[Federal Register Volume 63, Number 200 (Friday, October 16, 1998)]
[Rules and Regulations]
[Pages 55540-55547]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-27841]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300732; FRL-6035-2]
RIN 2070-AB78
Hexythiazox; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes a tolerance for residues of
hexythiazox [trans-5-(4-chlorophenyl)-N-cyclohexyl-4-methyl-2-
oxothiazolidine-3-carboxamide] (CAS No. 78587-05-0) and its metabolites
containing the (4-chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiety
(expressed as parts per million (ppm) of the parent compound) in or on
dried hops. BASF Corporation, Agricultural Products requested this
tolerance under the Federal Food, Drug and Cosmetic Act (FFDCA), as
amended by the Food Quality Protection Act of 1996 (Pub. L. 104-170).
DATES: This regulation is effective October 16, 1998. Objections and
requests for hearings must be received by EPA on or before December 15,
1998.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300732], 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-300732], 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. 119, Crystal
Mall #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
[[Page 55541]]
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-300732]. 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: Beth Edwards, 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) 305-5400, e-mail:
[email protected].
SUPPLEMENTARY INFORMATION: In the Federal Register of July 17, 1998 (63
FR 38644)(FRL-6019-1), EPA issued a notice pursuant to section 408 of
the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(e)
announcing the filing of a pesticide petition (4E4411) for a tolerance
on dried hops by BASF Corporation, Agricultural Products, P.O. Box
13528, Research Triangle Park, NC 27709. This notice included a summary
of the petition prepared by BASF Corporation, as required under the
FFDCA as amended by the Food Quality Protection Act (FQPA) of 1996.
There were no comments received in response to the notice of filing.
The petition requested that 40 CFR 180.448 be amended by
establishing a tolerance for residues of the insecticide hexythiazox,
in or on dried hops at 2.0 parts per million (ppm).
This action pertains only to imported hops. There are no U.S.
registrations for the use of hexythiazox on hops.
I. Risk Assessment and Statutory Findings
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).
II. 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 tolerance for residues of
hexythiazox on dried hops at 2.0 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. A battery of acute toxicity studies places technical grade
hexythiazox in Toxicity Category IV for acute oral LD50
(LD50 > 5,000 milligram/kilograms (mg/kg)), Category III for
dermal LD50 (LD50 > 5,000 mg/kg), Category III
for inhalation LC50 (LC50 > 2.0 mg/L), Category
III for primary eye irritation (showed mild irritation (reddened
conjunctiva)), Category IV for dermal irritation (non irritant).
Hexythiazox is a non-sensitizer.
2. In a 1-month feeding study in dogs, the No-Observed Adverse
Effect Level (NOAEL) was 1.75 mg/kg/day and the Lowest Observed Adverse
Effect Level (LOAEL) was 12.5 mg/kg/day, based on increased liver and
adrenal weights.
3. In a 1-year feeding study in dogs, the NOAEL was 2.5 mg/kg/day
and the LOAEL was 12.5 mg/kg/day, based on increased alkaline
phosphatase, increased adrenal and liver weights, and liver and adrenal
lesions.
4. In a carcinogenicity study in mice, the NOAEL was 36 mg/kg/day
and the LOAEL was 215 mg/kg/day. Effects were decreased bodyweight in
males and increased hepatocellular carcinomas and combined adenoma/
carcinomas.
5. In a chronic feeding/carcinogenicity study in rats, the NOAEL
(systemic) was 26 mg/kg/day and the LOAEL (systemic) was 180 mg/kg/day
based on decreased body weight gain and increased liver weights in both
sexes.
6. In a developmental toxicity study in rats, the maternal NOAEL
was 240 mg/kg/day and the maternal LOAEL was 720 mg/kg/day based on
increased ovarian weights. The developmental NOAEL was 240 mg/kg/day
and the developmental LOAEL was 720 mg/kg/day based on decreased bone
ossification.
7. In a developmental toxicity study in rabbits, the maternal NOAEL
was 1,080 mg/kg/day (HDT); the maternal LOAEL was not determined. The
developmental NOAEL was 1,080 mg/kg/day (HDT); the developmental LOAEL
was not determined.
