[Federal Register Volume 62, Number 43 (Wednesday, March 5, 1997)]
[Rules and Regulations]
[Pages 9974-9978]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-5201]



[[Page 9974]]

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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180

[OPP-300455; FRL-5591-5]
RIN No. 2070-AB78


Thiazopyr; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This document establishes tolerances for residues of the 
herbicide thiazopyr (3-pyridinecarboxylic acid, 2-(difluoromethyl)-5-
(4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-, 
methyl ester) and its metabolites determined as 2-(difluoromethyl)-6-
(trifluoromethyl)-3,4,5-pyridinetricarboxylic acid, all expressed as 
the parent equivalents in or on the raw agricultural commodities orange 
and grapefruit. Rohm and Haas Company submitted a petition to EPA under 
the Federal Food, Drug and Cosmetic Act as amended by the Food Quality 
Protection Act of l996 requesting the tolerances.

EFFECTIVE DATE: This regulation becomes effective March 5, 1997.

ADDRESSES: Written objections and hearing requests, identified by the 
docket control number, [OPP-300455], may 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 should be identified by the 
docket control number and submitted to: Public Response and Program 
Resources Branch, Field Operations Division (7506C), Office of 
Pesticide Programs, Environmental Protection Agency, 401 M St., SW., 
Washington, DC 20460. In person, bring copy of objections and hearing 
requests to: Rm. 1132, CM #2, 1921 Jefferson Davis Highway, Arlington, 
VA 22202.
    A copy of objections and hearing requests filed with the Hearing 
Clerk may also be submitted electronically to the OPP by sending 
electronic mail (e-mail) to: <a href="/cdn-cgi/l/email-protection#3d524d4d1059525e5658497d584d5c505c545113584d5c135a524b"><span class="__cf_email__" data-cfemail="274857570a4348444c4253674257464a464e4b0942574609404851">[email protected]</span></a>. 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 number [OPP-300455].
    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. 
Additional information on electronic submissions can be found below in 
this document.
FOR FURTHER INFORMATION CONTACT: By mail: Joanne I. Miller, Product 
Manager (PM) 23, Registration Division (7505C), Environmental 
Protection Agency, 401 M St., SW., Washington, DC 20460. Office 
location, telephone number and e-mail address: Rm. 237, CM #2, 1921 
Jefferson Davis Hwy., Arlington, VA 22202, (703) 305-6224; e-mail: 
<a href="/cdn-cgi/l/email-protection#8fe2e6e3e3eafda1e5e0eee1e1eacfeaffeee2eee6e3a1eaffeea1e8e0f9"><span class="__cf_email__" data-cfemail="076a6e6b6b6275296d6866696962476277666a666e6b2962776629606871">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION: In the Federal Register of October 21, 1993 
(58 FR 54354), EPA issued a notice pursuant to section 408(d) of the 
Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), 
announcing the filing of a pesticide tolerance petition by Monsanto 
Co., Suite 1100, 700 14th St., NW., Washington, DC 20005. The petition 
requested that 40 CFR part 180 be amended by adding a regulation for 
tolerances for combined residues of the herbicide thiazopyr (3-
pyridinecarboxylic acid, 2-(difluoromethyl)-5-(4,5-dihydro-2-
thiazolyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-, methyl ester) and 
its metabolites determined as 3-pyridinecarboxylic acid, 5-
(aminocarbonyl)-2-(difuoromethyl)-4-(2-methylpropyl)-6-trifluoromethyl-
, methyl ester and 3-pyridinecarboxylic acid, 2-(difluoromethyl)-4-(2-
methylpropyl)-5-((2-sulfoethyl)amino) carbonyl-6-(trifluoromethyl) and 
expressed as parent equivalents, in or on the raw agricultural 
commodities: Citrus, whole fruit at 0.05 ppm; cotton seed at 0.05 ppm 
and cotton forage at 0.2 ppm. The proposed analytical method for 
determining residues was gas chromatography with mass spectrometry.
    In the Federal Register of August 24, l994 (59 FR 43580) EPA issued 
a notice of an amendment to the petition. The tolerances requested were 
changed to residues of thiazopyr (3-pyridinecarboxylic acid, 2-
[difluoromethyl]-5-(4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-6-
(trifluoromethyl)-, methyl ester) and its metabolites determined as 3-
pyridinecarboxylic acid, 5-(aminocarbonyl)-2-(difluoromethyl)-4-(2-
methylpropyl)-6-trifluoromethyl)-, methyl ester and 3-
pyridinecarboxylic acid, 2-(difluoromethyl)-4-(2-methylpropyl)-5-(((2-
sulfoethyl) amino) carbonyl)-6-(trifluoromethyl) acid and expressed as 
parent equivalents, in or on citrus whole fruit at 0.05 ppm, cotton 
seed at 0.05 ppm and cotton forage at 0.2 ppm. Monsanto Co. requested 
the petition be amended to read: tolerances of 0.05 ppm for orange, 
whole fruit and 0.05 for grapefruit, whole fruit. The proposed 
analytical method for determining residues was mass spectral multiple-
ion detection.
    In the Federal Register of November 22, l996 (61 FR 59440)(FRL-
5573-8) EPA issued a third notice of filing to amend the petition to 
bring the petition in conformity with the Food Quality Protection Act 
(FQPA) of l996. The notice contained a summary of the petition prepared 
by the petitioner and this summary contained conclusions and arguments 
to support its conclusion that the petition complied with FQPA. In this 
instance the petitioner proposed to amend 40 CFR part 180 by 
establishing a regulation for tolerances for residues of thiazopyr in 
or on orange and grapefruit at 0.05 ppm on the whole fruit, the same as 
proposed in the previous EPA notices of filing.
    There were no comments or requests for referral to an advisory 
committee received in response to the notices of filing.
    The data submitted in the petition and other relevant material have 
been evaluated. The toxicology data listed below were considered in 
support of these tolerances.

