[Federal Register Volume 62, Number 250 (Wednesday, December 31, 1997)]
[Rules and Regulations]
[Pages 68208-68216]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-34104]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300595; FRL-5762-1]
RIN 2070-AB78
Hexythiazox; Pesticide Tolerances for Emergency Exemptions
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes a time-limited tolerance for
combined residues of hexythiazox (trans-5-(4-
[[Page 68209]]
chlorophenyl)-N-cyclohexyl-4-methyl-2-oxothiazolidine-3-carboxamide)
and its metabolites containing the (4-chlorophenyl)-4-methyl-2-oxo-3-
thiazolidine moiety in or on strawberries. This action is in response
to EPA's granting of an emergency exemption under section 18 of the
Federal Insecticide, Fungicide, and Rodenticide Act authorizing use of
the pesticide on strawberries. This regulation establishes a maximum
permissible level for residues of hexythiazox in this food commodity
pursuant to section 408(l)(6) of the Federal Food, Drug, and Cosmetic
Act, as amended by the Food Quality Protection Act of 1996. The
tolerance will expire and is revoked on July 1, 1998.
DATES: This regulation is effective December 31, 1997. Objections and
requests for hearings must be received by EPA on or before March 2,
1998.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300595], must be submitted to: Hearing
Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M St.,
SW., Washington, DC 20460. Fees accompanying objections and hearing
requests shall be labeled ``Tolerance Petition Fees'' and forwarded to:
EPA Headquarters Accounting Operations Branch, OPP (Tolerance Fees),
P.O. Box 360277M, Pittsburgh, PA 15251. A copy of any objections and
hearing requests filed with the Hearing Clerk identified by the docket
control number, [OPP-300595], must also be submitted 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,
bring a copy of objections and hearing requests to Rm. 1132, CM #2,
1921 Jefferson Davis Hwy., Arlington, VA.
A copy of objections and hearing requests filed with the Hearing
Clerk may also be submitted electronically by sending electronic mail
(e-mail) to: [email protected]. Copies of objections and
hearing requests must be submitted as an ASCII file avoiding the use of
special characters and any form of encryption. Copies of objections and
hearing requests will also be accepted on disks in WordPerfect 5.1/6.1
file format or ASCII file format. All copies of objections and hearing
requests in electronic form must be identified by the docket control
number [OPP-300595]. No Confidential Business Information (CBI) should
be submitted through e-mail. Electronic copies of objections and
hearing requests on this rule may be filed online at many Federal
Depository Libraries.
FOR FURTHER INFORMATION CONTACT: By mail: David Deegan, Registration
Division 7505C, Office of Pesticide Programs, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. Office location,
telephone number, and e-mail address: Crystal Mall #2, 1921 Jefferson
Davis Hwy., Arlington, VA, (703) 308-9358, e-mail:
[email protected].
SUPPLEMENTARY INFORMATION: EPA, on its own initiative, pursuant to
section 408(e) and (l)(6) of the Federal Food, Drug, and Cosmetic Act
(FFDCA), 21 U.S.C. 346a(e) and (l)(6), is establishing a tolerance for
combined residues of the insecticide hexythiazox (trans-5-(4-
chlorophenyl)-N-cyclohexyl-4-methyl-2-oxothiazolidine-3-carboxamide)
and its metabolites containing the (4-chlorophenyl)-4-methyl-2-oxo-3-
thiazolidine moiety , in or on strawberries at 3.0 part per million
(ppm). This tolerance will expire and is revoked on July 1, 1998. EPA
will publish a document in the Federal Register to remove the revoked
tolerance from the Code of Federal Regulations.
I. Background and Statutory Authority
The Food Quality Protection Act of 1996 (FQPA) (Pub. L. 104-170)
was signed into law August 3, 1996. FQPA amends both the Federal Food,
Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 301 et seq., and the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA), 7 U.S.C. 136 et
seq. The FQPA amendments went into effect immediately. Among other
things, FQPA amends FFDCA to bring all EPA pesticide tolerance-setting
activities under a new section 408 with a new safety standard and new
procedures. These activities are described below and discussed in
greater detail in the final rule establishing the time-limited
tolerance associated with the emergency exemption for use of
propiconazole on sorghum (61 FR 58135, November 13, 1996) (FRL-5572-9).
New 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....''
Section 18 of FIFRA authorizes EPA to exempt any Federal or State
agency from any provision of FIFRA, if EPA determines that ``emergency
conditions exist which require such exemption.'' This provision was not
amended by FQPA. EPA has established regulations governing such
emergency exemptions in 40 CFR part 166.
