[Federal Register Volume 67, Number 46 (Friday, March 8, 2002)]
[Notices]
[Pages 10722-10727]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-5446]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-1072; FRL-6825-8]


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-1072, must be 
received on or before April 8, 2002.

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-1072 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT: By mail: James A. Tompkins, 
Registration Division (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460; telephone number: (703) 305-5697; 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:

 
------------------------------------------------------------------------
                                                          Examples of
           Categories                 NAICS codes         potentially
                                                       affected entities
------------------------------------------------------------------------
Industry                          111                 Crop production
                                  112                 Animal production
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------

    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'' 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-1072. 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-1072 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

[[Page 10723]]

(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 number PF-1072. 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 Cosmetic 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: February 21, 2002.
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 E. I. du Pont Nemours and Company, and 
represents the view of the E. I. du Pont Nemours Company. 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.

E. I. du Pont Nemours and Company

PP 0F6120

    EPA has received a pesticide petition (0F6120) from E. I. du Pont 
de Nemours and Company, DuPont Agricultural Products, Barley Mill 
Plaza, Wilmington, DE 19880-0038 proposing, pursuant to section 408(d) 
of the FFDCA, 21 U.S.C. 346a(d), to amend 40 CFR part 180 by 
establishing a tolerance for residues of the herbicide chlorsulfuron: 
2-Chloro-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-yl) aminocarbonyl] 
benzenesulfonamide in or on the raw agricultural commodities grass 
forage at 11 parts per million (ppm) and grass hay at 19 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 qualitative nature of residue in plants is 
adequately understood. Metabolism studies have been conducted in both 
wheat and barley and the metabolic profiles are consistent. In wheat, 
14C-triazine chlorsulfuron and 14C-phenyl 
chlorsulfuron were applied foliarly to the field plots at the rates of 
0.25 ounce active indregient/acre (oz ai/A) and 1.5 oz ai/A. Samples of 
wheat were harvested on the day of application (forage), 7 days later 
(late forage), and 19 days later (hay). At maturity, 82 days after 
treatment, the grain heads and straw were harvested. Chlorsulfuron 
showed systemic absorption and translocation. The deposited 
radioactivity on surfaces is small. Combustion analysis of the 0-day, 
7-day, and 19-day 1x treatment resulted in total radioactive residue 
(TRRs) of approximately 1.155 ppm, 0.065 ppm, and 0.017 ppm 
14C-triazine chlorsulfuron equivalent, and 1.168 ppm, 0.102 
ppm, and 0.024 ppm 14C-phenyl chlorsulfuron equivalent, 
respectively. TRRs for the samples taken at maturity were 0.003 ppm for 
the straw, and at or below the limit of detection (0.001 ppm) for the 
grain. The primary metabolic pathway of chlorsulfuron in plants, 
involved hydroxylation of the intact parent molecule to yield 5-hydroxy 
chlorsulfuron, which subsequently underwent glucoside conjugation. The 
glucose conjugate of 5-hydroxy chlorsulfuron accounts for 49.5% and 
25.6% TRR (0.032 and 0.004 ppm) in

[[Page 10724]]