I. Toxicological Profile

    1. A battery of acute toxicity studies placing technical thiazopyr 
in Toxicity Categories III and IV.
    2. A 3-month feeding study in rats at dietary intakes of 0, 0.07, 
0.67, 6.60, 68, or 201 milligrams per kilogram per day (mg/kg/day) 
(males) and 0.08, 0.79, 8.0, 79 or 227 mg/kg/day (females) with a no 
observed effect level (NOEL) of 6.6 mg/kg/day, based on increased 
liver, thyroid and kidney weights, changes in clinical chemistry and 
hematological parameters and on gross and microscopic changes observed 
in the liver and thyroid at dose levels of 68 mg/kg/day and higher. At 
the 201 mg/kg/day dose diffuse thyroid follicular cell hypertrophy/
hyperplasia was observed.
    3. A 3-month feeding study in dogs at 0, 3, 6, 35 and 175 mg/kg/day 
(males) and 0, 2, 3, 35 and 160 mg/kg/day (females) with a NOEL of 2 
mg/kg/day, based on decreased body weight gain and increased SGPT 
levels at 3 and 6 mg/kg/day for males and females, respectively and 
above; decreased total protein and albumin concentration and

[[Page 9975]]

albumin/globulin ratio, increased AP, hepatocytic hypertrophy, oval 
cell proliferation and increased hepatocytic fatty content at 35 mg/kg/
day and above; and decreased calcium concentration which is thought to 
be related to the hypoalbuminemia, decreased cholesterol and 
triglyceride concentrations, slightly increased GGT and SGPT, 
follicular hyperplasia of thyroid, increased colloid content in 
follicles and increased relative thyroid weight at 175 mg/kg/day.
    4. A 3-week dermal study in rabbits at 0, 100, 500 and 1,000 mg/kg/
day with a NOEL of 100 mg/kg/day. The effects were increased mean 
absolute and relative kidney weights and minimal multifocal or 
periportal hepatocyte vacuolation.
    5. A 1-year feeding study in dogs at 0, 0.8, 7.8, 86 mg/kg/day 
(males) and 0, 0.8, 8.8, and 78 mg/kg/day (females). The NOEL was 0.8 
mg/kg/day and the LOEL is 7.8 mg/kg/day based upon hepatocellular 
hypertrophy/hyperplasia, which was observed at 7.8 to 8.8 mg/kg/day for 
males and females, respectively, and above. In addition, an increase of 
approximately 10% in prothrombin time was observed at 8.6 and 7.8 mg/
kg/day for males and females, respectively with both sexes, as well as 
increased SGOT, SGPT, GGT and ALK and decreases in cholesterol, 
albumin, total protein and calcium levels. An increase in absolute and 
relative liver weights were also observed at 2,000 ppm. Enlargement 
and/or discoloration in some of the high dose animals provided 
additional evidence of hepatotoxicity.
    6. A developmental toxicity study in rats at 0, 10, 100 and 250 mg/
kg/day. The maternal NOEL is 100 mg/kg/day and the maternal lowest 
observed effect level (LOEL) is 250 mg/kg/day based on increased liver 
weights, salivation, decreased body weight gains and food consumption. 
The developmental NOEL was 100 mg/kg/day and the developmental LOEL was 
250 mg/kg/day based on increased incidences of unossified sternebra(e) 
and 7th cervical rib variations.
    7. A developmental toxicity study in rabbits at 0, 10, 75 and 175 
mg/kg/day. The maternal NOEL was 75 mg/kg/day based on reduced body 
weight gain and food consumption. The developmental NOEL was 175 mg/kg/
day the highest dose tested. No effects were observed.
    8. A two-generation reproductive study in rats at 0, 0.72, 7.33 and 
72.9 mg/kg/day (males) and 0, 0.86, 8.49, 81.3 mg/kg/day (females). The 
parental/systemic NOEL was 0.72 mg/kg/day. The toxic effects were 
increased absolute and relative liver weight, hepatic discoloration, 
histologic evidence of hepatic hypertrophy and vacuolization in females 
in both generations. The reproductive NOEL was 72.9 mg/kg/day, the 
highest dose tested. There were no reproductive effects.
    9. A mouse carcinogenicity study at doses of 0, 0.17, 1.6, 16.9 
66.3 and 128.4 mg/kg/day (males) and 0,0.24, 2.6, 26.8, 108.1 and 215.9 
mg/kg/day (female). The systemic NOEL was 1.6 mg/kg/day. The effects 
were hepatocellular hypertrophy and amyloid deposition. At 66.3 mg/kg/
day the same lesions plus increased liver weights, random and 
periportal hepatocellular vacuolation were observed. At 128.4 mg/kg/day 
the same lesions plus distended abdomen, slight increase in ALP, SGOT 