Section 408(l)(6) of the FFDCA requires EPA to establish a time-
limited tolerance or exemption from the requirement for a tolerance for
pesticide chemical residues in food that will result from the use of a
pesticide under an emergency exemption granted by EPA under section 18
of FIFRA. Such tolerances can be established without providing notice
or period for public comment.
Because decisions on section 18-related tolerances must proceed
before EPA reaches closure on several policy issues relating to
interpretation and implementation of the FQPA, EPA does not intend for
its actions on such tolerance to set binding precedents for the
application of section 408 and the new safety standard to other
tolerances and exemptions.
II. Emergency Exemption for Hexythiazox on Strawberries and FFDCA
Tolerances
The state of California petitioned EPA to invoke provisions of
FIFRA section 18 to allow emergency use of the chemical hexythiazox
(Savey Ovicide/Miticide 50-WP, EPA Reg. No. 10163-208, manufactured by
Gowan) on 18,000 acres of strawberries in California to control two-
spotted spider mites. EPA reviewed this request and concluded that the
state is suffering from an urgent and non-routine situation, qualifying
for use of the requested product under section 18. EPA's review
concluded that there are no effective alternative chemicals available
to growers with which they can control this pest on strawberries. On
November 14, 1997, EPA authorized California to allow hexythiazox to be
used on 18,000 acres of strawberries to control two-spotted spider
mites. The exemption expires on April 1, 1998.
[[Page 68210]]
As part of its assessment of this emergency exemption, EPA assessed
the potential risks presented by residues of hexythiazox in or on
strawberries. In doing so, EPA considered the new safety standard in
FFDCA section 408(b)(2), and EPA decided that the necessary tolerance
under FFDCA section 408(l)(6) would be consistent with the new safety
standard and with FIFRA section 18. Consistent with the need to move
quickly on the emergency exemption in order to address an urgent non-
routine situation and to ensure that the resulting food is safe and
lawful, EPA is issuing this tolerance without notice and opportunity
for public comment under section 408(e), as provided in section
408(l)(6). Although this tolerance will expire and is revoked on July
1, 1998, under FFDCA section 408(l)(5), residues of the pesticide not
in excess of the amounts specified in the tolerance remaining in or on
strawberries after that date will not be unlawful, provided the
pesticide is applied in a manner that was lawful under FIFRA, and the
residues do not exceed a level that was authorized by this tolerance at
the time of that application. EPA will take action to revoke this
tolerance earlier if any experience with, scientific data on, or other
relevant information on this pesticide indicate that the residues are
not safe.
Because this tolerance is being approved under emergency conditions
EPA has not made any decisions about whether hexythiazox meets EPA's
registration requirements for use on strawberries or whether a
permanent tolerance for this use would be appropriate. Under these
circumstances, EPA does not believe that this tolerance serves as a
basis for registration of hexythiazox by a State for special local
needs under FIFRA section 24(c). Nor does this tolerance serve as the
basis for any State other than California to use this pesticide on this
crop under section 18 of FIFRA without following all provisions of
section 18 as identified in 40 CFR part 166. For additional information
regarding the emergency exemption for hexythiazox, contact the Agency's
Registration Division at the address provided above.
III. Risk Assessment and Statutory Findings
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. First, EPA determines the
toxicity of pesticides based primarily on toxicological studies using
laboratory animals. These studies address many adverse health effects,
including (but not limited to) reproductive effects, developmental
toxicity, toxicity to the nervous system, and carcinogenicity. Second,
EPA examines exposure to the pesticide through the diet (e.g., food and
drinking water) and through exposures that occur as a result of
pesticide use in residential settings.
A. Toxicity
1. Threshold and non-threshold effects. For many animal studies, a
dose response relationship can be determined, which provides a dose
that causes adverse effects (threshold effects) and doses causing no
observed effects (the ``no-observed effect level'' or ``NOEL'').
Once a study has been evaluated and the observed effects have been
determined to be threshold effects, EPA generally divides the NOEL from
the study with the lowest NOEL by an uncertainty factor (usually 100 or
more) to determine the Reference Dose (RfD). The RfD is a level at or
below which daily aggregate exposure over a lifetime will not pose
appreciable risks to human health. An uncertainty factor (sometimes
called a ``safety factor'') of 100 is commonly used since it is assumed
that people may be up to 10 times more sensitive to pesticides than the
test animals, and that one person or subgroup of the population (such
as infants and children) could be up to 10 times more sensitive to a
pesticide than another. In addition, EPA assesses the potential risks
to infants and children based on the weight of the evidence of the
toxicology studies and determines whether an additional uncertainty
factor is warranted. Thus, an aggregate daily exposure to a pesticide
residue at or below the RfD (expressed as 100% or less of the RfD) is
generally considered acceptable by EPA. EPA generally uses the RfD to
evaluate the chronic risks posed by pesticide exposure. For shorter
term risks, EPA calculates a margin of exposure (MOE) by dividing the
estimated human exposure into the NOEL from the appropriate animal
study. Commonly, EPA finds MOEs lower than 100 to be unacceptable. This
100-fold MOE is based on the same rationale as the 100-fold uncertainty
factor.
