[Federal Register Volume 62, Number 204 (Wednesday, October 22, 1997)]
[Rules and Regulations]
[Pages 54778-54784]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-27843]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-300548; FRL-5742-5]
RIN 2070-AB78


Pyrithiobac Sodium Salt; Time-Limited Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: 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 cottonseed at 
0.02 parts per million (ppm). E.I. du Pont de Nemours & Co., Inc., 
requested this tolerance under the Federal Food, Drug and Cosmetic Act 
(FFDCA), as amended by the Food Quality Protection Act of 1966 (Pub. L. 
104-170). The tolerance will expire on September 30, 1999.

DATES: This regulation is effective October 22, 1997. Objections and 
requests for hearings must be received by EPA on or before December 22, 
1997.

ADDRESSES: Written objections and hearing requests, identified by the 
docket control number, [OPP-300548], must be submitted to: Hearing 
Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M St., 
SW., Washington, DC 20460. Fees accompanying objections and hearing 
requests shall be labeled ``Tolerance Petition Fees'' and forwarded to: 
EPA Headquarters Accounting Operations Branch, OPP (Tolerance Fees), 
P.O. Box 360277M, Pittsburgh, PA 15251. A copy of any objections and 
hearing requests filed with the Hearing Clerk identified by the docket 
control number, [OPP-300548], must also be submitted to: Public 
Information and Records Integrity Branch, Information Resources and 
Services Division (7506C), Office of Pesticide Programs, Environmental 
Protection Agency, 401 M St., SW., Washington, DC 20460. In person, 
bring a copy of objections and hearing requests to Rm. 1132, CM #2, 
1921 Jefferson Davis Hwy., Arlington, VA.
    A copy of objections and hearing requests filed with the Hearing 
Clerk may also be submitted electronically by sending electronic mail 
(e-mail) to: [email protected]. Copies of objections and 
hearing requests must be submitted as an ASCII file avoiding the use of 
special characters and any form of encryption. Copies of objections and 
hearing requests will also be accepted on disks in WordPerfect 5.1 file 
format or ASCII file format. All copies of objections and hearing 
requests in electronic form must be identified by the docket control 
number [OPP-300548]. No Confidential Business Information (CBI) should 
be submitted through e-mail. Electronic copies of objections and 
hearing requests on this rule may be filed online at many Federal 
Depository Libraries.

FOR FURTHER INFORMATION CONTACT: By mail: James A. Tompkins, 
Registration Division 7505C, Office of Pesticide Programs, 
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. 
Office location, telephone number, and e-mail address: Crystal Mall #2, 
1921 Jefferson Davis Hwy., Arlington, VA, (703) 305-5697, e-mail: 
[email protected].

SUPPLEMENTARY INFORMATION: In the Federal Register of July 11, 1997 (62 
FR 37241)(FRL-5728-7), EPA, issued a notice pursuant to section 408 of 
the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(e) 
announcing the filing of a pesticide petition (PP 4F4391) for tolerance 
by E.I. du Pont de Nemours & Co., Inc., Barley Mill Plaza, P.O. Box 
80038, Wilmington, DE 19880-0038. This notice included a summary of the 
petition prepared by du Pont. There were two comments received in 
response to the notice of filing from cotton growers urging the 
extension of the time limited tolerance.
    The petition requested that 40 CFR 180.487 be amended by extending 
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 cottonseed at 0.02 ppm. This tolerance will 
expire on September 30, 1999.
    In the Federal Register of October 25, 1995 (60 FR 54607)(FRL-4982-
8), EPA established a time limited tolerance for residues of the 
herbicide pyrithiobac sodium in or on cottonseed at 0.02 ppm. The time 
limited tolerance will expire on September 30, 1997.

I. Risk Assessment and Statutory Findings

    New section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a 
tolerance (the legal limit for a pesticide chemical residue in or on a 
food) only if EPA determines that the tolerance is ``safe.'' Section 
408(b)(2)(A)(ii) defines ``safe'' to mean that ``there is a reasonable 
certainty that no harm will result from aggregate exposure to the 
pesticide chemical residue, including all anticipated dietary exposures 
and all other exposures for which there is reliable information.'' This 
includes exposure through drinking water and in residential settings, 
but does not include occupational exposure. Section 408(b)(2)(C) 
requires EPA to give special

[[Page 54779]]

consideration to exposure of infants and children to the pesticide 
chemical residue in establishing a tolerance and to ``ensure that there 
is a reasonable certainty that no harm will result to infants and 
children from aggregate exposure to the pesticide chemical 
residue....''
    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. First, EPA determines the 
toxicity of pesticides based primarily on toxicological studies using 
laboratory animals. These studies address many adverse health effects, 
including (but not limited to) reproductive effects, developmental 
toxicity, toxicity to the nervous system, and carcinogenicity. Second, 
EPA examines exposure to the pesticide through the diet (e.g., food and 
drinking water) and through exposures that occur as a result of 
pesticide use in residential settings.

