[Federal Register Volume 62, Number 58 (Wednesday, March 26, 1997)]
[Notices]
[Pages 14421-14423]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-7496]


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ENVIRONMENTAL PROTECTION AGENCY
[PF-722; FRL-5592-8]


DowElanco; Pesticide Tolerance Petition Filing

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice of Filing.

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SUMMARY: This notice is a summary announces the filing of a pesticide 
petition proposing the establishment of a regulation for residues of 
cloransulam-methyl in or on soybeans. This notice contains a summary 
was prepared by the petitioner, DowElanco.

DATES: Comments, identified by the docket number [PF-722], must be 
received on or before April 25, 1997.

ADDRESSES: By mail, submit written comments to Public Response and 
Program Resources Branch, Field Operations Division (7506C), Office of 
Pesticide 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 22202. Comments and data 
may also be submitted electronically be sending electronic mail (e-
mail) to: [email protected]. Electronic comments must be 
submitted as an ASCII file avoiding the use of special characters and 
any form of encryption. Comments and data will also be accepted on 
disks in WordPerfect 5.1 file format or in ASCII file format. All 
comments and data in electronic form must be identified by docket 
control number [PF-722]. Electronic comments on this notice may be 
filed online at many Federal Depository Libraries. Additional 
information on electronic submissions can be found below this document.
    Information submitted as a comments 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: Philip Errico, Product Manager (PM) 
25, Registration Division, (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, 401 M. St., SW., Washington, D.C. 
Office location, telephone number and e-mail address: Rm. 237, CM#2, 
1921 Jefferson Davis Highway, Arlington, VA 703-305-6027. e-mail: 
[email protected].

SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition (PP 
5F4560 from DowElanco, 9330 Zionsville Road, Indianapolis, IN 46268-
1054 proposing pursuant to section 408(d) of the Federal Food, Drug and 
Cosmetic Act, 21 U.S.C. section 346a(d), to amend 40 CFR part 180 by 
establishing a tolerance for residues of the herbicide N-(2-
carboxymethyl-6-chlorophenyl)-5-ethoxy-7-fluoro[1,2,4] 
triazolo[1,5c]pyrimidine-2-sulfonamide, (cloransulam-methyl) in or on 
the raw agricultural commodity soybeans at 0.02 ppm, soybean forage at 
0.1 part per million (ppm) and soybean hay at 0.2 ppm. The proposed 
analytical method is gas chromatography coupled with a mass selective 
detector (GC-MSD).
    EPA has determined that the petition contains data or information 
regarding the elements set forth in section 408(d)(2); however, EPA has 
not fully evaluated the sufficieny 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.
    Availability of the analytical method: The proposal analytical 
method of enforcement which measures residues of cloransulam-methyl in 
soybeans, and soybean forage and hay discussed below has not been 
validated by the Agency. Public versions of the analytical method can 
be obtained from the Pesticide Docket, U.S. Environmental Protection 
Agency, Office of Pesticide Programs, 401 M. St., SW., Washington, D.C. 
20460, (703) 305-5805.
    As required by section 408(d) of the FFDCA, as recently amended by 
the Food Quality Protection Act, DowElanco included in the petition a 
summary of the petition and authorization for the summary to be 
published in the Federal Register in a notice of receipt of the 
petition. The summary represents the views of DowElanco; EPA, as 
mentioned above, is in the process of evaluating the petition. As 
required by section 408(d)(3) EPA is including the summary as a part of 
this notice of filing. EPA may have made minor edits to the summary for 
the purpose of clarity.

