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hexythiazox (Savey) Pesticide Petition Filing 8/98



[Notices]               
[Page 45487-45497]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr26au98-58]

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ENVIRONMENTAL PROTECTION AGENCY

[PF-826; FRL-6023-5]

 
Notice of Filing of Pesticide Petitions

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of pesticide 
petitions proposing the establishment of regulations for residues of 
certain pesticide chemicals in or on various food commodities.
DATES: Comments, identified by the docket control number PF-826, must 
be received on or before September 25, 1998.
ADDRESSES: By mail submit written comments to: Public Information and 
Records Integrity Branch, Information Resources and Services Division 
(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 to: opp-
docket@epamail.epa.gov. Follow 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

[[Page 45488]]

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. 1132 at the 
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: The product manager listed in the 
table below:

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                                   Office location/                     
        Product Manager            telephone number          Address    
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Beth Edwards (PM 3)...........  Rm. 206, CM #2, 703-    1921 Jefferson  
                                 305-5400, e-            Davis Hwy,     
                                 mail:edwards.beth@epa   Arlington, VA  
                                 mail.epa.gov.                          
Sidney Jackson (PM 22)........  Rm. 233, CM #2, 703-    Do.             
                                 305-7610, e-mail:                      
                                 jackson.sidney@epamai                  
                                 l.epa.gov.                             
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SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as 
follows proposing the establishment and/or amendment of regulations for 
residues of certain pesticide chemicals 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 these petitions 
contain 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-826] (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:
    opp-docket@epamail.epa.gov


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

List of Subjects

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

Dated: August 13, 1998.

    James Jones,

Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Petitioner summaries of the pesticide petitions are printed below 
as required by section 408(d)(3) of the FFDCA. The summaries of the 
petitions were prepared by the petitioners and represent the views of 
the petitioners. EPA is publishing the petition summaries 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.


2. Gowan Company

PP 8F4985

    EPA has received a pesticide petition (PP 8F4985) from Gowan 
Company, P.O. Box 5569, Yuma, AZ 85366-5569 proposing pursuant to 
section 408(d) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 
346a(d), to amend 40 CFR part 180 by establishing a tolerance for 
residues of the acaricide hexythiazox in or on strawberries, apples, 
wet apple pomace, cottonseed and cotton gin byproducts. The chemical 
name of hexythiazox is trans-5-(4-chlorophenyl)-N-cyclohexyl-4-methyl-
2-oxothiazolidine-3-carboxamide. Metabolites containing the (4-
chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiety are included in the 
tolerance expression. Time-limited tolerances for strawberries, cotton 
seed and cotton gin byproducts are currently in effect. Gowan Company 
has proposed that the tolerances for cotton seed and cotton gin 
byproducts be geographically limited to California only. A permanent 
tolerance exists for apples, but Gowan Company proposes to increase the 
tolerance level in connection with a proposed change in the use 
pattern. A tolerance for residues in wet apple pomace has not been 
proposed previously.
    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 support granting of the petition. 
Additional data may be needed before EPA rules on the petition. The 
proposed analytical method is high performance liquid chromatography 
with an ultraviolet detector. As required by section 408(d) of the 
FFDCA, as recently amended by the Food Quality Protection Act (FQPA) 
Pub. L. 104-170, Gowan Company included in the petition a summary of 
the petition and authorization for the summary to be published in the 
Federal Register in a notice of receipt of the petition. The summary 
represents the views of Gowan Company; EPA, as mentioned above, is in 
the process of evaluating the petition. As required by section 
408(d)(3) of the FFDCA, EPA is including the summary as a part of this 
notice of filing.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of hexythiazox in apples, 
pears, grapes, and citrus has been studied. The major portion of the 
residue is parent compound. The metabolites are hydroxycyclohexyl and 
ketocyclohexyl analogs of hexythiazox and the amide formed by loss of 
the cyclohexyl ring.
    2. Animal metabolism. The metabolism of hexythiazox in goats, hens 
and rats has been studied. Metabolic pathways in animals are similar to 
those in plants.
    3. Analytical method. An adequate analytical method (HPLC with UV 
detection) is available for enforcement purposes. Parent compound and 
all of its metabolites are converted to a common moiety before 
analysis.
    4. Magnitude of residues--i. Strawberries. Seventy samples of 
treated strawberries were analyzed. The maximum residue observed (MRO) 
at a preharvest interval of 3-days was 2.06 ppm and the average residue 
was 0.67 ppm. A tolerance of 3 ppm was proposed.
    ii. Cotton. Twenty residue studies were conducted in the U.S., 
Brazil, and Spain. Four additional studies, including a processing 
study, were conducted in California. The MRO in cotton seed was 0.097 
ppm and the average residue was 0.065 ppm. A tolerance of 0.2 ppm was 
proposed. The maximum residue observed in cotton gin byproducts was 
2.29 ppm and the average residue was 1.07 ppm. A tolerance of 3 ppm was 
proposed. The proposed tolerances are geographically limited to 
California only. A field crop rotation study indicated that residues 
would not be present in crops planted 4-months after application of 
hexythiazox.
    iii. Apples--a total of 20 trials were conducted. The maximum 
residue in apples having a preharvest interval of 1-month was 0.38 ppm 
and the average residue was 0.14 ppm. A tolerance of 0.4 ppm was 
proposed. Processing studies indicated that hexythiazox residues 
concentrate by a factor of 1.7 in wet apple pomace, and a tolerance of 
0.7 ppm was proposed.

