[Federal Register Volume 66, Number 16 (Wednesday, January 24, 2001)]
[Notices]
[Pages 7644-7648]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-2182]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-993; FRL-6758-9]


Notice of Filing a Pesticide Petition to Establish a Tolerance 
for a Certain Pesticide Chemical in or on Food

AGENCY:  Environmental Protection Agency (EPA).

ACTION:  Notice.

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SUMMARY:  This notice announces the initial filing of a pesticide 
petition proposing the establishment of regulations for residues of a 
certain pesticide chemical in or on various food commodities.

DATES:  Comments, identified by docket control number PF-993, must be 
received on or before [insert date 30 days after date of publication in 
the Federal Register].

ADDRESSES:  Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I.C. of the SUPPLEMENTARY INFORMATION. To ensure 
proper receipt by EPA, it is imperative that you identify docket 
control number PF-993 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  By mail: Joanne I. Miller, 
Registration Support Branch, Registration Division (7505C), Office of 
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460; telephone number: (703) 305-6224; e-
mail address: [email protected].

SUPPLEMENTARY INFORMATION:   

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural 
producer, food manufacturer or pesticide manufacturer. Potentially 
affected categories and entities may include, but are not limited to:
    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in the table could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether or not this action might apply to certain entities. If you have 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

B. How Can I Get Additional Information, Including Copies of this 
Document and Other Related Documents?

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations,'' ``Regulations and Proposed Rules,'' and then look up the 
entry for this document under the ``Federal Register--Environmental 
Documents.'' You can also go directly to the Federal Register listings 
at http://www.epa.gov/fedrgstr/.
    2. In person. The Agency has established an official record for 
this action under docket control number PF-993. The official record 
consists of the documents specifically referenced in this action, any 
public comments received during an applicable comment period, and other 
information related to this action, including any information claimed 
as confidential business information (CBI). This official record 
includes the documents that are physically located in the docket, as 
well as the documents that are referenced in those documents. The 
public version of the official record does not include any information 
claimed as CBI. The public version of the official record, which 
includes printed, paper versions of any electronic comments submitted 
during an applicable comment period, is available for inspection in the 
Public Information and Records Integrity Branch (PIRIB), Rm. 119, 
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

    You may submit comments through the mail, in person, or 
electronically. To ensure proper receipt by EPA, it is imperative that 
you identify docket control number PF-993 in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs (OPP), Environmental Protection 
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by 
e-mail to: [email protected], or you can submit a computer disk as 
described above. Do not submit any information electronically that you 
consider to be CBI. Avoid the use of special characters and any form of 
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be 
identified by docket control

[[Page 7645]]

number PF-993. Electronic comments may also be filed online at many 
Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

    Do not submit any information electronically that you consider to 
be CBI. You may claim information that you submit to EPA in response to 
this document as CBI by marking any part or all of that information as 
CBI. Information so marked will not be disclosed except in accordance 
with procedures set forth in 40 CFR part 2. In addition to one complete 
version of the comment that includes any information claimed as CBI, a 
copy of the comment that does not contain the information claimed as 
CBI must be submitted for inclusion in the public version of the 
official record. Information not marked confidential will be included 
in the public version of the official record without prior notice. If 
you have any questions about CBI or the procedures for claiming CBI, 
please consult the person identified under FOR FURTHER INFORMATION 
CONTACT.

E. What Should I Consider as I Prepare My Comments for EPA?

    You may find the following suggestions helpful for preparing your 
comments:
    1. Explain your views as clearly as possible.
    2. Describe any assumptions that you used.
    3. Provide copies of any technical information and/or data you used 
that support your views.
    4. If you estimate potential burden or costs, explain how you 
arrived at the estimate that you provide.
    5. Provide specific examples to illustrate your concerns.
    6. Make sure to submit your comments by the deadline in this 
notice.
    7. To ensure proper receipt by EPA, be sure to identify the docket 
control number assigned to this action in the subject line on the first 
page of your response. You may also provide the name, date, and Federal 
Register citation.