and SGPT, abnormal coloration and enlargement of liver, decrease in 
absolute and relative spleen weights, increase in absolute and relative 
kidney weights, increase in eosinophilia in hepatocytes, kidney 
nephropathy and lymphocytic hyperplasia of the nesenteric lymph nodes 
were observed. There were no increases in neoplastic lesions in any of 
the treated groups.
    10. A 2-year rat carcinogenicity study at doses of 0, 0.04, 0.4, 
4.4, 44.2 or 136.4 mg/kg/day (males) and 0, 0.06, 0.6, 5.6, 56.3 or 
177.1 mg/kg/day (female) with a systemic NOEL of 4.4 mg/kg/day. The 
effects were protruding eyes, evidence of mild anemia, increased GGT 
and cholesterol, increased absolute and relative liver, kidney and 
thyroid weights and significant increase in microscopic lesions in the 
liver (hypertrophy and vacuolar changes), kidney (nephropathy) and 
thyroid (hypertrophy and hyperplasia); decreased mean body weight and 
body weight gain and food consumption. A statistically significant 
increase in thyroid follicular cell adenomas/cystadenomas were observed 
in males at 44.2 and 136.4 mg/kg/day. A nonsignificant increase in 
renal tubular adenomas in high-dose females was considered to be 
equivocal.
    The EPA's Health Effects Division Carcinogenicity Peer Review 
Committee classified thiazopyr as a Group C, possible human carcinogen 
and recommended that for the purpose of risk characterization a Margin 
of Exposure (MOE) approach should be used in evaluation of the 
consequences of human exposure.
    11. An acceptable study for inducing reverse mutation in Ames 
Salmonella strains of bacteria exposed with or without activation at 
doses up to 10,000 micrograms per plate. The study showed negative 
results.
    12. An acceptable study for inducing micronuclei in bone marrow 
cells of mice treated up to a lethal dose of 800 mg/kg. The study 
showed negative results.
    13. A mutagenic study with Chinese hamster ovary cells exposed in 
vitro with or without activation to doses up to 1,000 micrograms, the 
highest dose tested. The study showed negative results for inducing 
forward mutation at the hypoxanthine guanine phosphoribosyl transferase 
locus (HGPRT). On the basis of the studies on mutagenicity and 
genotoxicity, it is concluded that thiazopyr is not a mutagenic or 
genotoxic chemical.
    14. An acute neurotoxicity in rats at doses of 0, 500, 1,000 and 
2,000 mg/kg with a NOEL of 500 mg/kg. The effects were transient 
differences in functional observational battery and motor activity 
compared to control groups. The results of the study were considered to 
be inconclusive for neurotoxicity. At the highest dose (2,000 mg/kg) it 
was not possible to distinguish between neurotoxicity and general 
systemic toxicity.
    15. Two metabolism studies were conducted in rats with radio-
labeled thiazopyr. One with the <SUP>14C at the 4 position of the 
pyridine ring and one with the <SUP>14C at the 4' and 5' positions of 
the thiazole ring. The absorption of an orally administered dose was 
about 90%. The overall radiolabel recovery for all study groups was 
88.9, plus or minus 0.65%. No significant sex-related differences were 
observed in the total percent recovery. However, the distribution of 
recovery was sex-related. There was little radiolabel detected in 
tissues at study termination. Preferential sites for localization of 
the radiolabel included liver, adipose tissue, muscle and bone. The 
metabolic pathway is essentially an oxidative pathway. Vulnerable sites 
of the molecule are the thiazoline ring, the isobutyric side chain and 
the pyridine rings. Thiazopyr appears to be rapidly and extensively 
eliminated with low amounts of residues remaining in the tissues and 
carcasses. The percentage of radiolabel remaining in the carcasses 
following feeding thiazoline-labeled thiazopyr was between 6.9 and 
10.8%.
    16. Special mechanistic studies for mode of toxic action on thyroid 
function. The results of three studies on the effects of thiazopyr on 
thyroid function and mechanisms involved in the disposition of T4 in 
rats were reviewed. These studies are described below:
    a. Thiazopyr was administered through the diet, in rats, at 0 and 
150 mg/kg/day to determine the subchronic effect on hormone level and 
other biochemical endpoints. Animals were

