[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: 
[email protected].

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:
    [email protected]


    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 Q1* 
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