II. What Action is the Agency Taking?

    EPA has received a pesticide petition as follows proposing the 
establishment and/or amendment of regulations for residues of a certain 
pesticide chemical 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 this petition contains 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 support granting of the petition. Additional data 
may be needed before EPA rules on the petition.

List of Subjects

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


    Dated: January 12, 2001.
Peter Caulkins,

Acting Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by section 408(d)(3) of the FFDCA. The summary of the 
petition was prepared by the petitioner and represents the view of the 
petitioners. EPA is publishing the petition summary verbatim without 
editing it 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.

Aventis CropScience

F6160

     EPA has received a pesticide petition (F6160) from Aventis 
CropScience, P.O. Box 12014, 2 T.W. Alexander Drive, Research Triangle 
Park, NC 27709 proposing, pursuant to section 408(d) of the Federal 
Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 
CFR part 180 by establishing a tolerance for residues of Iodosulfuron-
methyl-sodium, methyl 4-iodo-2-[3-(4-methoxy-6-methyl-1,3,5-triazin-2-
yl)- ureidosulfonyl]benzoate, sodium salt in or on the raw agricultural 
commodityies corn grain at 0.05 parts per million (ppm), corn forage 
and stover at 0.1 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 iodosulfuron-methyl-sodium 
(methyl 4-iodo-2-[3-(4-methoxy-6- methyl-1,3,5-triazin-2-yl)-
ureidosulfonyl]benzoate, sodium salt) in wheat, as representative of 
the cereals grain crop grouping has been investigated and is 
understood. The results of two metabolism studies in wheat show that 
the total radioactive residue levels in wheat commodities were very 
low. The principal compound was the parent, iodosulfuron-methyl-sodium. 
The metabolism in wheat proceeded via hydrolysis of iodosulfuron-
methyl-sodium to three metabolites, AE F0031838 (2-amino-4-hydroxy-6-
hydroxymethyl-1,3,5-triazine), AE F075736 (methyl-2-[3-(4-methyoxy-6-
methyl-1,3,5-triazin-2-yl)ureidosulfonyl]benzoate), and AE 
F145741(methyl 2-[3-(4-hydroxy-6-methyl-1,3,5-triazin-2-
yl)ureidosulfonyl]-4-iodo-benzoate) in harvested straw and at extremely 
low levels in grain. A fourth metabolite, AE F059411(2-amino-4-methoxy-
6-methyl-1,3,5-triazine) was only detected in the straw, again at very 
low levels. All metabolites characterized in plants were also found in 
the animal metabolism studies.
    2. Analytical method. Based on the results of the metabolism 
studies, the analytical targets selected were only the parent compound, 
iodosulfuron-methyl-sodium and AE F075736, based on its potential 
toxicological significance. Extractable residues of iodosulfuron-
methyl-sodium and AE F075736 are extracted from the crop matrices corn 
grain, forage and stover by blending with acetonitrile. After blending, 
the extract is filtered, volume reduced, partitioned, evaporated to 
dryness, dissolved in dichloromethane and cleaned-up. The organic 
extract is rotary evaporated to dryness and analyzed by HPLC/UV. The 
limit of quantification (LOQ) is 0.025 ppm in corn grain and 0.05 ppm 
in corn forage and stover.
    3. Magnitude of residues. Residue trials were carried out in a 
total of 21 U.S. residue field trials using a water dispersible granule 
(WG) formulation containing 20 percent w/w iodosulfuron-methyl-sodium. 
The preparation was applied in a split application of 5 g/ha followed 
by 2.5 g/ha. Pre-harvest intervals were between 37 to 53, 58 to 102 and 
58 to 125 days for forage, grain and stover, respectively. Grain, 
stover and forage of field corn did not contain residues of 
iodosulfuron-methyl-sodium at or above the respective limits of 
quantification of 0.025, 0.05 and 0.05. Also no residues of the 
metabolite AE F075736 were found in corn grain, stover or forage at 
harvest above the respective limits of quantification of 0.025, 0.05 
and 0.05 mg/kg. It is proposed, therefore, that AE

[[Page 7646]]

