Acibenzolar-S-Methyl; Pesticide Tolerance

Note: EPA no longer updates this information, but it may be useful as a reference or resource.

[Federal Register: August 18, 2000 (Volume 65, Number 161)]
[Rules and Regulations]
[Page 50438-50446]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr18au00-6]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-301037; FRL-6737-6]
RIN 2070-AB78

Acibenzolar-S-Methyl; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes tolerances for residues of
acibenzolar-S-methyl in or on bananas; Brassica (cole) leafy
vegetables; fruiting vegetables; tomato, paste; leafy vegetables
(except spinach); and spinach. Novartis Crop Protection, Inc. 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 August 18, 2000. Objections and
requests for hearings, identified by docket control number OPP-301037
must be received by EPA on or before October 17, 2000.

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. To ensure proper receipt by EPA, your objections and
hearing requests must identify docket control number OPP-301037 in the
subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Daniel Kenny, Acting PM-22,
Registration Division (7505C), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave.,
NW.,Washington, DC 20460; telephone number: (703) 305-7546; and e-mail
address: kenny.dan@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:

------------------------------------------------------------------------
Examples of Potentially
Categories NAICS Affected Entities
------------------------------------------------------------------------
Industry 111 Crop production
112 Animal production
311 Food manufacturing
32532 Pesticide manufacturing
------------------------------------------------------------------------

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 under FOR FURTHER INFORMATION
CONTACT.

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,'' ``Regulations and Proposed Rules,'' 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-301037. 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.

[[Page 50439]]

II. Background and Statutory Findings

In theFederal Register of February 18, 1999 (64 FR 8102) (FRL-6061-
4) and theFederal Register of February 4, 2000 (65 FR 5639) (FRL-6398-
9), EPA issued notices 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 pesticide petitions (PP) for tolerance by Novartis Crop
Protection, Inc., P.O. Box 18300, Greensboro, NC 27419. These notices
included summaries of the petitions prepared by Novartis Crop
Protection, Inc., the registrant. There were no comments received in
response to the notices of filing.
The petitions requested that 40 CFR part 180 be amended by
establishing tolerances for residues of the fungicide acibenzolar-S-
methyl, benzo(1,2,3)thiadiazole-7-carbothioic acid-S-methyl ester, in
or on bananas at 0.1 part per million (ppm), Brassica (cole) leafy
vegetables at 1.0 ppm, fruiting vegetables at 1.0 ppm, leafy vegetables
(except spinach) at 0.25 ppm and spinach at 1.0 ppm. Agency review of
data submitted in support of the petitions indicated that a separate
tolerance of 3.0 ppm for tomato, paste should also be established.
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 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 tolerances for residues of acibenzolar-S-methyl on
bananas at 0.1 ppm; Brassica (cole) leafy vegetables at 1.0 ppm;
fruiting vegetables at 1.0 ppm; tomato, paste at 3.0 ppm; leafy
vegetables (except spinach) at 0.25 ppm; and spinach at 1.0 ppm. EPA's
assessment of exposures and risks associated with establishing the
tolerances 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 acibenzolar-S-
methyl are discussed in this unit as well as the no observed adverse
effect level (NOAEL) and the lowest observed adverse effect level
(LOAEL) from the toxicity studies reviewed.