wheat 7 and 19 days after 14C-triazine chlorsulfuron 
treatment; and for 30.3% and 24.6% TRR (0.031 ppm and 0.006 ppm) 7 and 
19 days after 14C-phenyl chlorsulfuron treatment. In the 19-
day triazine and phenyl labeled samples, 5-hydroxy chlorsulfuron was 
present at 0.001 ppm. After glucoside conjugation, the cleavage of the 
sulfonylurea linkage occurs to yield the corresponding sulfonamide 
conjugate and triazine. 14C-triazine chlorsulfuron treated 
wheat contains 6.5% TRR (0.004 ppm) triazine amine in the 7-day sample. 
The glucose conjugate of 5-hydroxy chlorsulfonamide accounts for 8.6% 
TRR (0.009 ppm) in the 7-day sample and 10.4% TRR (0.002 ppm) in the 
19-day sample from 14C-phenyl chlorsulfuron treated wheat.
    2. Analytical method. The analytical enforcement method exists for 
the determination of chlorsulfuron in cereal forage, hay, grain and 
straw and grass forage and hay. Samples are extracted in aqueous 
solution, acidified, purified and concentrated by reversed-phase solid-
phase extraction. Extracts are analyzed by liquid chromatography/mass 
spectrometry employing electrospray ionization (ESI-LC/MS).
    3. Magnitude of residues. It has been determined that the residue 
to be regulated is parent chlorsulfuron only. A study was conducted to 
determine the magnitude of residues of chlorsulfuron and its 
metabolite, 5-hydroxy chlorsulfuron in wheat forage, grain and straw 
following application of Glean FC herbicide, at the maximum label rate. 
Chlorsulfuron residues in wheat grain and straw were below 0.05 ppm, 
the limit of quantitation (LOQ) at all sites. Chlorsulfuron residues in 
wheat forage were below 0.05 ppm in all sites (PHI of 19 to 35 days) 
except one which had a residue level range of 0.31-0.60 ppm (PHI of 1 
day).
    Another study was conducted to determine the magnitude of residues 
of chlorsulfuron in wheat forage and hay at a 0 day PHI following 
application of chlorsulfuron at 0.5 oz a.i./A. The residues for wheat 
forage ranged between 0.66 and 5.0 ppm. The residues for wheat hay 
ranged between 0.56 and 12 ppm.
    An additional study determined the magnitude and decline of 
residues of chlorsulfuron in pasture grass forage and hay following 
application of chlorsulfuron at 1.0 oz a.i./A. The application was made 
with the shortest time to harvest allowed by the label (0 day PHI). 
Applications were made, when the grass was at a forageable stage of 
growth. At a 0 day PHI, the residue levels in the grass forage were 
between 1.2 and 11 ppm. The residue levels in the grass hay at 0-day 
PHI were between 1.0 and 19 ppm.
    In a greenhouse rotational crop study, wheat, sugar beets and rape 
plants were grown on soil, which had been treated with 14C-
chlorsulfuron at 1.0 oz/A and field-aged for periods of 4 and 12 
months. In all crops planted 4 months following chlorsulfuron 
treatment, intact 14C-chlorsulfuron, if present at all, was 
less than 0.2 parts per billion (ppb).