Lifetime feeding studies in two species of laboratory animals are
conducted to screen pesticides for cancer effects. When evidence of
increased cancer is noted in these studies, the Agency conducts a
weight of the evidence review of all relevant toxicological data
including short-term and mutagenicity studies and structure activity
relationship. Once a pesticide has been classified as a potential human
carcinogen, different types of risk assessments (e.g., linear low dose
extrapolations or MOE calculation based on the appropriate NOEL) will
be carried out based on the nature of the carcinogenic response and the
Agency's knowledge of its mode of action.
2. Differences in toxic effect due to exposure duration. The
toxicological effects of a pesticide can vary with different exposure
durations. EPA considers the entire toxicity data base, and based on
the effects seen for different durations and routes of exposure,
determines which risk assessments should be done to assure that the
public is adequately protected from any pesticide exposure scenario.
Both short and long durations of exposure are always considered.
Typically, risk assessments include ``acute,'' ``short-term,''
``intermediate term,'' and ``chronic'' risks. These assessments are
defined by the Agency as follows.
Acute risk, by the Agency's definition, results from 1-day
consumption of food and water, and reflects toxicity which could be
expressed following a single oral exposure to the pesticide residues.
High end exposure to food and water residues are typically assumed.
Short-term risk results from exposure to the pesticide for a period
of 1-7 days, and therefore overlaps with the acute risk assessment.
Historically, this risk assessment was intended to address primarily
dermal and inhalation exposure which could result, for example, from
residential pesticide applications. However, since enaction of FQPA,
this assessment has been expanded to include both dietary and non-
dietary sources of exposure, and will typically consider exposure from
food, water, and residential uses when reliable data are available. In
this assessment, risks from average food and water exposure, and high-
end residential exposure, are aggregated. High-end exposures from all 3
sources are not typically added because of the very low probability of
this occurring in most cases, and because the other conservative
assumptions built into the assessment assure adequate protection of
public health. However, for cases in which high-end exposure can
reasonably be expected from multiple sources (e.g. frequent and
widespread homeowner use in a specific geographical area), multiple
high-end risks will be aggregated and presented as part of the
comprehensive risk assessment/characterization. Since the toxicological
endpoint considered in this assessment reflects exposure over a period
of at least 7 days, an additional degree of conservatism is built into
the assessment; i.e., the risk assessment
[[Page 68211]]
nominally covers 1-7 days exposure, and the toxicological endpoint/NOEL
is selected to be adequate for at least 7 days of exposure. (Toxicity
results at lower levels when the dosing duration is increased.)
Intermediate-term risk results from exposure for 7 days to several
months. This assessment is handled in a manner similar to the short-
term risk assessment.
Chronic risk assessment describes risk which could result from
several months to a lifetime of exposure. For this assessment, risks
are aggregated considering average exposure from all sources for
representative population subgroups including infants and children.
B. Aggregate Exposure
In examining aggregate exposure, FFDCA section 408 requires that
EPA take into account available and reliable information concerning
exposure from the pesticide residue in the food in question, residues
in other foods for which there are tolerances, residues in groundwater
or surface water that is consumed as drinking water, and other non-
occupational exposures through pesticide use in gardens, lawns, or
buildings (residential and other indoor uses). Dietary exposure to
residues of a pesticide in a food commodity are estimated by
multiplying the average daily consumption of the food forms of that
commodity by the tolerance level or the anticipated pesticide residue
level. The Theoretical Maximum Residue Contribution (TMRC) is an
estimate of the level of residues consumed daily if each food item
contained pesticide residues equal to the tolerance. In evaluating food
exposures, EPA takes into account varying consumption patterns of major
identifiable subgroups of consumers, including infants and children.The
TMRC is a ``worst case'' estimate since it is based on the assumptions
that food contains pesticide residues at the tolerance level and that
100% of the crop is treated by pesticides that have established
tolerances. If the TMRC exceeds the RfD or poses a lifetime cancer risk
that is greater than approximately one in a million, EPA attempts to
derive a more accurate exposure estimate for the pesticide by
evaluating additional types of information (anticipated residue data
and/or percent of crop treated data) which show, generally, that
pesticide residues in most foods when they are eaten are well below
established tolerances.