I. Petition Summary

A. Residue Chemistry

    1. Plant metabolism. Nature of residue studies demonstrated that 
residues of cloransulam-methyl and its metabolites would not be 
expected to accumulate to significant levels in soybeans treated either 
pre-plant or post-emergence, and that it was appropriate to base the 
magnitude of total terminal residues and proposed tolerances only on 
residues of the parent compound, cloransulam-methyl. A rotational crop 
study showed no significant level of cloransulam-methyl or any 
structurally-related metabolite in any crop, or crop fractions, grown 
in rotation 120 days after soil treatment.
    2. Analytical method. Residue analytical methods were validated 
based upon gas chromatography coupled with a mass selective detector 
(GC- MSD). The limit of detection of the methods is 0.005 ppm and a 
level of quantitation is 0.01 ppm.
    3. Magnitude of residues. No detectable residues of cloransulam-
methyl resulted in soybeans from either preplant incorporated or post 
emergence applications, in soybean forage or hay

[[Page 14422]]

following preplant applications, and in the majority of cases, in 
soybean forage or hay following postemergence applications. No residues 
of cloransulam-methyl were detected in the soybeans or processed 
fractions above the analytical method limit of detection of 0.005 ppm 
following 5 x  the proposed maximum postemergence application rate.

B. Toxicological Profile

    1. Acute toxicity. Cloransulam-methyl acute toxicity is low. Acute 
oral LD50 in the rat is >5,000 mg/kg in both males and females and 
the acute dermal LD50 in the rabbit is >2,000 mg/kg. The 
inhalation LC50 in the rat is >3.77 mg/l of air, which is the 
highest obtainable respirable aerosol concentration. Cloransulam-methyl 
produced no indications of dermal irritation in rabbits or 
sensitization in the guinea pig, and only slight transient eye 
irritation in the rabbit following acute exposure.
    2. Genotoxicity. In a battery of short-term genotoxicity tests, 
cloransulam- methyl showed no evidence of a mutagenic potential. These 
tests included a bacterial reverse mutation assay (Ames test), an in 
vitro cytogenic assay in Chinese hamster ovary cells (CHO/HGPRT assay), 
an in vitro chromosomal aberration assay in rat lymphocytes, and an in 
vivo cytogenetic assay in mouse bone marrow cells.
    3. Reproductive and developmental toxicity. Cloransulam-methyl 
exhibited no effects on reproduction or fetal development. In a 
multigeneration reproduction study in rats, no effects on reproductive 
performance or neonatal survival were seen at the highest dose tested.
    In a developmental toxicity study in rats, no maternal or 
developmental toxicity was seen at the highest dose tested (limit test 
at 1,000 mg/kg).
    In a developmental toxicity study in rabbits, the maternal NOEL was 
100 mg/kg/day and the developmental NOEL was at least 300 mg/kg/day.
    4. Subchronic toxicity. In a 21-day repeated dermal application 
study in rabbits, cloransulam-methyl when given at a dose of 1,000 mg/
kg/day produced only slight anemia in female rabbits while male rabbits 
were unaffected at the highest dose tested. The NOEL was 500 mg/kg/day 
for females and 1,000 mg/kg/day in males. Cloransulam-methyl was 
evaluated in 13-week dietary studies in rats, mice and dogs. The 
primary target organs identified in these studies were the kidneys 
(rat), the liver (mouse and dog), and thyroid (rat). An NOEL was not 
determined in the rat base upon minor histopathological changes in the 
kidney (males) and the liver (females). In the mouse, the NOEL was 50 
mg/kg/day in male mice and 100 mg/kg/day in female mice based upon 
hepatocellular hypertrophy. An NOEL was not established in the dog 
based upon slightly lower body weights at the lowest dose tested, 40 
mg/kg/day.
    5. Chronic toxicity. In a 2-year combined chronic toxicity/
oncogenicity study in the rat, the NOEL for chronic toxicity was 10 mg/
kg/day based upon kidney and thyroid effects: hypertrophy of collecting 
duct epithelial cells and vacuolation consistent with fatty change in 
the proximal tubules of males and females, and an increase in the 
incidence of mineralization of the renal pelvis in males. Thyroid 
changes were confined to the high dose males and consisted of 
hyperplasia and hypertrophy of follicular epithelium. In a 2- year 
dietary feeding study in B6C3F1 mice, the NOEL for chronic toxicity was 
also 10 mg/kg/day base upon the liver as he primary target organ. There 
were increased liver weights and histologic changes consisting of 
centrilobular hypertrophy in males. Kidney weights were decreased in 
males and females, and depletion of the normal ctyoplasmic vacuoles and 
decreases in the incidence of renal mineralization and renal tubular 
degeneration were noted in males. All of these histologic changes were 
interpreted to be non-adverse. There was no evidence of an oncogenic 
response in either male or female mice or rats. In a 1-year chronic 
toxicity study in dogs, the NOEL was 5 mg/kg/day based upon an increase 
in accumulation of pigment in Kuppfer cells and hepatocytes with 
changes in hepatic-related serum chemistry parameters.
    6. Animal metabolism. Metabolism studies conducted on cloransulam- 
methyl indicated over 90 percent of a single or repeated dose was 
absorbed at 5 mg/kg and at 1,000 mg/kg/day, there was incomplete 
absorption of cloransulam-methyl, with only 28-30 percent of the dose 
absorbed. Urinary elimination was rapid with half-lives of 
approximately 6-9 hours. Sex dependent differences in disposition of 
the 5 mg/kg dose were traced to more efficient elimination of unchanged 
cloransulam-methyl in the female versus male kidney but are of no known 
toxicologic significance. Due to its rapid elimination, cloransulam-
methyl has little potential to accumulate upon repeated administration.
    7. Metabolite toxicology. The residue of concern for tolerance 
setting purposes is the parent material (cloransulam-methyl). Thus 
there is no need to address metabolite toxicity.