B. Toxicological Profile

    1. Acute toxicity. Based on EPA criteria, technical chlorsulfuron 
is in toxicity Category IV for oral and inhalation routes of exposure, 
and for dermal irritation. Chlorsulfuron is in toxicity Category III 
for eye irritation, and the dermal route of exposure. It is not a skin 
sensitizer.
    Acute oral toxicity in rats: LD50 = 5,545 milligrams/
kilogram (mg/kg) (M), 6,293 mg/kg (F) mg/kg (F)
    Acute dermal toxicity in rabbits: LD50 > 3,400 mg/kg
    Acute inhalation toxicity in rats: LC50 > 5.9 mg/L
    Primary eye irritation in rabbits: Moderate effects reversed within 
72 hours
    Primary dermal irritation in rabbits: non-irritant
    2. Genotoxicty. Technical chlorsulfuron has shown no genotoxic or 
mutagenic activity in the following in vitro and in vivo tests:
    In vitro Mutagenicity Ames Assay: Negative
    In vitro Mutagenicity CHO/HPRT Assay: Negative
    In vitro Cytogenetic Study: Negative
    In vitro DNA Repair Study: Negative
    In vitro UDS: Negative
    In vivo Dominant Lethal Mutagenicity: Negative
    3. Reproductive and developmental toxicity. In a multigeneration 
reproduction study in rats fed 0, 100, 500, or 2,500 ppm chlorsulfuron, 
the only observed effect on reproduction endpoints was slightly 
decreased fertility indices in rats from the 2,500 ppm group. Mean 
number of pups per litter, gestation, lactation, and viability indices, 
litter survival, and mean weanling body weights and weight gains were 
not adversely influenced by chlorsulfuron. No gross or 
histopathological abnormalities were observed in weanling rats. The no 
observed adverse effect level (NOAEL) based on decreased fertility 
indices was 500 ppm. The NOAEL based on systemic toxicity was 100 ppm.
    In studies conducted to evaluate potential developmental toxicity, 
chlorsulfuron was neither teratogenic nor uniquely toxic to the 
conceptus (i.e., not considered a developmental toxin). In the rat 
study, chlorsulfuron was administered by gavage to rats on days 7-16 of 
gestation at daily dose levels of 0, 55, 165, 500, or 1,500 mg/kg. 
There was evidence of maternal toxicity (spontaneous death, weight 
loss, reductions of feed consumption) at the two highest dose levels. 
The remaining groups showed no evidence of any effects on maternal body 
weights, feed consumption or clinical signs. No effects were seen in 
any experimental group on mean nidations, live fetuses per litter, in 
utero survival or on mean corpora lutea counts. Fetal toxicity was 
evident as a depression in fetal weights only at the highest dose 
tested (HDT). Treatment with chlorsulfuron did not result in any 
significant increase in fetal alterations (malformations or 
variations). Maternal toxicity was observed at daily dose levels 
greater than or equal to 500 mg/kg. Fetal toxicity was seen only at a 
level of 1,500 mg/kg, a maternally toxic dose. The NOAEL was 165 mg/kg/
day for the dam and 500 mg/kg/day for the conceptus. In the rabbit 
developmental toxicity study, chlorsulfuron was administered by gavage 
to rabbits on days 7-19 of gestation at daily dose levels of 0, 25, 75, 
200, or 400 mg/kg. Since no overt maternal or fetal toxicity was 
evident, a supplementary study was conducted in which chlorsulfuron was 
administered at daily dose levels of 0, 400, and 1,000 mg/kg. Maternal 
toxicity, evident at the highest level, 1,000 mg/kg/day, consisted of a 
significant incidence of mortality and abortions; a significant 
increase in the incidence of females with clinical signs and 
significantly decreased mean maternal body weight changes. In addition, 
mean maternal weight gains for days 7-29 were also significantly 
reduced. At 400 mg/kg/day, the only evidence of maternal toxicity was a 
significant reduction in mean maternal adjusted body weight gains on 
days 7-29. No other maternal toxic effects were seen at any dose level. 
There was no evidence of fetal toxicity seen in either study. 
Therefore, under the conditions of these studies, the NOAEL was 200 mg/
kg/day for the dam and > 1,000 mg/kg/day for the conceptus.
    4. Subchronic toxicity. In a ten-dose oral subacute test, 
chlorsulfuron was administered orally to male rats at a repeated dose 
level of 2,200 mg/kg/day for 10 days over a 2-week period. No test 
compound-related gross or histologic changes were observed.
    The rat was the most sensitive species to subchronic exposure of 
chlorsulfuron. Male and female rats were fed diets for 98 days that 
contained

[[Page 10725]]