Percent of crop treated estimates are derived from Federal and
private market survey data. 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 percent of crop
treated, the Agency is reasonably certain that exposure is not
understated for any significant subpopulation group. Further, regional
consumption information is taken into account through EPA's computer-
based model for evaluating the exposure of significant subpopulations
including several regional groups, to pesticide residues. For this
pesticide, the most highly exposed population subgroup (infants and
children) was not regionally based.
IV. 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
hexythiazox and to make a determination on aggregate exposure,
consistent with section 408(b)(2), for a time-limited tolerance for
combined residues of hexythiazox (trans-5-(4-chlorophenyl)-N-
cyclohexyl-4-methyl-2-oxothiazolidine-3-carboxamide) and its
metabolites containing the (4-chlorophenyl)-4-methyl-2-oxo-3-
thiazolidine moiety on strawberries at 3.0 ppm. 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 hexythiazox are
discussed below.
1. Acute toxicity. An acute dietary risk assessment is not
required, since EPA did not identify an acute toxicological endpoint.
2. Short - and intermediate - term toxicity. For short and
intermediate-term Margin of Exposure (MOE) calculations, EPA
recommended use of the maternal NOEL of 240 milligrams/kilogram/day
(mg/kg/day) from the developmental toxicity study in rats. At the
Lowest Eeffect Level (LEL) of 740 mg/kg/day, there was decreased food
consumption, decreased body weight and increased ovarian weights.
3. Chronic toxicity. EPA has established the RfD for hexythiazox at
0.025 mg/kg/day. This RfD is based on a one year feeding study in dogs
with a NOEL of 2.5 mg/kg/day and an uncertainty factor of 100. The
Lowest Observed Eeffect Level (LOEL) of 12.5 mg/kg/day was based on
hypertrophy of the adrenal cortex in both sexes.
4. Carcinogenicity. Hexythiazox has been classified as a Group C
chemical (possible human carcinogen) by EPA, based on an increased
incidence of female mouse liver tumors. EPA uses the Q1*
approach to assess this risk. The Q1* is 0.039 mg/kg/
day-1.
B. Exposures and Risks
1. From food and feed uses. Tolerances have been established (40
CFR 180.448) for the combined residues of hexythiazox (trans-5-(4-
chlorophenyl)-N-cyclohexyl-4-methyl-2-oxothiazolidine-3-carboxamide),
in or on a variety of raw agricultural commodities. Risk assessments
were conducted by EPA to assess dietary exposures and risks from
hexythiazox as follows:
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 one day or single exposure. The acute dietary (food only) risk
assessment is not required for this pesticide use, as the EPA did not
identify an acute dietary risk endpoint.
ii. Chronic exposure and risk. In conducting this chronic dietary
risk assessment, EPA has made conservative assumptions -- 100% of
strawberries, in addition to cotton seed commodities (oil and meal)
(previously approved under provisions of section 18) and apple
commodities will contain residues of hexythiazox and its metabolites
and those residues will be at the level of the tolerance. Percent crop
treated data were utilized for pear commodities. These conservative
assumptions result in an overestimate of human dietary exposure. Thus,
in making a safety determination for this tolerance, EPA is taking into
account this conservative exposure assessment.
The published tolerances for the regulated residue of hexythiazox,
plus this proposed section 18 use, result in a Anticipated Residue
Contribution (ARC) that is equivalent to the following percentages of
the RfD:
------------------------------------------------------------------------
Subgroup Percent
------------------------------------------------------------------------
U.S. Population............................................ <1
Nursing Infants............................................ <1
[[Page 68212]]
Non-Nursing Infants (<1 year old).......................... <1
Children (1-6 years old)................................... <1
Children (7-12 years old).................................. <1
------------------------------------------------------------------------
The subgroups listed above are: (1) the U.S. population (48
states); and (2) those for infants and children; and (3) the other
subgroups for which the percentage of the RfD occupied is greater than
that occupied by the subgroup U.S. population (48 states).
2. From drinking water. Based on information currently available to
EPA, hexythiazox is considered persistent in soil. EPA's current data
also indicates that hexythiazox and soil metabolites are not likely to
leach to groundwater. There are no established Maximum Contaminant
Levels for residues of hexythiazox in drinking water. No health
advisory levels for hexythiazox in drinking water have been
established.