A. Toxicity

    1. Threshold and non-threshold effects. For many animal studies, a 
dose response relationship can be determined, which provides a dose 
that causes adverse effects (threshold effects) and doses causing no 
observed effects (the ``no-observed effect level'' or ``NOEL'').
    Once a study has been evaluated and the observed effects have been 
determined to be threshold effects, EPA generally divides the NOEL from 
the study with the lowest NOEL by an uncertainty factor (usually 100 or 
more) to determine the Reference Dose (RfD). The RfD is a level at or 
below which daily aggregate exposure over a lifetime will not pose 
appreciable risks to human health. An uncertainty factor (sometimes 
called a ``safety factor'') of 100 is commonly used since it is assumed 
that people may be up to 10 times more sensitive to pesticides than the 
test animals, and that one person or subgroup of the population (such 
as infants and children) could be up to 10 times more sensitive to a 
pesticide than another. In addition, EPA assesses the potential risks 
to infants and children based on the weight of the evidence of the 
toxicology studies and determines whether an additional uncertainty 
factor is warranted. Thus, an aggregate daily exposure to a pesticide 
residue at or below the RfD (expressed as 100 percent or less of the 
RfD) is generally considered acceptable by EPA. EPA generally uses the 
RfD to evaluate the chronic risks posed by pesticide exposure. For 
shorter term risks, EPA calculates a margin of exposure (MOE) by 
dividing the estimated human exposure into the NOEL from the 
appropriate animal study. Commonly, EPA finds MOEs lower than 100 to be 
unacceptable. This 100-fold MOE is based on the same rationale as the 
100-fold uncertainty factor.
    Lifetime feeding studies in two species of laboratory animals are 
conducted to screen pesticides for cancer effects. When evidence of 
increased cancer is noted in these studies, the Agency conducts a 
weight of the evidence review of all relevant toxicological data 
including short-term and mutagenicity studies and structure activity 
relationship. Once a pesticide has been classified as a potential human 
carcinogen, different types of risk assessments (e.g., linear low dose 
extrapolations or MOE calculation based on the appropriate NOEL) will 
be carried out based on the nature of the carcinogenic response and the 
Agency's knowledge of its mode of action.
    2. Differences in toxic effect due to exposure duration. The 
toxicological effects of a pesticide can vary with different exposure 
durations. EPA considers the entire toxicity data base, and based on 
the effects seen for different durations and routes of exposure, 
determines which risk assessments should be done to assure that the 
public is adequately protected from any pesticide exposure scenario. 
Both short and long durations of exposure are always considered. 
Typically, risk assessments include ``acute'', ``short-term'', 
``intermediate term'', and ``chronic'' risks. These assessments are 
defined by the Agency as follows.
    Acute risk, by the Agency's definition, results from 1-day 
consumption of food and water, and reflects toxicity which could be 
expressed following a single oral exposure to the pesticide residues. 
High end exposure to food and water residues are typically assumed.
    Short-term risk results from exposure to the pesticide for a period 
of 1-7 days, and therefore overlaps with the acute risk assessment. 
Historically, this risk assessment was intended to address primarily 
dermal and inhalation exposure which could result, for example, from 
residential pesticide applications. However, since enaction of FQPA, 
this assessment has been expanded to include both dietary and non-
dietary sources of exposure, and will typically consider exposure from 
food, water, and residential uses when reliable data are available. In 
this assessment, risks from average food and water exposure, and high-
end residential exposure, are aggregated. High-end exposures from all 
three sources are not typically added because of the very low 
probability of this occurring in most cases, and because the other 
conservative assumptions built into the assessment assure adequate 
protection of public health. However, for cases in which high-end 
exposure can reasonably be expected from multiple sources (e.g. 
frequent and widespread homeowner use in a specific geographical area), 
multiple high-end risks will be aggregated and presented as part of the 
comprehensive risk assessment/characterization. Since the toxicological 
endpoint considered in this assessment reflects exposure over a period 
of at least 7 days, an additional degree of conservatism is built into 
the assessment; i.e., the risk assessment nominally covers 1-7 days 
exposure, and the toxicological endpoint/NOEL is selected to be 
adequate for at least 7 days of exposure. (Toxicity results at lower 
levels when the dosing duration is increased.)
    Intermediate-term risk results from exposure for 7 days to several 
months. This assessment is handled in a manner similar to the short-
term risk assessment.
    Chronic risk assessment describes risk which could result from 
several months to a lifetime of exposure. For this assessment, risks 
are aggregated considering average exposure from all sources for 
representative population subgroups including infants and children.

