in vitro systems and negative in in
vivo systems and is considered a genotoxic compound.
B. Threshold Effects
1. Chronic effects. Based on a complete and reliable toxicity
database, the EPA has adopted a reference dose (RfD) value of 0.013 mg/
kg bwt/day using the NOEL of 1.275 mg/kg bwt/day from a 2-year dog
feeding study and an uncertainty factor of 100. The endpoint effect in
this study was increased liver weights and hemosiderin and serum
alkaline phosphate (SAP) levels.
2. Acute effects. EPA has determined that the appropriate NOEL to
use to assess safety of acute exposure is 5 mg/kg bwt/day from a
developmental toxicity study in rabbits, based in increases in the
incidences of skeletal malformations in rabbit fetuses. EPA has
concluded that the subpopulation of concern for this endpoint are
females older than 13 years old.
C. Non-Threshold Effects
Carcinogenicity. Triallate has been classified by EPA as Group C -
possible human carcinogen. EPA based this classification on a
statistically significant increase in hepatocellular tumors in male
mice, with a positive trend and a borderline significant increase in
females. In addition, the increased incidence of renal tubular cell
adenoma, a rare tumor type, in male rats was considered by EPA to be
biologically significant although no absolute pair-wise statistical
significance was found. Triallate is considered genotoxic and has
structural similarities to carcinogenic analogues. EPA is currently
applying the extrapolation model approach for risk assessment and has
calculated the upper bound potency factor Q1* to be 0.08320
(mg/kg/day)-1.
D. Aggregate Exposure
For purposes of assessing the potential dietary exposure, the
theoretical maximum residue concentration (TMRC) and anticipated
chronic dietary risk assessment based on exposure to all crops for
which triallate is labelled is an appropriate estimate of aggregate
exposure. EPA has notified the petitioner that these analyses include
permanent tolerances of 0.05 ppm for peas, lentils, barley, and wheat,
as established under 40 CFR 180.314. Tolerances are also established
for canary grass; however, EPA's Dietary Risk Evaluation Section (DRES)
does not have consumption figures for this RAC, and its contribution is
expected to be negligible. Anticipated residues, and 100 percent of
crop treated was used for sugarbeet sugar. Sugarbeet foliage is a
potential animal feed item associated with this use. However, based on
the
[[Page 27032]]
results of animal metabolism studies, EPA has concluded that secondary
residues are not expected to occur in meat, milk, poultry, and eggs as
a result of this proposed use.
EPA has also conducted an acute dietary exposure assessment. It is
EPA policy to use ``high-end'' residue level estimates for acute
exposure analyses; in this case, tolerance levels were used for all
commodities.
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 available studies used in EPA's
assessment of environmental risk, triallate appears to be moderately
persistent and immobile to highly immobile in different soils. EPA's
``Pesticides in Ground Water Database'' (EPA 734-122-92-001, September
1992), shows no detections for triallate in ground water, and it does
not exceed the proposed criteria for establishing a pesticide as
restricted use due to ground water concerns. It was not a target of
EPA's National Survey of Wells for Pesticides, and is not listed as a
unregulated contaminant for monitoring in drinking watersupplies under
the Safe Drinking Water Act. No Maximum Contaminant Level or Health
Advisory levels have been established for triallate.
Previous experience with persistent and immobile pesticides for
which there have been available data to perform quantitative risk
assessments have demonstrated that drinking water exposure is typically
a small percentage of the total exposure when compared to the total
dietary exposure. This observation holds even for pesticides detected
in wells and drinking water at levels nearing or exceeding established
MCLs. Based on this experience and considering the low fraction of a
percent of the RfD (<.04 percent)="" occupied="" by="" dietary="" exposure="" to="" triallate,="" combined="" exposure="" from="" drinking="" water="" and="" dietary="" exposure="" would="" not="" be="" expected="" to="" result="" in="" an="" arc="" that="" exceeds="" 100="" percent="" of="" the="" rfd.="" therefore,="" potential="" triallate="" residues="" in="" drinking="" water="" are="" not="" likely="" to="" pose="" a="" human="" health="" concern.="" epa="" consideration="" of="" a="" common="" mechanism="" of="" toxicity="" is="" not="" appropriate="" at="" this="" time="" since="" there="" is="" no="" information="" to="" indicate="" that="" toxic="" effects="" produced="" by="" triallate="" would="" be="" cumulative="" with="" those="" of="" any="" other="" chemical="" compound.="" triallate="" is="" a="" thiocarbamate="" herbicide.