B. Toxicological Profile

    1. Acute toxicity. The acute oral and dermal LD<INF>50</INF> of 
technical hexythiazox is > 5,000 mg/kg, and the 4-hour acute inhalation 
LC<INF>50</INF> is > 2 mg/L. It is not a dermal irritant or sensitizer 
and is a mild eye irritant.
    2. Genotoxicity. The following genotoxicity tests were all 
negative: Ames gene mutation, CHO gene mutation, CHO chromosome 
aberration, mouse micronucleus and rat hepatocyte unscheduled DNA 
synthesis.
    3. Reproductive and developmental toxicity. Hexythiazox has not 
been observed to induce developmental or reproductive effects. The 
lowest reproductive or developmental no-observed effected level (NOEL) 
was 200 milligram/kilogram/day (mg/kg/day), the highest dose tested 
(HDT), in a 2-generation rat reproduction study.
    4. Chronic toxicity. The Office of Pesticide Programs has 
established the Reference Dose (RfD) for hexythiazox at 0.025 mg/kg/
day. The RfD for hexythiazox is based on a 1-year dog feeding study 
with a NOEL of 2.5 mg/kg/day and an uncertainty 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.
    5. Carcinogenicity. The Agency has classified hexythiazox as a 
category C (possible human) carcinogen based on an increased incidence 
of hepatocellular carcinomas (p = 0.028) and combined adenomas/
carcinomas (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 pre-neoplastic hepatic nodules in both males and 
females at the HDT. The decision supporting a category C classification 
was based primarily on the fact that only one species was affected and 
mutagenicity studies were negative. 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 liver tumors in the female mouse. 
A Q1* of 0.039 (mg/kg/day)-1 in human equivalents was calculated.

C. Aggregate Exposure

    Tolerances have been established (40 CFR 180.448) for combined 
residues of hexythiazox [trans-5-(4-chlorophenyl)-N-cyclohexyl-4-
methyl-2-oxothiazolidine-3-carboxamide] and its metabolites containing 
the (4-chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiety in or on 
apples at 0.02 ppm and pears at 0.3 ppm. Use on several other crops had 
been previously proposed [PP 6F4738], and an aggregate exposure 
analysis has taken into consideration all current and proposed uses. 
The nature and metabolism of

