Tebufenozide; Benzoic Acid, 3,5-dimethyl-1-(1,1-dimethylethyl)-2- (4-ethylbenzoyl) hydrazide; Pesticide Tolerance

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-300928; FRL-6382-6]

RIN 2070-AB78

Tebufenozide; Benzoic Acid, 3,5-dimethyl-1-(1,1-dimethylethyl)-2-

(4-ethylbenzoyl) hydrazide; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes a time limited tolerance for the

indirect or inadvertent combined residues of tebufenozide and its

metabolite benzoic acid, 3,5-dimethyl-1-(1,1-dimethylethyl)-2-4-(1-

hydroxyethyl)benzoylhydrazide in or on foliage of legume vegetables at

0.1 parts per million (ppm); forage, fodder, hay and straw of cereal

grains at 0.5 ppm; grass forage, fodder and hay at 0.5 ppm and forage,

fodder, straw and hay of non-grass animal feeds at 0.5 ppm. Rohm and

Haas Company requested these tolerances under the Federal Food, Drug,

and Cosmetic Act, as amended by the Food Quality Protection Act of

1996.

DATES: This regulation is effective October 21, 1999. Objections and

requests for hearings, identified by docket control number OPP-300928,

must be received by EPA on or before December 20, 1999.

ADDRESSES: Written objections and hearing requests may be submitted by

mail, in person, or by courier. Please follow the detailed instructions

for each method as provided in Unit VI. of the ``SUPPLEMENTARY

INFORMATION'' section. To ensure proper receipt by EPA, your objections

and hearing requests must identify docket control number OPP-300928 in

the subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Joseph Tavano, Registration

Division (7505C), Office of Pesticide Programs, Environmental

Protection Agency, 401 M St., SW., Washington, DC 20460; telephone

number: (703) 305-6411; and e-mail address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

You may be affected by this action if you are an agricultural

producer, food manufacturer, or pesticide manufacturer. Potentially

affected categories and entities may include, but are not limited to:

------------------------------------------------------------------------

Examples of

Categories NAICS Potentially

Affected Entities

------------------------------------------------------------------------

Industry 111 Crop production

112 Animal production

311 Food manufacturing

32532 Pesticide

manufacturing

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This listing is not intended to be exhaustive, but rather provides

a guide for readers regarding entities likely to be affected by this

action. Other types of entities not listed in the table could also be

affected. The North American Industrial Classification System (NAICS)

codes have been provided to assist you and others in determining

whether or not this action might apply to certain entities. If you have

questions regarding the applicability of this action to a particular

entity, consult the person listed in the ``FOR FURTHER INFORMATION

CONTACT'' section.

B. How Can I Get Additional Information, Including Copies of this

Document and Other Related Documents?

1. Electronically.You may obtain electronic copies of this

document, and certain other related documents that might be available

electronically, from the EPA Internet Home Page at http://www.epa.gov/.

To access this document, on the Home Page select ``Laws and

Regulations'' and then look up the entry for this document under the

``Federal Register--Environmental Documents.'' You can also go directly

to the Federal Register listings at http://www.epa.gov/fedrgstr/.

2. In person. The Agency has established an official record for

this action under docket control number OPP-300928. The official record

consists of the documents specifically referenced in this action, and

other information related to this action, including any information

claimed as Confidential Business Information (CBI). This official

record includes the documents that are physically located in the

docket, as well as the documents that are referenced in those

documents. The public version of the official record does not include

any information claimed as CBI. The public version of the official

record, which includes printed, paper versions of any electronic

comments submitted during an applicable comment period is available for

inspection in the Public Information and Records Integrity Branch

(PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Hwy.,

Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday,

excluding legal holidays. The PIRIB telephone number is (703) 305-5805.

II. Background and Statutory Findings

In the Federal Register of July 2, 1999 (64 FR 35999) (FRL-6085-6)

and September 1, 1999 (64 FR 47795) (FRL-6096-8), EPA issued a notice

pursuant to section 408 of the Federal Food, Drug, and Cosmetic Act

(FFDCA), 21 U.S.C. 346a as amended by the Food Quality Protection Act

of 1996 (FQPA) (Pub. L. 104-170) announcing the filing of a pesticide

petition (PP) for tolerance by Rohm and Haas Company, 100 Independence

Mall West, Philadelphia, PA 19106-2399. This notice included a summary

of the petition prepared by Rohm and Haas Company, the registrant.

There were no comments received inresponse to these notices of filing.

The petition requested that 40 CFR 180. 482 be amended by

establishing a tolerance for indirect or inadvertent residues of the

insecticide, tebufenozide benzoic acid, 3,5-dimethyl-1-(1,1-

dimethylethyl)-2-(4-ethylbenzoyl)hydrazide and its metabolite benzoic

acid, 3,5-dimethyl-1-(1,1-dimethylethyl)-2-4-

(hydroxyethyl)benzoyl]benzoyl in or on foliage of legume vegetables;

forage, fodder, hay and straw of cereal grains; grass forage, fodder

and hay; and forage, fodder, straw and hay of nongrass animal feeds at

0.1, 0.5, 0.5 and 0.5 part per million (ppm) respectively. Tebufenozide

is a reduced risk pesticide.

Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a

tolerance (the legal limit for a pesticide chemical residue in or on a

food) only if EPA determines that the tolerance is ``safe.'' Section

408(b)(2)(A)(ii) defines ``safe'' to mean that ``there is a reasonable

certainty that no harm will result from aggregate exposure to the

pesticide chemical residue, including all anticipated dietary exposures

and all other exposures for which there is reliable information.'' This

includes exposure through drinking water and in residential settings,

but does not include occupational exposure. Section 408(b)(2)(C)

requires EPA to give special consideration to exposure of infants and

children to the pesticide chemical residue in establishing a tolerance

and to ``ensure that there is a reasonable certainty that no harm will

result to infants and children from aggregate exposure to the pesticide

chemical residue....''

EPA performs a number of analyses to determine the risks from

aggregate

[[Page 56691]]

exposure to pesticide residues. For further discussion of the

regulatory requirements of section 408 and a complete description of

the risk assessment process, see the final rule on Bifenthrin Pesticide

Tolerances (62 FR 62961, November 26, 1997) (FRL-5754-7).

III. Aggregate Risk Assessment and Determination of Safety

Consistent with section 408(b)(2)(D), EPA has reviewed the

available scientific data and other relevant information in support of

this action. EPA has sufficient data to assess the hazards of and to

make a determination on aggregate exposure, consistent with section

408(b)(2), for a tolerance for the combined residues of tebufenozide

and its metabolite benzoic acid, 3,5-dimethyl-1-(1,1-dimethylethyl)-2-

[4-(1-hydroxyethyl)benzoyl]hydrazide on foliage of legume vegetables;

forage, fodder, hay and straw of cereal grains; grass forage, fodder

and hay and forage, fodder, straw and hay of nongrass animal feeds at

0.1, 0,5, 0.5 and 0.5 ppm respectively. EPA's assessment of the dietary

exposures and risks associated with establishing the tolerance follows.

A. Toxicological Profile

EPA has evaluated the available toxicity data and considered its

validity, completeness, and reliability as well as the relationship of

the results of the studies to human risk. EPA has also considered

available information concerning the variability of the sensitivities

of major identifiable subgroups of consumers, including infants and

children. The nature of the toxic effects caused by are discussed in

this unit.

1. Acute toxicity studies with technical grade: Oral

LD50 in the rat is > 5 grams for males and females -

Toxicity Category IV; dermal LD50 in the rat is = 5,000

milligram/kilogram (mg/kg) for males and females - Toxicity Category

III; inhalation LC50 in the rat is >4.5 mg/l - Toxicity

Category III; primary eye irritation study in the rabbit is a non-

irritant; primary skin irritation in the rabbit >5mg - Toxicity

Category IV. Tebufenozide is not a sentizer.

2. In a 21-day dermal toxicity study, Crl:CD rats (6/sex/dose)

received repeated dermal administration of either the technical 96.1%

product [RH-75,992] at 1,000 mg/kg/day (Limit-Dose) or the formulation

(23.1% a.i. product [RH-755,992 2F] at 0, 62.5, 250, or 1,000 mg/kg/

day, 6 hours/day, 5 days/week for 21 days. Under conditions of this

study, RH-75,992 Technical or RH-75,992 2F demonstrated no systemic

toxicity or dermal irritation at the highest dose tested (HDT) 1,000

mg/kg/day during the 21 day study. Based on these results, the NOAEL

for systemic toxicity and dermal irritation in both sexes is 1,000 mg/

kg/day HDT. A LOAEL for systemic toxicity and dermal irritation was not

established.

3. A 1-year dog feeding study with a lowest-observable-adverse-

effect level (LOAEL) of 250 ppm (9 mg/kg/day for male and female dogs)

based on decreases in RBC, HCT, and HGB, increases in Heinz bodies,

methemoglobin, MCV, MCH, reticulocytes, platelets, plasma total

bilirubin, spleen weight, and spleen/body weight ratio, and liver/body

weight ratio. Hematopoiesis and sinusoidal engorgement occurred in the

spleen, and hyperplasia occurred in the marrow of the femur and

sternum. The liver showed an increased pigment in the Kupffer cells.

The no-observed adverse effect level (NOAEL) for systemic toxicity in

both sexes is 50 ppm (1.9 mg/kg/day).

4. An 18-month mouse carcinogenicity study with no carcinogenicity

observed at dosage levels up to and including 1,000 ppm.

5. A 2-year rat carcinogenicity with no carcinogenicity observed at

dosage levels up to and including 2,000 ppm (97 mg/kg/day and 125 mg/

kg/day for males and females, respectively)

6. In a prenatal developmental toxicity study in Sprague-Dawley

rats (25/group) Tebufenozide was administered on gestation days 6-15 by

gavage in aqueous methyl cellulose at dose levels of 50, 250, or 1,000

mg/kg/day and a dose volume of 10 ml/kg. There was no evidence of

maternal or developmental toxicity; the maternal and developmental

toxicity NOAEL was 1,000 mg/kg/day.

7. In a prenatal developmental toxicity study conducted in New

Zealand white rabbits (20/group) Tebufenozide was administered in 5 ml/

kg of aqueous methyl cellulose at gavage doses of 50, 250, or 1000 mg/

kg/day on gestation days 7-19. No evidence of maternal or developmental

toxicity was observed; the maternal and developmental toxicity NOAEL

was 1,000 mg/kg/day.

