[Federal Register Volume 63, Number 224 (Friday, November 20, 1998)]
[Notices]
[Pages 64484-64489]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-31066]


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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-
[email protected]. 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.
------------------------------------------------------------------------

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:
    [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 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.

1. Bayer Corporation

 PP 8F5023

    EPA has received a pesticide petition (PP 8F5023) from Bayer 
Corporation, 8400 Hawthorn Road, Kansas City, MO 64120, 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 cyfluthrin: [cyano[4-fluoro-3-phenoxyphenyl]-methyl-3-
[2,2-dichloroethenyl]-2,2-dimethyl-cyclopropanecarboxylate] in or on 
the raw agricultural commodity soybean, bean at 0.03 parts per million 
(ppm); soybean, forage at 8.0 ppm; soybean, hay at 4.0 ppm; field corn, 
forage at 3.0 ppm; and field corn, fodder at 6.0 ppm. EPA has 
determined that the petition contains data or information regarding the 
elements set forth in section 408(d)(2) of the FFDCA; however, EPA has 
not fully evaluated the sufficiency of the submitted data at this time 
or whether the data supports granting of the petition. Additional data 
may be needed before EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of cyfluthrin in plants is 
adequately understood. Studies have been conducted to delineate the 
metabolism of radiolabeled cyfluthrin in various crops all showing 
similar results. The residue of concern is cyfluthrin.
    2. Analytical method. Adequate analytical methodology (gas/liquid 
chromatography with an electron capture detector) is available for 
enforcement purposes.
    3. Magnitude of residues. Cyfluthrin is the active ingredient in 
the registered end-use product Baythroid 2 Emulsifiable Pyrethroid 
Insecticide, EPA Reg. No. 3125-351. Data to support the proposed 
tolerances have been submitted to the Agency.

[[Page 64486]]

B. Toxicological Profile

    1. Acute toxicity. There is a battery of acute toxicity studies for 
cyfluthrin supporting an overall toxicity Category II for the active 
ingredient.
    2. Genotoxicty. Mutagenicity tests were conducted, including 
several gene mutation assays (reverse mutation and recombination assays 
in bacteria and a Chinese hamster ovary (CHO)/HGPRT assay); a 
structural chromosome aberration assay (CHO/sister chromatid exchange 
assay); and an unscheduled DNA synthesis assay in rat hepatocytes. All 
tests were negative for genotoxicity.
    3. Reproductive and developmental toxicity. An oral developmental 
toxicity study in rats with a maternal and fetal no observed adverse 
effect level (NOAEL) of 10 milligram/kilogram body weight/day (mg/kg/
bwt/day) highest dose tested (HDT).
    An oral developmental toxicity study in rabbits with a maternal 
NOAEL of 20 mg/kg/bwt/day and a maternal lowest effect level (LEL) of 
60 mg/kg/bwt/day, based on decreased body weight gain and decreased 
food consumption during the dosing period. A fetal NOAEL of 20 mg/kg/
bwt/day and a fetal LEL of 60 mg/kg/ bwt/day were also observed in this 
study. The LEL was based on increased resorptions and increased 
postimplantation loss.
    A 3-generation reproduction study in rats with systemic toxicity 
NOAELs of 7.5 and 2.5 mg/kg/bwt/day for parental animals and their 
offspring, respectively. At higher dose levels (HDLs), the body weights 
of parental animals and their offspring were reduced.
    4. Subchronic toxicity. A subchronic toxicity feeding study using 
rats demonstrated a NOAEL of 22.5 mg/kg/bwt/day, the HDT.
    A 6 month toxicity feeding study in dogs established a NOAEL of 5 
mg/kg/ bwt/day. The LEL was 15 mg/kg/bwt/day based on clinical signs 
and reduced thymus weights.
    5. Chronic toxicity. A 12 month chronic feeding study in dogs 
established a NOAEL of 4 mg/kg/bwt/day. The LEL for this study is 
established at 16 mg/kg/bwt/day, based on slight ataxia, increased 
vomiting, diarrhea and decreased body weight.
    A 24 month chronic feeding/carcinogenicity study in rats 
demonstrated a NOAEL of 2.5 mg/kg/bwt/day and LEL of 6.2 mg/kg/bwt/day, 
based on decreased body weights in males, decreased food consumption in 
males, and inflammatory foci in the kidneys in females.
    A 24 month carcinogenicity study in mice was conducted. Under the 
conditions of the study there were no carcinogenic effects observed. A 
24 month chronic feeding/carcinogenicity study in rats was conducted. 
There were no carcinogenic effects observed under the conditions of the 
study.
    6. Animal metabolism. A metabolism study in rats showed that 
cyfluthrin is rapidly absorbed and excreted, mostly as conjugated 
metabolites in the urine, within 48 hours. An enterohepatic circulation 
was observed.
    7. Metabolite toxicology. No toxicology data have been required for 
cyfluthrin metabolites. The residue of concern is cyfluthrin.
    8. Endocrine disruption. There is no evidence of endocrine effects 
in any of the studies conducted with cyfluthrin, thus, there is no 
indication at this time that cyfluthrin causes endocrine effects.