F075736 is not included in the tolerance expression. Tolerances of 
iodosulfuron-methyl-sodium are proposed at twice the limit of 
quantification of the analytical method, namely 0.05, 0.1 and 0.1 mg/kg 
in grain, stover and forage, respectively. In a corn processing study, 
no residues above 0.025 mg/kg were observed in corn grain following 
treatment of the crop at the nominal rate of 25 followed by 12.5 g/ha. 
This exaggerated rate is approximately eighteen times the maximum 
proposed label rate. Since no residues were observed in the raw 
agricultural commodity, neither analysis of the processed commodities 
nor tolerances are required. Although corn grain is fed to cattle and 
poultry and cattle may be grazed on forage or fed stover, tolerances in 
meat, milk or eggs are not necessary because none of these commodities 
contained iodosulfuron-methyl-sodium or its metabolite.

B. Toxicological Profile

    1. Acute toxicity. Iodosulfuron-methyl-sodium is slightly toxic 
following acute oral exposure, no more than slightly toxic following 
acute dermal exposure and practically non-toxic following acute 
inhalation exposure. The acute rat oral LD50 of 
iodosulfuron-methyl-sodium was 2,678 mg/kg (combined males plus 
females). The acute rat dermal LD50 was greater than 2,000 
mg/kg and the 4-hour rat inhalation LC50 was < 2.81 mg/l. 
Iodosulfuron-methyl-sodium was non-irritating to rabbit skin and caused 
corneal involvement or irritation clearing in 7 days or less. Based on 
these results, iodosulfuron-methyl-sodium would be classified as EPA 
Category IV for inhalation toxicity and dermal irritation and EPA 
Category III for eye irritation, dermal and oral toxicity. Technical 
iodosulfuron-methyl-sodium was not a sensitizer to skin.
    2. Genotoxicty. Testing for possible genotoxic properties of the 
technical active substance of iodosulfuron-methyl-sodium in several in 
vitro and in vivo test systems on different endpoints gave consistently 
negative results. The in vitro testing battery was comprised of 
investigations for gene mutation in bacterial and mammalian cells, 
examination of chromosomal aberration in Chinese Hamster cells and 
testing for unscheduled DNA-synthesis (UDS) in primary rat hepatocytes. 
The test program was complemented by a mouse micronucleus assay as an 
indirect investigation on the end-point chromosomal aberration in vivo. 
As there was no evidence of genotoxicity, the overall weight of 
evidence indicates that iodosulfuron-methyl-sodium is not genotoxic.
    3. Reproductive and developmental toxicity. A rat developmental 
toxicity (teratogenicity) study was conducted at dose levels of 0, 100, 
315, and 1,000 mg/kg/day. No increased mortality was noted. High dose 
dams exhibited clinical signs of toxicity including increased 
salivation, some body weight effects and statistically significantly 
decreased food consumption. Treatment-related fetal effects were seen 
only at the high dose of 1,000 mg/kg body weight, expressed by slightly 
increased incidences of retarded skeletal ossification, blood in the 
abdominal cavity and distended kidney pelvis. The mid dose dams 
reduction in food consumption was marginal (7.9 mg/kg versus 8.1 mg/kg 
for controls). Therefore, the no observable adverse effect level 
(NOAEL) with respect to maternal and fetal toxicity was 315 mg/kg body 
weight.
    A rabbit developmental (teratogenicity) toxicity study was 
conducted at dose levels of 0, 25, 100 and 400 mg/kg/day. No treatment 
related deaths or clinical signs were seen except reduced defecation at 
100 and 400 mg/kg. At 400 mg/kg, reduced body weight gain were 
observed. Food consumption was decreased in all dose level groups. No 
compound related effects were noted during necropsy except one animal 
