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diclosulam Pesticide Petition Filing 10/98

 

[Notices]               
[Page 64484-64489]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr20no98-50]

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ENVIRONMENTAL PROTECTION AGENCY

[PF-836; FRL-6030-9]

 
Notice of Filing of Pesticide Petitions

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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[[Page 64485]]

SUMMARY: This notice announces the initial filing of pesticide 
petitions proposing the establishment of regulations for residues of 
certain pesticide chemicals in or on various food commodities.
DATES: Comments, identified by the docket control number PF-836, must 
be received on or before December 21, 1998.
ADDRESSES: By mail submit written comments to: Public Information and 
Records Integrity Branch, Information Resources and Services Division 
(7502C), Office of Pesticides Programs, Environmental Protection 
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments 
to: Rm. 119, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically to: opp-
docket@epamail.epa.gov. Follow the instructions under ``SUPPLEMENTARY 
INFORMATION.'' No confidential business information should be submitted 
through e-mail.
    Information submitted as a comment concerning this document may be 
claimed confidential by marking any part or all of that information as 
``Confidential Business Information'' (CBI). CBI should not be 
submitted through e-mail. Information marked as CBI will not be 
disclosed except in accordance with procedures set forth in 40 CFR part 
2. A copy of the comment that does not contain CBI must be submitted 
for inclusion in the public record. Information not marked confidential 
may be disclosed publicly by EPA without prior notice. All written 
comments will be available for public inspection in Rm. 1132 at the 
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: The product manager listed in the 
table below:

------------------------------------------------------------------------
                                   Office location/
        Product Manager            telephone number          Address
------------------------------------------------------------------------
Mark Dow PM-03................  Rm. 214, CM #2, 703-    1921 Jefferson
                                 305-5533, e-            Davis Hwy,
                                 mail:dow.mark@epamail   Arlington, VA
                                 .epa.gov.
James Tompkins PM-25..........  Rm. 239, CM #2, 703-    Do.
                                 305-5697, e-
                                 mail:tompkins.james@e
                                 pamail.epa.gov.
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SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as 
follows proposing the establishment and/or amendment of regulations for 
residues of certain pesticide chemicals in or on various food 
commodities under section 408 of the Federal Food, Drug, and Comestic 
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these petitions 
contain data or information regarding the elements set forth in section 
408(d)(2); however, EPA has not fully evaluated the sufficiency of the 
submitted data at this time or whether the data supports granting of 
the petition. Additional data may be needed before EPA rules on the 
petition.
    The official record for this notice of filing, as well as the 
public version, has been established for this notice of filing under 
docket control number [PF-836] (including comments and data submitted 
electronically as described below). A public version of this record, 
including printed, paper versions of electronic comments, which does 
not include any information claimed as CBI, is available for inspection 
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The official record is located at the address in 
``ADDRESSES'' at the beginning of this document.
    Electronic comments can be sent directly to EPA at:
    opp-docket@epamail.epa.gov


    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption. Comments and data 
will also be accepted on disks in Wordperfect 5.1 file format or ASCII 
file format. All comments and data in electronic form must be 
identified by the docket number (insert docket number) and appropriate 
petition number. Electronic comments on notice may be filed online at 
many Federal Depository Libraries.

List of Subjects

    Environmental protection, Agricultural commodities, Food additives, 
Feed additives, Pesticides and pests, Reporting and recordkeeping 
requirements.

    Dated: October 27, 1998.

James Jones,

Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Petitioner summaries of the pesticide petitions are printed below 
as required by section 408(d)(3) of the FFDCA. The summaries of the 
petitions were prepared by the petitioners and represent the views of 
the petitioners. EPA is publishing the petition summaries verbatim 
without editing them in any way. The petition summary announces the 
availability of a description of the analytical methods available to 
EPA for the detection and measurement of the pesticide chemical 
residues or an explanation of why no such method is needed.


2. Dow AgroSciences

PP 6F4784, PP 7F4856

    EPA has received pesticide petitions (PP 6F4784 and PP 7F4856) from 
Dow AgroSciences, 9330 Zionsville Road, Indianapolis, IN 46268-1054, 
proposing pursuant to section 408(d) of the Federal Food, Drug, and 
Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR part 180 by 
establishing a tolerance for residues of the herbicide diclosulam (N-
(2,6-dichlorophenyl)-5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-c]pyrimidine-
2-sulfonamide) in or on the raw agricultural commodities soybean and 
peanut at 0.02 parts per million (ppm). EPA has determined that the 
petitions contain data or information regarding the elements set forth 
in section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated 
the sufficiency of the submitted data at this time or whether the data 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petitions.