[[Page 9976]]

assayed at 7, 14, 28, 56 or 90 days. Significant decreases in body 
weight gain were observed at 90 days. Early in the study the treated 
rats showed increases in TSH (ranging from 133 to 200% of controls) and 
decreases in T4 (ranging from 43% to 76% of controls). In addition 
there were increases in liver and thyroid weights and increases in 
thyroid follicular cell hypertrophy/hyperplasia. Reverse T3 was 
increased at 28 days, and T3 was either not affected or increased. 
There were indications of increases in hepatic UDPGT activity and 
significant increases in T4 UDPGT activity. Hepatic 5'-monodeiodinase 
activity was either not affected or decreased. The effects observed in 
this study were supportive of the theory that thiazopyr may induce 
thyroid tumors through a disruption in the thyroid-pituitary hormonal 
feedback mechanisms.
    b. A second study on the effects of thiazopyr on the biochemical 
mechanisms of thyroid toxicity in rats at doses of 0, 0.5, 1.5, 5, 15, 
50 or 150 mg/kg/day was conducted. Dose response effects on various 
biochemical parameters were observed. Two groups of the rats in the 
study were observed for reversibility of effects observed up to 56 and 
112 days. Doses at 15, 50 and 150 mg/kg/day significantly increased the 
liver weights. Thyroid weights were increased at doses of 50 and 150 
mg/kg/day. There was no significant effect on body weight or body 
weight gains during the study. The T4 UDPGT levels were increased by 
117 and 376% above controls at the 50 and 150 mg/kg/day dosages, 
respectively. Effects of 150 mg/kg/day were increases in T3, TSH and 
rT3 serum concentrations, and increased incidence of follicular cell 
hypertrophy/hyperplasia at the 150 mg/kg/day dose. A NOEL of 1.5 mg/kg/
day was determined based on liver weight increases. Thyroid weight was 
the only parameter that did not return to those similar to the 
controls. At the 56 and 112 day recovery periods the thyroid weights 
were 120 and 123% of control values, respectively.
    c. A third thyroid function study on the biochemical mechanisms 
involved with disposition of T4 in rats fed dosages of 0 and 150 mg/kg/
day for 56 days was conducted. Rats feed thiazopyr had increase T4 
UDPGT activity and total deiodinase activity in their livers. There was 
also a two-fold increase in mixed function oxidase enzyme activity. 
Results of the three studies suggest that increased glucuronidation, 
deiodination of T4 and T3, and increased rate of clearance of T4 from 
the blood and excretion of the hormone and its metabolites in the bile 
could significantly reduce the level of circulating T4 in the male rat.
    Results of these studies support the hypothesis that thiazopyr may 
induce thyroid tumors through a disruption of the thyroid-pituitary 
hormonal feedback mechanism circulating T4 in the male rat.

II. Aggregate Exposures

    1. Food and feed uses. The primary source for human exposure to 
thiazopyr will be from ingestion of both raw and processed agricultural 
commodities as proposed in the November 22, 1996 notice of filing cited 
above. Based on tolerances of 0.05 ppm in or on orange and grapefruit, 
the Theoretical Maximum Residue Contributions (TMRC) for the U.S. adult 
population and for U.S. children (1 to 6 years of age) were determined. 
