[Federal Register Volume 66, Number 155 (Friday, August 10, 2001)]
[Notices]
[Pages 42222-42226]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-20133]



[[Page 42222]]

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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: epa.gov">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.

[[Page 42223]]

    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

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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]
BILLING CODE 6560-50-S