8. In a 2-generation reproduction study in rats, the parental NOAEL
was 35 mg/kg/day and the parental LOAEL was 200 mg/kg/day based on
decreased body weight gain, decreased food consumption and efficiency,
and increased liver, kidney and ovarian weights. The reproductive NOAEL
was 35 mg/kg/day and the reproductive LOAEL was 200 mg/kg/day based on
decreased pup body weight during lactation, delayed hair growth and eye
opening.
B. Toxicological Endpoints
1. Acute toxicity. A dose and endpoint for acute dietary risk
assessment was not selected due to the lack of toxicological effects
attributable to a single exposure (dose) in studies available in the
data base including the developmental toxicity studies in rats and
rabbits with hexythiazox.
2. Short- and intermediate-term toxicity. A dose or endpoint for
short-, intermediate-, or long-term (non-cancer) dermal risk assessment
was not selected because of the lack of appropriate endpoints and the
lack of long-term exposure based on the current use pattern for
hexythiazox.
[[Page 55542]]
Except for some acute inhalation toxicity studies, there are no
inhalation toxicity studies available for use in selecting the dose and
endpoint for this risk assessment. There are LC50 studies on
the technical materials indicating a probable low toxicity.
3. Chronic toxicity. EPA has established the RfD for hexythiazox
at 0.025 mg/kg/day. This RfD is based on a 1-year feeding study in dogs
using a NOAEL of 2.5 mg/kg/day. The LOAEL was 12.5 mg/kg/day based on
increased alkaline phosphatase, increased adrenal and liver weights,
and liver and adrenal lesions.
4. Carcinogenicity. Hexythiazox is classified as a Group C chemical
(possible human carcinogen) with a Q1* = 2.22 x
10-2 mg/kg/day. This was based on hepatocellular carcinomas
in female mice.
C. Exposures and Risks
1. From food and feed uses. Tolerances have been established (40
CFR 180.448) for the residues of hexythiazox, on apples at 0.02 ppm and
pears at 0.30 ppm. There are also Section 18 uses for cotton,
strawberries and dates. Risk assessments were conducted by EPA to
assess dietary exposures from hexythiazox as follows:
The following assumptions were used in the chronic dietary (food)
risk assessment: Tolerance level residues for dried hops, and all other
commodities with published, pending, permanent or time-limited
hexythiazox tolerances; and, percent crop-treated information for
commodities with permanent tolerances. Thus, this risk assessment
should be viewed as partially refined. Further refinement using
anticipated residue values would result in a lower estimate of chronic
(non-cancer) dietary exposure (food only).
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:
a. 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.
b. That the exposure estimate does not underestimate exposure for
any significant subpopulation group.
c. 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 as required by the section 408(b)(2)(F), EPA
may require registrants to submit data on percent crop treated.
The Agency used percent crop treated (PCT) information as follows:
A routine chronic dietary exposure analysis for dried hops was
based on 6-8% of crop treated for apples, 1-5% of crop treated for
pears, < 1% of crop treated for cotton, < 1% of crop treated for
grapes, and < 1% of crop treated for peaches. These data were derived
from Doane and Maritz. This action pertains to dried hops grown in
Germany and imported to the United States. There are no available data
on hexythiazox use on hops which would be imported to the United
States.
The Agency believes that the three conditions listed Unit
II.C.1.a.-c. of this preamble have been met. With respect to Unit
II.C.1.a., the percent of crop treated estimates are derived from
Federal and private market survey data which are reliable and have a
valid basis. Typically, a range of estimates are supplied and the upper
end of this range is assumed for the exposure assessment. By using this
upper end estimate of the crop treated, the Agency is reasonably
certain that the percentage of the food treated is not likely to be
underestimated. As to Unit II.C.1.b. and c., 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 consumption of food bearing
hexythiazox in a particular area.
i. Acute exposure and risk. Acute dietary risk assessments are
performed for a food-use pesticide if a toxicological study has
indicated the possibility of an effect of concern occurring as a result
of a one day or single exposure. Due to the lack of toxicological
effects attributable to a single exposure (dose) in studies available
in the data base including the developmental toxicity studies in rats
and rabbits, there is no acute risk.
