[Federal Register Volume 64, Number 183 (Wednesday, September 22, 1999)]
[Rules and Regulations]
[Pages 51251-51258]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-24695]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300914; FRL-6380-1]
RIN 2070-AB
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 tolerance for residues of
tebufenozide in or on sugarcane and sugarcane molasses. Rohm and Haas
Company requested this tolerance under the Federal Food, Drug, and
Cosmetic Act, as amended by the Food Quality Protection Act of 1996.
DATES: This regulation is effective September 22, 1999. Objections and
requests for hearings, identified by docket control number OPP-300914,
must be received by EPA on or before November 22, 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-300914 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: tavanojoseph@epa.gov.
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:
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Examples of
Categories NAICS Potentially
Affected Entities
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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-300914. 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 August 19, 1998 (63 FR 44439) (FRL-6019-
6), 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) (Public Law 104-170) announcing
the filing of a pesticide petition (PP 7F4863) for a 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 in
response to the notice of filing.
The petition requested that 40 CFR 180.482 be amended by
establishing a tolerance for residues of the insecticide, tebufenozide,
in or on sugarcane and sugarcane molasses at 0.3 and 1.0 parts per
million (ppm) respectively. Tebufenozide is a reduced risk pesticide
and controls sugarcane borer and Mexican rice borer on sugarcane.
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
[[Page 51252]]
infants and children from aggregate exposure to the pesticide chemical
residue.''
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. 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 residues of tebufenozide on sugarcane
and sugarcane molasses at 1.0 and 3.0 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 tebufenozide 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
milligrams/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 sensitizer.
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 1,000 mg/kg/ 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 lowest
observable adverse effect level (LOAEL) for systemic toxicity and
dermal irritation was not established.
3. A 1-year dog feeding study with a 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 1,000
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 2-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 absorption was not established. The
[[Page 51253]]
majority of the radiolabeled material was eliminated or excreted in the
feces 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 bioaccumulation.
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 B-ring 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% males to 34% females of the
administered dose while urinary excretion accounted for 5%
of the administered dose and the carcass accounted for <0.5% of="" the="" administered="" dose="" for="" both="" males="" and="" females.="" thus="" systemic="" absorption="" (percent="" of="" dose="" recovered="" in="" the="" bile,="" urine="" and="" carcass)="" was="" 35%="" (males)="" to="" 39%="" (females).="" the="" majority="" of="" the="" radioactivity="" in="" the="" bile="" (20%="" (males)="" to="" 24%="" (females)="" of="" the="" administered="" dose)="" was="" excreted="" within="" the="" first="" 6="" hours="" postdosing="" indicating="" rapid="" absorption.="" furthermore,="" urinary="" excretion="" of="" the="" metabolites="" was="" essentially="" complete="" within="" 24="" hours="" postdosing.="" a="" large="" amount="" 67%="" (females)="" to="" 70%="" (males)="" of="" the="" administered="" dose="" was="" unabsorbed="" and="" excreted="" in="" the="" feces="" by="" 72="" hours.="" total="" recovery="" of="" radioactivity="" was="" 105%="" of="" the="" administered="" dose.="" a="" total="" of="" 13="" metabolites="" were="" identified="" in="" the="" bile;="" the="" parent="" compound="" was="" not="" identified="" i.e.="" -="" unabsorbed="" compound="" nor="" were="" the="" primary="" oxidation="" products="" seen="" in="" the="" feces="" in="" the="" pharmacokinetics="" study.="" the="" proposed="" metabolic="" pathway="" proceeded="" primary="" by="" oxidation="" of="" the="" benzylic="" carbons="" to="" alcohols,="" aldehydes="" or="" acids.="" bile="" contained="" most="" of="" the="" other="" highly="" oxidized="" products="" found="" in="" the="" feces.="" the="" most="" significant="" individual="" bile="" metabolites="" accounted="" for="" 5%="" to="" 18%="" of="" the="" total="" radioactivity="" (females="" and/or="" males).="" bile="" also="" contained="" the="" previously="" undetected="" (in="" the="" pharmacokinetics="" study="" ``a''="" ring="" ketone="" and="" the="" ``b''="" ring="" diol.="" the="" other="" major="" components="" were="" characterized="" as="" high="" molecular="" weight="" conjugates.="" no="" individual="" bile="" metabolite="" 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 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 interspecies
(10x) and intraspecies (10x) variation resulting in a chronic RfD of
1.8 mg/kg/day 100 = 0.018 mg/kg/day. For chronic dietary risk
assessment, the 10x factor to account for the protection of infants and
children (as required by FQPA) was removed. Therefore, the 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 residues of tebufenozide in or on sugarcane and
sugarcane molasses at 1.0 and 3.0 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 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),
[[Page 51254]]
EPA may require registrants to submit data on PCT.