Table 1.--Subchronic, Chronic and Other Toxicity
------------------------------------------------------------------------
Guideline No./Study Type Results
------------------------------------------------------------------------
870.3100 90-Day oral toxicity rats NOAEL: Males:126 mg/kg/day;
Females: 131 mg/kg/day
LOAEL: Males = 516 mg/kg/day;
Females = 554 mg/kg/day based
on decreased mean body
weights, decreased food
consumption and efficiency,
and increased liver and spleen
weights with correlates of
glycogen deposition and
hemosiderosis for the liver
and spleen, respectively.
------------------------------------------------------------------------
870.3150 90-Day oral toxicity dogs NOAEL = 50 mg/kg/day
LOAEL = 200 mg/kg/day based on
regenerative hemolytic anemia.
------------------------------------------------------------------------
870.3200 21/28-Day dermal toxicity rats NOAEL = 1,000 mg/kg/day
LOAEL = not identified
------------------------------------------------------------------------
870.3700a Prenatal developmental rats Maternal NOAEL = 200 mg/kg/day;
LOAEL = 400 mg/kg/day based on
hemorrhagic perineal
discharge.
Developmental NOAEL = not
identified (10 mg/kg/day)
LOAEL = 10 mg/kg/day (lowest
dose tested) based on
umbilical hernia.
------------------------------------------------------------------------
870.3700b Prenatal developmental Maternal NOAEL = 50 mg/kg/day
rabbits
LOAEL = 300 mg/kg/day based on
mortality, clinical signs of
toxicity, decreased maternal
body weight and food
consumption.
Developmental NOAEL = 300 mg/kg/
day LOAEL = 600 mg/kg/day
based on a marginal increase
in vertebral anomalies.
------------------------------------------------------------------------
870.3800 Reproduction and fertility Parental/Systemic NOAEL = 11-31
effects rats mg/kg/day LOAEL = 105-288 mg/
kg/day based on increased
weights and hemosiderosis of
the spleen.
Reproductive NOAEL = 223-604 mg/
kg/day LOAEL >223-604 mg/kg/
day based on no effects.
Offspring NOAEL = 11-31 mg/kg/
day LOAEL = 105-288 mg/kg/day
based on reduced pup body
weight gains and lower pup
body weights during lactation.
------------------------------------------------------------------------

[[Page 50440]]

870.4100a Chronic toxicity rats NOAEL = Males: 96.9 mg/kg/day;
Females: 111 mg/kg/day
LOAEL = Males: 312 mg/kg/day;
Females: 388 mg/kg/day based
on decreased body weight, body
weight gain and food
efficiency, mild hemolytic
anemia, and increased
incidence of alveolar foam
cells (females only).
------------------------------------------------------------------------
870.4100b Chronic toxicity dogs NOAEL = 25 mg/kg/day
LOAEL = 200 mg/kg/day based on
effects consistent with
hemolytic anemia, including
hematological effects,
hemosiderosis of the liver and
spleen, extramedullary
hematopoiesis of the spleen,
and increased liver weights.
------------------------------------------------------------------------
870.4200a Carcinogenicity rats NOAEL = Males: 96.9 mg/kg/day;
Females: 111 mg/kg/day
LOAEL = Males: 312 mg/kg/day;
Females: 388 mg/kg/day based
on decreased body weight, body
weight gain and food
efficiency, mild hemolytic
anemia, and increased
incidence of alveolar foam
cells (females only).
No evidence of carcinogenicity
------------------------------------------------------------------------
870.4200b Carcinogenicity mice NOAEL = Males:11.1 mg/kg/day;
Females: 10.8 mg/kg/day
LOAEL = Males: 237 mg/kg/day;
Females: 234 mg/kg/day based
on mild hemolytic anemia and
hemosiderosis of the liver,
spleen, and bone marrow, and
extramedullary hematopoiesis
of the spleen.
No evidence of carcinogenicity
------------------------------------------------------------------------
870.5100 Bacterial reverse mutation Negative with and without S-9
assay (Ames test) activation at 5000 g/
plate and less.
------------------------------------------------------------------------
870.5100 Bacterial reverse mutation Positive inS. typhimurium
assay (Ames test) Test Material: CGA- strain TA1537 at 277.8 g/plate and higher in the
methyl) absence of S-9. Negative with
S-9 activation at 5000 g/plate and less.
------------------------------------------------------------------------
870.5100 Bacterial reverse mutation Negative with or without S-9
assay (Ames test) Test Material: NOA- activation at 5000 g/
419191 (by-product of acibenzolar-S- plate and less
methyl)
------------------------------------------------------------------------
870.5100 Bacterial reverse mutation Negative with or without S-9
assay (Ames test) Test Material: CGA- activation at 5000 g/
323060 (plant metabolite of plate and less
acibenzolar-S-methyl)
------------------------------------------------------------------------
870.5300In vitro mammalian gene Negative with S-9 activation up
mutation assay to 1000 g/ml.
Negative without S-9
activation up to 100 g/ml.
Compound tested to cytotoxic
concentrations.
------------------------------------------------------------------------
870.5375In vitro mammalian chromosome Suggestive of clastogenicity in
aberration (CHO cells) the absence of S-9 activation
at 30 and 60 g/mL at
the 18-hour cell harvest time;
effect observed only in the
presence of cytotoxicity.
Increase in polyploid cells at
30 and 60 g/mL at the
42 hour harvest time both with
and without S- 9. Evidence of
cell cycle arresting activity
at G2.
------------------------------------------------------------------------
870.5395 Mammalian erythrocyte Negative at 16, 24, and 48,
micronucleus test hour sacrifices.
------------------------------------------------------------------------
870.5550 UDS in primary rat hepatocytes Negative at 500 g/ml
and less.
------------------------------------------------------------------------
870.7485 Metabolism and Following oral treatment of
pharmacokinetics rats rats, acibenzolar-S-methyl was
rapidly and nearly completely
(>90% of administered dose)
absorbed from the
gastrointestinal tract into
the general circulation. The
majority (88-95%) of the
administered dose was excreted
in the urine within the first
48 hours. The major metabolite
(79-92%) in the urine was the
carboxylic acid derivative of
the parent.
------------------------------------------------------------------------
Special studies: 28-Day dietary rats NOAEL = M: 403 mg/kg/day; F:
376 mg/kg/day
LOAEL = M: 1070 mg/kg/day; F:
1,000 mg/kg/day based on
decreased mean body weights,
decreased liver weights,
altered hematology parameters
accompanied by increased
spleen weights.
------------------------------------------------------------------------
28-Day oral gavage rats NOAEL = 100 mg/kg/day
LOAEL = 800 mg/kg/day based on
decreased body weights, and
decreased hemoglobin-related
parameters accompanied by
hemosiderosis of the spleen,
increased liver and spleen
weights, and decreased thymus
weights.
------------------------------------------------------------------------
28-Day oral capsule dogs NOAEL = 50 mg/kg/day
LOAEL = 250 mg/kg/day based on
decreased body weight,
decreased hemoglobin-related
parameters, hepatic and
splenic hemosiderosis.