[[Page 45495]]

hexythiazox in plants and animals is adequately understood.
    Hexythiazox is also registered for use on outdoor ornamental plants 
by commercial applicators only. It is believed that non-occupational 
exposure from this use is very low. Hexythiazox is not registered for 
greenhouse, lawn, garden, or residential use. The environmental fate of 
hexythiazox has been evaluated, and the compound is not expected to 
contaminate groundwater or surface water to any measurable extent.
    1. Chronic exposure. A chronic dietary exposure analysis was 
conducted for the general U.S. population and 26 population subgroups. 
In this analysis it was assumed that 100% of crops were treated. A 
chronic exposure of 0.000172 mg/kg/day was calculated for the average 
U.S. population. Non-nursing infants, the most heavily exposed 
subgroup, had a calculated exposure of 0.000972 mg/kg/day. Actual 
exposure would be much lower, however, because far less than 100% of 
crops would be treated.
    The Agency has not conducted a detailed analysis of potential 
exposure to hexythiazox via drinking water or outdoor ornamental 
plants. However, it is believed that chronic exposure from these 
sources is very small.
    2.  Acute exposure. No developmental, reproductive or mutagenic 
effects have been observed with hexythiazox. Therefore, an analysis of 
acute exposure has not been conducted.

D. Cumulative Effects

    At this time the Agency has not reviewed available information 
concerning the potentially cumulative effects of hexythiazox and other 
substances that may have a common mechanism of toxicity. For purposes 
of this petition only, the Agency is considering only the potential 
risks of hexythiazox in its aggregate exposure.

E. Safety Determination

    1. U.S. population--i. Chronic risk. Chronic risk was calculated 
using anticipated residue concentrations from all current and proposed 
uses of hexythiazox and assuming that 100% of each crop is treated. 
Dietary exposure of the general U.S. population was equivalent to 0.7% 
of the RfD. Exposure of the most heavily exposed subgroup, non-nursing 
infants, was equivalent to 3.9% of the RfD.
    ii. Oncogenic risk. Oncogenic risk was evaluated using anticipated 
residue concentrations and taking into account the percent of crop 
known or expected to be treated. Lifetime oncogenic risk for the U.S. 
population was calculated to be 4.5 x 10-7.
    iii. Acute risk. An estimate of acute risk with this compound has 
not been conducted since no acute reproductive or developmental effects 
have been observed.
    2. Infants and children. 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 study in the rat. The developmental toxicity 
studies are designed to evaluate adverse effects on the developing 
organism resulting from pesticide exposure during prenatal development 
to one or both parents. Reproduction studies provide information 
relating to effects from exposure to the pesticide on the reproductive 
capability of mating animals and data on systemic toxicity.
    No developmental or reproductive effects have been observed in any 
study with hexythiazox. The lowest acute NOEL was 2,400 ppm in the diet 
(200 mg/kg/day), the HDT, in the 2-generation rat reproduction study. 
In the rat developmental study, the maternal and fetotoxic NOEL was 240 
mg/kg/day and the developmental NOEL was 2,160 mg/kg/day, the HDT. In 
the rabbit developmental study, the maternal and developmental NOEL was 
1,080 mg/kg/day, the HDT.
    Taking into account current toxicological data requirements, the 
database for hexythiazox relative to prenatal and postnatal effects is 
complete. In the rat developmental study, the NOELs for maternal 
toxicity and fetotoxicity were the same, which suggests that there is 
no special prenatal sensitivity in the absence of maternal toxicity. 
Furthermore, the lowest developmental or reproductive NOEL is two 
orders of magnitude higher than the chronic NOEL on which the RfD is 
based. It is concluded that there is a reasonable certainty of no harm 
to infants and children from aggregate exposure to hexythiazox 
residues.

F. International Tolerances

    Codex MRLs of 0.5 mg/kg for residues of hexythiazox in strawberries 
and apples have been established. The U.S. tolerance proposals are 
somewhat at variance with the Codex MRLs because they are based upon 
different preharvest intervals. Also, it is believed that the U.S. 
proposed tolerance levels allow for a greater margin of safety than the 
Codex MRLs. There are no Codex MRLs for the other commodities in this 
petition. There are no Canadian or Mexican MRLs for hexythiazox. (Beth 
Edwards).

[FR Doc. 98-22430 Filed 8-25-98; 8:45 am]
BILLING CODE 6560-50-F