[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: opp-docket@epamail.epa.gov. 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:
miller.joanne@epamail.epa.gov.
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 14C at the 4 position of the
pyridine ring and one with the 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
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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