="" thiocarbamate="" herbicides="" are="" not="" applied="" to="" any="" significant="" degree="" in="" areas="" where="" triallate="" would="" be="" used="" to="" control="" wild="" oats="" in="" sugarbeet="" crops.="" thiocarbamates="" are="" only="" used="" to="" a="" small="" extent="" in="" other="" crops.="" hence,="" dietary="" exposure="" to="" thiocarbamate="" herbicides="" is="" expected="" to="" be="" minimal.="" considering="" the="" low="" fraction="" of="" the="" percent="" of="" the="" rfd=""><.04 percent)="" occupied="" by="" dietary="" exposure="" and="" the="" minimal="" exposure="" levels="" to="" other="" thiocarbamate="" herbicides="" through="" the="" diet;="" the="" combined="" exposure="" to="" other="" thiocarbamate="" herbicides="" would="" not="" be="" expected="" to="" pose="" a="" human="" health="" concern.="" there="" is="" also="" no="" data="" to="" indicate="" that="" there="" are="" similar="" mechanisms="" of="" toxicity="" between="" triallate="" and="" carbamate="" insecticides="" that="" inhibit="" cholinesterase="" activity.="" triallate="" does="" not="" inhibit="" cholinesterase="" activity="" in="" plasma,="" erythrocytes="" and="" brain="" in="" dogs="" after="" chronic="" exposure="" to="" triallate.="" triallate="" does="" not="" cause="" symptoms="" typical="" of="" cholinesterase="" inhibition="" in="" rats="" after="" acute="" or="" subchronic="" exposure="" to="" triallate.="" e.="" determination="" of="" safety="" for="" u.s.="" population="" and="" sub-populations.="" 1.="" upper="" bound="" carcinogenic="" exposure.="" based="" on="" epa's="">1*
value of 0.08320 (mg/kg/day)-1, the upper bound cancer risk
contributed by all the published uses, plus this new use on sugarbeets
was calculated by EPA to be 1.7 x 10-7 for the U.S.
Population in general; risks from the established uses contribute
approximately 1 x 10-7 to this risk, and the proposed use on
sugarbeets contributes approximately 0.7 x 10-7. The sub-
population with the highest exposure level were children (1 to 6 years
old) which has an upper bound cancer risk was 4.2 x 10-7.
These levels of risk are below the level of risk generally considered
to be of concern by EPA (1 x 10-6). EPA has concluded that
the dietary cancer risk posed by use of triallate is not considered to
be of concern.
2. Chronic dietary exposure. Using anticipated residues and
realistic estimates of percent of crop treated, the anticipated residue
concentration (ARC) for the overall U.S. Population is calculated by
EPA to be 0.000002 mg/kg bwt/day, representing 0.01 percent of the RfD,
for established uses and this proposed use on sugarbeets. The ARCs for
the U.S. Population and the 22 population subgroups all utilized <0.04 percent="" of="" the="" rfd,="" with="" the="" highest="" exposed="" subgroup,="" being="" children="" (1="" to="" 6="" years="" old),="" with="" 0.035="" percent="" of="" the="" rfd="" utilized.="" epa="" has="" concluded="" that="" the="" chronic="" dietary="" risk="" exposure="" from="" triallate="" appears="" to="" be="" minimal="" for="" this="" petition="" for="" use="" on="" sugarbeets,="" and="" does="" not="" exceed="" the="" rfd="" for="" any="" of="" the="" dres="" subgroups.="" 3.="" acute="" dietary="" exposure.="" epa="" used="" ``high-end''="" residue="" level="" estimates="" for="" acute="" exposure="" analyses;="" in="" this="" case,="" tolerance="" levels="" were="" used="" for="" all="" commodities.="" since="" the="" endpoint="" used="" for="" risk="" assessment="" of="" the="" acute="" risk="" is="" derived="" from="" a="" rabbit="" developmental="" study,="" epa="" concluded="" that="" the="" population="" subgroup="" of="" concern="" would="" be="" females="" (13+="" years="" old).="" the="" moe="" value="" calculated="" for="" this="" subgroup="" is="" 12,500,="" which="" is="" well="" above="" the="" level="" considered="" by="" epa="" to="" be="" of="" concern="" (="">100). EPA has concluded that there is little concern for
acute effects due to dietary exposure to this chemical.
4. Conclusion. Based on the above risk assessments, there is a
reasonable certainty that no harm will result from aggregate exposure
to triallate residues.
F. Determination of Safety for Infants and Children
In assessing the potential for additional sensitivity of infants
and children to residues of triallate, the developmental toxicity
studies in the rat and rabbit and the 2-generation reproduction study
in the rat should be 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
of mating animals and data on systemic toxicity. The results of these
studies indicate that triallate is not a specific teratogen or
reproductive toxin. The only evidence of developmental toxicity
occuring below maternally toxic doses was an increase in fused
sternebrae, increase number of bent hyoid arch bones, as well as
decreased body weight in rabbits. In most instances, fusion only
involved two adjacent sternebrae and not the entire chain.