In deriving the dietary exposure to thiazopyr and its metabolites, EPA 
assumed that 100% of the orange and grapefruit crops were cultured with 
the aid of this herbicide. A chronic exposure was used to estimate the 
TMRC. The TMRC for the U.S. population was estimated to be 0.000118 mg/
kg/day. The TMRC for children, 1 to 6 years of age was 0.000324 mg/kg/
day. The TMRC for children, 7 to 12 years of age was 0.000173 mg/kg/
day.
    2. Potable water. There is presently no EPA Lifetime Health 
Advisory level for thiazopyr and its degradates as drinking water 
contaminates. Thiazopyr has not been found in ground water. A monoacid 
degradate was found in wells at concentrations of up to 7.6 parts per 
billion (ppb). The wells were being monitored as part of a prospective 
ground water study in the state of Florida. Using a standard potable 
water ingestion of 2 liters per day by adults and 1 liter per day by 
children, the exposure from potable water to adults was determined to 
be 0.000217 mg/kg/day. Exposure to children was determined to be 
0.00076 mg/kg/day.
    3. Non-dietary uses. There are no non-dietary uses registered under 
the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), as 
amended.
    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.'' While 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 capability to 
resolve the scientific issues concerning common mechanism of toxicity 
in a meaningful way. EPA is commencing 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 enable the Agency to apply common mechanism issues to its 
pesticide risk assessments. At present, however, the Agency does not 
know how to apply the information in its files concerning common 
mechanism issues to risk assessments, and therefore believes that in 
most cases there is no ``available information'' concerning common 
mechanism that can be scientifically applied to tolerance decisions. 
Where it is clear that a particular pesticide may share a significant 
common mechanism with other chemicals, or where it is clear that a 
pesticide does not share a common mechanism with other chemicals, a 
tolerance decision may be affected by common mechanism issues. The 
Agency expects that most tolerance decisions will fall into the area in 
between, where EPA can not reasonably determine whether a pesticide 
does or does not share a common mechanism of toxicity with other 
chemicals (and, if so, how that common mechanism should be factored 
into a risk assessment). In such circumstances, the Agency will reach a 
tolerance decision based on the best, currently available and usable 
information, without regard to common mechanism issues. However, the 
Agency will also revisit such decisions when the Agency learns how to 
apply common mechanism information to pesticide risk assessments.
    In the case of thiazopyr, EPA has determined that it does not now 
have the capability to apply the information in its files to a 
resolution of common mechanism issues in a manner that would be useful 
in a risk assessment. This tolerance determination therefore does not 
take into account common mechanism issues. The Agency will reexamine 
the tolerances for thiazopyr, if reexamination is appropriate, after 
the Agency has determined how to apply common mechanism issues to its 
pesticide risk assessments.

