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hexythiazox (Savey) Pesticide Petition Filing 1/98


[Federal Register: January 28, 1998 (Volume 63, Number 18)]
[Notices]               
[Page 4252-4259]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr28ja98-81]

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ENVIRONMENTAL PROTECTION AGENCY

[PF-787; FRL-5763-6]

 
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-787, must 
be received on or before February 27, 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. 1132, 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 
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

[[Page 4253]]

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:

------------------------------------------------------------------------
                                   Office location/                     
        Product Manager            telephone number          Address    
------------------------------------------------------------------------
Amelia M. Acierto.............  Rm. 4W60, 4th. floor,   2800 Crystal    
                                 CSI #2, 703-308-8377,   Drive,         
                                 e-                      Arlington, VA  
                                 mail:acierto.amelia@e                  
                                 pamail.epa.gov.                        
Adam Heyward..................  Rm. 206, CM #2, 703-    1921 Jefferson  
                                 305-5518, e-mail:       Davis Hwy.,    
                                 heyward.                Arlington, VA  
                                 adam@epamail.epa.gov.                  
Joseph Tavano.................  Rm. 214, CM #2, 703-    Do.             
                                 305-6411, e-mail:                      
                                 tavano.joseph@epamail                  
                                 .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-787] (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. Comment 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 [PF-787] and appropriate petition 
number. Electronic comments on 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:January 20, 1998

James Jones,

Acting 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.

1. Gowan Company

PP 6F4738

     In May, 1996, EPA received a pesticide petition (PP 6F4738) from 
Gowan Company, P. O. Box 5569, Yuma, AZ 85366-5569. The petition 
proposed, pursuant to section 408 of the Federal Food, Drug, and 
Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 to 
establish tolerances for the acaricide hexythiazox and its metabolites 
in or on the raw agricultural commodities stone fruits (except plums) 
at 1 part per million (ppm), almonds at 0.2 ppm and almond hulls at 10 
ppm, and also in milk, cattle meat and cattle fat at 0.05 ppm, and 
cattle meat byproducts at 0.1 ppm (April 30, 1997, 62 FR 23455-23457) 
(FRL-5600-8). In April 1997, the registrant amended the tolerance 
petition by proposing to establish a tolerance for stone fruits 
including plums at 1 ppm, a tolerance for prunes at 5 ppm, and a 
tolerance for all tree nuts at 0.2 ppm. The proposed tolerances for 
animal products were unchanged. 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.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of hexythiazox in apples, 
citrus, grapes and pears 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. 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.
    3. Magnitude of residues. Twenty-four stone fruit residue trials 
were conducted over 3-years. The geographic distribution of the trials 
agrees with the recommendation given in the ``EPA Residue Chemistry 
Guidance''(1994). In these trials, the maximum combined residues of 
hexythiazox and its metabolites were 0.52 ppm. Twelve tree nut residue 
trials were conducted over 4 years. In these trials, the maximum 
combined residues of hexythiazox and its metabolites were 0.17 ppm in 
almond nutmeat and 7.5 ppm in the raw agricultural commodity almond 
hulls.

B. Toxicological Profile

    1. Acute toxicity. The acute oral and dermal LD<INF>50</INF> of 
technical hexythiazox is greater than 5,000 milligram/kilograms (mg/
kg), and the 4-hour acute inhalation LC<INF>50</INF> is greater than 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:

[[Page 4254]]

 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-effect-level (NOEL) 
observed was 200 milligram/kilograms/day (mg/kg/day), the highest dose 
tested, in a 2-generation rat reproduction study.
    4. Subchronic toxicity. The Office of Pesticide Programs has 
established the 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. Chronic toxicity. 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 highest dose tested (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 highest dose tested. 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 Q<SUP>1*</SUP> of 0.039 (mg/kg/
day)<SUP>-1</SUP> in human equivalents was calculated.