B. Aggregate Exposure

    In examining aggregate exposure, FFDCA section 408 requires that 
EPA take into account available and reliable information concerning 
exposure from the pesticide residue in the food in question, residues 
in other foods for which there are tolerances, residues in groundwater 
or surface water that is consumed as drinking water, and other non-
occupational exposures through pesticide use in gardens, lawns, or 
buildings (residential and other indoor uses). Dietary exposure to 
residues of a pesticide in a food commodity are estimated by 
multiplying the average daily consumption of the food forms of that 
commodity by the tolerance level or the anticipated pesticide residue 
level. The Theoretical Maximum Residue Contribution (TMRC) is an 
estimate of the level of residues consumed daily if each food item 
contained pesticide residues equal to the tolerance. In evaluating food 
exposures, EPA takes into account varying consumption patterns of major 
identifiable subgroups of consumers, including infants and children. 
The TMRC is a ``worst case'' estimate since it is based on the 
assumptions that food contains pesticide residues at the tolerance 
level

[[Page 54780]]

and that 100% of the crop is treated by pesticides that have 
established tolerances. If the TMRC exceeds the RfD or poses a lifetime 
cancer risk that is greater than approximately one in a million, EPA 
attempts to derive a more accurate exposure estimate for the pesticide 
by evaluating additional types of information (anticipated residue data 
and/or percent of crop treated data) which show, generally, that 
pesticide residues in most foods when they are eaten are well below 
established tolerances.
    Percent of crop treated estimates are derived from Federal and 
private market survey data. Typically, a range of estimates are 
supplied and the upper end of this range is assumed for the exposure 
assessment. By using this upper end estimate of percent of crop 
treated, the Agency is reasonably certain that exposure is not 
understated for any significant subpopulation group. Further, regional 
consumption information is taken into account through EPA's computer-
based model for evaluating the exposure of significant subpopulations 
including several regional groups, to pesticide residues. For this 
pesticide, the most highly exposed population subgroup (children 1 to 
6) was not regionally based.