C. Aggregate Exposure

    1. Dietary exposure-- Food. Dietary exposure was estimated using 
Novigen's Dietary Exposure Evaluation Model (DEEM) software; results 
from field trial and processing studies; consumption data from the USDA 
Continuing Surveys of Food Intake by Individuals (CSFIIs), conducted 
from 1989 through 1992; and information on the percentages of crops 
treated with cyfluthrin.
    Cyfluthrin is currently registered for use in alfalfa, carrots, 
citrus, cotton, peppers, radishes, sorghum, sunflower, sugarcane, sweet 
corn, and tomatoes. In addition, it has an import tolerance for hops. 
Various formulations are registered for use in food handling 
establishments and in combination with another active ingredient, for 
use in field corn, pop corn and sweet corn. For potential cyfluthrin 
use on soybeans and field corn the impact on the exposure assessment 
was examined.
    Chronic dietary exposure estimates with the current label uses for 
the overall U.S. population were 0.9% of the reference dose (RfD) 
(0.008 mg/kg/ bwt/day). When soybeans, field corn and potatoes were 
included the chronic dietary exposure estimates for the overall U.S. 
population were 0.8% of the RfD. For the most highly exposed population 
subgroups, non-nursing infants (<1 year) and children 1 to 6 years of 
age, the exposure was estimated to be 1.9% of the RfD and 1.8% of the 
RfD respectively for current label uses and 1.7% of the RfD and 1.7% of 
the RfD respectively for label uses plus potatoes, soybeans, field 
corn. The apparent drop in the percentage of the RfD when these uses 
are added may be explained by the lower limit of detection of the field 
trial data for these crops as opposed to the food handling data.
    Acute dietary exposures were estimated for the overall U.S. 
population, females 13 years and older, children, ages 1-6, and 7-12 
years, infants, non-nursing and nursing. The exposure was compared to 
the NOAEL of 20 mg/kg/ bwt/day to estimate the margin of exposures 
(MOEs).
    For the all the population subgroups studies the 95th and 99.9th 
percentile of exposure the MOEs were calculated to be over 18,000 and 
5,000 respectively for all current label uses and 9,900 and 3,800 
respectively for all label uses plus potatoes, field corn and soybeans.
    For women aged 13 years and older the 95th, and 99.9th percentile 
of acute exposure the MOEs were calculated as 66,746 and 18,390 
respectively for all current label uses and 33,704 and 11,516 
respectively for label uses plus potatoes, field corn, and soybeans.
    Lastly, for the potentially highest exposed population subgroups, 
non-nursing infants (<1 year) and children ages 1-6 years, the 95th, 
and 99.9th percentile of acute exposure to the MOEs were calculated at 
53,356; 18,346 and 5,179; 6,319 respectively for all current label uses 
and 19,624; 9,964 and 3802; 3943 respectively for label uses plus 
potatoes, field corn, and soybeans.
    2. Drinking water. Cyfluthrin is immobile in soil, therefore, will 
not leach into groundwater. Additionally, due the insolubility and 
lipophilic nature of cyfluthrin, any residues in surface water will 
rapidly and tightly bind to soil particles and remain with sediment, 
therefore not contributing to potential dietary exposure from drinking 
water.
    A screening evaluation of leaching potential of a typical 
pyrethroid was conducted using EPA's Pesticide Root Zone Model (PRZM3). 
Based on this screening assessment, the potential concentrations of a 
pyrethroid in ground water at 2 meters are essentially zero <0.001 
parts per billion (ppb). Surface water concentrations for pyrethroids 
were estimated using PRZM3 and Exposure Analysis Modeling System 
(EXAMS) using standard EPA cotton runoff and Mississippi pond 
scenarios. The maximum concentration predicted in the simulated pond 
was 52 parts per trillion (ppt). Concentration in actual drinking water 
would be much lower. Based on these analyses, the contribution of water 
to the dietary risk estimate is negligible.
    3. Non-dietary exposure. Non-occupational exposure to cyfluthrin 
may occur as a result of inhalation or contact from indoor residential, 
indoor commercial, and outdoor residential uses. Pursuant to the 
requirements of Federal Insecticide, Fungicide, and