ii. Chronic exposure and risk. The Reference dose (RfD) used for
chronic dietary analysis is 0.025 mg/kg/day. This assessment was done
using the Dietary Risk Evaluation System (DRES) with the 1977-78 food
consumption data. This chronic dietary (food) risk assessment used the
following assumptions: (a) Tolerance level residues for the proposed
tolerance and all other commodities with published, pending, permanent
or time-limited, hexythiazox tolerances; and, (b) percent crop-treated
information for commodities with permanent tolerances. Thus, this risk
assessment should be viewed as partially refined. Further refinement
using anticipated residue values would result in a lower estimate of
chronic (non-cancer) dietary exposure (food only).
The following table 1 summarizes the estimated dietary exposures
for the U.S. population and those population subgroups that include
infants and children. There are no population subgroups with risk
estimates above that of the U.S. population.
Table 1.-- Chronic (Non-cancer) Dietary Exposure and Risk for
Hexythiazox
------------------------------------------------------------------------
Exposure
Subgroup: (mg/kg Percent
bwt/day) Chronic RfD
------------------------------------------------------------------------
U.S. Population (48 States)...................... 0.00012 <1%
Nursing Infants (< 1 year old)................... 0.000028 <1%
Non-nursing Infants (< 1 year old)............... 0.00012 < 1%
Children (1 to 6 years old)...................... 0.00020 < 1%
Children (7 to 12 years old)..................... 0.00014 < 1%
------------------------------------------------------------------------
2. From drinking water. This action pertains only to imported hops.
There are no U.S. registrations for the use of hexythiazox on hops. No
residues of hexythiazox from this use will be expected to appear in
U.S. drinking water.
There are no Maximum Contaminant Levels (MCL) or Health Advisory
(HA) levels established for residues of hexythiazox in drinking water.
Hexythiazox is relatively immobile and not persistent.
i. Acute exposure and risk. Due to the lack of toxicological
effects attributable to a single exposure (dose) in studies available
in the data base including the developmental toxicity studies in rats
and rabbits, there is no acute risk.
ii. Chronic exposure and risk. The estimated average concentration
of hexythiazox in surface water (56-day average - for chronic exposure)
is 0.28 parts per billion (ppb). The ground water screening level for
hexythiazox is
[[Page 55543]]
0.00147 ppb. These estimates are based upon an application rate of
0.187 lbs active ingredient/acre (ai/A). This is the maximum
application rate requested for the emergency exemptions for use on hops
and dates. EPA used the Generic Estimated Environmental Concentration
(GENEEC- simulates the transport of a pesticide off the agricultural
field) model to estimate the chronic environmental concentration of
hexythiazox residues in surface water, and the SCI-GROW (Screening
Concentration In GROund Water) model to estimate the concentration of
hexythiazox residues in ground water. SCI-GROW is a prototype model for
estimating ``worst case'' ground water concentrations of pesticides.
SCI-GROW is biased in that studies where the pesticide is not detected
in ground water are not included in the data set. Thus, it is not
expected that SCI-GROW estimates would be exceeded. It should be noted
that the GENEEC model was designed for use in ecological risk
assessment. It is not an ideal tool for use in drinking water risk
assessment. GENEEC could overestimate actual drinking water
concentrations. Thus, this model should be considered a screening tool.
The Agency has calculated drinking water levels of concern
(DWLOC's) for chronic (non-cancer) exposure to hexythiazox in drinking
water for various population subgroups. The DWLOC's for hexythiazox
(chronic exposure) are summarized in the following table 2.
Table 2.-- Drinking Water Levels of Concern for Chronic (Non-cancer) Exposure to Hexythiazox
----------------------------------------------------------------------------------------------------------------
Max.