C. Aggregate Exposure

    1. Dietary Exposure
    a. Food. For Purpose of assessing the potential dietary exposure 
from use of cloransulam-methyl on soybeans, a conservative estimate of 
aggregate exposure is determined by TMRC assuming that 100 percent of 
the soybean crop has a residue of cloransulam-methyl at the tolerance 
level of 0.02 ppm. This results in an extremely conservative estimate 
of exposure for cloransulam-methyl, because no residues were detected 
in soybeans at a level 4 x  lower than the proposed tolerance level 
based upon applications made either at the proposed maximum label rate, 
or at a rate 5 x  higher than the proposed maximum application rate in 
an exaggerated rate residue study. The potential dietary exposure is 
obtained by multiplying the tolerance residue level on soybeans (0.02 
ppm) by the consumption data which estimates the amount of soybean 
products consumed by various population subgroups. The maximum 
potential average daily dose (ADD) of cloransulam-methyl values 
determined for various populations are clearly significant 
overestimates compared with actual exposure. When ADDs are compared to 
the Reference Dose (RfD), which used the lowest NOEL of 5 mg/kgBW/day 
from the 1-year dog chronic toxicity study and an uncertainty factor of 
100, the ADD for the average U.S. consumer utilizes only about 0.01 
percent of the RfD, and even the highest risk group, non-nursing 
infants, would theoretically be exposed to less than 0.07 percent of 
the RfD. If the margin of safety (MOS) or safety factor approach is 
used, the calculated MOSs are 7,600 for the average U.S. population and 
1,500 for non-nursing infants. DowElanco believes it is evident from 
these very conservative estimates that cloransulam-methyl poses no 
significant dietary risk to any human population.
    b. Drinking water. Another potential source of dietary exposure are 
residues in drinking water. Base upon the available environmental 
studies conducted with cloransulam-methyl wherein it's properties show 
little potential for mobility in soil and extremely rapid photolysis in 
water, DowElanco concludes, there is no anticipated exposure to 
residues of cloransulam-methyl in drinking water.
    2. Non-dietary exposure. There are no other uses currently 
registered for cloransulam-methyl. The proposed use in on soybeans 
involves application of cloransulam-methyl to crop grown in an 
agricultural environment. Thus, the

[[Page 14423]]

potential for non-occupational, non-dietary exposure to the general 
population is not expected to be significant.

D. Cumulative Effects

    There is no reliable information to indicate that cloransulam-
methyl has a common mechanism of toxicity with any other chemical 
compound or that potential toxic effects of cloransulam-methyl would be 
cumulative with those of any other pesticide chemical. Thus DowElanco 
believes it is appropriate to consider only the potential risks of 
cloransulam-methyl in its exposure assessment.

