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pyrithiobac-sodium Pesticide Petition Filing 7/01


ENVIRONMENTAL PROTECTION AGENCY

[PF-1034; FRL-6794-2]


Notice of Filing a Pesticide Petition to Establish a Tolerance
fora 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-1034, must be
received on or before September 10, 2001.

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-1034 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:
tompkins.jim@;epa.gov.

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,'' ``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-1034. 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-1034 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: opp-docket@epa.gov, 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-1034. 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.
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: July 25, 2001
James Jones,
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
petitioner. 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 of an
explanation of why no such method is needed.

DuPont Agricultural Products

PP 4F4391

    EPA has received a pesticide petition (PP 4F4391) from DuPont
Agricultural Products,Wilmington, DE proposing, pursuant to section
408(d) of FFDCA, 21 U.S.C. 346a(d), to amend 40 CFR part 180. This
regulation extends the time-limited tolerance for residues of the
herbicide pyrithiobac sodium salt (sodium 2-chloro-6-[(4,6-
dimethoxypyrimidin-2-yl)thio]benzoate) in or on the raw agricultural
commodity cottonseed at 0.02 parts per million (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 support granting of the petition. Additional data
may be needed before EPA rules on the petition.

Background and Statutory Findings

    In the Federal Register of October 22, 1997 (62 FR 54778) (FRL-
5746-6), and the Federal Register of October 20, 1999 (64 FR 56464)
(FRL-6386-5), EPA twice extended the time-limited tolerance pursuant to
FFDCA for residues of the herbicide pyrithiobac sodium salt (sodium 2-
chloro-6-[(4,6-dimethoxypyrimidin-2-yl)thio]benzoate) in or on the raw
agricultural commodity cottonseed at 0.02 ppm. The tolerance was issued
and renewed as a time-limited tolerance because EPA required additional
residue data on the commodity of cotton gin byproducts. At this time
EPA has not fully evaluated the sufficiency of the submitted data
supporting this petition. The petitioner proposes to again renew the
time-limited tolerance for an additional 3-year period and continue to
retain the pesticide labeling previously accepted under the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA), as amended, which
bears a restriction against feeding cotton gin byproducts from treated
fields to livestock. DuPont has requested this tolerance extension
pursuant to section 408(d) of the FFDCA, as amended, 21 U.S.C. 346a(d),
by the Food Quality Protection Act of 1996 (Public Law 104-170, 110
Stat. 1489). The request addresses the requirements of the new FFDCA
section 408(d)(2). The time-limited tolerance would expire on September
30, 2001. An adequately validated analytical method is available for
enforcement purposes. Pursuant to section 408(d)(2)(A)(i) of the FFDCA,
as amended, DuPont has submitted the following summary of information,
data and arguments in support of its pesticide petition. This summary
was proposed by DuPont and EPA has not yet fully evaluated the
additional data supporting this petition. EPA edited the document to
clarify the conclusions and arguments presented by DuPont and to remove
certain extraneous material.

A. Residue Chemistry

    1. Plant metabolism. The qualitative nature of the residues of
pyrithiobac sodium in cotton is adequately understood for the purposes
of this tolerance. Metabolism studies with pyrithiobac sodium indicate
the major metabolic pathway being o-dealkylation of the parent compound
resulting in o-desmethyl pyrithiobac sodium (O-DPS). O-DPS, both free
and conjugated, was the major metabolite identified in cotton foliage.
The results of a confined crop rotation study with pyrithiobac sodium
revealed the presence of a metabolite 2-chloro-6-sulfobenzoic acid
(CSBA) not seen in the cotton metabolism study. This metabolite
appeared to originate from soil metabolism of pyrithiobac sodium. Since
preemergence applications of pyrithiobac sodium are allowed, crop
residues of CSBA were considered a possibility. In consideration of PP
4F4391 CBTS, in consultation with the HED Metabolism Committee has
previously concluded that for the proposed use on cotton, none of the
pyrithiobac sodium metabolites including O-DPS and CSBA warrant
inclusion in the tolerance regulation, and that the only residue of
concern is the parent, pyrithiobac sodium.
    2. Analytical method. There is a adequately validated practical
analytical method available using HPLC-UV with column switching, to
measure levels of pyrithiobac sodium in or on cotton with a limit of
quantitation that allows monitoring of cottonseed at or above tolerance
levels. EPA has provided information on this method to FDA for future
publication in PAM II.
    3. Magnitude of residues. Crop field trial residue data from a 60-
day PHI study shows that the established pyrithiobac sodium time-
limited tolerance on cottonseed of 0.02 ppm will not be exceeded when
Staple* is used as directed. An adequate cottonseed processing study
shows that pyrithiobac sodium does not concentrate in cottonseed
processed commodities; thus no tolerances on these commodities are
required.

B. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as

[[Page 42224]]

the relationship of the results of the studies to human risk. EPA has
also considered available information concerning the variability of the
sensitivities of major identifiable subgroups of consumers, including
infants and children. The nature of the toxic effects caused by
pyrithiobac sodium are discussed in this unit.
    1. Acute toxicity. Pyrithiobac sodium technical has been placed in
EPA Toxicity Category II for acute eye irritation based on the test
article inducing irritation in the form of corneal opacity, iritis and
conjunctival redness, and discharge in the eyes of rabbits after
receiving ocular doses of 36 mg (0.1 mL). Signs of irritation were
clear within 14 days of treatment. Pyrithiobac sodium has been placed
in Toxicity Category III for acute dermal toxicity based on the test
article being nonlethal and nonirritating at the limit dose of 2,000
milligrams/kilogram (mg/kg) (highest dose tested). Pyrithiobac sodium
has been placed in Toxicity Category III for acute oral toxicity based
on acute oral LD50s of 3,200 and 3,300 mg/kg for male and
female rats, respectively. Pyrithiobac sodium has been placed in
Category IV for the remaining acute toxicity tests based on the
following: A rat acute inhalation study with an LC50 6.9 mg/
L; and a primary dermal irritation test that did not induce a dermal
irritation response. A dermal sensitization test with pyrithiobac
sodium technical in guinea pigs demonstrated no significant effects.
EPA has concluded that no endpoint exists to suggest any evidence of
significant toxicity from acute, short-termor intermediate term
exposures from the use of pyrithiobac sodium on cotton.
    2. Genotoxicity. Pyrithiobac sodium technical was negative (non-
mutagenic and non-genotoxic) in the following tests: Ames microbial
mutation assay; the hypoxanthine-guanine phosphoribosyl transferase
gene mutation assay using Chinese hamster ovary cells; induction of
unscheduled DNA synthesis (UDS) in primary rat hepatocytes; and
induction of micronuclei in the bone marrow cells of mice. Pyrithiobac
sodium was positive in anin vitro assay for chromosome aberrations in
human lymphocytes. Based on the weight of these data, pyrithiobac
sodium is neither genotoxic nor mutagenic.
    3. Reproductive and developmental toxicity.A two-generation
reproduction study with rats treated in the diet with pyrithiobac
sodium demonstrated a maternal no observed adverse effect level (NOAEL)
of 1,500 ppm (103 mg/kg/day) and a maternal lowest observed adverse
effect level (LOAEL) of 7,500 ppm (508 mg/kg/day), based on decreased
body weight/gain and food efficacy. The reproductive and offspring
NOAEL of 7,500 ppm (508 mg/kg/day) and LOAEL of 20,000 ppm (1,551 mg/
kg/day) were also demonstrated based on decreased offspring body
weight. Pyrithiobac sodium was not teratogenic when administered to
rats or rabbits. A developmental toxicity study with pyrithiobac sodium
in rats demonstrated a maternal NOAEL of 200 mg/kg and a maternal LOAEL
of 600 mg/kg due to increased incidence of peritoneal staining. A
developmental NOAEL of 600 mg/kg and LOAEL of 1,800 mg/kg were
demonstrated based on an increased incidence of skeletal variations. A
developmental toxicity study with pyrithiobac sodium in rabbits
demonstrated maternal and developmental NOAELs of 300 mg/kg and a
maternal LOAEL of 1,000 mg/kg based on mortality, decreased body weight
gain and feed consumption, increased incidence of clinical signs, and
an increase in early resorptions. A developmental LOAEL of 1,000 mg/kg
was based on decreased fetal body weight gain.
    4. Subchronic toxicity. In a 90-day feeding study in rats conducted