C. Aggregate Exposure

    Tolerances have been established (40 CFR 180.448) for the combined 
residues of hexythiazox [trans-5-(4-chlorophenyl)-N-cyclohexyl-4-
methyl-2-oxothiazolidine-3-carboxamide] 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. The nature and metabolism of 
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. Dietary exposure. The Agency has calculated in the Federal 
Register of February 21, 1996 (61 FR 6152-6154) (FRL-5350-6), that 
current uses on apples and pears would result in an exposure of 
0.000051 mg/kg/day for the U.S. population, assuming that all residues 
are at tolerance levels and 100% of the crops are treated. Non-nursing 
infants, the subgroup having the highest exposure, would have an 
exposure of 0.000600 mg/kg/day. Using the same conservative 
assumptions, it is calculated that the current and proposed uses 
together would result in an exposure of 0.001133 mg/kg for the U.S. 
population and 0.007256 mg/kg/day for non-nursing infants, which 
remains the most highly exposed subgroup.
    Actual exposure will be much lower, however. Only a small fraction 
of these crops will be treated with hexythiazox, and average residues 
are far below the tolerance levels. For example, residues in apples 
treated at 10 times the currently approved application rate remained 
below the limit of quantitation, 0.01 ppm. Also, residues in apple 
juice are expected to be less than 50% of the residue level in the 
whole fruit. Average residues in stone fruits except cherries are 
expected to be 7% of the proposed tolerance level, average residues in 
cherries are expected to be 11% of the tolerance level and average 
residues in almond nutmeat are expected to be below 20% of the proposed 
tolerance level. Furthermore, only a very small percentage of crops 
(less than 1% up to 5%, depending on the crop) are expected to be 
treated with hexythiazox. When actual residues rather than tolerance 
levels and the percentage of treated crop are taken into account, then 
the actual exposure is estimated to be 0.0000069 mg/kg/day for the U.S. 
population.
    2. Drinking water. 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.
    3. Non-dietary 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. Determination of Safety for U.S. Population

    1. Chronic risk. The Agency has calculated (FR 61 6152-6154), 
assuming that residues are at tolerance levels and 100% of crops are 
treated, that the current use on apples and pears utilizes 0.2% of the 
reference dose (RfD) for the U.S. population and 2.4% of the RfD for 
non-nursing infants. Using these same assumptions, it is calculated 
that all current and proposed uses would result in TMRCs equivalent to 
4.5% of the RfD for the U.S. population and 29.0% of the RfD for non-
nursing infants. However, when actual residues rather than tolerance 
levels and the percent of crop treated are taken into account, actual 
chronic risk for the U.S. population is expected to be only 0.43% of 
the RfD.
    The actual dietary carcinogenic risk to the U.S. population is 
calculated to be 2.7  x  10<SUP>-7</SUP>, which is below the Agency's 
criterion of 1  x  10<SUP>-6</SUP>.
    2. Acute risk. An estimate of acute risk with this compound has not 
been conducted since no acute reproductive or developmental effects 
have been observed.

F. Determination of Safety for 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 pre-natal 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 highest dose tested, 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

[[Page 4255]]

NOEL was 2,160 mg/kg/day, the highest dose tested. In the rabbit 
developmental study, the maternal and developmental NOEL was 1,080 mg/
kg/day, the highest dose tested.
    Taking into account current toxicological data requirements, the 
database for hexythiazox relative to pre-natal and post-natal 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 pre-natal 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.

G. International Tolerances

    Codex maximum residue levels (MRLs) of 1 mg/kg (1 ppm) have been 
established for residues of hexythiazox in cherries and peaches. The 
U.S. tolerance proposal for stone fruits is in harmony with these MRLs. 
There are no Codex MRLs for the other commodities in this petition. 
There are no Canadian or Mexican MRLs for hexythiazox. (Adam Heyward)

[FR Doc. 98-2088 Filed 1-27-98; 8:45 am]
BILLING CODE 6560-50-F