9974 Federal Register / Vol. 62, No. 43 / Wednesday, March 5, 1997 / Rules and Regulations

40 CFR Part 180

[OPP–300455; FRL–5591–5]

RIN No. 2070–AB78

Thiazopyr; Pesticide Tolerances

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Final rule.

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 (email) 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 email. 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
Federal Register / Vol. 62, No. 43 / Wednesday, March 5, 1997 / Rules and Regulations 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
9976 Federal Register / Vol. 62, No. 43 / Wednesday, March 5, 1997 / Rules and Regulations

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 nondietary 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
Federal Register / Vol. 62, No. 43 / Wednesday, March 5, 1997 / Rules and Regulations 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 gasliquid 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
9978 Federal Register / Vol. 62, No. 43 / Wednesday, March 5, 1997 / Rules and Regulations

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 § 180.496 to read as

folllows:

§ 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]

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