A. Residue Chemistry

    1. Plant metabolism. Nature of residue studies demonstrated that 
residues of diclosulam would not be expected to accumulate to 
significant levels in soybeans or peanuts grown on soil treated with 
diclosulam, and that it was appropriate to base the magnitude of total 
terminal residues and proposed tolerances only on residues of the 
parent compound, diclosulam.
    2. Analytical method. Analytical method is available for the 
determination of diclosulam in soybeans and peanuts at a limit of 
quantitation (LOQ) of 0.01 ppm that is suitable for the enforcement of 
the proposed tolerance of 0.02 ppm.
    3. Magnitude of residues. No detectable residues of diclosulam are 
expected to result from soil applications to fields intended for 
soybeans or peanuts under the proposed maximum label conditions. On the 
basis of the limit of detection (LOD) of 0.003 ppm for diclosulam in 
the analytical method, a tolerance of 0.02 ppm is proposed for soybeans 
and peanuts. Soybeans and peanuts treated with 3 times the maximum 
label rates also resulted in no detectable residues of diclosulam in 
the soybean and peanuts or processed meal and oils. Thus, no tolerances 
are being proposed for diclosulam in any processed products.

B. Toxicological Profile

    1. Acute toxicity--Diclosulam acute toxicity is low. The acute oral 
LD<INF>50</INF> in the rat is >5,000 milligrams/kilogram (mg/kg) in 
both males and females and the acute dermal LD<INF>50</INF> in the 
rabbit is >2,000 mg/kg. The inhalation LC<INF>50</INF> in the rat is 
>5.04 mg/l of air. Diclosulam produced no indications of dermal 
irritation in rabbits or sensitization in the guinea pig, and only very 
slight transient eye irritation in the rabbit following acute exposure. 
End use formulations of diclosulam have similar low acute toxicity 
profiles.
    2. Genotoxicty. In a battery of short-term in vitro genotoxicity 
tests (Ames, CHO/HGPRT, chromosomal aberration) and an in vivo 
cytogenetic assay, diclosulam was negative.
    3. Reproductive and developmental toxicity. Diclosulam exhibited no 
effects on reproduction or fetal development. No effects on 
reproduction or fetal development in a multigeneration reproduction 
study in rats and no effects on reproductive performance or neonatal 
survival were seen at the highest dose tested (HDT) (limit test at 
1,000 milligrams/kilogram/day (mg/kg/day). In a developmental toxicity 
study in rabbits, the maternal no observed adverse effect level (NOAEL) 
was 65 mg/kg/day and the developmental NOAEL was at least 650 mg/kg/
day.
    4. Subchronic toxicity. Thirteen-week dietary toxicity studies in 
rats, mice and dogs were conducted. The primary target organs 
identified in these studies were the kidneys (rat), and the liver (rat, 
mouse and dog). In the rat 13-week study the NOAELs were 50 mg/kg/day 
in the male and 100 mg/kg/day in the female, based on liver 
histopathologic evaluation in males and decreased body weights in 
females. In the mouse, the NOAEL was 100 mg/kg/day based upon 
hepatocellular hypertrophy. An NOAEL of 5 mg/kg/day was established in 
the dog based upon centrilobular hepatocellular hypertrophy at 25 mg/
kg/day. In a 21-day repeated dermal application study in rabbits, 
diclosulam when given at a dose of 1,000 mg/kg/day produced no signs of 
dermal irritation or systemic toxicity.
    5. Chronic toxicity. In a 2-year combined chronic toxicity/
oncogenicity study in the rat, the NOAEL for chronic toxicity was 5 mg/
kg/day based upon kidney effects characterized as slight, subtle 
alteration in kidney tubular morphology, mostly within the 
corticomedullary junction which likely represented more a physiologic 
adaptation than a pathological change indicative of a toxic injury. 
There was no evidence of an oncogenic response. In a 2-year dietary 
feeding study in B6C3F1 mice conducted at 50, 100, 250 and 500 mg/kg/
day, 50 mg/kg/day was considered the NOAEL in males and the NOAEL in 
females based upon histologic changes in the kidney. The lesion noted 
in male mice was a reduced vacuolation of the kidney tubular epithelium 
at all dose levels. Decreased absolute and relative kidney weights were 
seen at 100 mg/kg/day and above. In female mice, focal dilation with 
hyperplasia of the lining epithelium of the renal cortical tubules was 
seen at 100 mg/kg/day and above. There was no evidence of an oncogenic 
response. In a 1-year chronic toxicity study in dogs, the NOAEL was 
considered 25 mg/kg/day, the HDT. Measurable toxicity was anticipated 
based on the results of the 13-week study in dogs; however, the only 
treatment related effects were slight elevations in serum alkaline 
phosphatase and creatinine levels at 25 mg/kg/day, which were 
considered within the normal limits of variability in dogs.
    6. Animal metabolism. Metabolism studies conducted on diclosulam 
indicated over 80% of a single or repeated dose of 5 mg/kg was 
absorbed, while at 500 mg/kg/day, there was incomplete absorption of 
diclosulam, with only 15-20% of the dose absorbed. Urinary elimination 
was rapid with half-lives of approximately 7-12 hours. Sex dependent 
differences in disposition of the 5 mg/kg dose were traced to more 
efficient elimination of unchanged diclosulam in the female versus male 
kidney but are of no known toxicologic significance. Due to its rapid 
elimination, diclosulam has little potential to accumulate upon 
repeated administration.