II. Aggregate Risk Assessment and Determination of Safety

    Consistent with section 408(b)(2)(D), EPA has reviewed the 
available scientific data and other relevant information in support of 
this action, EPA has sufficient data to assess the hazards of 
pyrithiobac sodium and to make a determination on aggregate exposure, 
consistent with section 408(b)(2), for a time-limited tolerance for 
residues of pyrithiobac sodium on cottonseed at 0.02 ppm. EPA's 
assessment of the dietary exposures and risks associated with 
establishing the tolerance follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its 
validity, completeness, and reliability as well as 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 
salt are discussed below.
    1. A rat acute oral study with a LD50 of 3,300 
milligrams (mg)/kilogram (kg) for males and a LD50 3,200 mg/
kg for females.
    2. A 90-day rat feeding study with a No Observed Effect Level 
(NOEL) of 50 ppm (3.25 mg/kg/day for males and 4.14 mg/kg/day for 
females) and a Lowest Observed Effect Level (LOEL) of 500 ppm (31.8 mg/
kg/day for males and 40.5 mg/kg/day for females), based on decrease 
body weight gains and increased rate of hepatic B-oxidation in males.
    3. A 90-day mouse feeding study with a NOEL of 500 ppm (83.1 mg/kg/
day for males and 112 mg/kg/day for females) and a LOEL of 1,500 ppm 
(263 mg/kg/day for males and 384 mg/kg/day for females) based on 
increased liver weight and an increased incidence of hepatocellular 
hypertrophy in males and decreased neutrophil count in females.
    4. A 3-month dog feeding study with a NOEL of 5,000 ppm (165 mg/kg/
day) and a LOEL of 20,000 ppm (626 mg/kg/day), based on decrease red 
blood cell count, hemoglobin, and hematocrit in females and increased 
liver weight in both sexes.
    5. A 21-day rat dermal study with a Dermal Irritation NOEL of 50 
mg/kg/day and a dermal irritation LOEL of 500 mg/kg/day based on 
increased incidence of erythema and edema, and with a systemic dermal 
NOEL of 500 mg/kg/day and a Systemic Dermal LOEL of 1,200 mg/kg/day 
based on body weight gain inhibition.
    6. A 90-day rat neurotoxicity screening battery with a systemic 
NOEL of 7,000 ppm (466 mg/kg/day for males and 588 mg/kg/day for 
females) and a systemic LOEL of 20,000 ppm (1376 mg/kg/day for males 
and 1,609 mg/kg/day for females), based on decreased hind grip strength 
and increased foot spay in males, and a neurotoxicity NOEL of 20,000 
ppm [Highest Dose Tested (HDT)].
    7. A 78-week dietary carcinogenicity study in mice with a NOEL of 
1,500 ppm 217 mg/kg/day (males) and 319 mg/kg/day (females) and a LOEL 
of 5,000 ppm 745 mg/kg/day (males) and 1,101 mg/kg/day (females) based 
on decreased body weight/gain in both sexes, treatment related increase 
in the incidence of foci/focus of hepatocellular alternation in males, 
and increased incidence of glomerulonephropathy murine in both sexes, 
and an increased incidence of infarct in the kidney and keratopathy of 
the eyes. There was evidence of carcinogenicity based on significant 
differences in the pair-wise comparisons of hepatocellular adenomas and 
combined adenoma/carcinoma in the 150 and 1,500 dose groups (but not at 
the high dose of 5,000 ppm) with the controls. The carcinogenic effects 
observed are discussed below.
    8. A 24-month rat chronic feeding/carcinogenicity study with a 
systemic NOEL of 1,500 ppm (58.7 mg/kg/day for males and 278 mg/kg/day 
for females) and a systemic LOEL of 5,000 ppm (200 mg/kg/day for males 
and 918 mg/kg/day for females) based on decreases in body weight, body 
weight gains and food efficiency in females, increased incidence of eye 
lesions in males and females, mild changes in hematology and urinalysis 
in both sexes, clinical signs suggestive of urinary tract dysfunction 
in males and females, increased incidence of focal cystic degeneration 
in the liver in males, increased rate of hepatic peroxisomal B-
oxidation in males and an increased incidence of inflammatory and 
degenerative lesions in the kidney in females. There was evidence of 
carcinogenicity based on a significant dose-related increasing trend in 
kidney tubular combined adenoma/carcinoma in male rats and a 
significant dose related increasing trend in kidney tubular bilateral 
and/or unilateral adenomas in females. The carcinogenic effects 
observed are discussed further below.
    9. A 1-year dog chronic feeding study with a NOEL of 5,000 ppm (143 
mg/kg/day for males and 166 mg/kg/day for females) and a LOEL of 20,000 
ppm (580 mg/kg/day for males and 647 mg/kg/day for females) based on 
decreases in body weight gain and increased liver weight.
    10. A two generation reproduction study in rats with a maternal 
NOEL of 1,500 ppm (103 mg/kg/day) and a maternal LOEL of 7,500 ppm (508 
mg/kg/day ppm), based on decreased body weight/gain and food efficacy. 
The Reproductive and Offspring NOEL is 7,500 ppm (508 mg/kg/day) and 
the reproductive and offspring LOEL is 20,000 ppm (1,551 mg/kg/day), 
based on decreased pup body weight.
    11. A developmental toxicity study in rabbits with a maternal and 
developmental NOEL of 300 mg/kg and a Maternal LOEL of 1,000 mg/kg 
based on deaths, decreased body weight gain and feed consumption, 
increased incidence of clinical signs, and an increase in abortions and 
a developmental LOEL of 1,000 mg/kg, based on decreased fetal body 
weight gain.
    12. A developmental toxicity study in rats with a maternal NOEL 200 
mg/kg and a maternal LOEL of 600 mg/kg due to increased incidence of 
peritoneal staining. The developmental NOEL is 600 mg/kg and the 
developmental LOEL is 1,800 mg/kg based on the increased incidence of 
skeletal variations.

[[Page 54781]]

    13. No evidence of gene mutation was observed in a test for 
induction of forward mutations at the HGPRT locus in Chinese hamster 
ovary cells. No evidence was observed for inducing reverse gene 
mutation in two independent assays with Salmonella typhimurium with and 
without mammalian metabolic activation. Pyrithiobac sodium was negative 
for the induction of micronuclei in the bone marrow cells of mice, and 
negative for induction of unscheduled DNA synthesis in rat primary 
hepatocytes. Pyrithiobac sodium was positive for inducing chromosome 
aberrations assay in human lymphocytes.
    14. A rat metabolism study showed that radio labeled pyrithiobac 
sodium is excreted in urine and feces with > 90% being eliminated 
within 48 hours. A sex difference was observed in the excretion and 
biotransformation. Females excreted a greater amount of the radiolabel 
in the urine than males following all doing regimens, with a 
corresponding lower amount being eliminated in the feces compared to 
the males.