Dietary Exposure
Exposure from Bodyweight Daily Water DWLOC
Population Subgroup (mg/kg Water (kg) Consumption (g/
bwt/day) (mg/kg (Liters) L)
bwt/day)
----------------------------------------------------------------------------------------------------------------
U.S. Population (48 States).......................... 0.00012 0.025 70 2 870
Females (20 yrs and older, not pregnant or nursing).. 0.000099 0.025 60 2 750
Children (1 - 6 years old)........................... 0.00019 0.025 10 1 250
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To calculate the DWLOC for chronic (non-cancer) exposure relative
to a chronic toxicity endpoint, the chronic dietary food exposure (from
DRES) was subtracted from the chronic RfD (0.025 mg/kg bwt/day) to
obtain the acceptable chronic (non-cancer) exposure to hexythiazox in
drinking water. DWLOC's were then calculated using default body weights
and drinking water consumption figures as indicated in columns 4 and 5
of table 2 above. Therefore, the DWLOC's do not exceed EPA's levels of
concern.
The Agency has calculated a drinking water level of concern (DWLOC)
for chronic (cancer) exposure to hexythiazox in surface and ground
water for the U.S. population (48 States). The DWLOC for hexythiazox
(cancer exposure) is summarized in the following table 3.
Table 3.-- Drinking Water Levels of Concern for Chronic (Cancer) Exposure to Hexythiazox
----------------------------------------------------------------------------------------------------------------
Max.
Dietary Exposure
Exposure from Bodyweight Daily Water DWLOC
Population Subgroup (mg/kg Water (kg) Consumption (g/
bwt/day) (mg/kg (Liters) L)
bwt/day)
----------------------------------------------------------------------------------------------------------------
U.S. Population (48 States).......................... 0.000019 0.000026 70 2 0.91
----------------------------------------------------------------------------------------------------------------
To calculate the DWLOC for chronic (cancer) exposure relative to a
chronic (cancer) toxicity endpoint, the chronic (cancer) dietary food
exposure was subtracted from the maximum allowable hexythiazox exposure
relative to the Q1* to obtain the acceptable chronic (non-
cancer) exposure to hexythiazox in drinking water. The maximum
allowable hexythiazox exposure is calculated to be 0.000045 mg/kg bwt/
day (i.e. negligible risk level (1.0 x 10-6) divided by the
Q1* (0.0222 mg/kg bwt/day-1)). The DWLOC was then
calculated using default body weights and drinking water consumption
figures as indicated in columns 4 and 5 of table 3 above.
3. From non-dietary exposure. This action pertains to an import
tolerance. In addition, hexythiazox is not registered for any
residential uses. Therefore, there is no risk associated with non-
dietary exposure.
4. Cumulative exposure to substances with common mechanism of
toxicity. Section 408(b)(2)(D)(v) requires that, when considering
whether to establish, modify, or revoke a tolerance, the Agency
consider ``available information'' concerning the cumulative effects of
a particular pesticide's residues and ``other substances that have a
common mechanism of toxicity.''
EPA does not have, at this time, available data to determine
whether 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. For the purposes of this tolerance action, therefore,
EPA has not assumed that hexythiazox 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
[[Page 55544]]
chemicals, see the Final Rule for Bifenthrin Pesticide Tolerances (62
FR 62961, November 26, 1997).
D. Aggregate Risks and Determination of Safety for U.S. Population
1. Chronic risk. Using tolerance level residues and percent crop
treated exposure assumptions described above, EPA has concluded that
aggregate exposure to hexythiazox from food will utilize < 1% of the
RfD for the U.S. population. There are no population subgroups with
risk estimates above that of the U.S. population. 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.
The following table 4 summarizes the estimated dietary exposures
for the U.S. population and those population subgroups that include
infants and children.