at 400 mg/kg which had white depression on the liver. Fetal weights, 
crown rump lengths, litter sizes, number of live fetuses and placental 
weights were not affected by administration of iodosulfuron-methyl-
sodium. The NOEL was considered to be 25 mg/kg for maternal toxicity 
and 400 mg/kg for fetal toxicity. In a 2-generation rat reproduction 
study with iodosulfuron-methyl-sodium, dietary concentrations of 0, 50, 
500, and 5,000 ppm were administered to Wistar male and female rats. 
Iodosulfuron- methyl-sodium did not cause adverse effects on 
reproduction, fertility, mating behavior in parents or malformations in 
the offspring at any dose level tested. Treatment-related changes in 
parental animals were limited to significant decreases in body weight 
gains for males and females. Depression of body weight gain was also 
seen during the gestation periods in females. Retarded body weight gain 
in pups at the high dose level of 5,000 ppm was seen during lactation. 
At 5,000 ppm, a slightly statistically significant increase in the 
number of supernumerary implantation sides was observed in F1 females 
only. Based on depression of body weight development in parental 
animals during all phases and on toxicity to the fetuses/offspring at 
5,000 ppm, the NOEL for parental animals and offspring was determined 
to be 500 ppm (equivalent to daily test substance intakes of 25.6 to 
116.8 mg/kg/ body weight depending on the phase of the study).
    4. Subchronic toxicity. In a 90-day rat feeding study, 
iodosulfuron-methyl-sodium was administered at dietary concentrations 
of 0, 200, 1,000, 5,000 and 10,000 ppm to groups of 10 male and 10 
female Sprague Dawley rats. Futher 10 males and 10 females fed either 
0, 5,000 or 10,000 ppm were maintained on control diet for a further 4 
weeks to examine reversibility of possible effects. Treatment related 
depression in body weight gains was seen in males and females at 10,000 
ppm and at 5,000 ppm after 13 weeks. Depression of body weight gains 
was partly reversible during the 4-week recovery period. Overall food 
consumption was reduced in the 10,000 ppm males. No effects on food 
consumption were observed in the other dose level groups. Food 
consumption was comparable in all groups after the 4-week recovery 
period. Total red cell count and hemoglobin and hematocrit were 
slightly to marginally reduced in females at 10,000 ppm. No such 
changes could be seen in the respective recovery animals. Liver weight 
to body weight ratio was slightly increased in females at 1,0000 ppm 
compared to controls. This effect was no longer seen in recovery 
animals. Based on body weight effects at 10,000 and 5,000 ppm and the 
hepatocyte enlargement in males at 10,000 ppm, the NOEL was considered 
to be 10,000 ppm, equivalent to a daily intake of 71 mg/kg/day. In a 
90-day feeding study in mice, iodosulfuron-methyl-sodium was 
administered at dietary concentrations of 0, 700, 2,100, and 7,000 ppm. 
There were no treatment related deaths or clinical signs. Terminal body 
weight was reduced and body weight gain in males at 7,000 ppm compared 
to controls. There were no treatment-related effects on food 
consumption or hematological evaluations. A treatment-related 
statistically significant increase in alkaline phosphatase was seen in 
males at 7,000 ppm. Treatment related effects on organ weights were 
observed in livers of males at 7,000 ppm and 2,100 ppm and in females 
at 7,000 ppm. Based on depression of body weight development in males 
and liver effects in both sexes at 7,000 ppm and liver effects in males 
at 2,100 ppm, the NOEL was considered to be 700 ppm, equivalent to 
daily intakes of 119 mg/kg body weight for males and 139 mg/kg body 
weight for females. In a 90-day dog