B. Toxicological Endpoints

    1. Acute toxicity. EPA has concluded that no endpoint exists to 
suggest any evidence of significant toxicity from 1-day or single-event 
exposure.
     2. Short - and intermediate - term toxicity. EPA has concluded 
that available evidence does not indicate any evidence of significant 
toxicity from short and intermediate term exposure.
    3. Chronic toxicity. EPA has established the RfD for pyrithiobac 
sodium at 0.587 milligrams/kilogram/day (mg/kg/day). This RfD is based 
on the systemic NOEL of 58.7 mg/kg/day for males in the rat chronic 
feeding study with a 100-fold safety factor to account for interspecies 
extrapolation and intraspecies variability.
    4. Carcinogenicity. The Health Effects Division Carcinogenicity 
Peer Review Committee has concluded that the available data provide 
limited evidence of the carcinogenicity of pyrithiobac sodium in mice 
and rats and has classified pyrithiobac sodium as a Group C (possible 
human carcinogen with limited evidence of carcinogenicity in animals) 
in accordance with Agency guidelines, published in the Federal Register 
in 1986 (51 FR 33992, September 24, 1986) and recommended that for the 
purpose of risk characterization, a low dose extrapolation model should 
be applied to the experimental animal tumor data for quantification for 
human risk (Q1*). This decision was based on liver adenomas, 
carcinomas and combined adenoma/carcinomas in the male mouse and rare 
kidney tubular adenomas, carcinomas and combined adenoma/carcinomas in 
male rats. 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.

B. Exposures and Risks

    1. From food and feed uses. Time limited tolerances have been 
established (40 CFR 180.487) for the residues of pyrithiobac sodium in 
or on the raw agricultural commodity cottonseed at 0.02 ppm until 
September 30, 1997. Processing studies for cotton have shown that 
pyrithiobac sodium does not concentrate in cottonseed processed 
commodities. Risk assessments were conducted by EPA to assess dietary 
exposures and risks from herbicide pyrithiobac sodium salt (sodium 2-
chloro-6-[(4,6-dimethoxypyrimidin-2-yl)thio]benzoate) as follows:
    Based on the assumption that 100% of the crop is treated with 
pyrithiobac sodium, the upper bound limit of the dietary carcinogenic 
risk is calculated in the range of one incidence in a billion (1.0  x  
10-9).
    Using the NOEL of 58.7 mg/kg/day from the most sensitive species in 
the rat chronic feeding study with a 100-fold safety factor, the 
Reference Dose (RfD) for systemic effects is 0.58 mg/kg/day. The 
theoretical maximum residue contribution (TMRC) from the established 
and proposed tolerances is 0.000001 mg/kg/day and utilizes less than 1 
percent of the RfD for the overall U.S. population. For exposure of the 
most highly exposed subgroup in the population, children 1 through 6 
years old, the TMRC is 0.000001 mg/kg/day which is still less than 1 
percent of the RfD.
    2. From drinking water. Pyrithiobac sodium concentration in surface 
water has been estimated by using the Generic Expected Environmental 
Concentrations (GENEEC) model. The worst case exposure estimate for 
surface water is 7.76 parts per billion (ppb) and for ground water is 
0.778 ppb. Based on the estimated exposures to pyrithiobac sodium from 
drinking water, the percentage of the RfD utilized for children (1 
through 6 years old) would be 0.1% of the RfD. The exposure for the 
general U.S. population would be less than 0.1% of the RfD.
    The worst case estimate for cancer risk from the estimated residues 
of pyrithiobac sodium in drinking water is 2.3  x  10-7 .
    3. From non-dietary exposure. There are no non-food uses of 
pyrithiobac sodium currently registered under the FIFRA, as amended. No 
non-dietary exposures are expected for the general population.
    4. Cumulative exposure to substances with common mechanism of 
toxicity. Section 408(b)(2)(D)(v) requires that, when considering 
whether to establish, modify, or revoke a tolerance, the Agency 
consider ``available information'' concerning the cumulative effects of 
a particular pesticide's residues and ``other substances that have a 
common mechanism of toxicity.'' The Agency believes that ``available 
information'' in this context might include not only toxicity, 
chemistry, and exposure data, but also scientific policies and 
methodologies for understanding common mechanisms of toxicity and 
conducting cumulative risk assessments. For most pesticides, although 
the Agency has some information in its files that may turn out to be 
helpful in eventually determining whether a pesticide shares a common 
mechanism of toxicity with any other substances, EPA does not at this 
time have the methodologies to resolve the complex scientific issues 
concerning common mechanism of toxicity in a meaningful way. EPA has 
begun a pilot process to study this issue further through the 
examination of particular classes of pesticides. The Agency hopes that 
the results of this pilot process will increase the Agency's scientific 
understanding of this question such that EPA will be able to develop 
and apply scientific principles for better determining which chemicals 
have a common mechanism of toxicity and evaluating the cumulative 
effects of such chemicals. The Agency anticipates, however, that even 
as its understanding of the science of common mechanisms increases, 
decisions on specific classes of chemicals will be heavily dependent on 
chemical specific data, much of which may not be presently available.
    Although at present the Agency does not know how to apply the 
information in its files concerning common mechanism issues to most 
risk assessments, there are pesticides as to which the common mechanism 
issues can be resolved. These pesticides include pesticides that are 
toxicologically dissimilar to existing chemical substances (in which 
case the Agency can conclude that it is unlikely that a pesticide 
shares a common mechanism of activity with other substances) and 
pesticides that produce a common toxic metabolite (in which case common 
mechanism of activity will be assumed).
    EPA does not have, at this time, available data to determine 
whether pyrithiobac sodium salt has a common