III. Determination of Safety for U.S. Population and Non-nursing 
Infants

    1. The U.S. population. Based on a NOEL of 0.8000 milligrams per 
kilogram of body weight per day (mg/kg bwt/day) from a 2-year dog 
feeding study that showed a liver effect of hepatocellular hypertrophy 
and hyperplasia, and using a safety or uncertainty factor of 100 to

[[Page 9977]]

account for the interspecies extrapolation and intraspecies 
variability, the Agency has determined a Reference Dose (RfD) of 0.008 
mg/kg bwt/day for this assessment of risk. Based on the available 
toxicity data and the available exposure data identified above, the 
proposed tolerances will utilize 1.5% of the RfD for the U.S. 
population. Including an estimated exposure of 7.6 ppb in potable 
water, the dietary exposure for the U.S. adult population, assuming the 
ingestion of 2 liters of water per day, increases to 0.000335 mg/kg/day 
and utilizes 4.6% of the RfD.
    2.  Non-nursing infants. Using the RfD of 0.008 mg/kg/bwt/day as 
described above and the TMRC of 0.000251 mg/kg/day determined of non-
nursing infants, the proposed tolerances utilize 13.97% (3.1% dietary 
and 10.87% potable water) of the RfD.
    3.  Nonfood uses. There are no nonfood uses of thiazopyr registered 
under FIFRA, as amended.