[[Page 50441]]

------------------------------------------------------------------------
90-Day Dietary mice NOAEL = M: 30.6 mg/kg/day; F:
47.4 mg/kg/day;
LOAEL = M: 152 mg/kg/day; F:
220 mg/kg/day based on
decreased mean body weights
and body weight gain in males,
increased spleen weights and
splenic histopathology in both
sexes.
------------------------------------------------------------------------
Special Developmental toxicity rats Maternal and developmental
NOAELS and LOAELS could not be
identified by this protocol.
The most pronounced maternal
and developmental toxicity
occurred when dams were
treated on GD 6-15.
------------------------------------------------------------------------
Special Developmental toxicity rats Maternal and developmental
NOAELS and LOAELS could not be
identified by this protocol.
The most pronounced maternal
and developmental toxicity
occurred when dams were
treated on GD 6-7 and 8-9.
------------------------------------------------------------------------
Dermal developmental toxicity rats Maternal NOAEL 500
mg/kg/day LOAEL >500 mg/kg/day
based on no effects.
Developmental NOAEL 500 mg/kg/day LOAEL >500 mg/
kg/day based on no effects.
------------------------------------------------------------------------
Range-finding 1-generation reproduction Parental/Systemic NOAEL = 209
rats mg/kg/day LOAEL = 410 mg/kg/
day based on decreased body
weight gain and food
consumption in females.
Reproductive NOAEL = 410 mg/kg/
day LOAEL = 728 mg/kg/day
based on total resorptions in
all dams.
Offspring NOAEL = 209 mg/kg/day
LOAEL = 410 mg/kg/day based on
reduced pup body weight gains
and lower pup body weights
during lactation.
------------------------------------------------------------------------