[[Page 54782]]

mechanism of toxicity with other substances or how to include this 
pesticide in a cumulative risk assessment. Unlike other pesticides for 
which EPA has followed a cumulative risk approach based on a common 
mechanism of toxicity, pyrithiobac sodium does not appear to produce a 
toxic metabolite produced by other substances. For the purposes of this 
tolerance action, therefore, EPA has not assumed that pyrithiobac 
sodium has a common mechanism of toxicity with other substances.

C. Aggregate Risks and Determination of Safety for U.S. Population

    1. Acute, short-term, and intermediate term risk. EPA has concluded 
that no endpoint exists to suggest any evidence of significant toxicity 
from acute, short-term or intermediate-term exposures from the use of 
pyrithiobac sodium on cotton.
    2. Chronic risk. Using the exposure assumptions described above, 
EPA has concluded that aggregate exposure to pyrithiobac sodium from 
food and drinking water will utilize less than 0.1% of the RfD for the 
U.S. population. For the major identifiable subgroup with the highest 
aggregate exposure, children (1 through 6 years old), the aggregate 
exposure to pyrithiobac sodium from food and drinking water will 
utilize less than 0.2% of the RfD. EPA generally has no concern for 
exposures below 100% of the RfD because the RfD represents the level at 
or below which daily aggregate dietary exposure over a lifetime will 
not pose appreciable risks to human health.

D. Aggregate Cancer Risk for U.S. Population

    Based on the upper bound potency factor (Q1*) of 1.05 
x  10-3 (mg/kg/day)-1, the aggregate upper bound 
lifetime cancer risk from the use of pyrithiobac sodium on cotton from 
worst case estimates of residues in food and drinking water is 2.3  x  
10-7.

E. Aggregate Risks and Determination of Safety for Infants and Children

    1. Safety factor for infants and children--a. In general. In 
assessing the potential for additional sensitivity of infants and 
children to residues of pyrithiobac sodium, EPA considered data from 
developmental toxicity studies in the rat and rabbit and a two-
generation reproduction study in the rat. The developmental toxicity 
studies are designed to evaluate adverse effects on the developing 
organism resulting from pesticide exposure during prenatal development 
to one or both parents. Reproduction studies provide information 
relating to effects from exposure to the pesticide on the reproductive 
capability of mating animals and data on systemic toxicity.
    FFDCA section 408 provides that EPA shall apply an additional 
tenfold margin of safety for infants and children in the case of 
threshold effects to account for pre- and post-natal toxicity and the 
completeness of the database unless EPA determines that a different 
margin of safety will be safe for infants and children. Margins of 
safety are incorporated into EPA risk assessments either directly 
through use of a MOE analysis or through using uncertainty (safety) 
factors in calculating a dose level that poses no appreciable risk to 
humans. EPA believes that reliable data support using the standard MOE 
and uncertainty factor (usually 100 for combined inter- and intra-
species variability)) and not the additional tenfold MOE/uncertainty 
factor when EPA has a complete data base under existing guidelines and 
when the severity of the effect in infants or children or the potency 
or unusual toxic properties of a compound do not raise concerns 
regarding the adequacy of the standard MOE/safety factor.
    b. Developmental and Reproductive toxicity studies. The pre- and 
post-natal toxicology data base for pyrithiobac sodium is complete with 
respect to current toxicological data requirements. The results of 
these studies indicate that infants and children are not more sensitive 
to exposure, based on the results of the oral rat and rabbit 
developmental toxicity studies and the two-generation reproductive 
toxicity study in rats. Therefore, EPA concludes an additional tenfold 
safety factor is not necessary.
    2. Chronic risk. Using the conservative exposure assumptions 
described above, EPA has concluded that aggregate exposure to 
pyrithiobac sodium from food and drinking water will utilize less than 
0.2% of the RfD for infants and children. EPA generally has no concern 
for exposures below 100% of the RfD because the RfD represents the 
level at or below which daily aggregate dietary exposure over a 
lifetime will not pose appreciable risks to human health. EPA concludes 
that there is a reasonable certainty that no harm will result to 
infants and children from aggregate exposure to pyrithiobac sodium 
residues.