Chronic exposure and risk. Because the Agency lacks sufficient
water-related exposure data to complete a comprehensive drinking water
risk assessment for many pesticides, EPA has commenced and nearly
completed a process to identify a reasonable yet conservative bounding
figure for the potential contribution of water-related exposure to the
aggregate risk posed by a pesticide. In developing the bounding figure,
EPA estimated residue levels in water for a number of specific
pesticides using various data sources. The Agency then applied the
estimated residue levels, in conjunction with appropriate toxicological
endpoints (RfD's or acute dietary NOEL's) and assumptions about body
weight and consumption, to calculate, for each pesticide, the increment
of aggregate risk contributed by consumption of contaminated water.
While EPA has not yet pinpointed the appropriate bounding figure for
exposure from contaminated water, the ranges the Agency is continuing
to examine are all below the level that would cause hexythiazox to
exceed the RfD if the tolerance being considered in this document were
granted. The Agency has therefore concluded that the potential
exposures associated with hexythiazox in water, even at the higher
levels the Agency is considering as a conservative upper bound, would
not prevent the Agency from determining that there is a reasonable
certainty of no harm if the tolerance is granted.
3. From non-dietary exposure. Hexythiazox is not currently
registered for use on any residential non-food sites. The Agency does
not expect there to be any meaningful non-dietary residential exposure
to hexythiazox.
4. Cumulative exposure to substances with common mechanism of
toxicity. Section 408(b)(2)(D)(v) requires that, when considering
whether to establish, modify, or revoke a tolerance, the Agency
consider ``available information'' concerning the cumulative effects of
a particular pesticide's residues and ``other substances that have a
common mechanism of toxicity.'' The Agency believes that ``available
information'' in this context might include not only toxicity,
chemistry, and exposure data, but also scientific policies and
methodologies for understanding common mechanisms of toxicity and
conducting cumulative risk assessments. For most pesticides, although
the Agency has some information in its files that may turn out to be
helpful in eventually determining whether a pesticide shares a common
mechanism of toxicity with any other substances, EPA does not at this
time have the methodologies to resolve the complex scientific issues
concerning common mechanism of toxicity in a meaningful way. EPA has
begun a pilot process to study this issue further through the
examination of particular classes of pesticides. The Agency hopes that
the results of this pilot process will increase the Agency's scientific
understanding of this question such that EPA will be able to develop
and apply scientific principles for better determining which chemicals
have a common mechanism of toxicity and evaluating the cumulative
effects of such chemicals. The Agency anticipates, however, that even
as its understanding of the science of common mechanisms increases,
decisions on specific classes of chemicals will be heavily dependent on
chemical specific data, much of which may not be presently available.
Although at present the Agency does not know how to apply the
information in its files concerning common mechanism issues to most
risk assessments, there are pesticides as to which the common mechanism
issues can be resolved. These pesticides include pesticides that are
toxicologically dissimilar to existing chemical substances (in which
case the Agency can conclude that it is unlikely that a pesticide
shares a common mechanism of activity with other substances) and
pesticides that produce a common toxic metabolite (in which case common
mechanism of activity will be assumed).
EPA does not have, at this time, available data to determine
whether hexythiazox 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,
hexythiazox does not appear to produce a toxic metabolite produced by
other substances. According to information evaluated related to this
action, hexythiazox is a member of the thiazolidinone class of
pesticides and there are no other members of this class. For the
purposes of this tolerance action, therefore, EPA has not assumed that
hexythiazox has a common mechanism of toxicity with other substances.
C. Aggregate Risks and Determination of Safety for U.S. Population
1. Chronic risk. Using the conservative exposure assumptions
described above, and taking into account the completeness and
reliability of the toxicity data, EPA has concluded that dietary
exposure (food only) to hexythiazox will utilize <1% of the RfD for the
U.S. population. The major identifiable subgroup with the highest
aggregate exposure is non-nursing infants. EPA generally has no concern
for exposures below 100% of the RfD because the RfD represents the
level at or below which daily aggregate dietary exposure over a
lifetime will not pose appreciable risks to human health. Despite the
potential for exposure to hexythiazox in drinking water EPA does not
expect the aggregate exposure to exceed 100% of the RfD. EPA concludes
that there is a reasonable certainty that no harm will result from
aggregate exposure to hexythiazox residues.
2. 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. EPA believes that uses of hexythiazox may
constitute a short- and/or intermediate-term exposure scenario.
However, the Agency is not, at this time, able to complete a
comprehensive residential risk assessment for many pesticides,
including hexythiazox. Because there are no residential non-food uses
registered for hexythiazox, and because there are no other chemicals
that share its class, and based on the lack of an identified acute
toxicological endpoint for hexythiazox, and the low percentage (<1%) of
the RfD occupied by food and water, in the best scientific judgment of
EPA, short- and intermediate-term aggregate risk will not exceed the
Agency's level of concern.