B. Toxicological Endpoints

The dose at which no adverse effects are observed (the NOAEL) from
the toxicology study identified as appropriate for use in risk
assessment is used to estimate the toxicological level of concern
(LOC). However, the lowest dose at which adverse effects of concern are
identified (the LOAEL) is sometimes used for risk assessment if no
NOAEL was achieved in the toxicology study selected. An uncertainty
factor (UF) is applied to reflect uncertainties inherent in the
extrapolation from laboratory animal data to humans and in the
variations in sensitivity among members of the human population as well
as other unknowns. An UF of 100 is routinely used, 10X to account for
interspecies differences and 10X for intra species differences. No
NOAEL for developmental toxicity was observed in the rat developmental
study for acibenzolar-S-methyl. Because no NOAEL was observed, an
additional 3X uncertainty factor is being applied to the 100X
uncertainty factor to account for intra- and inter-species variability,
resulting in a 300X UF for toxicological endpoints derived from this
study.
For dietary risk assessment (other than cancer) the Agency uses the
UF to calculate an acute or chronic reference dose (acute RfD or
chronic RfD) where the RfD is equal to the NOAEL divided by the
appropriate UF (RfD = NOAEL/UF). Where an additional safety factor is
retained due to concerns unique to the FQPA, this additional factor is
applied to the RfD by dividing the RfD by such additional factor. The
acute or chronic Population Adjusted Dose (aPAD or cPAD) is a
modification of the RfD to accommodate this type of FQPA Safety Factor.
For non-dietary risk assessments (other than cancer) the UF is used
to determine the LOC. For example, when 100 is the appropriate UF (10X
to account for interspecies differences and 10X for intraspecies
differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to
exposures (margin of exposure (MOE) = NOAEL/exposure) is calculated and
compared to the LOC.
The linear default risk methodology (Q*) is the primary method
currently used by the Agency to quantify carcinogenic risk. The Q*
approach assumes that any amount of exposure will lead to some degree
of cancer risk. A Q* is calculated and used to estimate risk which
represents a probability of occurrence of additional cancer cases
(e.g., risk is expressed as 1 x 10^-6 or one in a million).
Under certain specific circumstances, MOE calculations will be used for
the carcinogenic risk assessment. In this non-linear approach, a
``point of departure'' is identified below which carcinogenic effects
are not expected. The point of departure is typically a NOAEL based on
an endpoint related to cancer effects though it may be a different
value derived from the dose response curve. To estimate risk, a ratio
of the point of departure to exposure (MOEcancer = point of
departure/exposures) is calculated.

Table 2.--Summary of Toxicological Dose and Endpoints for Acibenzolar-S-Methyl for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
FQPA SF\1\ and Level
Exposure Scenario Dose Used in Risk of Concern for Risk Study and
Assessment, UF Assessment Toxicological Effects
----------------------------------------------------------------------------------------------------------------
Acute Dietary females 13-50 years of LOAEL = 10 mg/kg/day UF FQPA SF = 10; aPAD = Developmental toxicity
age. = 300 Acute RfD = acute RfD rats; LOAEL = 10 mg/
0.033 mg/kg/day FQPA SF = 0.0033 mg/kg/ kg/day based on
day increased incidence of
rare malformations
(umbilical hernias).
----------------------------------------------------------------------------------------------------------------
Chronic Dietary females 13-50 years LOAEL = 10 mg/kg/day UF FQPA SF = 10 aPAD = Developmental toxicity
of age. = 300 Acute RfD = acute RfD rats; LOAEL = 10 mg/
0.033 mg/kg/day FQPA SF = 0.0033 mg/kg/ kg/day based on
day increased incidence of
rare malformations
(umbilical hernias).
----------------------------------------------------------------------------------------------------------------

[[Page 50442]]

Chronic Dietary all other NOAEL = 10.8 mg/kg/day FQPA SF = 3; cPAD = Carcinogenicity - mice;
populations, including infants and UF = 100; Chronic RfD chronic RfD LOAEL = Females = 234
children. = 0.11 mg/kg/day FQPA SF = 0.0367 mg/kg/ mg/kg/day based on
day mild hemolytic anemia
and hemosiderosis of
the liver, spleen, and
bone marrow, and
extramedullary
hematopoiesis of the
spleen.
----------------------------------------------------------------------------------------------------------------
\1\ The reference to the FQPA Safety Factor refers to any additional safety factor retained due to concerns
unique to the FQPA.