[[Page 7647]]

feeding study, iodosulfuron-methyl-sodium was administered to beagle 
dogs at dietary concentrations of 0, 200, 1,200 and 7,200 ppm. 
iodosulfuron-methyl-sodium at dietary concentrations of 7,200 ppm 
showed effects on the hemapoietic system, in particular on maturation 
of blood cells in the bone marrow for both sexes. Decreased body weight 
gain was also seen in the highest dose. At 7,200 ppm, increased 
absolute and relative liver weights for males and females were 
observed. Absolute kidney weights in males and relative kidney weights 
in males and females were increased. Absolute and relative spleen 
weights were increased in males at 7,200 ppm. All dogs, at 7,200 ppm, 
had a generalized hemapoietic hyperplasia. Extramedullary hemopoiesis 
was also detected in the spleen for males and females, in the liver for 
females and in the mediastinal lymph node for male dogs. At 1,200 ppm 
one of four females had generalized hemopoietic hyperplasia in the 
sternal medullary cavities with moderate extramedullary hemopoiesis in 
the spleen and a reduction in the mature granulocyte forms in the 
marrow smear. The dietary concentrations of 7,200 ppm clearly exceeded 
the maximum tolerated dose (MTD). Based on the findings in one female 
at 1,200 ppm, the NOEL was considered to be 200 ppm, equating to 8.1 
mg/kg/day for males and 8.4 mg/kg/day for females.
    5. Chronic toxicity. Testing was performed in Sprague-Dawley rats 
and CD-1 mice using dietary concentrations up to and including 7,000 
ppm and 1,750 ppm respectively. In the combined chronic toxicity/
carcinogenicity study an interim sacrifice in 10 animals per sex and 
group as an early check for possible effects was performed after 12 
months. Doses of 331 mg/kg bw (males) or 452 mg/kg bw (females) in rats 
caused marked decreases of body weight gains and terminal body weights 
of high dose animals. Slight body weight effects were also seen in the 
mid dose of 29.7 mg/kg bw (m) or 39.1 mg/kg bw (famales). The NOAEL was 
equivalent to a dietary intake of 2.96 mg/kg bw (males) or 3.91 mg/kg 
bw (females). No body weight effects but hepatotoxicity was seen in 
mice in line with the results of the 90-day study. Liver effects in the 
form of pigment deposition were seen in most of the males and part of 
the females at the top dose of 1,750 ppm. With respect to the marked 
lipofuscin storage as observed in the 90-day study the high dose of the 
oncogenicity study had been selected at 1,750 ppm and pigment 
deposition was seen even at this lower dose due to the longer study 
duration. In addition hepatocyte enlargement and increased mononuclear 
cell infiltration was seen in both sexes at the high dose and also in 
males at the mid dose. There were no significant increases in 
neoplastic changes in rats or mice after administration of the 
mentioned doses for the animals natural lifespan. Based on the 
available chronic toxicity data, Aventis CropScience believes the 
Reference Dose (RfD) for iodosulfuron-methyl-sodium is 0.03 mg/kg/day 
based on the most sensitive species, rat. Iodosulfuron-methyl-sodium 
was not oncogenic in rats or mice and is not likely to be carcinogenic 
in humans. Aventis Crop Science believes, iodosulfuron-methyl-sodium 
should be classified as a `` Not Likely'' carcinogen based on the lack 
of carcinogenicity in rats and mice.
    6. Animal metabolism. The absorption, distribution metabolism and 
excretion of, iodosulfuron-methyl-sodium is well understood mammals. 
Wistar rats were orally administered low doses of 10 mg/kg/ body weight 
and 500 mg/kg body weight. After specific toxic effects had become 
obvious in the dog, absorption, distribution, elimination and in 
particular metabolism were also examined in Beagle dogs using an oral 
low dose of 6 mg/kg bw which was close to the 90-day NOEL, as well as 
an oral high dose of 200 mg/kg bw. The influence of the label position 
was examined using two different labels (U-14C-phenyl and 2-14C-
triazinyl-label), iodosulfuron-methyl-sodium was metabolized by 
hydrolysis of the methylester of the benzoic acid function to AE 
F145740 (4-iodo- 2-[3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)-
ureidosulfonyl]benzoic acid and o-demethylation at the 1,3,5-traizine 
leading to AE F145741 after single and repeated dosing. Oxidative 
hydroxylation of the 6-methyl group of the 1,3,5-triazinyl moiety was 
also observed. Breakdown of the sulfonylurea bridge possibly due to 
amidases leads to AE F114368 (methyl 2-sulfamoylbenzoate) and AE 
0031850 (2-aminosulfonyl-4-iodo-benzoic acid) which cyclised to AE 
F143133 (6-iodo-1,2-benzisothiazol-3(2H)-one-1,1-dioxide). The cleavage 
of the iodine-phenyl- bond resulting in AE F075736 and AE F161778 
(methyl 2-[3-(4-hydroxy-6-methyl-1,3,5-triazin-2- 
yl)ureidosulfonyl]benzoate) was observed to be a minor metabolic 
reaction. Overall no significant difference in the metabolic profile 
between sexes, dose levels or following repeated dosing in the rat were 
found. Metabolites identified in the dog study were the same as those 
found in rats The metabolism of, iodosulfuron-methyl-sodium in 
ruminants is adequately understood. A dairy cow was dosed with the 
compound at a level equivalent to 14.23 ppm in the diet for 7 days. The 
compound appeared to be well absorbed and rapidly excreted mainly in 
the urine. Total residue levels were very low. The major metabolite 
identified in all tissues and milk was unchanged, iodosulfuron-methyl-
sodium together with up to 7 minor metabolites. All of the metabolic 
products of iodosulfuron-methyl-sodium were also observed in the rat. 
The metabolism of iodosulfuron-methyl-sodium in poultry is also 
adequately understood. Laying hens were fed the compound at a level 
equivalent to 10 ppm in the diet for 14 days. Residue levels were low 
in all commodities. Unchanged iodosulfuron-methyl-sodium was the major 
metabolite identified in all of the tissues and yolks. Up to 6 minor 
metabolites of iodosulfuron-methyl-sodium were also detected in all 
tissues and excreta which were identical to those formed in the rat.
    7. Endocrine disruption. No special studies have been conducted to 
investigate the potential of iodosulfuron- methyl-sodium to induce 
estrogenic or other endocrine effects. However, no evidence of 
estrogenic or other endocrine effects have been noted in any of the 
standard toxicology studies that have been conducted with this product 
and there is no reason to suspect that any such effects would be 
likely.