[[Page 64487]]

Rodenticide Act (FIFRA) as amended by the Food Quality Protection Act 
(FQPA) of 1996 non-dietary and aggregate risk analyses for cyfluthrin 
were conducted. The analyses include evaluation of potential non-
dietary acute application and post-application exposures. Non-
occupational, non-dietary exposure was assessed based on the assumption 
that a flea infestation control scenario represents a ``worst case'' 
scenario. For the flea control infestation scenario indoor fogger, and 
professional residential turf same day treatments were included for 
cyfluthrin. Deterministic (point values) were used to present a worse 
case upper-bound estimate of non-dietary exposure. The non-dietary 
exposure estimates were expressed as systemic absorbed doses for a 
summation of inhalation, dermal, and incidental ingestion exposures. 
These worst-case non-dietary exposures were aggregated with chronic 
dietary exposures to evaluate potential health risks that might be 
associated with cyfluthrin products. The chronic dietary exposures were 
expressed as an oral absorbed dose to combine with the non-dietary 
systemic absorbed doses for comparison to a systemic absorbed dose 
NOAEL. Results for each potential exposed subpopulation (of adults, 
children 1-6 years, and infants <1 year) were compared to the systemic 
absorbed dose NOAEL for cyfluthrin to provide estimates of MOE.
    The large MOEs for cyfluthrin clearly demonstrate a substantial 
degree of safety. The total non-dietary MOEs are 3,800, 2,700, and 
2,500 for adults, children (1-6 years), and infants (<1 year), 
respectively. The aggregate MOE for adults is approximately 3,700 and 
the MOEs for infants and children exceed 2,400.
    The non-dietary methods used in the analyses can be characterized 
as highly conservative. This is due to the conservatism inherent in the 
calculation procedures and input assumptions. An example of this is the 
conservatism inherent in the jassercise methodology's over-
representation of residential post-application exposures. It is 
important to acknowledge that these MOEs are likely to significantly 
underestimate actual MOEs due to a variety of conservative assumptions 
and biases inherent in the derivatization of exposure by this method. 
Therefore, it can be concluded that large MOEs associated with 
potential non-dietary and aggregate exposures to cyfluthrin will result 
in little or no health risks to exposed persons. The aggregate risk 
analysis demonstrates compliance with the health-based requirements of 
the FQPA of 1996 for the current label uses. The additional use of 
cyfluthrin on field corn and soybean crops will have no impact on the 
analysis for non-dietary exposure.

D. Cumulative Effects

    Bayer will submit information for EPA to consider concerning 
potential cumulative effects of cyfluthrin consistent with the schedule 
established by EPA at 62 FR 42020 (August 4, 1997) and other EPA 
publications pursuant to the FQPA.