with pyrithiobac sodium at dietary levels of 0, 10, 50, 500, 7,000 and
20,000 ppm, the NOAEL was 500 ppm (31.8 and 40.5 mg/kg/day, M/F) and
the LOAEL was 7,000 ppm (466 and 588 mg/kg/day, M/F) based on decreased
body weight gains and increased rate of hepatic B-oxidation in males.
In a 90-day feeding study in mice conducted with pyrithiobac sodium at
dietary levels of 0, 10, 50, 500, 1,500 and 7,000 ppm, the NOAEL was
500 ppm (83.1 and 112 mg/kg/day, M/F) and the LOEL was 1,500 ppm (263
and 384 mg/kg/day, M/F) based on increased liver weight and increased
incidence of hepatocellular hypertrophy in males and decreased
neutrophil count in females. In a 90-day feeding study in dogs
conducted with pyrithiobac sodium at dietary levels of 0, 50, 5,000, or
20,000 ppm, the NOAEL was 5,000 ppm (165 mg/kg/day) and the LOAEL was
20,000 ppm (626 mg/kg/day) based on decreased red blood cell count,
hemoglobin, and hematocrit in females and increased liver weight in
both sexes. In a 21-day dermal study with rats conducted with
pyrithiobac sodium at exposure levels of 0, 50, 500, or 1,200 mg/kg/
day, the dermal irritation NOAEL was 500 mg/kg/day and the dermal
irritation LOAEL was 1,200 mg/kg/day. There were no systemic effects
observed at this high dose; therefore, the systemic NOAEL is considered
to be 1,200 mg/kg/day.
    5. Chronic toxicity. A 1-year feeding study in dogs conducted with
pyrithiobac sodium resulted in a NOAEL of 5,000 ppm (143 and 166 mg/kg/
day, M/F) and a LOAEL of 20,000 ppm (580 and 647 mg/kg/day, M/F) based
on decreases in body weight gain and increased liver weight. A 78-week
dietary oncogenicity study conducted in mice resulted in a systemic
NOAEL is 1,500 ppm (217 and 319 mg/kg/day, M/F); the LOAEL is 5,000 ppm
(745 and 1,101 mg/kg/day, M/F), based on decreased body weight gain and
glomerulonephropathy (murine) in both sexes and treatment related
increase in the incidence of foci/focus of hepatocellular alteration in
males. There was evidence of carcinogenicity based on significant
differences in the pair-wise comparisons of hepatocellular adenomas or
adenomas plus carcinomas in the 150 and 1,500 ppm males (but not at the
high dose of 5,000 ppm). A 2-year dietary study in rats resulted in
systemic NOAELs of 1,500 ppm (58.7 mg/kg/day) for males and 5,000 ppm
(278 mg/kg/day) for females. The LOAEL was 5,000 ppm (200 and 918 mg/
kg/day, M/F). The LOAEL was based on the following: Increased incidence
of eye lesions and mild changes in hematology and urinalysis, and
clinical signs indicative of urinary tract dysfunction (both sexes);
decreased body weight, body weight gain and food efficiency and an
increased incidence of inflammatory and degenerative microscopic
lesions in the kidney (females); and increased incidence of focal
cystic degeneration in the liver and increased rate of hepatic
peroxisome beta-oxidation (males). There was evidence of oncogenicity
based on an increasing trend for kidney tubular combined adenoma/
carcinoma in male rats and an increasing trend for kidney tubular
adenomas in female rats. Although the incidences were low, they were
statistically significant. The highest dose level tested in male rats
(5,000 ppm) was considered adequate for assessment of oncogenic
potential, that in female rats (15,000 ppm) exceeded the Maximum
Tolerated Dose (MTD).
    6. Animal metabolism. Disposition and metabolism of pyrithiobac
sodium were tested in male and female rats using two radiolabeled forms
of pyrithiobac sodium, both orally and intravenously. Essentially all
of the dose was excreted in the urine and feces, with greater than 90%
being excreted within 48 hours. The major compound eliminated in urine
and feces was O-DPS (desmethyl metabolite), formed by