0, 100, 500, or 2,500 ppm chlorsulfuron. Male rats fed diets at 500 or 
2,500 ppm exhibited decreased urine pH and decreased plasma creatinine. 
Rats in the 500 and 2,500 ppm groups also exhibited decreased monocyte 
counts. These findings show that the NOAEL for chlorsulfuron was 100 
ppm for male and female rats (98-day dietary). In the mouse study, 
groups of male and female mice were fed chlorsulfuron at levels of 0, 
500, 2,500, 5,000, or 7,500 ppm. No meaningful differences in weight 
gain, food consumption, or food efficiency existed between control and 
treated mice fed chlorsulfuron. Male mice fed 5,000 or 7,500 ppm had 
lower erythrocyte count and higher mean corpuscular volumes and mean 
corpuscular hemoglobin values than control males. Female mice fed 5,000 
or 7,500 ppm, had fewer neutrophilic granulocytes and more lymphocytes 
than control females. No hematologic effects were seen in mice fed 500 
or 2,500 ppm chlorsulfuron. Gross pathologic findings in mice at all 
feeding levels and microscopic findings in mice fed 7,500 ppm were 
considered to be spontaneous or the result of intercurrent disease. No 
effects attributable to the feeding of chlorsulfuron were observed in 
mice fed 500 or 2,500 ppm chlorsulfuron. Therefore, the NOAEL for male 
and female mice is 2,500 ppm (90-day dietary).
    5. Chronic toxicity. In a long-term feeding study with 
chlorsulfuron, male and female mice were fed diets of 0, 100, 500, or 
5,000 ppm chlorsulfuron. Mean body weights and weight gains of mice in 
the 5,000 ppm treatment groups were decreased when compared to those of 
their respective control groups. The NOAEL for chronic (2-year dietary) 
exposure of chlorsulfuron in mice was 500 ppm for male and female mice. 
No behavioral, clinical, hematological, gross pathological or 
histological abnormalities were observed, that could be related to the 
dietary administration of chlorsulfuron. Chlorsulfuron was not 
oncogenic when administered to male and female mice for 2 years at 
levels of 100, 500, or 5,000 ppm. In a long-term feeding study, male 
and female rats were fed diets containing 0, 100, 500, or 2,500 ppm 
chlorsulfuron. Mild to moderate reduction in mean body weights and 
weight gains in male rats from the 500 and 2,500 ppm treatment groups 
was observed. No other behavioral, nutritional, clinical, or 
hematological abnormalities that could be attributed to chlorsulfuron 
treatment were observed during the feeding study. The NOAEL (2-year 
dietary) in male and female rats was 100 ppm (5 mg/kg). Chlorsulfuron 
was not an oncogen in rats.
    In a 1-year chronic study with dogs, male and female dogs were fed 
dietary levels of 0, 100, 2,000, or 7,500 ppm chlorsulfuron. There were 
slight body weight decreases and hematological changes in females in 
the 7,500 ppm treatment group. Therefore, the NOAEL (1-year dietary) is 
2,000 ppm.
    6. Animal metabolism. Due to its rapid elimination, metabolism of 
chlorsulfuron in animals is minimal. O-Demethylation and cleavage of 
the sulfonylurea linkage were observed.
    Rats were dosed with 14C-phenyl labeled chlorsulfuron. 
Chlorsulfuron and its metabolites were excreted rapidly from the rats. 
An average of 85% of the recovered radioactivity was excreted in the 
urine and 12% in the feces. Less than 1% of any of the various doses 
was retained in the body organs. Most (85%) of the excreted 
radioactivity was present, as intact chlorsulfuron with minor amounts 
of 2-chlorobenzene-sulfonamide and two polar metabolites.
    Results from a metabolism study with two radioactive forms of 
chlorsulfuron (14C-triazine and 14C-phenyl) in 
lactating goats show that chlorsulfuron is readily excreted unchanged 
in urine and feces of the goat. The target dose for each test goat was 