8. In a 1993 two-generation reproduction study in Sprague-Dawley

rats tebufenozide was administered at dietary concentrations of 0, 10,

150, or 1,000 ppm (0, 0.8, 11.5, or 154.8 mg/kg/day for males and 0,

0.9, 12.8, or 171.1 mg/kg/day for females). The parental systemic NOAEL

was 10 ppm (0.8/0.9 mg/kg/day for males and females, respectively) and

the LOAEL was 150 ppm (11.5/12.8 mg/kg/day for males and females,

respectively) based on decreased body weight, body weight gain, and

food consumption in males, and increased incidence and/or severity of

splenic pigmentation. In addition, there was an increased incidence and

severity of extramedullary hematopoiesis at 2,000 ppm. The reproductive

NOAEL was 150 ppm. (11.5/12.8 mg/kg/day for males and females,

respectively) and the LOAEL was 2,000 ppm (154.8/171.1 mg/kg/day for

males and females, respectively) based on an increase in the number of

pregnant females with increased gestation duration and dystocia.

Effects in the offspring consisted of decreased number of pups per

litter on postnatal days 0 and/or 4 at 2,000 ppm (154.8/171.1 mg/kg/day

for males and females, respectively) with a NOAEL of 150 ppm (11.5/12.8

mg/kg/day for males and females, respectively).

9. In a 1995 2-generation reproduction study in rats tebufenozide

was administered at dietary concentrations of 0, 25, 200, or 2,000 ppm

(0, 1.6, 12.6, or 126.0 mg/kg/day for males and 0, 1.8, 14.6, or 143.2

mg/kg/day for females). For parental systemic toxicity, the NOAEL was

25 ppm (1.6/1.8 mg/kg/day in males and females, respectively), and the

LOAEL was 200 ppm (12.6/14.6 mg/kg/day in males and females), based on

histopathological findings (congestion and extramedullary

hematopoiesis) in the spleen. Additionally, at 2,000 ppm (126.0/143.2

mg/kg/day in M/F), treatment-related findings included reduced parental

body weight gain and increased incidence of hemosiderin-laden cells in

the spleen. Columnar changes in the vaginal squamous epithelium and

reduced uterine and ovarian weights were also observed at 2,000 ppm,

but the toxicological significance was unknown. For offspring, the

systemic NOAEL was 200 ppm. (12.6/14.6 mg/kg/day in males and females),

and the LOAEL was 2,000 ppm (126.0/143.2 mg/kg/day in M/F) based on

decreased body weight on postnatal days 14 and 21.

10. Several mutagenicity tests which were all negative. These

include an Ames assay with and without metabolic activation, an in vivo

cytogenetic assay in rat bone marrow cells, and in vitro chromosome

aberration assay in CHO cells, a CHO/HGPRT assay, a reverse mutation

assay with E. Coli, and an unscheduled DNA synthesis assay (UDS) in rat

hepatocytes.

11. The pharmacokinetics and metabolism of tebufenozide were

studied in female Sprague-Dawley rats (3-6/sex/group) receiving a

single oral dose of 3 or 250 mg/kg of RH-5992, 14C labeled

in one of three positions (A-ring, B-ring or N-butylcarbon). The extent

of

[[Page 56692]]

absorption was not established. The majority of the radiolabeled

material was eliminated or excreted in the feces within 48 hours within

48 hours; small amounts (1 to 7% of the administered dose) were

excreted in the urine and only traces were excreted in expired air or

remained in the tissues. There was no tendency for bioacculmulation.

Absorption and excretion were rapid.

A total of 11 metabolites, in addition to the parent compound, were

identified in the feces; the parent compound accounted for 96 to 99% of

the administered radioactivity in the high dose group and 35 to 43% in

the low dose group. No parent compound was found in the urine; urinary

metabolites were not characterized. The identity of several fecal

metabolites was confirmed by mass spectral analysis and other fecal

metabolites were tentatively identified by cochromatography with

synthetic standards. A pathway of metabolism was proposed based on

these data. Metabolism proceeded primarily by oxidation of the three

benzyl carbons,. two methyl groups on the Bring and an ethyl group on

the A ring to alcohols, aldehydes or acids. The type of metabolite

produced varies depending on the position oxidized and extent of

oxidation. The butyl group on the quaternary nitrogen also can be

leaved (minor), but there was no fragmentation of the molecule between

the benzyl rings.

No qualitative differences in metabolism were observed between

sexes, when high or low dose groups were compared or when different

labeled versions of the molecule were compared.

12. The absorption and metabolism of tebufenozide were studied in a

group of male and female bile-duct cannulated rats. Over a 72 hour

period, biliary excretion accounted for 30% (Male) to 34% (Female) of

the administered dose while urinary excretion accounted for

5% of the administered dose and the carcass accounted for

5% of the total administered dose. Total bile

radioactivity accounted for 17% of the total administered

dose.

No major qualitative differences in biliary metabolites were

observed between sexes. The metabolic profile in the bile was similar

to the metabolic profile in the feces and urine.

B. Toxicological Endpoints

1. Acute toxicity. Toxicity observed in oral toxicity studies were

not attributable to a single dose (exposure). No neuro or systemic

toxicity was observed in rats given a single oral administration of

tebufenozide at 0, 500, 1,000, or 2,000 mg/kg. No maternal or

developmental toxicity was observed following oral administration of

tebufenozide at 1,000 mg/kg/day (Limit-Dose) during gestation to

pregnant rats or rabbits. Thus the risk from acute exposure is

considered negligible.