The Agency used PCT information as follows:
Estimates of PCT were used for the following crops. In all cases
the maximum estimate was used.
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Crops Average Maximum
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Almonds........................... <1%><1% apples............................="" 1%="" 2%="" beans/peas,="" dry...................="" 0%="" 1%="" cotton............................="" 1%="" 4%="" walnuts...........................="" 10%="" 16%="" cabbage,="" fresh....................="" 2%="" 3%="" cole="" crops........................="" 1%="" 2%="" spinach,="" fresh....................="" 2%="" 3%="" spinach,="" processed................="" 20%="" 29%="" ------------------------------------------------------------------------="" the="" agency="" believes="" that="" the="" three="" conditions,="" discussed="" in="" section="" 408="" (b)(2)(f)="" in="" this="" unit="" concerning="" the="" agency's="" responsibilities="" in="" assessing="" chronic="" dietary="" risk="" findings,="" have="" been="" met.="" the="" pct="" estimates="" are="" derived="" from="" federal="" and="" private="" market="" survey="" data,="" which="" are="" reliable="" and="" have="" a="" valid="" basis.="" typically,="" a="" range="" of="" estimates="" are="" supplied="" and="" the="" upper="" end="" of="" this="" range="" is="" assumed="" for="" the="" exposure="" assessment.="" by="" using="" this="" upper="" end="" estimate="" of="" the="" pct,="" the="" agency="" is="" reasonably="" certain="" that="" the="" percentage="" of="" the="" food="" treated="" is="" not="" likely="" to="" be="" underestimated.="" the="" regional="" consumption="" information="" and="" consumption="" information="" for="" significant="" subpopulations="" is="" taken="" into="" account="" through="" epa's="" computer-based="" model="" for="" evaluating="" the="" exposure="" of="" significant="" subpopulations="" including="" several="" regional="" groups.="" use="" of="" this="" consumption="" information="" in="" epa's="" risk="" assessment="" process="" ensures="" that="" epa's="" exposure="" estimate="" does="" not="" understate="" exposure="" for="" any="" significant="" subpopulation="" group="" and="" allows="" the="" agency="" to="" be="" reasonably="" certain="" that="" no="" regional="" population="" is="" exposed="" to="" residue="" levels="" higher="" than="" those="" estimated="" by="" the="" agency.="" other="" than="" the="" data="" available="" through="" national="" food="" consumption="" surveys,="" epa="" does="" not="" have="" available="" information="" on="" the="" regional="" consumption="" of="" food="" to="" which="" may="" be="" applied="" in="" a="" particular="" area.="" i.="" acute="" exposure="" and="" risk.="" acute="" dietary="" risk="" assessments="" are="" performed="" for="" a="" food-use="" pesticide="" if="" a="" toxicological="" study="" has="" indicated="" the="" possibility="" of="" an="" effect="" of="" concern="" occurring="" as="" a="" result="" of="" a="" 1-day="" or="" single="" exposure.="" 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.="" this="" risk="" is="" considered="" to="" be="" negligable.="" ii.="" chronic="" exposure="" and="" risk.="" in="" conducting="" the="" deem="" (dietary="" exposure="" evaluation="" model)="" for="" chronic="" dietary="" (food="" only)="" analysis,="" epa="" used="" tolerance="" level="" residues="" and="" some="" pct="" (tier="" 2).="" for="" the="" subject="" crops,="" the="" tolerances="" used="" are:="" 10="" ppm="" for="" sugarcane,="" 3.0="" ppm="" for="" sugarcane="" molasses.="" the="" analysis="" evaluates="" individual="" food="" consumption="" as="" reported="" by="" respondents="" in="" the="" usda="" continuing="" surveys="" of="" food="" intake="" by="" individuals="" conducted="" in="" 1989="" through="" 1992.="" summaries="" of="" the="" arc="" and="" their="" representations="" as="" percentages="" of="" the="" cpad="" for="" the="" general="" population="" and="" subgroups="" of="" interest="" are="" presented="" in="" the="" following="" table.="" table="" 1.--chronic="" exposure="" analysis="" by="" the="" deem="" system="" for="" tebufenozide="" --------------------------------------------------------------------------------------------------------------------------------------------------------="" population="" subgroup="" exposure="" (mg/kg/day)="" cpad%\1\="" --------------------------------------------------------------------------------------------------------------------------------------------------------="" u.s.