Table 4.-- Chronic (Non-cancer) Dietary Exposure and Risk for
Hexythiazox
------------------------------------------------------------------------
Exposure
Subgroup (mg/kg bwt/ Percent
day) Chronic RfD
------------------------------------------------------------------------
U.S. Population (48 States)................... 0.00012 < 1%
Nursing Infants (< 1 year old)................ 0.000028 < 1%
Non-nursing Infants (< 1 year old)............ 0.00012 < 1%
Children (1 to 6 years old)................... 0.00020 < 1%
Children (7 to 12 years old).................. 0.00014 < 1%
------------------------------------------------------------------------
The estimated average concentration (highest value) of hexythiazox
in surface and ground water (0.28 ppb) is less than EPA's levels of
concern for hexythiazox in drinking water (870, 750 and 250 ppb) as a
contribution to chronic (non-cancer) aggregate exposure. Therefore,
taking into account the present uses and the use proposed in this
action, EPA concludes with reasonable certainty that residues of
hexythiazox in drinking water (when considered along with other sources
of chronic (non-cancer) exposure for which EPA has reliable data) would
not result in unacceptable levels of chronic (non-cancer) aggregate
human health risk estimates at this time.
EPA bases this determination on a comparison of estimated average
concentrations of hexythiazox in surface water to back-calculated
``levels of concern'' for hexythiazox in drinking water. The estimates
of hexythiazox in surface and ground water are derived from water
quality models that use conservative assumptions (health-protective)
regarding the pesticide transport from the point of application to
surface and ground water. Because EPA considers the aggregate risk
resulting from multiple exposure pathways associated with a pesticide's
uses, levels of concern in drinking water may vary as those uses
change. If new uses are added in the future, EPA will reassess the
potential impacts of hexythiazox residues in drinking water as a part
of the chronic (non-cancer) aggregate risk assessment process.
Despite the potential for hexythiazox exposure from water, EPA
concludes that there is a reasonable certainty that no harm will result
to infants, children, or adults from chronic (non-cancer) aggregate
exposure to hexythiazox residues.
2. Aggregate cancer risk for U.S. population. The assumptions of
this carcinogenic dietary (food) risk assessment are the same as
discussed above under Chronic (non-cancer) Risk (food only). Exposure
data for strawberries, cotton seed oil and cotton seed meal were
amortized over 6 years (second year section 18) for this cancer
exposure assessment; the exposure estimate for dates was amortized over
5 years (first year section 18). EPA assumes a duration of 5 years for
first year section 18 requests. For repeat section 18 requests, the
duration is considered to be the number of years that previous section
18s have been granted for that commodity plus 5 years. For the U.S.
population (48 States), the hexythiazox dietary exposure is estimated
to be 0.019 g/kg bwt/day. This exposure estimate results in a cancer
risk estimate (food only) of 4.3 x 10-7.
This cancer risk estimate is less than the Agency's level of
concern. It is normally not the Agency's policy to amortize exposure
data for risk calculations when establishing tolerances. However,
because tolerance level residues and partially refined percent crop
treated estimates were used for this action, the Agency believes that
the cancer risk is overestimated.
The estimated average concentration (highest value) of hexythiazox
in surface and ground water (0.28 ppb) is less than EPA's level of
concern for hexythiazox in drinking water as a contribution to chronic
(cancer) aggregate exposure (0.91 ppb). Therefore, taking into account
the present uses and the use proposed in this action, EPA concludes
with reasonable certainty that residues of hexythiazox in drinking
water (when considered along with other sources of chronic (cancer)
exposure for which EPA has reliable data) would not result in
unacceptable levels of chronic (cancer) aggregate human health risk
estimates at this time. EPA bases this determination on a comparison of
estimated average concentrations of hexythiazox in surface and ground
water to a back-calculated ``level of concern'' for hexythiazox in
drinking water. The estimates of hexythiazox in surface and ground
water are derived from water quality models that use conservative
assumptions (health-protective) regarding the pesticide transport from
the point of application to surface and ground water. Because EPA
considers the aggregate risk resulting from multiple exposure pathways
associated with a pesticide's uses, a level of concern in drinking
water may vary as those uses change. If new uses are added in the
future, EPA will reassess the potential impacts of hexythiazox residues
in drinking water as a part of the chronic (cancer) aggregate risk
assessment process.
Despite the potential for hexythiazox exposure from water, EPA
concludes that there is a reasonable certainty that no harm will result
to infants, children, or adults from chronic (cancer) aggregate
exposure to hexythiazox residues.
3. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
from aggregate exposure to hexythiazox residues.