[[Page 42225]]

demethylation of the pyrimidine ring. There was evidence that
conjugation with glucuronic acid and 5-hydroxylation of the pyrimidine
ring of pyrithiobac sodium were additional minor routes of metabolism
in the rat.
    7. Metabolite toxicology. At this time, there is no evidence that
the metabolites of pyrithiobac sodium as identified in either the plant
metabolism, confined crop rotation, or animal metabolism studies are of
toxicological concern.
    8. Endocrine disruption. No special studies investigating potential
estrogenic or other endocrine effects of pyrithiobac sodium have been
conducted. However, the standard battery of required toxicology studies
has been completed and found acceptable. These include an evaluation of
the potential effects on reproduction and development, and an
evaluation of the pathology of the endocrine organs following repeated
or long-term exposure to doses that far exceed likely human exposures.
Based on these studies there is no evidence to suggest that pyrithiobac
sodium has an adverse effect on the endocrine system.

C. Aggregate Exposure

    1. Dietary exposure-- i. Food. For purposes of assessing the
potential dietary exposure under this tolerance, an estimate of
aggregate exposure is made using the time-limited tolerance on
cottonseed at 0.02 ppm. The potential exposure is obtained by
multiplying the tolerance level residues by the consumption data which
estimates the amount of cottonseed products translated as cottonseed
meal and cottonseed oil eaten by various population subgroups.
Cottonseed is fed to animals, thus exposure of humans to residues of
cottonseed might result if such residues are transferred to meat, milk,
poultry, or eggs. However, in consideration of PP 4F4391 CBTS has
previously concluded that secondary residues in meat, milk, poultry and
eggs are not expected from the use of cottonseed (undelinted) as an
animal feed. There are no other established tolerances or registered
uses for pyrithiobac sodium in the United States. Based on a NOAEL of
58.7 mg/kg/day, from the chronic rat toxicity study and a 100-fold
safety factor, the reference dose (RfD) is 0.58 mg/kg/day. Assuming
residues at tolerance levels and that 100% of the crop is being
treated, a theoretical maximum residue contribution (TMRC) of 0.000001
mg/kg/day is calculated. With the above assumptions (which lead to a
conservative assessment of risk), dietary (food) exposure to
pyrithiobac sodium will utilize significantly less than 1% of the RfD
for the overall U.S. population. For the most highly exposed subgroup
(children aged 1 to 6 years), the TMRC is 0.000001 mg/kg/day, which is
still less than 1% of the RfD. Pyrithiobac sodium is classified as a
group C carcinogen (possible human carcinogen with limited evidence of
carcinogenicity in animals). The unit risk, Q1* (mg/kg/
day)-1, is 1.05 x10-3 (mg/kg/day)-1 in
human equivalents based on kidney tumors in male rats and mice. Based
on this upper bound potency factor (Q1*), a 70-year lifespan, and the
assumption that 100% of the crop is treated with pyrithiobac sodium,
the upper-bound limit of a dietary carcinogenic risk is calculated in
the range of 1 incidence in a billion (1.0 x 10-9).
    ii. Drinking water. Other potential dietary sources of exposure of
the general population to pesticides are residues in drinking water.
There is no maximum contaminant level established for residues of
pyrithiobac sodium. Based on maximum exposure estimates developed using
screening models, the exposure based on drinking water is less than
0.1% of the RfD. In addition, the Environmental Fate and Effects
Division (EFED) of EPA has previously concluded after preliminary
evaluation of the results of a prospective ground water monitoring
study conducted at a highly vulnerable site that pyrithiobac sodium may
not be stable enough to leach to ground water at most use sites, even
in sandy soils. Based on the results of environmental fate studies and
the conditions of use, the potential for drinking water to contribute
to the dietary exposure of pyrithiobac sodium is minimal.
    2. Non-dietary exposure. Pyrithiobac sodium is not currently
registered for any use which could result in non-occupational, non-
dietary exposure to the general population.