45 mg/goat/day, which is equivalent to a daily dietary intake of 25 
ppm, assuming daily food consumption of 1.8 kg. The results of this 
study indicate that chlorsulfuron is readily excreted unchanged in 
urine and feces of the goat. A majority of the cumulative dose was 
excreted in the urine (69-75%) and feces (5.9-7.6%).
    Additional radioactivity was recovered in the cage wash and 
accounted for 3.8-6.7% of the dose. O-desmethylchlorsulfuron was 
identified in the feces indicating there is O-dealkylation of 
chlorsulfuron most likely by gut microflora. The appearance of 4-
methoxy-6-methyl-1,3,5-triazin-2-amine and 2-chlorobenzenesulfonamide 
indicates hydrolysis of the amide linkage in the sulfonylurea bridge. 
Neither of these metabolites was present in the urine or feces, 
suggesting they are further metabolized before being excreted. Total 
milk residues reached steady-state after 24 hours, indicating 
bioaccumulation of residues in milk is unlikely. The highest tissue 
residues were found in the kidney and liver, because urinary and fecal 
excretion are the primary routes of elimination for chlorsulfuron. It 
is unlikely that chlorsulfuron or any of its metabolites will 
bioaccumulate in the tissues or milk of the lactating goat.
    The poultry metabolism study was conducted at 1 ppm 14C-
chlorsulfuron in feed for up to 14 days in laying hens. After 14 days, 
85-99% of the total radioactivity was accounted for in the hen excreta, 
with the majority being 14C-chlorsulfuron. These data are 
consistent with previous research; demonstrating no accumulation of 
chlorsulfuron residues in animal tissues and minimal metabolism of the 
chlorsulfuron molecule in the rat and goat.
    Dairy cattle were fed chlorsulfuron at dietary levels of 2, 10, and 
50 ppm for 28 days. The chlorsulfuron residue levels in milk rose 
within 3 days to steady-state plateaus, remaining constant during 
fortified feeding, and decreased to below the analytical detection 
limit of 0.010 ppm within 3 days of terminating the fortified feeding. 
Average steady-state residue levels in the milk during fortified 
feeding, were 0.064 ppm for cows fed at the 50 ppm dietary rate and 
0.013 ppm for cows fed at the 10 ppm dietary rate. No more than 0.2% of 
the ingested chlorsulfuron appeared as residues in the milk. 
Chlorsulfuron was rapidly eliminated from the animal in the urine and 
feces. Average concentrations of chlorsulfuron in urine and feces were 
24 ppm and 0.6 ppm, respectively, for cows fed chlorsulfuron at the 50 
ppm dietary level. Chlorsulfuron was detected in the kidney 0.25 ppm, 
liver 0.024 ppm, and lean muscle < 0.010 ppm of the cow fed at the 50 
ppm dietary level, but was undetected (< 0.01 ppm in subcutaneous fat. 
Chlorsulfuron residues in all analyzed tissue decreased to< 0.010 ppm 
for all cows within 8-days of returning to a diet without 
chlorsulfuron. Addition of the proposed grass tolerances will not 
significantly increase the dietary burden for cattle since tolerances 
already exist for cereal feed commodities. The total dietary burden of 
chlorsulfuron for cattle will remain less than 50 ppm.
    7. Metabolite toxicology. There is no evidence that the metabolites 
of chlorsulfuron as identified in either the plant, or animal 
metabolism studies are of any toxicological significance.
    8. Endocrine disruption. Chronic, lifespan, and multigenerational 
bioassays in mammals and acute, and subchronic studies on aquatic 
organisms and wildlife did not reveal endocrine effects. Any endocrine 
related effects, would have been detected in this definitive array of 
required tests. The probability of any such effect due to agricultural 
uses of chlorsulfuron is negligible.