2. Short- and intermediate-term toxicity. No dermal or systemic

toxicity was seen in rats receiving 15 repeated dermal applications of

the technical (97.2%) product at 1,000 mg/kg/day (Limit- Dose) as well

as a formulated (23% a.i) product at 0, 62.5, 250, or 1,000 mg/kg/day

over a 21 day period. The Agency noted that in spite of the

hematological effects seen in the dog study, similar effects were not

seen in the rats receiving the compound via the dermal route indicating

poor dermal absorption. Also, no developmental endpoints of concern

were evident due to the lack of developmental toxicity in either rat or

rabbit studies. This risk is considered to be negligable.

3. Chronic toxicity. EPA has established the chronic population

adjusted dose (cPAD) for tebufenozide at 0.018 mg/kg/day. This endpoint

is based on the NOAEL of 1.8 mg/kg/day from a chronic toxicity study in

dogs. Growth retardation, alterations in hematology parameters, changes

in organ weights, and histopathological lesions in the bone, spleen and

liver were observed at the LOAEL of 8.7 mg/kg/day in this study. An

uncertainty factor (UF) of 100 was applied to account for inter- (10 x)

and intra- (10 x) species variation resulting in a chronic RfD of 1.8

mg/kg/day 100 = 0.018 mg/kg/day. For chronic dietary risk

assessment, the 10 x factor to account for the protection of infants

and children (as required by FQPA) was removed. Therefore, the chronic

population adjusted dose (cPAD) is identical to the chronic RfD, cPAD =

chronic RfD = 0.018 mg/kg/day. Removing the 10x factor is supported by

the following factors:

i. Developmental toxicity studies showed no increased sensitivity

in fetuses when compared to maternal animals following in utero

exposures in rats and rabbits.

ii. Multi-generation reproduction toxicity studies in rats showed

no increased sensitivity in pups as compared to adults and offspring.

(iii) There are no data gaps.

4. Carcinogenicity. Tebufenozide has been classified as a Group E,

``no evidence of carcinogenicity for humans,'' chemical by EPA.

C. Exposures and Risks

1. From food and feed uses. Tolerances have been established (40

CFR 180.482) for the residues of tebufenozide, in or on a variety of

raw agricultural commodities. In today's action, Tolerances will be

established for the indirect or inadvertent combined residues of

tebufenozide and its metabolite benzoic acid, 3,5-dimethyl-1-(1,1-

dimethylethyl)-2-[4-(1-hydroxyethyl)benzoyl]hydrazide in or on foliage

of legume vegetables; forage, fodder, hay and straw of cereal grains;

grass forage, fodder and hay and forage, fodder, straw and hay of

nongrass animal feeds at 0.1, 0.5, 0.5 and 0.5 ppm respectively. Risk

assessments were conducted by EPA to assess dietary exposures from as

follows:

Section 408(b)(2)(F) states that the Agency may use data on the

actual percent of crop treated (PCT) for assessing chronic dietary risk

only if the Agency can make the following findings: That the data used

are reliable and provide a valid basis to show what percentage of the

food derived from such crop is likely to contain such pesticide

residue; that the exposure estimate does not underestimate exposure for

any significant subpopulation group; and if data are available on

pesticide use and food consumption in a particular area, the

[[Page 56693]]

exposure estimate does not understate exposure for the population in

such area. In addition, the Agency must provide for periodic evaluation

of any estimates used. To provide for the periodic evaluation of the

estimate of PCT as required by section 408(b)(2)(F), EPA may require

registrants to submit data on PCT.

The Agency used PCT information as follows:

Estimates of percent crop treated were used for the following

crops. In all cases the maximum estimate was used.

------------------------------------------------------------------------

Percentage

Commodity ---------------------------------------

Average Maximum

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Almonds:........................ 1

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U.S. Population (48 States)..... 0.0017 10

Children (1-6 years old)........ 0.0038 21

Females (13+/nursing)........... 0.0017 10

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\1\ cPAD% = Exposure/cPAD X 100%

The subgroups listed above are: (1) the U.S. population (48 states);

(2) highest exposed population subgroup that includes infants and

children; and (3) Female 13+.

This chronic dietary (food only) risk assessment should be viewed

as conservative. Further refinement using anticipated residue values

and additional % crop treated information would result in a lower

estimate of chronic dietary exposure.

2. From drinking water-- i. Acute exposure and risk. Because no

acute dietary endpoint was determined, the Agency concludes that there

is a reasonable certainty of no harm from acute exposure from drinking

water.

ii. Chronic exposure and risk. EPA calculated the Tier I Estimated

Environmental Concentrations (EECs) for tebufenozideusing GENEEC

(surface water) and SCI-GROW (ground water) for use in the human health

risk assessment. For chronic exposure, the worst case EECs for surface

water and ground water were 16.5 ppb and 1.04 ppb, respectively. These

values represent upper-bound estimates of the concentrations that might

be found in surface and ground water. These modeling data were compared

to the chronic drinking water levels of comparison (DWLOCs) for

tebufenozide in ground and surface water.

For purposes of chronic risk assessment, the estimated maximum

concentration for tebufenozide in surface and ground waters (16.5

ppb=16.5 g/L) was compared to the back-calculated human health DWLOCs

for the chronic (non-cancer) endpoint. These DWLOCs for various

population categories are summarized in the following table.