C. Exposure Assessment

1. Dietary exposure from food and feed uses. No tolerances have
previously been established for acibenzolar-S-methyl. Risk assessments
were conducted by EPA to assess dietary exposures from acibenzolar-S-
methyl in food as follows:
i. Acute exposure. 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. The Dietary Exposure Evaluation Model (DEEM
analysis evaluated the individual food consumption as reported by
respondents in the USDA 1989-1992 nationwide Continuing Surveys of Food
Intake by Individuals (CSFII) and accumulated exposure to the chemical
for each commodity. After a Tier I acute dietary analysis based on
tolerance level residues and assuming 100 percent crop treated resulted
in risk estimates that were unacceptably high, a probabilistic (i.e.,
Monte Carlo) acute dietary exposure assessment was performed using the
distribution of residues observed in the crop field trials and
projected percent market share information (leafy vegetables,16%;
fruiting vegetables 14%; brassica vegetables (2%). The refined analysis
estimated acute dietary exposure of females, 13-50 years old, to
acibenzolar-S-methyl at the 99.9th percentile of exposure.
ii. Chronic exposure. In conducting this chronic dietary risk
assessment the Dietary Exposure Evaluation Model (DEEM
analysis evaluated the individual food consumption as reported by
respondents in the USDA 1989-1992 nationwide Continuing Surveys of Food
Intake by Individuals (CSFII) and accumulated exposure to the chemical
for each commodity. The following assumptions were made for the chronic
exposure assessments: that residues would be present in or on treated
crops at tolerance levels and that 100% of crops would be treated.
iii. Anticipated residue and percent crop treated information.
Section 408(b)(2)(E) authorizes EPA to use available data and
information on the anticipated residue levels of pesticide residues in
food and the actual levels of pesticide chemicals that have been
measured in food. If EPA relies on such information, EPA must require
that data be provided 5 years after the tolerance is established,
modified, or left in effect, demonstrating that the levels in food are
not above the levels anticipated. Following the initial data
submission, EPA is authorized to require similar data on a time frame
it deems appropriate. As required by section 408(b)(2)(E), EPA will
issue a data call-in for information relating to anticipated residues
to be submitted no later than 5 years from the date of issuance of this
tolerance.
Section 408(b)(2)(F) states that the Agency may use data on the
actual percent of food treated for assessing chronic dietary risk only
if the Agency can make the following findings: Condition 1, 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; Condition 2, that the exposure estimate does not
underestimate exposure for any significant subpopulation group; and
Condition 3, 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 percent crop
treated (PCT) as required by section 408(b)(2)(F), EPA may require
registrants to submit data on PCT.
The Agency used percent crop treated (PCT) information as follows:
A probabilistic (i.e., Monte Carlo) acute dietary risk assessment
for acibenzolar-S-methyl was based on the following PCT projections:
leafy vegetables (16%); fruiting vegetables (14%); brassica vegetables
(2%).
The Agency believes that the three conditions previously discussed
have been met. With respect to Condition 1, EPA finds that the PCT
information described above for acibenzolar-S-methyl on leafy
vegetables, fruiting vegetables and brassica vegetables is reliable and
has a valid basis. The PCT information is based on reliable estimates
of the potential market for acibenzolar-S-methyl and the petitioner's
estimate of the market share it expects to capture. Based on available
information, including the petitioner's research and experience in
these markets, information on other registered pesticides, and
prevalence of target weeds, EPA believes the petitioner's estimates do
not underestimate the percent of these crops that may be treated. As to
Conditions 2 and 3, 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 acibenzolar-S-
methyl may be applied in a particular area.
2. Dietary exposure from drinking water. The Agency lacks
sufficient monitoring exposure data to complete a comprehensive dietary
exposure analysis and risk assessment for acibenzolar-S-methyl in
drinking water. Because the Agency does not have comprehensive
monitoring data, drinking water concentration estimates

[[Page 50443]]

are made by reliance on simulation or modeling taking into account data
on the physical characteristics of acibenzolar-S-methyl.
The Agency uses the Generic Estimated Environmental Concentration
(GENEEC) or the Pesticide Root Zone/Exposure Analysis Modeling System
(PRZM/EXAMS) to estimate pesticide concentrations in surface water and
SCI-GROW, which predicts pesticide concentrations in groundwater. In
general, EPA will use GENEEC (a tier 1 model) before using PRZM/EXAMS
(a tier 2 model) for a screening-level assessment for surface water.
The GENEEC model is a subset of the PRZM/EXAMS model that uses a
specific high-end runoff scenario for pesticides. GENEEC incorporates a
farm pond scenario, while PRZM/EXAMS incorporate an index reservoir
environment in place of the previous pond scenario. The PRZM/EXAMS
model includes a percent crop area factor as an adjustment to account
for the maximum percent crop coverage within a watershed or drainage
basin.
None of these models include consideration of the impact that
processing (mixing, dilution, or treatment) of raw water for
distribution as drinking water would likely have on the removal of
pesticides from the source water. The primary use of these models by
the Agency at this stage is to provide a coarse screen for sorting out
pesticides for which it is highly unlikely that drinking water
concentrations would ever exceed human health levels of concern.
Since the models used are considered to be screening tools in the
risk assessment process, the Agency does not use estimated
environmental concentrations (EECs) from these models to quantify
drinking water exposure and risk as a %RfD or %PAD. Instead, drinking
water levels of comparison (DWLOCs) are calculated and used as a point
of comparison against the model estimates of a pesticide's
concentration in water. DWLOCs are theoretical upper limits on a
pesticide's concentration in drinking water in light of total aggregate
exposure to a pesticide in food, and from residential uses. Since
DWLOCs address total aggregate exposure to acibenzolar-S-methyl they
are further discussed in the aggregate risk sections below.
Based on the GENEEC and SCI-GROW models the estimated environmental
concentrations (EECs) of acibenzolar-S-methyl in surface water and
ground water for acute exposures are estimated to be 0.64 parts per
billion (ppb) for surface water and negligible for ground water. The
EECs for chronic exposures are estimated to be 0.02 ppb for surface
water and negligible for ground water.
3. From non-dietary exposure. The term ``residential exposure'' is
used in this document to refer to non-occupational, non-dietary
exposure (e.g., for lawn and garden pest control, indoor pest control,
termiticides, and flea and tick control on pets). Acibenzolar-S-methyl
is not registered for use on any sites that would result in residential
exposure.
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 acibenzolar-S-methyl 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,
acibenzolar-S-methyl 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 acibenzolar-S-methyl 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. Safety Factor for Infants and Children