="" population="" (48="" contiguous="" states)....................="" 0.0017="" 10%="" children="" (1-6="" years="" old)..................................="" 0.0038="" 21%="" females="" (13+/nursing).....................................="" 0.0017="" 10%="" --------------------------------------------------------------------------------------------------------------------------------------------------------="" \1\="" cpad%="Exposure" over="" cpad="" x="" 100%="" the="" subgroups="" listed="" above="" are:="" (1)="" the="" u.s.="" population="" (48="" contiguous="" 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="" pct="" 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="" tebufenozide="" using="" 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="" parts="" per="" billion="" (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.
[[Page 51255]]
Table 2.--Drinking Water Levels of Comparison for Chronic Exposure to Tebufenozide
----------------------------------------------------------------------------------------------------------------
EEC Calc.
Chronic RfD Food Max. Water DWLOC Max. (g/ m>g/L)
(mg/kg/day) (mg/kg/day) L)
----------------------------------------------------------------------------------------------------------------
U.S. Population (48 Contiguous 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
----------------------------------------------------------------------------------------------------------------
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 drinking water
estimated concentration (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 a 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 tebufenozide 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,
tebufenozide 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 tebufenozide 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, EPA 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 yrs). 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 EPA'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. 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.
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. 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 prenatal and postnatal toxicity and
the completeness of the data base 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
interspecies and intraspecies 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.
2. Prenatal and postnatal sensitivity. The toxicology data base
for tebufenozide included acceptable developmental toxicity studies in
both rats and rabbits as well as a 2-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
[[Page 51256]]
tebufenozide. No maternal or developmental findings were observed in
the prenatal developmental toxicity studies at doses up to 1,000 mg/kg/
day in rats and rabbits. In the 2-generation reproduction studies in
rats, effects occurred at the same or lower treatment levels in the
adults as in the offspring.
3. Conclusion. There is a complete toxicity data base for
tebufenozide and exposure data are 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.
4. Acute risk. Since no acute toxicological endpoints were
established, no acute aggregate risk exists.
5. 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 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.
6. Short- or intermediate-term risk. Short and intermediate term
risks are judged to be negligible due to the lack of significant
toxicological effects observed.
7. 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
1. Analytical methods - sugarcane. The HPLC/UV methods (Rohm and
Haas Method TR 34-95-66, TR 34-94-41, and TR34-97-115) used for
determining residues of tebufenozide in/on sugarcane are adequate for
collection of residue data. Adequate method validation and concurrent
method recovery data have been submitted for these methods. The
validated limit of quantitation (LOQ) is 0.01 ppm for residues of
tebufenozide in/on sugarcane and sugarcane processed commodities.
2. Analytical methods - sugarcane and sugarcane processed
commodities. The petitioner also submitted an enforcement method (TR34-
97-115) for sugarcane and sugarcane processed commodities. This method
has been adequately validated by an independent laboratory validation
(ILV). EPA concludes that this proposed enforcement method (TR 34-97-
115) is very similar to the previous enforcement method on apples,
which has been successfully validated by the Agency Analytical Lab.