IV. Determination of Safety for Infants and Children

    Risk to infants and children was determined by use of two 
developmental toxicity studies. One study in rats had a NOEL for 
developmental toxicity of 100 mg/kg/day, based on an increase in the 
incidence of unossified sternebrae and 7th cervical rib variations. The 
maternal NOEL was also 100 mg/kg/day based on toxic effects of 
increased liver weights, salivation, decreased body weight gains and 
food consumption. Fetal toxicity was only observed at maternally toxic 
doses. No malformations were observed at any dose. A second study in 
rabbits had a maternal NOEL of 75 mg/kg/day based on effects in 
reducing body weight gain and food consumption. There were no 
development effects at l75 mg/kg/day, the highest dose tested.
    In a reproduction study in rats, the parental NOEL was 0.72 to 8.1 
mg/kg/day. The reproductive toxicity NOEL was 72.9 to 81.3 mg/kg/day. 
There were no treatment-related effects on any reproductive parameter 
in the adults or their offspring. Overall, thiazopyr was not associated 
with significant developmental or reproductive effects below maternally 
toxic doses.
    FFDCA section 408 provides that EPA shall apply an additional 
safety factor for infants and children in the case of threshold effects 
to account for pre-and post-natal toxicity and the completeness of the 
database unless EPA determines that such additional factor is not 
necessary to protect the safety of infants and children. EPA believes 
that reliable data support using a different safety factor (usually 
100x) and not the additional safety factor when EPA has a complete data 
base 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 traditional safety factors.
    The toxicological database for evaluating pre- and post-natal 
toxicity for thiazopyr is mostly complete. Available data indicate that 
no developmental toxicity was observed in the rabbit study at the 
highest dose tested (175 mg/kg/day). Maternal toxicity was observed in 
the rabbit in the 175 mg/kg/day dose group which consisted of 
reductions in body weight gain and food consumption. In the rat 
developmental study, a reduction in maternal body weight gain and body 
weight was observed at the highest dose tested (250 mg/kg/day). 
Developmental toxicity was observed in the high dose (250 mg/kg/day) as 
increased incidences of unossified sternebra and 7th cervial rib 
variations.
    The NOEL for systemic (parental) toxicity is 0.72 mg/kg/day. The 
NOEL for reproductive toxicity is 72.9 mg/kg/day (highest dose tested). 
There were no reproductive effects noted in the study. These data taken 
together suggest minimal concern for developmental or reproductive 
toxicity and do not indicate any increased pre- or post-natal 
sensitivity in the offspring; no additional uncertainty factor for 
increased sensitivity in infants and children is appropriate.
    The percent of the RfD that will be utilized by the aggregate 
exposure to thiazopyr will range from 7.148% for non-nursing infants, 
up to 13.55% for children (1 to 6 years of age). Therefore, EPA 
concludes that there is a reasonable certainty that no harm will result 
to infants and children from aggregate exposure.

V. Other Considerations

A. Endocrine Effects

    An evaluation of the potential effects on the endocrine systems of 
mammals was partially determined by chronic toxicology studies 
described above. There were observed pathology of the endocrine organs 
in those studies. Three supplemental rat studies were conducted to 
determine the mode of toxic action of thiazopyr on thyroid function. 
The mode of toxic action as indicated by effects of thiazopyr on serum 
hormone levels, hepatic enzyme activity, and thyroid-pituitary hormonal 
feedback mechanisms.

B. Metabolism in Plants and Animals

    The metabolism of thiazopyr in plants and animals is adequately 
understood for the purposes of these tolerances. There were no crop 
residues found after the preemergence use in the culture of orange and 
grapefruit. The metabolites that were identified in a radiolabeled 
thiazopyr study and converted to two common entities: amide ester and 
sulfonic diacid. However, the Agency has accepted enforcement 
analytical methodology that uses only one common entity to determine 
greater than 70% of the expected thiazopyr residues.

C. Analytical Method

    There is a practical analytical method for detecting and measuring 
levels of thiazopyr and its metabolites in or on food with a limit of 
detection that allows monitoring of food with residues at or above the 
levels set in these tolerances. The proposed analytical method for 
determining residues is gas-liquid chromatography with mass selective 
detection. Thiazopyr and its metabolites are converted to a common 
moiety which is quantified. The quantitation limit of this method is 
0.015 ppm for whole orange fruit. EPA has provided information on this 
method to FDA. Because of the long lead time from establishing these 
tolerances to publication, the enforcement methodology is being made 
available in the interim to anyone interested in pesticide enforcement 
when requested by mail from: Calvin Furlow, Public Response Branch, 
Field Operations Division (7506C), Office of Pesticide Programs, 
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. 
Office location and telephone umber: Rm. 1130A, CM #2, 1921 Jefferson 
Davis Hwy., Arlington, VA 22202, (703)-305-5937.

D. International Tolerances

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

E. Summary of Findings

    The analysis for thiazopyr using tolerance level residues shows 
that the proposed uses in the culture of orange and grapefruit will not 
cause exposure to exceed the levels at which the Agency believes there 
is an appreciable risk. All population subgroups examined by EPA are 
exposed to thiazopyr residues at levels below 100 percent of the RfD 
for chronic effects.
    Based on the information cited above, the Agency has determined 
that the establishment of these tolerances by adding a new section to 
40 CFR part 180

[[Page 9978]]

will be safe; therefore, the tolerances are established as set forth 
below.

