[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
----------------------------------------------------------------------------------------------------------------

    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