[[Page 68213]]
D. Aggregate Cancer Risk for U.S. Population
Based on published tolerances (none are currently pending) and
this proposed section 18 use, an upper bound lifetime dietary (food
only) cancer risk estimate of 9.6 x 10-7 was calculated
for the hexythiazox regulated residue. The calculation used the
conservative exposure assumptions described above for generating ARC's
and amortized the cancer risk over a 70-year lifetime (i.e., 5/70, for
this 1st year section 18 use). This section 18 use contributes 4.1 x
10-6 to the upper bound lifetime dietary (food only) cancer
risk and 2.9 x 10-7 if the cancer risk is amortized over a
70-year lifetime.
The cancer risk estimate for the existing hexythiazox uses plus the
amortized risk estimate for strawberries does not exceed EPA's level of
concern.
EPA believes the registered uses do not constitute a chronic
exposure scenario. Thus, no non-dietary, non-occupational chronic
exposure to hexythiazox is expected, or is a factor in aggregate cancer
risk .
E. Aggregate Risks and Determination of Safety for Infants and Children
1. Safety factor for infants and children -- i. In general. In
assessing the potential for additional sensitivity of infants and
children to residues of hexythiazox, EPA considered data from
developmental toxicity studies in the rat and rabbit and a two-
generation reproduction study in the rat. This is generally the case --
edit if different studies. The developmental toxicity studies are
designed to evaluate adverse effects on the developing organism
resulting from maternal pesticide exposure during gestation.
Reproduction studies provide information relating to effects from
exposure to the pesticide on the reproductive capability of mating
animals and data on systemic toxicity.
FFDCA section 408 provides that EPA shall apply an additional
tenfold margin of safety for infants and children in the case of
threshold effects to account for pre-and post-natal toxicity and the
completeness of the database unless EPA determines that a different
margin of safety will be safe for infants and children. Margins of
safety are incorporated into EPA risk assessments either directly
through use of a 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 MOE
and uncertainty factor (usually 100 for combined inter- and intra-
species variability)) and not the additional tenfold MOE/uncertainty
factor when EPA has a complete data base under existing guidelines and
when the severity of the effect in infants or children or the potency
or unusual toxic properties of a compound do not raise concerns
regarding the adequacy of the standard MOE/safety factor.
ii. Developmental toxicity studies -- a. Rats. In the rat
developmental study, the maternal (systemic) NOEL was 240 mg/kg/day.
The maternal LOEL of 720 mg/kg/day was based on decreased food
consumption and decreased body weight. The developmental (fetal) NOEL
was 240 mg/kg/day. The developmental LOEL was based on slight delayed
ossification.
b. Rabbits. In the rabbit developmental toxicity study, the
maternal (systemic) NOEL was 1080 mg/kg/day at the highest dose tested
(HDT). The developmental (fetal) NOEL was 1080 mg/kg/day at the highest
dose tested.
iii. Reproductive toxicity study -- Rats. In the 2-generation
reproductive toxicity study in rats, the parental (systemic) NOEL was
20 mg/kg/day. The LOEL of 120 mg/kg/day was based on decreased body
weight and decreased food consumption. The developmental NOEL was 20
mg/kg/day. The developmental LOEL of 120 mg/kg/day was based on
decreased body weight and delayed maturation. The reproductive NOEL was
120 mg/kg/day at the highest dose tested.
iv. Pre- and post-natal sensitivity. The pre- and post-natal
toxicology data base for hexythiazox is complete with respect to
current toxicological data requirements. There are no pre- or post-
natal toxicity concerns for infants and children, based on the results
of the rat and rabbit developmental toxicity studies and the 2-
generation rat reproductive toxicity study. In the developmental study
in rats, the developmental NOEL and LOEL is the same as the maternal
NOEL and LOEL demonstrating that no extra-sensitivity for infants and
children is present. In rabbits, there are no maternal or developmental
effects up to the limit dose of 1080 mg/kg/day HDT. In the 2-generation
reproductive toxicity study in rats, there are no pup effects at doses
below maternal effects and the common effects in both pups and parental
animals decreased body weight also demonstrates that there is no extra-
sensitivity for infants and children.
v. Conclusion. Based on the above, EPA concludes that reliable data
support use of the standard 100-fold uncertainty factor and that an the
additional safety factor is not needed to protect the safety of infants
and children.