E. Safety Determination

    1. U.S. population. Based on the exposure assessments described 
above and on the completeness and reliability of the toxicity data, it 
can be concluded that total aggregate exposure to cyfluthrin from all 
label uses plus soybeans and field corn will utilize less than 2% of 
the RfD for chronic dietary exposures and that MOE in excess of 1,000 
exist for aggregate exposure to cyfluthrin for non-occupational 
exposure. EPA generally has no concerns for exposures below 100% of the 
RfD, because the RfD represents the level at or below which daily 
aggregate exposure over a lifetime will not pose appreciable risks to 
human health. MOE of 100 or more (300 for infants and children) also 
indicate an adequate degree of safety. Thus, it can be concluded that 
there is a reasonable certainty that no harm will result from aggregate 
exposure to cyfluthrin residues.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of cyfluthrin, the data 
from developmental studies in both rat and rabbit and a 2-generation 
reproduction study in the rat can be considered. The developmental 
toxicity studies evaluate any potential adverse effects on the 
developing animal resulting from pesticide exposure of the mother 
during prenatal development. The reproduction study evaluates any 
effects from exposure to the pesticide on the reproductive capability 
of mating animals through 2-generations, as well as any observed 
systemic toxicity. The toxicology data which support these uses of 
cyfluthrin include:
    i. A rat oral developmental toxicity study in which maternal and 
fetal NOAELs of 10 mg/kg/bwt/day HDT were observed.
    ii. An oral developmental toxicity study in which rabbits had a 
maternal NOAEL of 20 mg/kg/bwt/day and a maternal LEL of 60 mg/kg/bwt/
day, based on decreased body weight gain and decreased food consumption 
during the dosing period. A fetal NOAEL of 20 mg/kg/bwt/day and a fetal 
LEL of 60 mg/kg/bwt/day were also observed in this study. The LEL was 
based on increased resorptions and increased postimplantation loss.
    iii. An oral developmental toxicity study performed with beta-
cyfluthrin, the resolved isomer mixture of cyfluthrin, has been 
submitted to the Agency and is currently under review.
    iv. A developmental toxicity study in rats exposed via inhalation 
to liquid aerosols of cyfluthrin revealed developmental toxicity, but 
only in the presence of maternal toxicity. The developmental NOAEL was 
0.46 mg/m3 on the basis of reduced placental and fetal weights, and 
delayed ossification. The NOAEL for overt maternal toxicity was <0.46 
mg/m3, the lowest dose tested (LDT).
    In a rat 3-generation reproduction study, systemic toxicity NOAELs 
of 7.5 and 2.5 mg/kg/bwt/day for parental animals and their offspring, 
respectively, were observed. At higher dose levels, the body weights of 
parental animals and their offspring were reduced. Another multiple-
generation reproduction study in rats has been submitted to the Agency 
and is currently under review.
    To assess acute dietary exposure and determine a MOE for the 
overall U.S. population and certain subgroups, the Agency has used the 
rabbit developmental toxicity study which had a maternal NOAEL of 20 
mg/kg/bwt/day. Because the toxicological endpoint is one of 
developmental toxicity, the population group of concern for this 
analysis was women aged 13 and above. This subgroup most closely 
approximates women of child-bearing age. The MOE is calculated as the 
ratio of the NOAEL to the exposure. The Agency calculated the MOE to be 
over 600. Generally, MOE's greater than 100 for data derived from 
animal studies are regarded as showing no appreciable risk.
    FFDCA section 408 provides that EPA may apply an additional safety 
factor for infants and children. The additional safety factor may be 
used when pre- and post-natal threshold effects were observed in 
studies or to account for incompleteness of the toxicity database.
    The results of the 3-generation study in rats provided evidence 
suggesting that, with respect to effects of cyfluthrin on body weight, 
pups were more sensitive than adult rats. Thus, the Agency determined 
that an additional 3-fold uncertainty factor (UF) should be used in 
risk assessments to ensure adequate protection of infants and children.

[[Page 64488]]

    Generally, the EPA considers MOE of at least 100 to indicate an 
adequate degree of safety. With an additional 3x UF, this would be 300 
for infants and children. Using the exposure assessments described 
above and based on the described toxicity data aggregate exposure to 
infants and children indicate a margin of exposure in excess of 3,800. 
Thus, it can be concluded that there is a reasonable certainty that no 
harm will result to infants and children from aggregate exposure to 
cyfluthrin residues.

F. Conclusions

    The available data indicate that there is reasonable certainty of 
no harm from the aggregate exposure from all currently registered uses 
of cyfluthrin plus potatoes, field corn and soybeans.

G. International Tolerances

    There are no Codex maximum residue levels (MRLs) currently 
established for residues of cyfluthrin on soybean commodities. There is 
a Codex MRLs for maize of 0.05 ppm.

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 
LD50 in the rat is >5,000 milligrams/kilogram (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 
>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