E. Aggregate Risks and Determination of Safety for Infants and Children
1. Safety factor for infants and children-- i. In general. In
assessing the potential for additional sensitivity of infants and
children to residues of hexythiazox, EPA considered data from
developmental toxicity studies in the rat and rabbit and a 2-generation
reproduction study in the rat. The developmental toxicity studies are
designed to evaluate adverse effects on the developing organism
resulting from maternal pesticide exposure 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
[[Page 55545]]
case of threshold effects to account for pre-and post-natal toxicity
and the completeness of the database unless EPA determines that a
different margin of safety will be safe for infants and children.
Margins of safety are incorporated into EPA risk assessments either
directly through use of a margin of exposure (MOE) analysis or through
using uncertainty (safety) factors in calculating a dose level that
poses no appreciable risk to humans. EPA believes that reliable data
support using the standard uncertainty factor (usually 100 for combined
inter- and intra-species variability) and not the additional tenfold
MOE/uncertainty factor when EPA has a complete data base under existing
guidelines and when the severity of the effect in infants or children
or the potency or unusual toxic properties of a compound do not raise
concerns regarding the adequacy of the standard MOE/safety factor.
ii. Developmental toxicity studies. In a developmental toxicity
study, 24 pregnant rats (strain not specified) received hexythiazox
(NA-73) in gum Arabic by gavage at dose levels of 0, 240, 720, or 2,160
mg/kg/day from G.D. (gestation day) 7-17. The maternal NOAEL was 240
mg/kg/day. The maternal LOAEL was 720 mg/kg/day based on increased
ovarian weights. The developmental NOAEL was 240 mg/kg/day. The
developmental LOAEL was 720 mg/kg/day based on reduced bone
ossification. In a developmental toxicity study in rabbits, pregnant
NZW rabbits (12-14/dose) received hexythiazox (NA-73) at dose levels of
0, 120, 360 or 1,080 mg/kg/day from GD 6 to 18. No maternal or
developmental toxicity was noted at 1,080 mg/kg/day at the highest dose
tested. Both maternal and developmental NOAEL's were 1,080 mg/kg/day,
the highest dose tested.
iii. Reproductive toxicity study. In a reproductive toxicity study,
Fisher rats (20-30/dose group) were fed hexythiazox (NA-73) in the diet
at doses of 0, 60, 400, or 2,400 ppm (0, 5, 35 or 200 mg/kg/day) for 2-
generations. No reproductive toxicity was noted. The parental
(systemic) NOAEL was 35 mg/kg/day. The parental (systemic) LOAEL of 200
mg/kg/day was based on decreased body weight gain, food consumption and
food efficiency as well as increased liver, kidney and ovarian weights.
No histopathological changes were noted in the ovaries. The
reproductive NOAEL was 35 mg/kg/day. The reproductive LOAEL was 200 mg/
kg/day based on decreased pup body weight during lactation, in addition
to delays in hair growth and eye opening.
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. The results of these studies
indicate that infants and children are not more sensitive to exposure,
based on the results of the rat and rabbit developmental toxicity
studies as well as the 2-generation reproductive toxicity study in
rats.
v. Conclusion. There is a complete toxicity database for
hexythiazox and exposure data is complete or is estimated based on data
that reasonably accounts for potential exposures. Considering this and
the fact that no pre- or post-natal toxicity was shown, EPA concluded
that infants and children would be safe without the aditional tenfold
safety factor.
2. Chronic risk. Using the exposure assumptions described above,
EPA has concluded that aggregate exposure to hexythiazox from food will
utilize < 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, EPA does not
expect the aggregate exposure to exceed 100% of the RfD.
3. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to infants and children from aggregate exposure to hexythiazox
residues.