D. Cumulative Effects

    Pyrithiobac sodium is based on a new chemical class; there are no
known registered herbicides with similar structure. Therefore, EPA
should consider only the potential risks of pyrithiobac sodium in its
exposure assessment. The herbicidal activity of pyrithiobac sodium is
due to the inhibition of acetolactate synthase (ALS), an enzyme only
found in plants. ALS is part of the biosynthetic pathway leading to the
formation of branched chain amino acids. Animals lack ALS and this
biosynthetic pathway. This lack of ALS contributes to the low toxicity
of pyrithiobac sodium in animals. There is no evidence to indicate of
suggest that pyrithiobac sodium has any toxic effects on mammals that
would be cumulative with those of any other chemical.

E. Safety Determination

    1. U.S. population. EPA has concluded that no endpoint exists to
suggest any evidence of significant toxicity from acute, short-term or
immediate-term exposure form the use of pyrithiobac sodium on cotton.
Based on a complete and reliable toxicity data base, the EPA has
adopted an reference dose (RfD) value of 0.58 mg/kg/day using the NOAEL
of 58.7 mg/kg/day, from the 2-year chronic toxicity study in rats and a
100-fold safety factor. Using crop tolerance levels and assuming 100%
of the crop being treated a Theoretical Maximum Residue Contribution
(TMRC) was calculated for the overall U.S. population and 22 population
subgroups. This analysis concluded that aggregate exposure to
pyrithiobac sodium will utilize significantly less that 1% of the RfD
for either the entire U.S. population or any subgroup population. The
TMRC for the most highly exposed subgroup identified as children aged 1
thru 6 years was 0.000001 mg/kg/day. EPA generally has no concern for
exposure 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 risk to human health. The unit risk, Q1* (mg/kg/
day)-1, of pyrithiobac sodium is 1.05 x 10-3 (mg/
kg/day)-1 in human equivalents based on male kidney tumors.
Based on this upper bound potency factor (Q1*) and assuming a 70-year
lifetime exposure, an upper-bound limit of a dietary carcinogenic risk
is calculated in the range of 1 incidence in a billion (1.0 x
10-9). This indicates a negligible cancer risk. Based on
these risk assessments, EPA concludes that there is a reasonable
certainty that no harm will result from aggregate exposure of the U.S.
population to pyrithiobac sodium residues.
    2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of pyrithiobac sodium,
data from the previously discussed developmental and reproduction
toxicity studies were considered. Developmental studies are designed to
evaluate adverse effects on developing organism resulting from
pesticide exposure during prenatal development. Reproduction studies
provide information relating to reproductive and other effects on
adults and offspring from prenatal and postnatal exposure to the
pesticide. Based on the weight of these data, pyrithiobac sodium was
not a

[[Page 42226]]

reproductive toxicant. Maternal and developmental effects (NOAELs,
LOAELs) were comparable indicating no increase in susceptibility of
developing organisms. 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 prenatal and postnatal toxicity and
the completeness of the data base. Based on current toxicological data
requirements, the data base for pyrithiobac sodium relative to prenatal
and postnatal effects for children is complete. Since the data indicate
that infants and children are not more sensitive to exposure, the
standard 100-fold safety factor was used. The NOAEL of 58.7 mg/kg/day
from the 2-year rat study with pyrithiobac sodium, which was used to
calculate the RfD, is lower than any of the NOAELs defined in the
developmental and reproductive toxicity studies with pyrithiobac
sodium. As stated above, aggregate exposure assessments utilized
significantly less than 1% of the RfD for either the entire U.S.
population or any of 22 population subgroups including infants and
children. Therefore, it may be concluded that there is reasonable
certainty that no harm will result to infants and children from
aggregate exposure to pyrithiobac sodium residues.

F. International Tolerances

    There are no established Codex MRLs for pyrithiobac sodium on
cottonseed. An established Mexican tolerance for pyrithiobac sodium on
cottonseed is identical to the U.S. tolerance. Compatibility of
tolerance levels is not a issue at this time.
[FR Doc. 01-20133 Filed 8-9-01; 8:45 am]