III. Other Considerations

A. Metabolism In Plants and Animals

    The metabolism of pyrithiobac sodium in plants and animals is 
adequately understood for purposes of this tolerance.

B. Analytical Enforcement Methodology

    An adequate analytical method, High Pressure Liquid Chromatography 
- Ultra Violet (HPLC-UV) with column switching, is available for 
enforcement purposes. Because of the long lead time from establishing 
these tolerances to publication of the enforcement methodology in the 
Pesticide Analytical Manual, Vol. II, the analytical methodology is 
being made available in the interim to anyone interested in pesticide 
enforcement when requested from: Calvin Furlow, Public Information and 
Records Integrity Branch, Information Resources and Records Service 
(7506C), Office of Pesticide Programs, Environmental Protection Agency, 
401 M St., SW., Washington, DC 20460. Office location and telephone 
number: Room 1130A, CM#2, 1921 Jefferson Davis Highway, Arlington, VA 
22202, (703-305-5937).

C. Magnitude of Residues

    The nature of the residue in plants is adequately understood for 
the purposes of this time-limited tolerance.

D. International Residue Limits

    There are no Codex Alimentarius Commission (Codex) Maximum Residue 
Levels (MRLs) for pyrithiobac sodium.

IV. Conclusion

    The analysis for pyrithiobac sodium using tolerance level residues 
for all population subgroups examined by EPA shows the use on cotton 
will not cause exposure at which the Agency believes there is an 
appreciable risk. Based on the information cited above, EPA has 
determined that the extension of the time limited tolerance for 
residues of pyrithiobac sodium in cottonseed at 0.02 ppm until 
September 30, 1999 by amending 40 CFR 180.487 will be safe; therefore, 
the tolerances are extended as set forth below.

V. Objections and Hearing Requests

    The new FFDCA section 408(g) provides essentially the same process 
for persons to ``object'' to a tolerance regulation issued by EPA under 
new section 408(e) and (l)(6) as was provided in the old section 408 
and in section 409. However, the period for filing objections is 60 
days, rather than 30 days. EPA currently has procedural regulations 
which govern the submission of objections and hearing requests. These 
regulations will require some modification to reflect the new law. 
However, until those modifications can be made, EPA will continue to 
use

[[Page 54783]]

those procedural regulations with appropriate adjustments to reflect 
the new law.
    Any person may, by December 22, 1997, file written objections to 
any aspect of this regulation and may also request a hearing on those 
objections. Objections and hearing requests must be filed with the 
Hearing Clerk, at the address given above (40 CFR 178.20). A copy of 
the objections and/or hearing requests filed with the Hearing Clerk 
should be submitted to the OPP docket for this rulemaking. The 
objections submitted must specify the provisions of the regulation 
deemed objectionable and the grounds for the objections (40 CFR 
178.25). Each objection must be accompanied by the fee prescribed by 40 
CFR 180.33(i). If a hearing is requested, the objections must include a 
statement of the factual issues on which a hearing is requested, the 
requestor's contentions on such issues, and a summary of any evidence 
relied upon by the requestor (40 CFR 178.27). A request for a hearing 
will be granted if the Administrator determines that the material 
submitted shows the following: There is genuine and substantial issue 
of fact; there is a reasonable possibility that available evidence 
identified by the requestor would, if established, resolve one or more 
of such issues in favor of the requestor, taking into account 
uncontested claims or facts to the contrary; and resolution of the 
factual issues in the manner sought by the requestor would be adequate 
to justify the action requested (40 CFR 178.32). Information submitted 
in connection with an objection or hearing request may be claimed 
confidential by marking any part or all of that information as 
Confidential Business Information (CBI). Information so marked will not 
be disclosed except in accordance with procedures set forth in 40 CFR 
part 2. A copy of the information that does not contain CBI must be 
submitted for inclusion in the public record. Information not marked 
confidential may be disclosed publicly by EPA without prior notice.