C. Aggregate Exposure

    1. Dietary exposure. Iodosulfuron-methyl-sodium is proposed for use 
as an herbicide on corn. No non- agricultural uses are anticipated. The 
potential sources of exposure would consist of any potential residues 
in food and drinking water. As indicated in Unit B. there are no acute 
toxicity concerns and thus only chronic exposure has been evaluated.
    i. Food. Chronic dietary analysis was conducted to estimate 
exposure to potential iodosulfuron- methyl-sodium residues in/on corn. 
A Tier One analysis was conducted using the DEEM software and the 1994-
1996 CSFII food consumption data. It was assumed that residues were at 
tolerance levels of 0.05 ppm (twice the limit of quantification) in 
grain and that 100% of crop was treated. Additionally, based on the 
results from appropriate studies, it was assumed that there was no 
concentration into processed commodities and that contributions

[[Page 7648]]

from residues in meat, milk or eggs are not required. A chronic RfD of 
0.03 mg/kg /day is derived from the most sensitive species, rat. Using 
these inputs the chronic dietary exposure estimate from residues of 
iodosulfuron-methyl-sodium for the U.S. population was 0.000079 mg/kg /
day or 0.3% of its RfD. For the sub-population with the highest 
exposure, non-nursing infants, the chronic dietary exposure estimate 
from residues of iodosulfuron-methyl-sodium was 0.000201 mg/kg /day, or 
0.7% of its RfD. These values are highly conservative, having been 
based on worst case assumptions of tolerance level residues and 100% of 
the crop treated.
    ii. Drinking water. EPA's Standard Operating Procedure (SOP) for 
drinking water exposure and risk assessments was used to perform the 
drinking water assessment. This SOP uses a variety of tools to conduct 
drinking water assessment. These tools include water models such as 
SCI-GROW, GENEEC, PRZMS/EXAMS, and monitoring data. If monitoring data 
are not available then the models are used to predict potential 
residues in surface and ground water and the highest value is assumed 
to be the potential drinking water residue. In the case of 
iodosulfuron-methyl-sodium monitoring data do not exist therefore model 
calculations were used to estimate a water residue. The calculated 
drinking water levels of comparison (DWLOC) for chronic exposures for 
all adults and children greatly exceed the drinking water estimated 
concentrations (DWEC) from the models. The chronic DWLOC for adults is 
1,047 ppb. The chronic DWLOC for children/toddlers is 298 ppb. The 
worst case chronic DWEC is 0.015 ppb based on a PRZM/EXAMS simulation 
of runoff into surface water in a standard EPA exposure assessment 
scenario for corn (MLRA 111, Ohio). The DWEC represents combined 
residues of iodosulfuron-methyl-sodium and its metabolite AE F075736, 
expressed as iodosulfuron-methyl-sodium equivalents.
    2. Non-dietary exposure. Exposure to iodosulfuron-methyl-sodium for 
the mixer/loader/ground boom/aerial applicator was calculated using the 
Pesticide Handlers Exposure Database (PHED). It was assumed that the 
product would be applied to a maximum of 50 hectares per day (125 A/
day) by ground boom applicator and 140 hectares per day (350 A/day) by 
aerial applicator at a maximum use rate of 2 grams active ingredient. 
Normal work attire consisting of long-sleeved shirt, long pants, and 
protective gloves was assumed in the PHED assessment. Margins of 
exposure (MOEs) for a 70 kg operator were calculated utilizing a dermal 