Drinking Water Levels of Comparison for Chronic Exposure to Tebufenozide

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Chronic RfD (mg/kg/ Food Exposure (mg/kg/ Max. Water Exposure EEC Calc.Max. (g/L) m>g/L)

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U.S. Population (48 states)........ 0.018 0.0017 0.016 560 16.5

Female (13+ years)................. 0.018 0.0017 0.016 480 16.5

Children (1-6)..................... 0.018 0.0038 0.014 140 16.5

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[[Page 56694]]

In performing this risk assessment, EPA has calculated drinking

water levels of comparison (DWLOCs) for each of the DEEM population

subgroups. Within each subgroup, the population with the highest

estimated exposure was used to determine the maximum concentration of

tebufenozide that can occur in drinking water without causing an

unacceptable human health risk. As a comparison value, EPA has used the

16.5-ppb value in this risk assessment, as this represents a worst-case

scenario. The DWLOCs for tebufenozide are above the DWEC of 16.5 ppb

for all population subgroups. Therefore, the human health risk from

exposure to tebufenozide through drinking water in not likely to exceed

EPA's level of concern.

3. From non-dietary exposure. Tebufenozide is not currently

registered for use on any residential non-food sites. Therefore there

are no non-dietary acute, chronic, short- or intermediate-term exposure

scenarios.

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.''

EPA does not have, at this time, available data to determine

whether has a common mechanism of toxicity with other substances or how

to include this pesticide in a cumulative risk assessment. Unlike other

pesticides for which EPA has followed a cumulative risk approach based

on a common mechanism of toxicity, does not appear to produce a toxic

metabolite produced by other substances. For the purposes of this

tolerance action, therefore, EPA has not assumed that has a common

mechanism of toxicity with other substances. For information regarding

EPA's efforts to determine which chemicals have a common mechanism of

toxicity and to evaluate the cumulative effects of such chemicals, see

the final rule for Bifenthrin Pesticide Tolerances (62 FR 62961,

November 26, 1997).

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

1. Acute risk. Since no acute toxicological endpoints were

established, no acute aggregate risk exists.

2. Chronic risk. Using the somewhat conservative exposure

assumptions described above, and taking into account the completeness

and reliability of the toxicity data, HED has concluded that dietary

(food only) exposure to tebufenozide will utilize 10% of the cPAD for

the U.S. population, and 21% of the cPAD for the most highly exposed

population subgroup (Children 1-6 yr). Submitted environmental fate

studies suggest that tebufenozide is moderately persistent to

persistent and mobile; thus, tebufenozide could potentially leach to

ground water and runoff to surface water under certain environmental

conditions. The modeling data for tebufenozide indicate levels less

than HED's DWLOCs. EPA generally has no concern for exposures below

100% of the cPAD. Since there are no registered residential uses of

tebufenozide, there is no potential for exposure to tebufenozide from

residential uses. HED concludes that there is a reasonable certainty

that no harm will result to adults, infants and children from chronic

aggregate exposure to tebufenozide residues.

3. Short- and intermediate-term risk. Short- and intermediate-term

aggregate exposure takes into account chronic dietary food and water

(considered to be a background exposure level) plus indoor and outdoor

residential exposure.

Since there are currently no registered indoor or outdoor

residential non-dietary uses of tebufenozide and no short- or

intermediate-term toxic endpoints, short- or intermediate-term

aggregate risks do not exist.

4. Aggregate cancer risk for U.S. population. Since tebufenozide

has been classified as a Group E, ``no evidence of carcinogenicity for

humans,'' this risk does not exist.

5. Determination of safety. Based on these risk assessments, EPA

concludes that there is a reasonable certainty that no harm will result

from aggregate exposure to tebufenozide residues.

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

1. Safety factor for infants and children-- i. In general. In

assessing the potential for additional sensitivity of infants and

children to residues of , EPA considered data from developmental

toxicity studies in the rat and rabbit and a 2-generation reproduction

study in the rat. The developmental toxicity studies are designed to

evaluate adverse effects on the developing organism resulting from

maternal pesticide exposure gestation. Reproduction studies provide

information relating to effects from exposure to the pesticide on the

reproductive capability of mating animals and data on systemic

toxicity.

FFDCA section 408 provides that EPA shall apply an additional

tenfold margin of safety for infants and children in the case of

threshold effects to account for pre-and post-natal toxicity and the

completeness of the database unless EPA determines that a different

margin of safety will be safe for infants and children. Margins of

safety are incorporated into EPA risk assessments either directly

through use of a margin of exposure (MOE) analysis or through using

uncertainty (safety) factors in calculating a dose level that poses no

appreciable risk to humans. EPA believes that reliable data support

using the standard uncertainty factor (usually 100 for combined inter-

and intra-species variability) and not the additional tenfold MOE/

uncertainty factor when EPA has a complete data base under existing

guidelines and when the severity of the effect in infants or children

or the potency or unusual toxic properties of a compound do not raise

concerns regarding the adequacy of the standard MOE/safety factor.

ii. Pre- and post-natal sensitivity. The toxicology data base for

tebufenozide included acceptable developmental toxicity studies in both

rats and rabbits as well as a two-generation reproductive toxicity

study in rats.The data provided no indication of increased sensitivity

of rats or rabbits to in utero and/or postnatal exposure to

tebufenozide. No maternal or developmental findings were observed in

the prenatal developmental toxicity studies at doses up to 1000 mg/kg/

day in rats and rabbits. In the two-generation reproduction studies in

rats, effects occurred at the same or lower treatment levels in the

adults as in the offspring.

iii. Conclusion. There is a complete toxicity database for

tebufenozide and exposure data is complete and reasonably accounts for

potential exposures. For the reasons summarized above, EPA concluded

that an additional safety factor is not needed to protect the safety of

infants and children.

2. Acute risk. Since no acute toxicological endpoints were

established, no acute aggregate risk exists.