[[Page 10726]]

C. Aggregate Exposure

    1. Dietary exposure. Since pasture grasses are cattle feed 
commodities, rather than food commodities, addition of grass forage and 
hay tolerances, will not contribute directly to dietary exposure.
    i. Food. A dietary exposure assessment for chlorsulfuron was 
conducted using the Dietary Exposure Evaluation Model Versions 6.79 
(Acute Module) and 6.76 (Chronic Module) of DEEM. Dietary exposure to 
chlorsulfuron, was based upon the following food commodities: Barley, 
oat, wheat, milk, and meat. For this assessment, it was assumed that 
100% of the crop was treated with chlorsulfuron. Based on a comparison 
with the use profile for most other herbicides, this is an extremely 
conservative estimate. Chlorsulfuron is not an acute toxicant, however, 
for completeness an acute dietary risk assessment was conducted. The 
predicted acute exposure for the U.S. population subgroup was 0.0039 
milligrams/kilograms bodyweight/day (mg/kg bwt/day) at the 
95th percentile. The population subgroup with the highest 
predicted level of acute exposure at the 95th percentile was 
the children, age 1-6 years old subgroup with an exposure of 0.0084 mg/
kg bwt/day. Based on a NOAEL of 165 mg/kg bwt/day from the repeated 
dose developmental toxicity study, and a 100-fold safety factor, the 
acute reference dose (aRfD) would be 1.65 mg/kg bwt/day. For the U.S. 
population, the predicted exposure at the 95th percentile is 
equivalent to 0.24% of the aRfD. For the population subgroup with the 
highest level of exposure (children 1-6 years old ), the exposure at 
the 95th percentile would be equivalent to 0.51% of the 
aRfD. Because the predicted exposures expressed as percentages of the 
aRfD, are well below 100%, there is reasonable certainty that no acute 
effects would result from dietary exposure to chlorsulfuron.
    The predicted chronic exposure for the U.S. population subgroup was 
0.0013 mg/kg bwt/day. The population subgroup with the highest 
predicted level of chronic exposure was the children, age 1-6 year 
subgroup with an exposure of 0.0038 mg/kg bwt/day. Based on a chronic 
NOAEL of 5 mg/kg bwt/day and a 100-fold safety factor, the chronic 
reference dose (cRfD) would be 0.05 mg/kg bwt/day. For the U.S. 
population, the predicted exposure is equivalent to 2.5% of the cRfD. 
For the population subgroup with the highest level of exposure 
(children, 1-6 years old), the exposure would be equivalent to 7.7% of 
the cRfD. Because the predicted exposures, expressed as percentages of 
the cRfD, are well below 100%, there is reasonable certainty, that no 
chronic effects would result from dietary exposure to chlorsulfuron.
    ii. Drinking water. Surface water exposure was estimated using the 
Generic Expected Environmental Concentration (GENEEC) model, a 
screening level model for determining concentrations of pesticides in 
surface water. GENEEC uses the soil/water partition coefficient, 
hydrolysis half life, and maximum label rate to estimate surface water 
concentration. In addition, the model contains a number of conservative 
underlying assumptions. Therefore, the drinking water concentrations 
derived from GENEEC for surface water are likely to be overestimated. 
Ground water exposures were estimated, using SCI-GROW and predicted 
levels were below those predicted by GENEEC; so GENEEC estimates were 
used below. EPA uses drinking water levels of comparison (DWLOCs) as a 
surrogate measure to capture risk associated with exposure to 
pesticides in drinking water. A DWLOC is the concentration of a 
pesticide in drinking water, that would be acceptable as an upper limit 
in light of total aggregate exposure to that pesticide from food, 
water, and residential uses. A DWLOC will vary, depending on the 
residue level in foods, the toxicity endpoint, and with drinking water 
consumption patterns and body weights for specific subpopulations.
    iii. Acute exposure and risk. The acute DWLOCs are 58 ppm for the 
U.S. population and 16 ppm for the subpopulation with the highest 
exposure (infants < 1 year old). The estimated maximum concentration of 
chlorsulfuron in surface water (7.4 ppb derived from GENEEC, is much 
lower than the acute DWLOCs. Therefore, one can conclude with 
reasonable certainty that residues of chlorsulfuron in drinking water 
do not contribute significantly to the aggregate acute human health 
risk.
    iv. Chronic exposure and risk. The chronic DWLOCs are 1.7 ppm for 
the U.S. population and 0.5 ppm for the subpopulation with the highest 
exposure (children 1-6 years old). These DWLOCs values are 
significantly higher than the GENEEC 56-day estimated environmental 
concentration of 7.3 ppb for chlorsulfuron in surface water. Therefore, 
one can conclude with reasonable certainty that residues of 
chlorsulfuron in drinking water, do not contribute significantly to the 
aggregate chronic human health risk.
    v. Acute risk. Using the exposure assumptions described above, 
DuPont concluded with reasonable certainty that the aggregate exposure 
to chlorsulfuron to food will utilize less than 1% of the aRfD for all 
population subgroups. EPA generally has no concern for exposures below 
100% of the aRfD because the aRfD represents the level at or below 
which a single day's aggregate exposure will not pose appreciable risks 
to human health. Despite the theoretical potential for exposure to 
chlorsulfuron in drinking water, the aggregate exposure (food + water) 
will not exceed the Agency's level of concern.
    vi. Chronic risk. Using the exposure assumptions described above, 
DuPont has concluded that aggregate exposure to chlorsulfuron from food 
will utilize less than 8% of the cRfD for all population subgroups. EPA 
generally has no concern for exposures below 100% of the cRfD because 
the cRfD represents the level at or below which daily aggregate dietary 
exposure over a lifetime will not pose appreciable risks to human 
health. Despite the theoretical potential for exposure to chlorsulfuron 
in drinking water, the aggregate exposure will not exceed 100% of the 
cRfD.
    2. Non-dietary exposure. Chlorsulfuron is not registered for any 
use that could result in non-occupational or non-dietary exposure to 
the general population.

