[Federal Register Volume 63, Number 137 (Friday, July 17, 1998)]
[Notices]
[Pages 38644-38646]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-19247]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-820; FRL-6019-1]


BASF Corporation; Pesticide Tolerance Petition Filing

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of a pesticide 
petition proposing the establishment of regulations for residues of a 
certain pesticide chemical in or on various food commodities.
DATES: Comments, identified by the docket control number PF-820, must 
be received on or before August 17, 1998.
ADDRESSES: By mail submit written comments to: Information and Records 
Integrity Branch, Public Information and Services Divison (7502C), 
Office of Pesticides Programs, Environmental Protection Agency, 401 M 
St., SW., Washington, DC 20460. In person bring comments to: Rm. 119, 
CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically by following 
the instructions under ``SUPPLEMENTARY INFORMATION.'' No confidential 
business information should be submitted through e-mail.
    Information submitted as a comment concerning this document may be 
claimed confidential by marking any part or all of that information as 
``Confidential Business Information'' (CBI). CBI should not be 
submitted through e-mail. Information marked as CBI will not be 
disclosed except in accordance with procedures set forth in 40 CFR part 
2. A copy of the comment 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. All written 
comments will be available for public inspection in Rm. 119 at the 
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: Beth Edwards, Insecticide Branch, 
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: Rm. 206, Crystal 
Mall #2, 1921 Jefferson Davis Highway, Arlington, VA 22202, (703) 305-
5400; e-mail: [email protected].
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition as 
follows proposing the establishment and/or amendment of regulations for 
residues of certain pesticide chemical in or on various food 
commodities under section 408 of the Federal Food, Drug, and Comestic 
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that this petition 
contains data or information regarding the elements set forth in 
section 408(d)(2); however, EPA has not fully evaluated the sufficiency 
of the submitted data at this time or whether the data supports 
granting of the petition. Additional data may be needed before EPA 
rules on the petition.
    The official record for this notice of filing, as well as the 
public version, has been established for this notice of filing under 
docket control number [PF-820] (including comments and data submitted 
electronically as described below). 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 official record is located at the address in 
``ADDRESSES'' at the beginning of this document.
    Electronic comments can be sent directly to EPA at:
    [email protected]


    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption. Comment and data 
will also be accepted on disks in Wordperfect 5.1/6.1 file format or 
ASCII file format. All comments and data in electronic form must be 
identified by the docket control number (PF-820) and appropriate 
petition number. Electronic comments on this notice may be filed online 
at many Federal Depository Libraries.

List of Subjects

    Environmental protection, Agricultural commodities, Feed additives, 
Food additives, Pesticides and pests, Reporting and recordkeeping 
requirements.

    Dated: July 13, 1998.
James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by section 408(d)(3) of the FFDCA. The summary of the 
petition was prepared by the petitioner and represents the views of the 
petitioner. EPA is publishing the petition summary verbatim without 
editing them in any way. The petition summary announces the 
availability of a description of the analytical methods available to 
EPA for the detection and measurement of the pesticide chemical 
residues or an explanation of why no such method is needed.

BASF Corporation

PP 4E4411

    EPA has received a pesticide petition (PP 4E4411) from BASF 
Corporation, Agricultural Products, P.O. Box 13528, Research Triangle 
Park, NC 27709 proposing pursuant to section 408(d) of the Federal 
Food, Drug, and Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR 
180.448 by establishing a tolerance for residues of hexythiazox [trans-
5-(4-chlorophenyl)-N-cyclohexyl-4-methyl-2-oxothiazolidine-3-
carboxamide] and its metabolites containing the (4-chlorophenyl)-4-
methyl-2-oxo-3-

[[Page 38645]]

thiazolidine moiety (expressed as parts per million (ppm) of the parent 
compound), in or on the raw agricultural commodity dried hops. The 
proposed analytical method is gas chromatography using Nitrogen 
Phosphorous detection. EPA has determined that the petition contains 
data or information regarding the elements set forth in section 
408(d)(2) of the FFDCA; however, EPA has not fully evaluated the 
sufficiency of the submitted data at this time or whether the data 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1. Plant and animal metabolism. BASF Corporation notes that 
metabolism in plants and animals is understood.
    2. Analytical method. The proposed analytical method involves 
methanol extraction, clean-up by partition, and detection of residues 
by gc with npd.
    3. Magnitude of residues. Nine residue trials were conducted in 
Bavaria Germany. The method of detection had a limit of detection of 
0.05 ppm. After kiln drying, hops residues ranged from 0.61 to 1.53 ppm 
and averaged approximately 0.9 ppm.