3. Chronic risk. Using the exposure assumptions described in this

unit, EPA has concluded that aggregate exposure to tebufenozide from

food will utilize 21% of the cPAD for infants and children. Submitted

environmental fate studies suggest that tebufenozide is moderately

persistent to persistent and mobile; thus, tebufenozide could

potentially leach to ground water and runoff to surface water under

certain environmental conditions. The modeling data for tebufenozide

indicate levels less than HED's DWLOCs. EPA generally has no concern

for exposures

[[Page 56695]]

below 100% of the cPAD because the cPAD represents the level at or

below which daily aggregate dietary exposure over a lifetime will not

pose appreciable risks to human health. Since there are no registered

residential uses of tebufenozide, there is no potential for exposure to

tebufenozide from residential uses. EPA concludes that there is a

reasonable certainty that no harm will result to adults, infants and

children from chronic aggregate exposure to tebufenozide residues.

4. Short- or intermediate-term risk. Short and intermediate term

risks are judged to be negligible due to the lack of significant

toxicological effects observed.

5. Determination of safety. Based on these risk assessments, EPA

concludes that there is a reasonable certainty that no harm will result

to infants and children from aggregate exposure to tebufenozide

residues.

IV. Other Considerations

A. Metabolism in Plants and Animals

The qualitative nature of the residue in plants is adequately

understood based upon acceptable apple, sugar beet, and rice metabolism

studies. EPA has concluded that the residue of regulatory concern is

tebufenozide per se.The qualitative nature of the residues in animals

is also adequately understood based on acceptable poultry and ruminant

metabolism studies. For animals, EPA has concluded that the residues of

regulatory concern are tebufenozide and its metabolites benzoic acid,

3,5-dimethyl-1-(1,1-dimethylethyl)-2-((4-carboxymethyl)

benzoyl)hydrazide) , benzoic acid, 3-hydroxymethyl,5-methyl-1-(1,1-

dimethylethyl)-2-(4-ethylbenzoyl)hydrazide , the stearic acid conjugate

of benzoic acid, 3-hydroxymethyl,5-methyl-1-(1,1-dimethylethyl)-2-(4-

ethylbenzoyl)hydrazide and benzoic acid, 3-hydroxymethyl-5-methyl-1-

(1,1-dimethylethyl)-2-(4-(1-hydroxyethyl)benzoyl)hydrazide.

B. Analytical Enforcement Methodology

The petitioner has submitted method validation/concurrent recovery

studies for a proposed enforcement method. This HPLC/MS method, Rohm

and Haas Method TR 34-99-10 which is a combination of methods TR 34-97-

91 and TR 34-98-149, is to be used for determining residues of

tebufenozide in/on rotated crops. The method, entitled ``Tolerance

Enforcement Method for RH-5992 and Its Metabolites in Rotation Crops''

has undergone successful independent laboratory validation . It also

has been adequately radiovalidated and an HPLC/MS-MS confirmatory

method exists. The proposed enforcement method for rotated crops for

determining residues of tebufenozide and metabolites, is adequate for

collection of residue data.A copy of the method has been forwarded to

the Analytical Chemistry Branch (ACB) for petition method validation

(PMV) as a possible enforcement method. The proposed enforcement method

has not been subjected to a complete Agency method validation at this

time. EPA has conducted a preliminary review of the method that

indicates that it appears to be suitable for enforcement purposes

pending the outcome of the actual method validation. Given that the

registrant has provided concurrent fortification data to demonstrate

that the method is adequate for data collection purposes and has

provided the Agency with a successful Independent Laboratory

Validation, coupled with EPA's preliminary review, EPA concludes that

the method is suitable as an enforcement method to support tolerances

associated with a conditional registration only. As a condition of the

registration, the Agency will require a successful method validation

and the registrant will be required to make any necessary modifications

to the method resulting from the laboratory validation.

This method may be requested from: Calvin Furlow, PRRIB, IRSD

(7502C), Office of Pesticide Programs, Environmental Protection Agency,

401 M St., SW., Washington, DC 20460; telephone number: (703) 305-5229;

e-mail address: [email protected]..

C. Magnitude of Residues

The foliage portions of representative crops from the cereal grain

and legume crop groups show quantifiable residues of the tebufenozide

metabolite RH-1788 at the 30-day plantback interval. A tolerance is

required on those commodities which have quantifiable residues: cereal

grain straw and hay, and foliage of legume vegetables. Given the

limited amount of data, the cereal grain tolerances should be extended

to forage and fodder as well. Tolerances on rotated crops would

normally require the same number and geographic location of residue

field trials as those required were they primary crops. In this case,

the crops for which rotational crop tolerances are requested, small

grains and legumes, have much greater production acreage and geographic

distribution than most of the registered tebufenozide primary crop

uses. Rather than requiring the number and geographic diversity of the

rotated crop field trials, which would entail trying to grow and treat

primary crops in regions where tebufenozide is unlikely to be used, EPA

will require using the number and geographic diversity for field trials

of a primary crop likely to be rotated to grains/legumes and with a use

pattern which would produce the conditions for highest possible residue

in rotated crops.

The most significant crops or crop groups which are rotated and

have registered tebufenozide uses are Brassica (cole) and leafy

vegetables, cotton, and fruiting vegetables. The primary crops which

have the essentially the highest use pattern, (0.92 lb ai/A/season),

shortest PHI (7 days), highest current tolerances (2-10 ppm vs 0.8 for

fruiting vegetables), and are most likely to be rotated are Brassica

(cole) and leafy vegetables. Leaf lettuce is the crop within these crop

groups with the highest consumption by the general population. Eight

trials are normally required to establish a tolerance on leaf lettuce.