VI. 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 (1)(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 governs 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 those procedural regulations with appropriate adjustments to 
reflect the new law.
    Any person may, by May 5, 1997, file written objections to any 
aspect of this regulation (including the automatic revocation 
provision) 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 issue(s) on which a hearing is requested, the 
requestor's contentions on such issues, and a summary of any evidence 
relied upon by the objector (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 a 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 issue(s) 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.

VII. Public Docket

    A record has been established for this rulemaking under docket 
number [OPP-300455]. A public version of this record, 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 
Response and Program Resources Branch, Field Operation Division 
(7506C), Office of Pesticide Programs, Environmental Protection Agency, 
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA. EPA has 
also established a special record for post-FQPA tolerances which 
contains documents of general applicability. This record can be found 
in the same location.
    The official record for this rulemaking, as well as the public 
version, as described above, is kept in paper form. Accordingly, in the 
event there are objections and hearing requests, 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. The official rulemaking 
record is the paper record maintained at the Virginia address in 
``ADDRESSES'' at the beginning of this document.

VIII. Regulatory Assessment Requirements

    Under Executive Order 12866 (58 FR 51735, Oct. 4, 1993), this 
action is not a ``significant regulatory action'' and since this action 
does not impose any information collection requirements subject to 
approval under the Paperwork Reduction Act, 44 U.S.C. 3501 et seq., it 
is not subject to review by the Office of Management and Budget. In 
addition, this action does not impose any enforceable duty, or contain 
any ``unfunded mandates'' as described in Title II of the Unfunded 
Mandates Reform Act of 1995 (Pub. L. 104-4), or require prior 
consultation as specified by Executive Order 12875 (58 FR 58093, 
October 28, l993), or special considerations as required by Executive 
Order 12898 (59 FR 7629, February 16, l994).
    Because tolerances established on the basis of a petition under 
section 408(d) of FFDCA do not require issuance of a proposed rule, the 
regulatory flexibility analysis requirements of the Regulatory 
Flexibility Act (RFA), 5 U.S.C. 604(a), do not apply. Prior to the 
recent amendment of the FFDCA, EPA had treated such rulemakings as 
subject to the RFA; however, the amendments to the FFDCA clarify that 
no proposal is required for such rulemakings and hence that the RFA is 
inapplicable.
    Under 5 U.S.C. 801(a)(1)(A) of the Administrative Procedure Act 
(APA) as amended by the Small Business Regulatory Enforcement Fairness 
Act of 1996 (Title II of Pub. L. 104-121, 110 Stat. 847), EPA 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 the 
rule in today's Federal Register. This rule is not a ``major rule'' as 
defined by 5 U.S.C. 804(2) of the APA as amended.

List of Subjects in 40 CFR Part 180

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

    Dated: February 19, 1997.

Stephanie R. Irene,

Acting Director, Office of Pesticide Programs.

    Therefore, 40 CFR part 180 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 adding Sec. 180.496 to read as folllows:


Sec. 180.496  Thiazopyr; tolerances for residues.

    Tolerances are established for combined residues of the herbicide 
thiazopyr (3-pyridinecaroxylic acid, 2-(difluoromethyl)-5-(4,5-dihydro-
2-thiazolyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-, methyl ester) and 
its metabolites determined as 2-(difluoromethyl)-6-(trifluoromethyl)-
3,4,5-pyridinetricarboxylic acid, all expressed as the parent 
equivalents in or on the following raw agricultural commodities:

------------------------------------------------------------------------
                Commodities                       Parts per million     
------------------------------------------------------------------------
Grapefruit................................  0.05                        
Orange....................................  0.05                        
------------------------------------------------------------------------

[FR Doc. 97-5201 Filed 3-4-97; 8:45 am]
BILLING CODE 6560-50-F


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