NOEL of 810 mg/kg body weight/day from the rat dermal toxicity study 
and an inhalation NOAEL of 8 mg/kg body weight/day based on a 90-day 
dog feeding study. There were no signs of developmental toxicity in the 
rabbit developmental toxicity study. The combined MOE (inhalation plus 
dermal) for iodosulfuron-methyl-sodium was 1,101,000 for a ground 
operator undertaking mixing, loading and spraying. For aerial 
application where the mixer/loader was assumed to be a different 
operator from the pilot combined MOEs were 629,000 for the mixer/loader 
and 10,131,000 for the pilot. The results indicate that large margins 
of safety exist for the proposed use of iodosulfuron-methyl-sodium. The 
timing of iodosulfuron-methyl-sodium application to corn is such that 
field reentry shortly after spraying is atypical. Therefore estimations 
of worker reentry exposure were not considered necessary.

D. Cumulative Effects

    There is no available data at this time to determine whether 
iodosulfuron-methyl-sodium has a common mechanism of toxicity with 
other substances or how to include this pesticide in a cumulative risk 
assessment. Therefore a cumulative assessment was not done for this 
chemical.

E. Safety Determination

    1.  U.S. population. Using the conservative assumptions described 
above, based on the completeness and reliability of the toxicity data, 
it is concluded that aggregate exposure, in this case food only, to the 
proposed uses of iodosulfuron-methyl-sodium will utilize at most 0.3% 
of the reference dose for the U.S. population. The actual exposure is 
likely to be much less as more realistic data and models are developed. 
EPA generally has no concern 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 risk to human 
health. Drinking water levels of comparison based on the dietary 
exposure are much greater than highly conservative estimated levels, 
and would be expected to be well below the 100% level of the RfD, if 
they occur at all. Therefore, there is a reasonable certainty that no 
harm will occur to the U.S. Population from aggregate exposure (food 
and drinking water) to iodosulfuron-methyl-sodium.
    2. Infants and children. No evidence of increased sensitivity to 
fetuses was noted in developmental toxicity studies in rats or rabbits. 
There has been no indication of reproductive effects or indication of 
increased sensitivity to the offspring in the 2-generation rat 
reproduction study. No additional safety factor to protect infants and 
children is necessary as there is no evidence of increased sensitivity 
in infants and children.
    Using the conservative assumptions described in the exposure 
section above, the percent of the reference dose that will be used for 
exposure to residues of iodosulfuron-methyl-sodium in food for non-
nursing infants (the most highly exposed sub group) is 0.7%. The 
children (1-6) exposure uses 0.6% of the reference dose. As in the 
adult situation, drinking water levels of comparison are much higher 
than the worst case drinking water estimated concentrations and are 
expected to use well below 100% of the reference dose, if they occur at 
all. Therefore, there is a reasonable certainty that no harm will occur 
to infants and children from aggregate exposure to residues of 
iodosulfuron-methyl-sodium.

F. International Tolerances

    There are no Codex Alimentarius Commission maximum residue levels 
established for residues of iodosulfuron-methyl-sodium.
[FR Doc. 01-2182 Filed 1-23-01; 8:45 am]
BILLING CODE 6560-50-S