1. Safety factor for infants and children--i. In general. 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 on toxicity and exposure unless EPA determines that a
different margin of safety will be safe for infants and children.
Margins of safety are incorporated into EPA's 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.
ii. Prenatal and postnatal sensitivity. The Agency concluded that
there is concern for the increased susceptibility of infants and
children to exposure to acibenzolar-S-methyl based on the developmental
toxicity study in rats where treatment-related developmental
malformations, anomalies and variations were observed at doses equal to
or below the NOAEL for maternal toxicity.
iii. Conclusion. The toxicology database for Acibenzolar-S-Methyl
is incomplete. Subchronic neurotoxicity, developmental neurotoxicity
and an additional mutagenicity study (Ames study) are required. The
Agency concluded that the FQPA Safety Factor be retained at 10X based
on (1) a quantitative increase in susceptibility of fetuses (compared
to dams) in the rat developmental toxicity study (developmental
malformations occurred at a dose level which was considerably below the
NOAEL for maternal toxicity); (2) a concern that the treatment-related
developmental malformations (umbilical hernia) observed in rat fetuses
occurred at the lowest dose tested (NOAEL was not established) in the
rat developmental toxicity study; (3) the requirement for a
developmental neurotoxicity study in rats based on the occurrence of
treatment-related effects in nervous system tissues in the rat
developmental toxicity study; and (4) the potential for the requested
uses of acibenzolar-S-methyl to result in acute and chronic dietary
exposure. When assessing acute and chronic dietary exposures, the
Agency concluded that the FQPA safety factor should be retained at 10X
for the female, 13-50 years old, population subgroup (the only
population subgroup of concern for acute exposures). When assessing
chronic dietary exposure, however, the Committee concluded that the
safety factor can be reduced to 3X for the general population,
including infants and children (with the exception of the
aforementioned female 13-50 population subgroup) since there is no
concern for increased susceptibility due toin utero exposure for
persons other than females 13-50, but there still remains a data gap
for a developmental neurotoxicity study in rats.

E. Aggregate Risks and Determination of Safety

To estimate total aggregate exposure to a pesticide from food,
drinking water, and residential uses, the Agency calculates DWLOCs
which are used as a point of comparison against the model estimates of
a pesticide's concentration in water (EECs). DWLOC values are not
regulatory standards for drinking water. DWLOCs are theoretical upper
limits on a pesticide's concentration in drinking

[[Page 50444]]