The registrant has submitted two trials each on small grains and

legumes. Therefore, EPA will require 6 additional crop field trials

(the number of residue trials required for leaf lettuce) for the

foliages of both rotated small cereal grains (e.g., wheat, barley, or

oats) and legumes, for a total of 12 additional trials, to establish

the requested tolerances on cereal grains and legumes for a 30-day

plantback interval. The guidelines would normally require 63 total

trials on these crops groups. A significant reduction in data will be

acceptable in this case since this is a reduced risk pesticide,

residues are found only in livestock feed items, and those residues do

not impact tolerances for animal commodities. Additional data will not

be required for grass forage, fodder, and straw and on non-grass animal

feeds (forage, fodder, straw, and hay).The small grain and legume

foliage data will be translated to these commodities. Up to 4 years may

be required to generate and review the additional rotational crop data.

To allow the rotation of crops while additional data are generated, EPA

is issuing time-limited tolerances on cereal grain forage, fodder,

straw, and hay; grass forage, fodder, and straw and non-grass animal

feeds (forage, fodder, straw, and hay) at 0.5 ppm, and legume forage at

0.1 ppm. Upon receipt of the additional data, the proposed tolerance

levels will be revisited.

D. International Residue Limits

No CODEX, Canadian or Mexican limits for tebufenozide have been

were established on cereal grain forage, fodder, straw, and hay; grass

forage,

[[Page 56696]]

fodder, and straw and non-grass animal feeds (forage, fodder, straw,

and hay) and legume forage. Therefore, international harminization is

not an issue at this time.

E. Rotational Crop Restrictions

EPA has determined that crops which the label allows to be treated

directly can be planted at any time. All other crops can not be planted

within 30 days of application.

V. Conclusion

Therefore, time limited tolerances are established for the combined

residues of tebufenozide benzoic acid, 3,5-dimethyl-1-(1,1-

dimethylethyl)-2-(4-ethylbenzoyl)hydrazide and its metabolite benzoic

acid, 3,5-dimethyl-1-(1,1-dimethylethyl)-2-[4-(1-

hydroxyethyl)benzoyl]hydrazide in cereal grain forage, fodder, straw,

and hay; grass forage, fodder, and straw and non-grass animal feeds

(forage, fodder, straw, and hay) at 0.5 ppm, and legume forage at 0.1

ppm.

VI. Objections and Hearing Requests

Under section 408(g) of the FFDCA, as amended by the FQPA, any

person may file an objection to any aspect of this regulation and may

also request a hearing on those objections. The EPA procedural

regulations which govern the submission of objections and requests for

hearings appear in 40 CFR part 178. Although the procedures in those

regulations require some modification to reflect the amendments made to

the FFDCA by the FQPA of 1996, EPA will continue to use those

procedures, with appropriate adjustments, until the necessary

modifications can be made. The new section 408(g) provides essentially

the same process for persons to ``object'' to a regulation for an

exemption from the requirement of a tolerance issued by EPA under new

section 408(d), as was provided in the old FFDCA sections 408 and 409.

However, the period for filing objections is now 60 days, rather than

30 days.

A. What Do I Need to Do to File an Objection or Request a Hearing?

You must file your objection or request a hearing on this

regulation in accordance with the instructions provided in this unit

and in 40 CFR part 178. To ensure proper receipt by EPA, you must

identify docket control number OPP-300928 in the subject line on the

first page of your submission. All requests must be in writing, and

must be mailed or delivered to the Hearing Clerk on or before December

20, 1999.

1. Filing the request . Your objection must specify the specific

provisions in the regulation that you object to, and the grounds for

the objections (40 CFR 178.25). If a hearing is requested, the

objections must include a statement of the factual issues(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).

Information submitted in connection with an objection or hearing

request may be claimed confidential by marking any part or all of that

information as CBI. Information so marked will not be disclosed except

in accordance with procedures set forth in 40 CFR part 2. 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.

Mail your written request to: Office of the Hearing Clerk (1900),

Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.

You may also deliver your request to the Office of the Hearing Clerk in

Room M3708, Waterside Mall, 401 M St., SW., Washington, DC 20460. The

Office of the Hearing Clerk is open from 8 a.m. to 4 p.m., Monday

through Friday, excluding legal holidays. The telephone number for the

Office of the Hearing Clerk is (202) 260-4865.

2. Tolerance fee payment. If you file an objection or request a

hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or

request a waiver of that fee pursuant to 40 CFR 180.33(m). You must

mail the fee to: EPA Headquarters Accounting Operations Branch, Office

of Pesticide Programs, P.O. Box 360277M, Pittsburgh, PA 15251. Please

identify the fee submission be labeling it ``Tolerance Petition Fees.''

EPA is authorized to waive any fee requirement ``when in the

judgement of the Administrator such a waiver or refund is equitable and

not contrary to the purpose of this subsection.'' (cite). For

additional information regarding the waiver of these fees, you may

contact James Tompkins by phone at (703) 305-5697, by e-mail at

[email protected], or by mailing a request for information to Mr.

Tompkins at Registration Division (7505C), Office of Pesticide

Programs, Environmental Protection Agency, 401 M St., SW., Washington,

DC 20460.