2. Chronic risk. Using the conservative exposure assumptions
described above, EPA has concluded that aggregate exposure to
hexythiazox from food will utilize less than 1% of the RfD for infants
and children. EPA generally has no concern for exposures below 100% of
the RfD because the RfD represents the level at or below which daily
aggregate dietary exposure over a lifetime will not pose appreciable
risks to human health. Despite the potential for exposure to
hexythiazox in drinking water and from non-dietary, non-occupational
exposure, EPA does not expect the aggregate exposure to exceed 100% of
the RfD. Therefore, taking into account the completeness and
reliability of the toxicity data, the conservative exposure assessment
and the fact that residential uses do not fall under a chronic exposure
scenario, EPA concludes that there is a reasonable certainty that no
harm will result to infants and children from aggregate exposure to
hexythiazox residues.
V. Other Considerations
A. Metabolism In Plants and Animals
1. For the purpose of this section 18 request, the nature of the
residue in plants is adequately understood. The residue of concern is
hexythiazox and its metabolites containing the (4-chlorophenyl)-4-
methyl-2-oxo-3-thiazolidine moiety (as specified in 40 CFR 180.448).
2. Although no livestock commodity tolerances are established, the
nature of the residue in animals is considered to be understood. The
residue of concern is hexythiazox and its metabolites containing the
(4-chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiety.
B. Analytical Enforcement Methodology
Adequate methods to enforce the tolerance expression have been
submitted for publication in PAM II. The approved method is designated
as AMR 985-87 which has been used in a variety of commodities. This
method is available in PP#5F3254, and by request from U.S. EPA, IRSD/
PIRIB (7502C), 401 M St., SW., Washington DC 20460.
C. Magnitude of Residues
1. Residues of hexythiazox and its metabolites containing the (4-
chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiety (expressed as parent
compound) are not expected to exceed 0.10 ppm in/on cotton, undelinted
seed. A time-limited tolerance is being established at this level.
[[Page 68214]]
2. It is unknown if residues will concentrate in processed products
of cotton seed. Therefore, the tolerance level for the RAC has been
adjusted to account for any possible concentration of the residue.
Additional tolerances on processed products of cotton are not required
for this section 18 request.
3. Residue data are not available for cotton gin byproducts. For
the purpose of this section 18 request, EPA has estimated residue
levels in cotton gin byproducts. A search by EPA of the data currently
available indicates two chemicals for which tolerances are established
on both cotton gin byproducts and cotton seed. One use is for an at-
planting use of an insecticide. The other cotton seed/cotton gin
byproducts tolerance pair, 6 ppm and 100 ppm respectively, was
established for a preharvest desiccant use of a herbicide. Since this
preharvest desiccant use would be considered a worst case scenario, the
hexythiazox residues on cotton gin byproducts will be estimated based
on the concentration factor from that use, 16.6x (100/6). Thus, EPA
estimates that the residue level of hexythiazox on cotton gin
byproducts will be 2 ppm. A time-limited tolerance is being established
at 2 ppm for hexythiazox residues in/on cotton gin byproducts. EPA
notes that residue data for hexythiazox in/on cotton gin byproducts
will be required for a section 3 registration decision to be made.
4. Tolerances for secondary residues of hexythiazox in livestock
commodities are not established. Livestock feedstuffs for cattle (dairy
and beef), poultry (discussed below)and swine are derived from cotton
(meal,seed, and hulls). The maximum dietary burden from established
tolerances on apples and this time-limited tolerance are 0.53 ppm for
beef cattle, and 0.51 ppm for dairy cattle. EPA has previously reviewed
a hexythiazox feeding study in dairy cows, in which the only measurable
residues were in kidney and liver. For the purpose of this time-limited
tolerance, EPA has translated these data to swine commodities. Based
upon available data, EPA would not expect detectable residues of
hexythiazox and its metabolites in commodities derived from cattle
(beef and dairy), and swine.
5. Poultry feedstuffs are derived from cotton (cotton seed meal).
Data concerning the potential for secondary residues in poultry are
available. The maximum dietary burden from poultry, resulting from use
associated with this time-limited tolerance is 0.02 ppm. Hexythiazox
tolerances are not established on other poultry feed items. Based upon
the total radioactive residue levels from the poultry metabolism study,
tolerances for secondary residues of hexythiazox in poultry commodities
are not required for this section 18 request.
D. International Residue Limits
There are no Codex, Canadian or Mexican maximum residue limits
established for hexythiazox and its metabolites on cotton seed. Thus,
harmonization is not an issue for this time-limited tolerance.
E. Rotational Crop Restrictions
Strawberries are not normally rotated in southern California. Thus,
rotational crop considerations are not an issue for this section 18.
VI. Conclusion
Therefore, the tolerance is established for combined residues of
hexythiazox (trans-5-(4-chlorophenyl)-N-cyclohexyl-4-methyl-2-
oxothiazolidine-3-carboxamide) in strawberries at 3.0 ppm.