water in light of total aggregate exposure to a pesticide in food and
residential uses. In calculating a DWLOC, the Agency determines how
much of the acceptable exposure (i.e., the PAD) is available for
exposure through drinking water e.g., allowable chronic water exposure
(mg/kg/day) = cPAD - (average food + residential exposure). This
allowable exposure through drinking water is used to calculate a DWLOC.
A DWLOC will vary depending on the toxic endpoint, drinking water
consumption, and body weights. Default body weights and consumption
values as used by the USEPA Office of Water are used to calculate
DWLOCs: 2L/70 kg (adult male), 2L/60 kg (adult female), and 1L/10 kg
(child). Actual body weights and drinking water consumption values vary
on an individual basis. This variation will be taken into account in
more refined screening-level and quantitative drinking water exposure
assessments. Different populations will have different DWLOCs.
Generally, a DWLOC is calculated for each type of risk assessment used:
acute, short-term, intermediate-term, chronic, and cancer.
When EECs for surface water and groundwater are less than the
calculated DWLOCs, OPP concludes with reasonable certainty that
exposures to the pesticide in drinking water (when considered along
with other sources of exposure for which OPP has reliable data) would
not result in unacceptable levels of aggregate human health risk at
this time. Because OPP considers the aggregate risk resulting from
multiple exposure pathways associated with a pesticide's uses, levels
of comparison in drinking water may vary as those uses change. If new
uses are added in the future, OPP will reassess the potential impacts
of residues of the pesticide in drinking water as a part of the
aggregate risk assessment process.
1. Acute risk. Using the exposure assumptions discussed in this
unit for acute exposure, the acute dietary exposure (at the 99.9th
percentile of exposure) from food to acibenzolar-S-methyl will occupy
87% of the aPAD for females 13 years and older, the only population
subgroup of concern for acute dietary exposure (i.e., no significant
acute effects relevant to other subgroups were identified in acute
toxicity studies for acibenzolar-S-methyl). In addition, there is
potential for acute dietary exposure to acibenzolar-S-methyl in
drinking water. After calculating DWLOCs and comparing them to the EECs
for surface and ground water, EPA does not expect the aggregate
exposure to exceed 100% of the aPAD.

Table 3.--Aggregate Risk Assessment for Acute Exposure to Acibenzolar-S-Methyl
----------------------------------------------------------------------------------------------------------------
Surface Ground
Population Subgroup a PAD (mg/ % aPAD Water EEC Water EEC Acute DWLOC (ppb)
kg) (Food) (ppb) (ppb)
----------------------------------------------------------------------------------------------------------------
Females 13-50 years 0.0033 87 0.64 Negligibl 12
e
----------------------------------------------------------------------------------------------------------------

2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to
acibenzolar-S-methyl from food will utilize 6% of the cPAD for the U.S.
population, 52% of the cPAD for females 13 to 50 years old, 3% of the
cPAD for infants less than 1 year old and 11% of the cPAD for children
1 to 6 years old, the subgroup of children with the highest estimated
food exposure to acibenzolar-S-methyl. There are no residential uses
for acibenzolar-S-methyl that result in chronic residential exposure to
acibenzolar-S-methyl. In addition, there is potential for chronic
dietary exposure to acibenzolar-S-methyl in drinking water. After
calculating the DWLOCs and comparing them to the EECs for surface and
ground water, EPA does not expect the aggregate exposure to exceed 100%
of the cPAD.

Table 4.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Acibenzolar-S-Methyl
----------------------------------------------------------------------------------------------------------------
Surface Ground Chronic
Population Subgroup cPAD mg/ % cPAD Water EEC Water EEC DWLOC
kg/day (Food) (ppb) (ppb) (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. Population 0.0367 6 0.02 negligibl 1200
e
----------------------------------------------------------------------------------------------------------------
All Infants 1 year 0.0367 3 0.02 negligibl 360
e
Children 1-6 years 0.0367 11 0.02 negligibl 320
e
----------------------------------------------------------------------------------------------------------------
Females 13-50 years 0. 0033 52 0.02 negligibl 50
e
----------------------------------------------------------------------------------------------------------------

3. Short-term risk. Short-term aggregate exposure takes into
account residential exposure plus chronic exposure to food and water
(considered to be a background exposure level). Acibenzolar-S-methyl is
not registered for use on any sites that would result in residential
exposure. Therefore, the aggregate risk is the sum of the risk from
food and water, which do not exceed the Agency's level of concern.
4. Intermediate-term risk. Intermediate-term aggregate exposure
takes into account residential exposure plus chronic exposure to food
and water (considered to be a background exposure level). Acibenzolar-
S-methyl is not registered for use on any sites that would result in
residential exposure. Therefore, the aggregate risk is the sum of the
risk from food and water, which do not exceed the Agency's level of
concern.
5. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the general population, and to infants and children from aggregate
exposure to acibenzolar-S-methyl residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

The petitioner has proposed a residue analytical method for
tolerance

[[Page 50445]]

enforcement that uses liquid chromatography with UV detection (HPLC-
UV). This method is currently being validated by the Analytical
Chemistry Branch laboratories, BEAD (7503C), Office of Pesticide
Programs. Upon successful completion of the EPA validation and the
granting of this registration the method will be forwarded to FDA for
publication in a future revision of the Pesticide Analytical Manual,
Vol-II (PAM-II). Prior to publication in PAM-II and upon request, the
method will be available prior to the harvest season from the
Analytical Chemistry Branch (ACB), BEAD (7503C), Environmental Science
Center, 701 Mapes Road, Ft George G. Meade, MD 20755-5350; contact
Francis D. Griffith, Jr, telephone (410) 305-2905, e-mail
griffith.francis@epa.gov. The analytical standards for this method are
also available from the EPA National Pesticide Standard Repository at
the same location.