If you would like to request a waiver of the tolerance objection

fees, you must mail your request for such a waiver to: James Hollins,

Information Resources and Services Division (7502C), Office of

Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,

Washington, DC 20460.

3. Copies for the Docket. In addition to filing an objection or

hearing request with the Hearing Clerk as described in Unit VI.A. of

this preamble, you should also send a copy of your request to the PIRB

for its inclusion in the official record that is described in Unit

I.B.2. of this preamble. Mail your copies, identified by docket number

OPP-300928, to: Public Information and Records Integrity Branch,

Information Resources and Services Division (7502C), Office of

Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,

Washington, DC 20460. In person or by courier, bring a copy to the

location of the PRIB described in Unit I.B.2. of this preamble. You may

also send an electronic copy of your request via e-mail to: opp-

[email protected]. Please use an ASCII file format and avoid the use of

special characters and any form of encryption. Copies of electronic

objections and hearing requests will also be accepted on disks in

WordPerfect 5.1/6.1 file format or ASCII file format. Do not include

any CBI in your electronic copy. You may also submit an electronic copy

of your request at many Federal Depository Libraries.

B. When Will the Agency Grant a Request for a Hearing?

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 issues(s) in the manner sought

by the requestor would be adequate to justify the action requested (40

CFR 178.32).

VII. Regulatory Assessment Requirements

This final rule establishes a tolerance under section 408(d) of the

FFDCA in response to a petition submitted to the Agency. The Office of

Management and Budget (OMB) has exempted these types of actions from

review under Executive Order 12866, entitled Regulatory Planning and

Review (58 FR 51735, October 4, 1993). This final rule does not contain

any information collections subject to OMB approval under the Paperwork

Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose any enforceable

duty or contain any unfunded mandate as described under Title II of the

Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 104-4). Nor

does it require prior

[[Page 56697]]

consultation with State, local, and tribal government officials as

specified by Executive Order 12875, entitled Enhancing the

Intergovernmental Partnership (58 FR 58093, October 28, 1993) and

Executive Order 13084, entitled Consultation and Coordination with

Indian Tribal Governments (63 FR 27655, May 19, 1998), or special

consideration of environmental justice related issues under Executive

Order 12898, entitled Federal Actions to Address Environmental Justice

in Minority Populations and Low-Income Populations (59 FR 7629,

February 16, 1994) or require OMB review in accordance with Executive

Order 13045, entitled Protection of Children from Environmental Health

Risks and Safety Risks (62 FR 19885, April 23, 1997). The Agency has

determined that this action will not have a substantial direct effect

on States, on the relationship between the national government and the

States, or on the distribution of power and responsibilities among the

various levels of government, as specified in Executive Order 12612,

entitled Federalism (52 FR 41685, October 30, 1987). This action

directly regulates growers, food processors, food handlers and food

retailers, not States. This action does not alter the relationships or

distribution of power and responsibilities established by Congress in

the preemption provisions of the Federal Food, Drug, and Cosmetic Act,

21 U.S.C. 346a(b)(4). This action does not involve any technical

standards that would require Agency consideration of voluntary

consensus standards pursuant to section 12(d) of the National

Technology Transfer and Advancement Act of 1995 (NTTAA), Public Law

104-113, section 12(d) (15 U.S.C. 272 note). In addition, since

tolerances and exemptions that are established on the basis of a

petition under FFDCA section 408(d), such as the tolerance in this

final rule, do not require the issuance of a proposed rule, the

requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et

seq.) do not apply.

VIII. Submission to Congress and the Comptroller General

The Congressional Review Act, 5 U.S.C. 801 et seq., as added by

the Small Business Regulatory Enforcement Fairness Act of 1996,

generally provides that before a rule may take effect, the agency

promulgating the rule must submit a rule report, which includes a copy

of the rule, to each House of the Congress and to the Comptroller

General of the United States. EPA will submit 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 United States

prior to publication of this rule in the Federal Register. This rule

is not a ``major rule'' as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

Environmental protection, Administrative practice and procedure,

Agricultural commodities, Pesticides and pests, Reporting and

recordkeeping requirements.

Dated: October 12, 1999.

James Jones,

Director, Registration Division, Office of Pesticide Programs.

Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

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

follows:

Authority: 21 U.S.C. 321(q), (346a), and 371.

2. In Sec. 180.482, by adding text to paragraph (d) to read as

follows:

Sec. 180.482 Tebufenozide; tolerances for residues.

* * * * *

(d) Indirect or inadvertent residues. Tolerances are established

for the indirect or inadvertent combined residues of tebufenozide

benzoic acid, 3,5-dimethyl-1-(1,1-dimethylethyl)-2-(4-

ethylbenzoyl)hydrazide and its metabolite benzoic acid, 3,5-dimethyl-1-

(1,1-dimethylethyl)-2- [4-(1-hydroxyethyl)benzoyl]hydrazide in or on

the raw agricultural commodities when present therin as a result of the

application of tebufenozide to growing crops listed in paragraph (a) of

this section to read as follows:

------------------------------------------------------------------------

Expiration/

Commodity Parts per million Revocation Date

------------------------------------------------------------------------

Foliage of legume vegetables.... 0.1 9/30/03

Forage, fodder, hay and straw of 0.5 9/30/03

cereal grains.

Forage, fodder, straw and hay of 0.5 9/30/03

non-grass animal feeds.

Grass forage, fodder and hay.... 0.5 9/30/03

------------------------------------------------------------------------

[FR Doc. 99-27393 Filed 10-20-99; 8:45 am]

Billing Code 6560-50-F