D. Cumulative Effects

    Chlorsulfuron belongs to the sulfonylurea class of crop protection 
chemicals. While other structurally similar compounds in this class are 
registered herbicides, the herbicidal activity of sulfonylureas is due 
to the inhibition of acetolactate synthase (ALS), an enzyme found only 
in plants. This enzyme is part of the biosynthesis pathway leading to 
the formation of branched chain amino acids. Animals lack ALS and this 
biosynthetic pathway. This lack of ALS contributes to the relatively 
low toxicity of sulfonylurea herbicides in animals. There is no 
reliable information that would indicate or suggest that chlorsulfuron 
has any toxic effects on mammals that would be cumulative with those of 
any other chemical.

E. Safety Determination

    1. U.S. population. The proposed analytical methods involve 
extraction, purification and concentration by reversed-phase solid-
phase extraction. Extracts are analyzed by liquid chromatography/mass 
spectrometry

[[Page 10727]]

employing electrospray ionization (ESI-LC/MS).
    Based on data and information submitted by DuPont, EPA previously 
determined that the establishment of tolerances of chlorsulfuron on 
wheat, barley, oats, milk and meat would protect the public health, 
including the health of infants and children. Establishment of a new 
tolerance of 11 ppm for chlorsulfuron on grass, forage and 19 ppm on 
grass, hay will not adversely impact public health. The proposed new 
tolerances are for feed commodities and will not directly impact human 
dietary intake. The proposed use on grass will only pose a small 
incremental increase in potential dietary burden for cattle. It has 
been determined that the existing meat and milk tolerances will 
accommodate this proposed new use on pasture grasses.
    Based on the completeness and reliability of the toxicology 
database and using the conservative assumptions presented earlier, EPA 
has established a RfD of 0.05 mg/kg/day. This was based on the NOAEL 
for the chronic rat study, females (5.0 mg/kg/day) and a 100-fold 
safety factor. It has been concluded that the aggregate exposure was 
less than 8% of the RfD. Generally, exposures below 100% of the RfD are 
of no concern because it represents the level at or below which daily 
aggregate dietary exposure over a lifetime will not pose appreciable 
risk to human health. Thus, there is reasonable certainty that no harm 
will result from aggregate exposures to chlorsulfuron residues.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of chlorsulfuron, data 
from the previously discussed developmental and multigeneration 
reproductive toxicity studies were considered.
    Developmental studies are designed to evaluate adverse effects on 
the developing organism resulting from pesticide exposure during pre-
natal development. Reproduction studies provide information relating to 
reproductive and other effects on adults and offspring from pre-natal 
and post-natal exposures to the pesticide. The studies with 
chlorsulfuron demonstrated no evidence of developmental toxicity at 
exposures below those causing maternal toxicity. This indicates that 
developing animals are not more sensitive to the effects of 
chlorsulfuron administration than adults.
    FFDCA section 408 provides that EPA may apply an additional 
uncertainty factor for infants and children in the case of threshold 
effects to account for pre- and post-natal toxicity and the 
completeness of the database. Based on current toxicological data 
requirements, the data base for chlorsulfuron relative to pre-natal and 
post-natal effects for children is complete. In addition, the NOAEL of 
5.0 mg/kg/day in the chronic rat study (and upon which the RfD is 
based) is much lower than the NOAELs defined in the reproduction and 
developmental toxicology studies. The sub-population with the highest 
level of exposure was children (1-6 years old), where exposure was 
approximately 7.7% of the RfD. Based on these conservative analyses, 
there is reasonable certainty that no harm will result to infants and 
children from aggregate exposures to chlorsulfuron.

F. International Tolerances

    There are no Codex MRLs established for chlorsulfuron.
[FR Doc. 02-5446 Filed 3-7-02; 8:45 am]
BILLING CODE 6560-50-S