III. Other Considerations
A. Metabolism in Plants and Animals
Additional plant metabolism data were not submitted for this
tolerance. Metabolism studies have been submitted and reviewed in
conjunction with petitions for hexythiazox tolerances on apples,
grapes, citrus and pears. In studies with foliar application, there was
very little translocation of hexythiazox from the leaves. Recovery of
residues for hexythiazox and its hydroxylated metabolites was 95% in
apple leaves 91 days after application, 69 and 63% in pear and citrus
leaves 90 days after application, and 92% in grape leaves 56 days after
application. Given the fairly limited metabolism of hexythiazox
observed in these crops and that hops is a minor crop, the Agency
concludes that the nature of the residue is understood for the purposes
of this tolerance. The residue of concern is hexythiazox and its
metabolites containing the (4-chlorophenyl)-4-methyl-2-oxo-3-
thiazolidine moiety. Livestock feedstuffs are not derived from hops
(OPPTS 860.1000). Thus, the nature of the residue in livestock is not
of concern for the proposed tolerance.
B. Analytical Enforcement Methodology
BASF has proposed Method 343/1 for enforcement of the proposed
tolerance. An independent laboratory validation of this method was
performed by Horizon Labs (MRID 439235-02). Satisfactory recoveries
were obtained by the independent laboratory. The method has been
successfully validated by the Agency. Minor deficiencies (additional
interference testing for 3 ais and minor revisions) concerning this
method are outstanding. The Agency concludes an adequate method (Method
343/1, MRID 439235-01.) is available for enforcement purposes; this
method is available from PIRIB/IRSD.
Data concerning the recovery of hexythiazox via the FDA
Multiresidue Methods of PAM I have been submitted. Hexythiazox is
recoverable by the FDA multiresidue methods. Data concerning the
recovery of hexythiazox metabolites (PT-1-8, PT-1-2 and PT-1-4) via the
FDA Multiresidue Methods have not been submitted. The Agency concludes
adequate analytical methods are available to enforce the proposed
tolerance for residues of hexythiazox and its metabolites in/on
imported hops (dried). The Agency further concludes submission of the
additional multiresidue data for hexythiazox metabolites will not be
required for this tolerance on imported hops.
C. Magnitude of Residues
Four trials were performed in Bavaria (MRID 433616-04). Ordoval was
diluted in water to 0.045% and applied at a rate of 3,333 litres/
hectare (L/ha) (150 g ai/ha, 1X) using a mistblower. Hops were
harvested 28 days after application and kiln dried. The dried hops were
processed into beer, resulting in the fractionation of residues into
spent hops, brewers yeast, dregs and beer. Currently, residue data for
processed hops products are not required. Samples were analyzed using
BASF Method 343. The method was validated at 0.5 and 10 ppm. The
average recoveries were 79.8 16.1% (n=8) for fresh hops
and 69.6 15.2% (n=2) for dried hops. The maximum residue
observed in the treated dried hops was 1.53 ppm.
Five trials were performed in Bavaria (MRID 433616-05). Ordoval was
diluted in water to 0.045% and applied at a rate of 3,333 L/ha (150 g
ai/ha, 1X) using a mistblower. Hops were harvested 27 days after
application and kiln dried. Samples were analyzed using BASF Method
343. The method was validated at 0.5 and 1.0 ppm (fresh) or 1.0 and
[[Page 55546]]
10.0 ppm (dried). The average recoveries were 77.9 20.6%
(n=6) for fresh hops and 82.3 4.8% (n=2) for dried hops.
The maximum residue observed in the treated dried hops was 0.79 ppm.
The maximum residue observed in dried hops was 1.53 ppm. These data
support the establishment of a 2.0 ppm tolerance for residues of
hexythiazox and its metabolites containing the (4-chlorophenyl)-4-
methyl-2-oxo-3-thiazolidine moiety in/on hops cones, dried.
D. International Residue Limits
There is no Codex proposal, nor Canadian or Mexican limits for
residues of hexythiazox on hops. Therefore, a compatibility issue is
not relevant to the proposed tolerance. However, Codex limits are
established for hexythiazox per se on other crops. As the U.S.
enforcement method converts hexythiazox and its metabolites to a common
moiety, harmonization would require new enforcement methodology to be
developed and validated.
IV. Conclusion
Therefore, the tolerance is established for residues of hexythiazox
in/on dried hops at 2.0 ppm.
V. 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 December 15, 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 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
Confidential Business Information (CBI). Information so marked will not
be disclosed except in accordance with procedures set forth in 40 CFR
part 2. A copy of the information that does not contain CBI must be
submitted for inclusion in the public record. Information not marked
confidential may be disclosed publicly by EPA without prior notice.