E. Safety Determination

    1. U.S. population. Using the conservative exposure assumptions 
described above, and based on the completeness and reliability of the 
toxicity data, DowElanco has concluded that aggregate exposure to 
cloransulam-methyl will utilize only about 0.01 percent of the RfD for 
the U.S. population. EPA generally has no concern for exposures below 
100 percent of the RfD because the RfD represents the level at or below 
which daily aggregate dietary exposure over a lifetime will not pose 
appreciable risks to human health. Therefore, DowElanco concludes that 
there is a reasonable certainty that no harm will result from aggregate 
exposure to cloransulam-methyl residues (<0.02 ppm) on soybeans. The 
complete toxicology profile for cloransulam-methyl shows no evidence of 
physiological effects characteristic of the disruption of the hormone 
estrogen. Based upon this observation, cloransulam-methyl does not meet 
the criteria for an estrogenic compound.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of cloransulam-methyl, 
data from developmental toxicity studies in rats and rabbits and a 
multigeneration reproduction study in the rat are considered. The 
developmental toxicity studies are designed to evaluate adverse effects 
on the developing organism resulting from pesticide exposure during 
prenatal development to one or both parents. Reproduction studies 
provide information relating to effects from exposure to the pesticide 
on the reproductive capability and potential systemic toxicity of 
mating animals and on various parameters associated with the well-being 
of offspring.
    FFDCA section 408 provides that EPA may apply an additional safety 
factor for infants and children in the case of threshold effects to 
account for pre- and post-natal toxicity and the completeness of the 
data base. Base on the current toxicological data requirements, the 
data base for cloransulam-methyl relative to pre- and post-natal 
effects for children is complete. Further, for cloransulam-methyl, the 
NOEL in the chronic feeding study which was used to calculate the RfD 
(0.05 mg/kg/day) is already lower than the NOELs from the developmental 
studies in rats and rabbits by a factor of more than 60 to 200-fold.
    Concerning the reproduction study in rats, there were no effects on 
reproduction or fetal development, even at a dose 100 x  the NOEL used 
to establish the RfD. Therefore, DowElanco concludes that an additional 
uncertainty factor is not needed and that the RfD at 0.05 mg/kg/day is 
appropriate for assessing risk to infants and children.
    Using the conservative exposure assumptions previously described, 
the percent RfD utilized by the aggregate exposure to residues of 
cloransulam-methyl on soybeans is 0.07 percent for non-nursing infant, 
the most sensitive population subgroup. Thus, based on the completeness 
and reliability of the toxicity data and the conservative exposure 
assessment, DowElanco concludes that there is a reasonable certainty 
that no harm will result to infants and children from aggregate 
exposure to cloransulam-methyl on soybeans.

F. International Tolerances

    There are no Codex maximum residue levels established for residues 
of cloransulam-methyl on soybeans or any other food or feed crop.

II. Public Record

    Interested persons are invited to submit comments on this notice of 
filing. Comments must bear a notation indicating the docket control 
number, [PF-722]. All written comments filed in response to this 
petition will be available in the Public Response and Program Resources 
Branch, at the address given above from 8:30 a.m. to 4 p.m., Monday 
through Friday, except legal holidays.
    A record has been established for this notice under docket control 
number [PF-722] 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 public 
record is located in Rm. 1132 of the Public Response and Program 
Resources Branch, Field Operations Division (7506C), Office of 
Pesticide Programs, Environmental Protection Agency, Crystal Mall #2, 
1921 Jefferson Davis Highway, Arlington, VA.
    Electronic comments can be sent directly to EPA at:
    [email protected]


    Electronic comments must be submitted as ASCII file avoiding the 
use of special characters and any form of encryption.
    The official record for this notice, as well as the public version, 
as described above will be kept in paper form. Accordingly, EPA will 
transfer all comments received electronically into printed, paper form 
as they are received and will place the paper copies in the official 
record which will also include all comments submitted directly in 
writing. The official record is the paper record maintained at the 
address in ``ADDRESSES'' at the beginning of this document.

    Authority: 21 U.S.C. 346a.

List of Subjects

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping.

    Dated: March 13, 1997.

Stephen L. Johnson,
Director, Registration Division, Office of Pesticide Programs.

[FR Doc. 97-7496 Filed 3-25-97; 8:45 am]
BILLING CODE 6560-50-F