Therefore EPA concludes that no Agency validation is needed for the
proposed enforcement method (TR 34-97-115) for sugarcane and sugarcane
processed commodities. The method is suitable for publication in the
Pesticide Analytical Manual, Volume II (PAM II) with an alphabetical
designation (i.e., letter method).
3. Analytical methods - animal tissues. A submitted HPLC/UV Method,
Rohm and Haas Method TR 34-96-109, has been determined to be adequate
for collecting data on residues of tebufenozide in animal tissues. The
validated LOQ for tebufenozide in animal tissue is 0.02. The LOQ for
each of the metabolites studied are as follows: RH-2703 in liver, 0.02
ppm; RH-9886 and RH-0282 in meat 0.02 ppm; RH-9526 in fat, 0.02 ppm.
The limits of detection (LODs) for the analytes are 0.006 ppm in
tissues. The method has been sent to ACB/BEAD for validation as a
possible enforcement method.
4. Multiresidue methods. Rohm and Haas has previously submitted
data involving multiresidue method testing. Tebufenozide was not
recoverable by FDA Test Protocols A, B, D, or E; analysis by Protocol C
was marginally successful. No further data are required at this time.
These methods 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: furlow.calvin@epa.gov.
C. Magnitude of Residues
Samples of sugarcane from the residue field trials were stored
frozen for 5-14 months prior to analysis, and sugarcane processed
commodities were stored frozen for 2-11 months. EPA concludes that the
submitted residue data for sugarcane are adequate to support the
permanent tolerance petition for sugarcane and sugarcane molasses.
EPA concludes that the geographic representation of the crop field
trials on sugarcane is adequate and that data are sufficient to support
the proposed 1.0 ppm tolerance for residues of tebufenozide in/on
sugarcane.
The submitted sugarcane processing studies are adequate. The
concentration factor for molasses is 4.5. Multiplying the average
concentration factor (4.5) and the highest average field trial (HAFT)
residue (0.63) gives 3.0 ppm. Therefore EPA has determined that
tolerance for sugarcane molasses should be set at 3.0 ppm (instead of
proposed 6.0 ppm) based on the available processing studies. No
tolerance is needed for refined sugar. Tolerances for livestock
commodities have been established; therefore, residues of tebufenozide
in meat, milk, poultry and eggs from the use on sugarcane are covered.
D. International Residue Limits
No CODEX, Canadian or Mexican limits for tebufenozide have been
established on sugarcane.
E. Rotational Crop Restrictions
EPA has determined that crops which the label allows tebufenozide
to be treated directly can be planted at any time. All other crops can
not be planted within 12 months of application.
[[Page 51257]]
V. Conclusion
Therefore, the tolerance is established for residues of
tebufenozide in sugarcane and sugarcane molasses at 1.0 and 3.0 ppm,
respectively.
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-300914 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 November
22, 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 by 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.'' For additional
information regarding the waiver of these fees, you may contact James
Tompkins by phone at (703) 305-5697, by e-mail at tompkins.jim@epa.gov,
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 PIRIB
for its inclusion in the official record that is described in Unit
I.B.2. of this preamble. Mail your copies, identified by docket control
number OPP-300914, 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 PIRIB described in Unit I.B.2. of this preamble. You
may also send an electronic copy of your request via e-mail to: docket@epa.gov. 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 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
[[Page 51258]]
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: September 9, 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 alphabetically in paragraph (b), the
following commodities to the table to read as follows:
Sec. 180.482 Tebufenozide; tolerances for residues.
* * * * *
(b) * * *
------------------------------------------------------------------------
Parts Expiration/
Commodity per Revocation
million Date
------------------------------------------------------------------------
* * * * *
Sugarcane........................................ 1.0 N/A
Sugarcane molasses............................... 3.0 N/A
* * * * *
------------------------------------------------------------------------
* * * * *
[FR Doc. 99-24695 Filed 9-21-99; 8:45 am]
BILLING CODE 6560-50-F