B. International Residue Limits

There are no maximum residue limits for acibenzolar-S-methyl that
have been established by Codex or in Canada or Mexico; therefore, no
compatibility issues exist with Codex in regard to the proposed U.S.
tolerances discussed in this review.

C. Conditions

The registration of acibenzolar-S-methyl will be conditioned upon
submission of the following toxicology studies: Developmental
neurotoxicity study in rats; subchronic neurotoxicity study in rats;
and an additional mutagenicity study (Ames test).

V. Conclusion

Therefore, tolerances are established for residues of acibenzolar-
S-methyl, benzo(1,2,3)thiadiazole-7-carbothioic acid-S-methyl ester, in
or on bananas at 0.1 ppm; Brassica (cole) leafy vegetables at 1.0 ppm;
fruiting vegetables at 1.0 ppm; tomato, paste at 3.0 ppm; leafy
vegetables (except spinach) at 0.25 ppm; and spinach at 1.0 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-301037 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 October
17, 2000.
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, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460. You may also deliver your request to the Office
of the Hearing Clerk in Rm. C400, 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, 1200 Pennsylvania Ave., NW., 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, 1200 Pennsylvania
Ave., NW., 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., 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. Mail your
copies, identified by docket control number OPP-301037, to: Public
Information and Records Integrity Branch, Information Resources and
Services Division (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
In person or by courier, bring a copy to the location of the PIRIB
described in Unit I.B.2. You may also send an electronic copy of your
request via e-mail to: opp-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 6.1/8.0 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

[[Page 50446]]

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 FFDCA section 408(d)
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, entitledRegulatory 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. 3501et 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 any prior consultation as specified by Executive Order
13084, entitledConsultation and Coordination with Indian Tribal
Governments (63 FR 27655, May 19, 1998); special considerations as
required by Executive Order 12898, entitledFederal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations (59 FR 7629, February 16, 1994); or require OMB review or
any Agency action under Executive Order 13045, entitledProtection of
Children from Environmental Health Risks and Safety Risks (62 FR 19885,
April 23, 1997). 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). 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. In addition, 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 13132,
entitled Federalism (64 FR 43255, August 10, 1999). Executive Order
13132 requires EPA to develop an accountable process to ensure
``meaningful and timely input by State and local officials in the
development of regulatory policies that have federalism implications.''
``Policies that have federalism implications'' is defined in the
Executive Order to include regulations that have ``substantial direct
effects on the 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.'' This final
rule 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 FFDCA section 408(n)(4).

VIII. Submission to Congress and the Comptroller General

The Congressional Review Act, 5 U.S.C. 801et 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 final rule in the Federal Register. This final
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: August 9, 2000.

Joseph J. Merenda
Acting Director, 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. Section 180.561 is added to read as follows:

Sec. 180.561 Acibenzolar-S-methyl; tolerances for residues.

(a) General. Tolerances are established for residues of
acibenzolar-S-methyl, benzo(1,2,3)thiadiazole-7-carbothioic acid-S-
methyl ester, in or on the following raw agricultural commodities:

------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
Bananas\1\.................................................. 0.1
Brassica (cole) leafy vegetables............................. 1.0
Fruiting vegetables.......................................... 1.0
Leafy vegetables............................................. 0.25
Spinach...................................................... 1.0
Tomato, paste................................................ 3.0
------------------------------------------------------------------------
\1\ There are no United States registrations for bananas.

(b)Section 18 emergency exemptions. [Reserved]
(c)Tolerances with regional registrations. [Reserved]
(d)Indirect or inadvertent residues. [Reserved]

[FR Doc. 00-21080 Filed 8-17-00; 8:45 am]
BILLING CODE 6560-50-S

Acibenzolar-S-Methyl; Pesticide Tolerance

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