B. Toxicological Profile

    1. Acute toxicity. For the technical grade active ingredient:
    Acute oral toxicity--Rat. LD50 >5,000 milligram/
killograms (mg/kg) (Tox Category IV); Acute Dermal Toxicity (rat) 
LD50 > 5,000 mg/kg (Tox Category III); Acute Inhalation 
Toxicity (rat) LC50 > 2.0 mg/l (4 hrs) (Tox Category IV); 
Primary Eye Irritation (rabbit) - Hexythiazox is a mild ocular irritant 
(Tox Category III); Primary Dermal irritation (rabbit) - Hexythiazox is 
not a dermal irritant (Tox Category IV); Dermal Sensitization (guinea 
pig) - Hexythiazox is not a dermal sensitizer.
    2. Genotoxicty. All mutagenicity tests were negative. Ames Testing. 
Negative (Accession No. 072941). In vitro cytogenicity (Chinese hamster 
ovary cells): Negative (MRID 00156894). Rat primary hepatocyte 
unscheduled DNA synthesis assay (MRID 00156893). Mammalian cell forward 
gene mutation assay (MRID 00155154).
    3. Reproductive and developmental toxicity--i. Developmental 
toxicity--Rat. The maternal toxicity NOEL was determined to be 240 mg/
kg/day. The fetotoxicity NOEL was 240 mg/kg/day, and the compound was 
not embryotoxic at the highest dose tested (HDT), 2,160 mg/kg/day (MRID 
00147578).
    ii. Developmental toxicity-- Rabbit. No development or maternal 
toxicity was observed at the HDT, 1,080 mg/kg/day (MRID 00146555).
    iii. Multi-generation reproduction-- Rat. The parental toxicity 
NOEL was determined to be 20 mg/kg/day. No reproductive effects were 
observed at 2,400 ppm (200 mg/kg/day), the HDT.
    4. Chronic toxicity. The data submitted in support of this 
tolerance and other relevant material have been reviewed. The 
toxicological and metabolism data considered in support of this 
tolerance are discussed in detail in related documents published in the 
Federal Registers of April 26, 1989 (54 FR 17947), and February 21, 
1996 (61 FR 6552) (FRL-5350-6) .
    5. Chronic toxicity non-rodent--Dog and rodent--Rat. The NOEL for 
chronic effects for hexythiazox is 2.5 mg/kg/day, based upon a 1-year 
dog study, and the RfD is 0.025 mg/kg/day (MRID 00146556, 00151359, and 
00156895). A 2-year rat study showed a systemic NOEL of 430 ppm (21.5 
mg/kg/day, MRID 00146559). No evidence of oncogenicity was observed in 
this study.
    6. Oncogenicity in the rodent-- Mouse. Hexythiazox produced an 
oncogenic effect in the livers of female mice (MRID 00147577, 00156896, 
40328701, and 40328702) with a systemic NOEL of 250 ppm (37.5 mg/kg/
day). The Agency has calculated an oncogenic potential of Q* = 0.039 
(mg/kg/day)-1.
    7. Hormonal effects. No specific hormonal effects testing has been 
conducted with hexythiazox, however, the compound was tested in two 
developmental bioassays and a multi-generation reproduction bioassay. 
No hormonal effects were noted in these relevant tests.
    8. Threshold effects. A chronic dietary exposure/risk assessment 
has been performed for hexythiazox using the established reference dose 
(RfD) of 0.025 mg/kg-bwt/day. The RfD was based on a NOEL of 2.5 mg/kg/
day from a 1-year dog feeding study.
    9. Non-threshold effects. The Agency has classified hexythiazox as 
a class C (possible human) carcinogen based on a significantly 
increased incidence of hepatocellular carcinomas (p=0.028), and 
adenomas/carcinomas combined (p=0.024) in female mice at the HDT (1,500 
ppm) when compared to the controls as well as a significantly increased 
(p> 0.001) incidence of preneo-plastic hepatic nodules in both males 
and females at the HDT (1,500 ppm). The decision supporting a Category 
C classification (rather than a Category B) was based primarily on the 
fact that only one species was affected (mouse), mutagenicity assays 
did not support upgrading to a B classification, and structure-activity 
relationship of hexythiazox to other compounds supported a C 
classification. In classifying hexythiazox as a Category C carcinogen, 
the Agency concluded that a quantitative estimate of the carcinogenic 
potential for humans should be calculated because of the increased 
incidence of malignant liver tumors in the female mouse.
    Thus, a Q* of 3.9 x 10-2 (mg/kg/day)-1 in human 
equivalents has been calculated. A full review of the data indicates 
that although hexythiazox is a carcinogen in mice, the risks would be 
extremely small from the proposed use on hops. Estimated dietary 
carcinogenic risk to the general population based on the highly 
conservative assumptions that all imported hops are treated with 
hexythiazox and would bear residues at the proposed tolerance level is 
estimated to be approximately 3 x10-7. In fact, the Agency 
estimated in 1993, that the most conservative estimate of the 
percentage of beer containing foreign grown hops (including imported 
beer and domestic beer brewed with imported hops) to be approximately 
49%. In addition, the average residue seen in the residue studies 
supporting this tolerance was approximately 0.9 ppm. Incorporating this 
information into the risk calculation the estimated oncogenic risk from 
the proposed use is reduced to approximately 7 x 10-8. Even 
this is an overestimation, as the calculations assume that the level of 
hexythiazox in finished beer is the same as the level in the dried 
hops. BASF has supplied information which demonstrates that finished 
beer brewed with hops containing an average level of 1.16 ppm results 
in hexythiazox levels of <0.05 ppm in the finished beer. Assuming a 
level of 0.05 ppm in beer produced from hops would further reduce the 
theoretical risk to approximately 4 x 10-9.
    A chronic dietary exposure/risk assessment has been performed for 
hexythiazox using a RfD of 0.025 mg/kg-bwt/day. The RfD was based on a 
NOEL of 2.5 mg/kg/day from a 1-year dog feeding study and a safety 
factor of 100. The endpoint effect of concern was hypertrophy of the 
adrenal cortex in both sexes, decreased red blood cell counts, 
hemoglobin content and hematocrit in males. The analysis was performed 
using tolerance level residues and 100% crop treated information. The 
exposure for established tolerances and the current proposal utilizes 
<1% of the RfD for the U.S.population.