[[Page 64489]]

    7. Metabolite toxicology. The residue of concern for tolerance 
setting purposes is the parent material (diclosulam). Thus, there is no 
need to address metabolite toxicity.

C. Aggregate Exposure

    1. Dietary exposure--Food. For Purposes of assessing the potential 
dietary exposure from use of diclosulam on soybeans and peanuts, a 
conservative estimate of aggregate exposure is determined by 
Theoretical Maximum Residue Contribution (TMRC) assuming that 100% of 
the soybeans and peanuts have a residue of diclosulam at the proposed 
tolerance level of 0.02 ppm. This results in an extremely conservative 
estimate of exposure for diclosulam, because no residues are expected 
in these commodities at the proposed maximum label rate. The potential 
dietary exposure is obtained by multiplying the tolerance residue level 
on soybeans and peanuts (0.02 ppm) by the consumption data which 
estimates the amount of soybean and peanut products consumed by various 
population subgroups. The maximum potential average daily dose (ADD) of 
diclosulam values determined for various populations are clearly 
significant overestimates compared with actual exposure. When ADDs are 
compared to the Reference Dose (RfD), which uses the lowest NOAEL of 5 
mg/kg/day from the 2-year rat chronic toxicity study and an uncertainty 
factor of 100, the ADD for all U.S. consumers including the highest 
exposed group, non-nursing infants under 1-year old, would 
theoretically be exposed to about 0.1% of the RfD.
    2. Drinking water. Another potential source of dietary exposure are 
residues in drinking water. Based upon the available field dissipation 
and field run off studies conducted with diclosulam there is little 
potential for exposure to diclosulam in drinking water to cause any 
human health concern.

D. Cumulative Effects

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

E. Safety Determination

    1. U.S. population. Using the conservative exposure assumptions 
described above, and based on the completeness and reliability of the 
toxicity data, Dow AgroSciences has concluded that aggregate exposure 
to diclosulam potentially can utilize about 0.1% of the RfD for non-
nursing infants under 1-year old, theoretically the most exposed 
population. EPA generally has no concern for exposures below 100% of 
the RfD because the RfD represents the level at or below which daily 
aggregate dietary exposure over a lifetime will not pose appreciable 
risks to human health. Therefore, Dow AgroSciences concludes that there 
is a reasonable certainty that no harm will result from aggregate 
exposure to diclosulam residues in on soybeans and peanuts and its 
processed products.
    The complete toxicology profile for diclosulam shows no evidence of 
physiological effects characteristic of the disruption of the hormone 
estrogen. Based upon this observation, diclosulam does not meet the 
criteria for an estrogenic compound.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of diclosulam, data 
from developmental toxicity studies in rats and rabbits and a 
multigeneration reproduction study in the rat are considered. The 
developmental toxicity studies are designed to evaluate adverse effects 
on the developing organism resulting from pesticide exposure during 
prenatal development to one or both parents. Reproduction studies 
provide information relating to effects from exposure to the pesticide 
on the reproductive capability and potential systemic toxicity of 
mating animals and on various parameters associated with the well-being 
of offspring.
    FFDCA section 408 provides that EPA may apply an additional safety 
factor for infants and children in the case of threshold effects to 
account for pre- and post-natal toxicity and the completeness of the 
data base. Based on the current toxicological data requirements, the 
data base for diclosulam relative to pre- and post-natal effects for 
children is complete. Further, for diclosulam, the NOAEL in the chronic 
feeding study which was used to calculate the RfD (5 mg/kg/day) is 
already lower than the NOAELs from the developmental studies in rats 
and rabbits by a factor of more than 200-fold.
    Concerning the reproduction study in rats, there were no effects on 
reproduction or fetal development, even at a dose over 100 times the 
NOAEL used to establish the RfD. Therefore, Dow AgroSciences concludes 
that an additional uncertainty factor is not needed and that the RfD at 
0.05 mg/kg/day is appropriate for assessing risk to infants and 
children.
    Using the conservative exposure assumptions previously described, 
the percent RfD utilized by the aggregate (diet, and drinking water) 
exposure to residues of diclosulam on soybeans and peanuts is 0.000051 
mg/kg/day for non-nursing infants under 1-year old, theoretically the 
most exposed population subgroup. Thus, based on the completeness and 
reliability of the toxicity data and the conservative exposure 
assessment, Dow AgroSciences concludes that there is a reasonable 
certainty that no harm will result to infants and children from 
aggregate exposure to diclosulam on soybeans and peanuts.

F. International Tolerances

    There are no Codex maximum residue levels established for residues 
of diclosulam on soybeans, peanuts or any other food or feed crop.

[FR Doc. 98-31066 Filed 11-19-98; 8:45 am]
BILLING CODE 6560-50-F