VI. Public Docket

    EPA has established a record for this rulemaking under docket 
control number [OPP-300548] (including any comments and data submitted 
electronically). A public version of this record, including printed, 
paper versions of electronic comments, which does not include any 
information claimed as CBI, is available for inspection from 8:30 a.m. 
to 4 p.m., Monday through Friday, excluding legal holidays. The public 
record is located in Room 1132 of the Public Information and Records 
Integrity Branch, Information Resources and Services Division (7506C), 
Office of Pesticide Programs, Environmental Protection Agency, Crystal 
Mall #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Electronic comments may be sent directly to EPA at:
    [email protected].

    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption.
    The official record for this rulemaking, as well as the public 
version, as described above will be kept in paper form. Accordingly, 
EPA will transfer any copies of objections and hearing requests 
received electronically into printed, paper form as they are received 
and will place the paper copies in the official rulemaking record which 
will also include all comments submitted directly in writing. The 
official rulemaking record is the paper record maintained at the 
Virginia address in ``ADDRESSES'' at the beginning of this document.

VII. Regulatory Assessment Requirements

    This final rule establishes a tolerance under FFDCA section 408(d) 
in response to a petition submitted to the Agency. The Office of 
Management and Budget (OMB) has exempted these types of actions from 
review under Executive Order 12866, entitled Regulatory Planning and 
Review (58 FR 51735, October 4, 1993). This final rule does not contain 
any information collections subject to OMB approval under the Paperwork 
Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose any enforceable 
duty or contain any unfunded mandate as described under Title II of the 
Unfunded Mandates Reform Act of 1995 (UMRA) (Pub. L. 104-4). Nor does 
it require any prior consultation as specified by Executive Order 
12875, entitled Enhancing the Intergovernmental Partnership (58 FR 
58093, October 28, 1993), or special considerations as required by 
Executive Order 12898, entitled Federal Actions to Address 
Environmental Justice in Minority Populations and Low-Income 
Populations (59 FR 7629, February 16, 1994), or require OMB review in 
accordance with Executive Order 13045, entitled Protection of Children 
from Environmental Health Risks and Safety Risks (62 FR 19885, April 
23, 1997).
    In addition, since these tolerances and exemptions that are 
established on the basis of a petition under FFDCA section 408(d), such 
as the tolerance in this final rule, do not require the issuance of a 
proposed rule, the requirements of the Regulatory Flexibility Act (RFA) 
(5 U.S.C. 601 et seq.) do not apply. Nevertheless, the Agency has 
previously assessed whether establishing tolerances, exemptions from 
tolerances, raising tolerance levels or expanding exemptions might 
adversely impact small entities and concluded, as a generic matter, 
that there is no adverse economic impact. The factual basis for the 
Agency's generic certification for tolerance actions published on May 
4, 1981 (46 FR 24950) and was provided to the Chief Counsel for 
Advocacy of the Small Business Administration.

VIII. Submission to Congress and the General Accounting Office

    Under 5 U.S.C. 801(a)(1)(A), as added by the Small Business 
Regulatory Enforcement Fairness Act of 1996, the Agency has submitted a 
report containing this rule and other required information to the U.S. 
Senate, the U.S. House of Representatives, and the Comptroller General 
of the General Accounting Office prior to publication of this rule in 
today's Federal Register. This is not a ``major rule'' as defined by 5 
U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.


    Dated: October 1, 1997.

Daniel M. Barolo,

Director, Office of Pesticide Programs.
    Therefore, 40 CFR Chapter I is amended as follows:

PART 180--[AMENDED]

    1. The authority citation for part 180 continues to read as 
follows:

    Authority : 21 U.S.C. 346a and 371.

    2. By revising Sec. 180.487 to read as follows:


Sec.  180.487   Pyrithiobac sodium; tolerances for residues.

    (a) General. (1) Time-limited tolerances are established for 
residues of the herbicide, pyrithiobac-sodium, sodium 2-chloro-6-[(4,6-
dimethoxypyrimidin-2-yl)thio]benzoate, in or on the food commodities in 
the table in paragraph (a)(2). The tolerance will expire on the date 
specified in the table.
    (2) Residues in these commodities not in excess of the established 
tolerance resulting from the use described in the following table 
remaining after expiration of the time-limited tolerance

[[Page 54784]]

will not be considered to be actionable if the herbicide is applied 
during the term of and in accordance with the provisions of paragraph 
(a) of this section.

------------------------------------------------------------------------
                                      Parts per    Expiration/revocation
             Commodity                 million             date         
------------------------------------------------------------------------
Cottonseed.........................         0.02  Sept. 30, 1999        
------------------------------------------------------------------------

    (b) Section 18 emergency exemptions. [Reserved]
    (c)  Tolerances with regional registrations. [Reserved]
    (d)  Indirect or inadvertent residues. [Reserved]

[FR Doc. 97-27843 Filed 10-21-97; 8:45 am]
BILLING CODE 6560-50-F