C. Aggregate Exposure

    1. Dietary exposure. The exposure for established tolerances and 
the current

[[Page 38646]]

proposal utilizes <1% of the RfD for the U.S. population. Non-nursing 
infants -6. This risk number includes the very conservative 
assumptions that all apples and pears are treated with hexythiazox and 
that all resulting residues are at the tolerance level. In its recent 
FR Notice establishing the tolerance in apples the Agency recognized 
these conservative overestimations and concluded ``in reality, the 
Agency knows that all apples would not be treated with this pesticide 
and expect that even apples receiving maximum treatment will have 
residues far below tolerance level. For example, in field trials 
conducted using application rates 10 times the label amount, residues 
in apples still did not exceed the tolerance level. Further, the 
maximum residue level (MRL) in apple juice would be expected to be less 
than 50% of the residue level in whole fruit. Based on an assessment of 
the cancer risks of the proposed use of hexythiazox, the Agency 
believes that the proposed use of hexythiazox on apples will pose an 
extremely small risk to humans.'' The current proposal will not 
increase the theoretical oncogenic risk significantly.
    In addition, the Agency has concluded that based on the residue and 
feeding levels of spent hops ``meat and milk tolerances are not 
required for this petition.''
    2. ``Other'' exposure. Other potential sources of exposure of the 
general population to residues of pesticides are residues in drinking 
water and exposure from non-occupational sources. Since this tolerance 
is for an ``imported use,'' BASF does not anticipate exposure to 
residues of hexythiazox in drinking water. BASF has not estimated non-
occupational exposure for hexythiazox. Since the current registrations 
for hexythiazox in the United States are limited to commercial apple/
pear production, the potential for non-occupational exposure to the 
general population is considered to be insignificant.

D. Cumulative Effects

    BASF also considered the potential for cumulative effects of 
hexythiazox and other substances that have a common mechanism of 
toxicity. BASF is unaware of any conclusive data regarding the 
potential for hexythiazox to share a common mechanism for toxic effects 
with any other compound. In dietary assessment, the food factor for 
hops is only 0.03%. Therefore, BASF concluded that any concern 
regarding a common mechanism of toxicity would be insignificant.

E. Safety Determination

    1. U.S. population. Using the exposure assumptions described above, 
BASF concludes that aggregate exposure to hexythiazox will utilize 
approximately <1% of the RfD for the U.S. population. EPA generally has 
no concern for exposures below 100% of the RfD. In addition the 
calculated theoretical oncogenic risk associated with this use is more 
than 100 times less than the Agency's general level of concern (1 x 
10-6).
    Therefore, based on the completeness and reliability of the 
toxicity data and the conservative exposure assessment, BASF concludes 
that there is a reasonable certainty that no harm will result from 
aggregate exposure to residues of hexythiazox, including all 
anticipated dietary exposure and all other non-occupational exposures.
    2. Infants and children. The toxicity database includes both 
developmental and reproductive testing in which no significant concerns 
were identified. BASF therefore believes the established RfD of 0.025 
mg/kg/day is the appropriate approach for assessing risk in children. 
Based on the completeness and reliability of the toxicity data and the 
conservative exposure assessment, BASF concludes that there is a 
reasonable certainty that no harm will result to infants and children 
from aggregate exposure to the residues of hexythiazox, including all 
anticipated dietary exposure and all other non-occupational exposures.

F. Other Considerations

    The qualitative nature of the residues in plants and animals is 
adequately understood. There is a practical analytical method for 
detecting and measuring levels of hexythiazox in or on food with a 
limit of detection that allows monitoring of food with residues at or 
above the levels set in these tolerances.

G. International Tolerances

    A maximum residue level has not been established for hexythiazox by 
the Codex Alimentarius Commission.
[FR Doc. 98-19247 Filed 7-16-98; 8:45 am]
BILLING CODE 6560-50-F