Consequently, this type of skeletal defect is considered a minor
anomaly rather than a major malformation. The incidence of bent hyoid
arch bones was increased from control values but within the
laboratory's historical control range. The LEL for fetotoxicity in
rabbits was considered by EPA to be 15 mg/kg/day and the NOEL was 5 mg/
kg/day.
The 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 completeness of the database or for significant
developmental effects. The toxicological database relative to pre-and
post-natal effects of triallate is complete. There are no developmental
effects that are of substantial concern. Thus, an additional safety
factor is not necessary.
[[Page 27033]]
The cancer risk and percent of the RfD that will be utilized by
aggregate exposure to residues of triallate is less than 1 x
10-6 and 0.04 percent of the RfD, respectively, for all
populations and subgroups including infants and children. Therefore,
based on the completeness and reliability of the toxicity data and the
conservative exposure assessment, it is concluded that there is a
reasonable certainty that no harm will result to infants and children
from aggregate exposures to triallate.
G. Estrogenic 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, developmental, or reproductive
toxicity studies to indicate any endocrine-modulating activity by
triallate. The subchronic and chronic toxicity studies examines tissues
from the male and female reproductive system. 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.
Triallate only caused effects in the reproduction study at doses that
were maternally toxic including an increase in mortality. Thus, these
results demonstrate that triallate is not a specific reproductive
toxin.
H. Chemical Residue
Permanent tolerances are established for triallate parent at 0.05
ppm for peas, lentils, barley and wheat, as established under 40 CFR
180.314. Triallate is metabolized in plants and animals to one major
metabolite, TCPSA (2,3,3-trichloroprop-2-enesulfonic acid), and
numerous natural constituents. Since the establishment of permanent
tolerances for triallate, EPA has decided that TCPSA should also be
regulated. Based on results of residue trials, tolerances have been
proposed by Monsanto for combined residues of triallate and TCPSA in
sugarbeet commodities at 0.1 ppm in sugarbeet roots, 0.5 ppm in
sugarbeet tops, and 0.2 ppm in sugarbeet pulp. A practical method for
determining triallate has been approved by EPA and is available from
the Field Operations Division, Office of Pesticide Programs. Monsanto
is in the process of developing a practical method for TCPSA. These
methods include extraction followed by partitioning with methylene
chloride to isolate triallate fromTCPSA. The triallate portion is
eluted through a Florsil clean-up column, concentrated and quantitated
by capillary GC using electron capture detection (ECD). The TCPSA
portion is isolated using a phase transfer catalyst, derivatized
cleaned up using SPE, and quantitated by capillary GC using ECD.
Residue studies show that TCPSA is the major residue in sugarbeet
foliage, but is not a significant residue in sugarbeet roots since it
was not detected above the lower limit of method validation (0.01 ppm)
when triallate was applied at maximum application rates. Since
sugarbeet foliage seldom enters interstate commerce, EPA has informed
the petitioner that enforcement of the proposed tolerances would be
limited to sugarbeet roots and dried pulp. As triallate is the primary
residue in sugarbeet roots and dried pulp, EPA has concluded that the
currently available enforcement for parent only is adequate to enforce
the tolerances on a time-limited basis.
Sugarbeet foliage is considered by EPA as an animal feed item.
However, EPA has informed the petitioner that based on animal
metabolism studies and animal residue studies, secondary residues are
not expected to occur in meat, milk, poultry, and eggs as a result of
this proposed use.
I. Environmental Fate
Laboratory studies indicate that triallate degrades in soil with a
half-lives ranging from 18 to 21 days. Field dissipation studies show
that triallate degrades with half-lives ranging from 20 to 190 days,
but 190 days is clearly an outlier based on all other data. Average
field half-life from all other locations is 49 days. Triallate
metabolizes to CO2, bound residues, and TCPSA. Triallate and
TCPSA do not appear to move below a 6-inch depth.
In a laboratory study conducted with worst-case conditions, 50
percent of applied triallate volatized from agricultural sand with a
very low organic content. Triallate volatility decreases from soils
with higher organic content since triallate binds to organic matter in
the soil. Triallate is typically soil incorporated when applied so
volatization is minimized. Triallate is fairly stable to hydrolysis and
photolysis.
Triallate is not likely to leach into ground water. Triallate was
immobile in batch adsorption/desorption studies, and soil column and
soil tlc results confirmed its low mobility. Triallate is unlikely to
runoff into surface water, it would stick to the soil. If triallate did
get into surface water, it would be part of the sediment and undergo
microbial degradation.
[FR Doc. 97-12910 Filed 5-15-97; 8:45 am]
BILLING CODE 6560-50-F