VII. Objections and Hearing Requests
The new FFDCA section 408(g) provides essentially the same process
for persons to ``object'' to a tolerance regulation issued by EPA under
new section 408(e) and (l)(6) as was provided in the old section 408
and in section 409. However, the period for filing objections is 60
days, rather than 30 days. EPA currently has procedural regulations
which govern the submission of objections and hearing requests. These
regulations will require some modification to reflect the new law.
However, until those modifications can be made, EPA will continue to
use those procedural regulations with appropriate adjustments to
reflect the new law.
Any person may, by March 2, 1998, file written objections to any
aspect of this regulation and may also request a hearing on those
objections. Objections and hearing requests must be filed with the
Hearing Clerk, at the address given above (40 CFR 178.20). A copy of
the objections and/or hearing requests filed with the Hearing Clerk
should be submitted to the OPP docket for this rulemaking. The
objections submitted must specify the provisions of the regulation
deemed objectionable and the grounds for the objections (40 CFR
178.25). Each objection must be accompanied by the fee prescribed by 40
CFR 180.33(i). If a hearing is requested, the objections must include a
statement of the factual issues on which a hearing is requested, the
requestor's contentions on such issues, and a
[[Page 68215]]
summary of any evidence relied upon by the requestor (40 CFR 178.27). A
request for a hearing will be granted if the Administrator determines
that the material submitted shows the following: There is 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 in the manner sought by the requestor
would be adequate to justify the action requested (40 CFR 178.32).
Information submitted in connection with an objection or hearing
request may be claimed confidential by marking any part or all of that
information as 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.
VIII. Public Record and Electronic Submissions
EPA has established a record for this rulemaking under docket
control number [OPP-300595] (including any comments and data submitted
electronically). A public version of this record, including printed,
paper versions of electronic comments, which does not include any
information claimed as CBI, is available for inspection from 8:30 a.m.
to 4 p.m., Monday through Friday, excluding legal holidays. The public
record is located in Rm. 1132 of the Public Information and Records
Integrity Branch, Information Resources and Services Division (7506C),
Office of Pesticide Programs, Environmental Protection Agency, Crystal
Mall #2, 1921 Jefferson Davis Highway, Arlington, VA.
Electronic comments may be sent directly to EPA at:
[email protected].
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption.
The official record for this rulemaking, as well as the public
version, as described above will be kept in paper form. Accordingly,
EPA will transfer any copies of objections and hearing requests
received electronically into printed, paper form as they are received
and will place the paper copies in the official rulemaking record which
will also include all comments submitted directly in writing. The
official rulemaking record is the paper record maintained at the
Virginia address in ``ADDRESSES'' at the beginning of this document.
IX. Regulatory Assessment Requirements
This final rule establishes a time-limited tolerance under FFDCA
section 408(l)(6). 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) (Pub. L. 104-4). Nor does it require any
prior consultation as specified by Executive Order 12875, entitled
Enhancing the Intergovernmental Partnership (58 FR 58093, October 28,
1993), or special considerations as required by 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).
In addition, since these tolerances and exemptions that are
established under FFDCA section 408(l)(6), such as the tolerances 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. Nevertheless, the Agency has previously assessed
whether establishing tolerances, exemptions from tolerances, raising
tolerance levels or expanding exemptions might adversely impact small
entities and concluded, as a generic matter, that there is no adverse
economic impact. The factual basis for the Agency's generic
certification for tolerance acations published on May 4, 1981 (46 FR
24950), and was provided to the Chief Counsel for Advocacy of the Small
Business Administration.
X. Submission to Congress and the General Accounting Office
Under 5 U.S.C. 801(a)(1)(A), as added by the Small Business
Regulatory Enforcement Fairness Act of 1996, the Agency has submitted a
report containing this rule and other required information to the U.S.
Senate, the U.S. House of Representatives, and the Comptroller General
of the General Accounting Office prior to publication of this rule in
today's Federal Register. This is not a ``major rule'' as defined by 5
U.S.C. 804(2).
[[Page 68216]]
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: December 19, 1997.
Peter Caulkins,
Acting 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. 346a and 371.
2. In Sec. 180.448, paragraph (b) is amended by adding and
alphabetically inserting the following commodity to the table to read
as follows:
Sec. 180.448 Hexythiazox; tolerances for residues.
* * * * *
(b) * * *
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Commodity Parts per million Expiration/Revocation Date
--------------------------------------------------------------------------------------------------------------------------------------------------------
* * * * * * *
Strawberries.............................................. 3.0 7/1/98
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* * * * *
[FR Doc. 97-34104 Filed 12-30-97; 8:45 am]
BILLING CODE 6560-50-F