VI. Public Record and Electronic Submissions
EPA has established a record for this rulemaking under docket
control number [OPP-300732] (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 Room 119 of the Public Information and Records
Integrity Branch, Information Resources and Services Division (7502C),
Office of Pesticide Programs, Environmental Protection Agency, Crystal
Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA.
Objections and hearing requests may be sent by e-mail directly to
EPA at:
[email protected].
E-mailed objections and hearing requests 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 in this unit 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.
VII. Regulatory Assessment Requirements
A. Certain Acts and Executive Orders
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, 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 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. 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 actions published on May
4, 1981 (46 FR 24950) and was provided to the Chief Counsel for
Advocacy of the Small Business Administration.
[[Page 55547]]
B. Executive Order 12875
Under Executive Order 12875, entitled Enhancing the
Intergovernmental Partnership (58 FR 58093, October 28, 1993), EPA may
not issue a regulation that is not required by statute and that creates
a mandate upon a State, local, or tribal government, unless the Federal
government provides the funds necessary to pay the direct compliance
costs incurred by those governments. If the mandate is unfunded, EPA
must provide to OMB a description of the extent of EPA's prior
consultation with representatives of affected State, local, and tribal
governments, the nature of their concerns, copies of any written
communications from the governments, and a statement supporting the
need to issue the regulation. In addition, Executive Order 12875
requires EPA to develop an effective process permitting elected
officials and other representatives of State, local, and tribal
governments ``to provide meaningful and timely input in the development
of regulatory proposals containing significant unfunded mandates.''
Today's rule does not create an unfunded Federal mandate on State,
local, or tribal governments. The rule does not impose any enforceable
duties on these entities. Accordingly, the requirements of section 1(a)
of Executive Order 12875 do not apply to this rule.
C. Executive Order 13084
Under Executive Order 13084, entitled Consultation and Coordination
with Indian Tribal Governments (63 FR 27655, May 19,1998), EPA may not
issue a regulation that is not required by statute, that significantly
or uniquely affects the communities of Indian tribal governments, and
that imposes substantial direct compliance costs on those communities,
unless the Federal government provides the funds necessary to pay the
direct compliance costs incurred by the tribal governments. If the
mandate is unfunded, EPA must provide to OMB, in a separately
identified section of the preamble to the rule, a description of the
extent of EPA's prior consultation with representatives of affected
tribal governments, a summary of the nature of their concerns, and a
statement supporting the need to issue the regulation. In addition,
Executive Order 13084 requires EPA to develop an effective process
permitting elected officials and other representatives of Indian tribal
governments ``to provide meaningful and timely input in the development
of regulatory policies on matters that significantly or uniquely affect
their communities.''
Today's rule does not significantly or uniquely affect the
communities of Indian tribal governments. This action does not involve
or impose any requirements that affect Indian tribes. Accordingly, the
requirements of section 3(b) of Executive Order 13084 do not apply to
this rule.
VIII. Submission to Congress and the Comptroller General
The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and to the Comptroller General of the
United States. EPA will submit a report containing this rule and other
required information to the U.S. Senate, the U.S. House of
Representatives, and the Comptroller General of the United States prior
to publication of the rule in the Federal Register. This rule is not a
``major rule'' as defined by 5 U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: October 1, 1998.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
PART 180-- [AMENDED]
1. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 346a and 371.
2. In Sec. 180.448 by revising paragraph (a) to read as follows:
Sec. 180.448 Hexythiazox; tolerances for residues.
(a) General. Tolerances are established for the combined residues
of the miticide 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 (expressed as
parts per million of the parent compound) in or on the following
commodities:
------------------------------------------------------------------------
Parts
Commodity per
million
------------------------------------------------------------------------
Apples......................................................... 0.02
Hops........................................................... 2.0
Pears.......................................................... 0.30
------------------------------------------------------------------------
* * * * *
[FR Doc. 98-27841 Filed 10-15-98; 8:45 am]
BILLING CODE 6560-50-F