[Federal Register Volume 65, Number 165 (Thursday, August 24, 2000)]
[Notices]
[Pages 51612-51616]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-21674]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-964; FRL-6739-1]


Notice of Filing a Pesticide Petition to Establish a Tolerance 
for a Certain Pesticide Chemical in or on Food

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 docket control number PF-964, must be 
received on or before September 25, 2000.

ADDRESSES: Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I.C. of the SUPPLEMENTARY INFORMATION. To ensure 
proper receipt by EPA, it is imperative that you identify docket 
control number PF-964 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  By mail: Daniel C. Kenny, Fungicides 
Branch, Registration Division (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460; telephone number: (703) 305-7546; e-mail address: 
[email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural 
producer, food manufacturer or pesticide manufacturer. Potentially 
affected categories and entities may include, but are not limited to:

 
------------------------------------------------------------------------
                                                          Examples of
           Categories                 NAICS codes         potentially
                                                       affected entities
------------------------------------------------------------------------
Industry                          111                 Crop production
                                  112                 Animal production
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------

    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in the table could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether or not this action might apply to certain entities. If you have 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

B. How Can I Get Additional Information, Including Copies of this 
Document and Other Related Documents?

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations,'' ``Regulations and Proposed Rules,'' and then look up the 
entry for this document under the ``Federal Register--Environmental 
Documents.'' You can also go directly to the Federal Register listings 
at http://www.epa.gov/fedrgstr/.
    2. In person. The Agency has established an official record for 
this action under docket control number PF-964. The official record 
consists of the documents specifically referenced in this action, any 
public comments received during an applicable comment period, and other 
information related to this action, including any information claimed 
as confidential business information (CBI). This official record 
includes the documents that are physically located in the docket, as 
well as the documents that are referenced in those documents. The 
public version of the official record does not include any information 
claimed as CBI. The public version of the official record, which 
includes printed, paper versions of any electronic comments submitted 
during an applicable comment period, is available for inspection in the 
Public Information and Records Integrity Branch (PIRIB), Rm. 119, 
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

    You may submit comments through the mail, in person, or 
electronically. To ensure proper receipt by EPA, it is imperative that 
you identify docket control number PF-964 in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs (OPP), Environmental Protection 
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by 
e-mail to: ``[email protected],'' or you can submit a computer disk as 
described above. Do not submit any information electronically that you 
consider to be CBI. Avoid the use of special characters and any form of 
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be 
identified by docket control

[[Page 51613]]

number PF-964. Electronic comments may also be filed online at many 
Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

    Do not submit any information electronically that you consider to 
be CBI. You may claim information that you submit to EPA in response to 
this document as CBI by marking any part or all of that information as 
CBI. Information so marked will not be disclosed except in accordance 
with procedures set forth in 40 CFR part 2. In addition to one complete 
version of the comment that includes any information claimed as CBI, a 
copy of the comment that does not contain the information claimed as 
CBI must be submitted for inclusion in the public version of the 
official record. Information not marked confidential will be included 
in the public version of the official record without prior notice. If 
you have any questions about CBI or the procedures for claiming CBI, 
please consult the person identified under FOR FURTHER INFORMATION 
CONTACT.

E. What Should I Consider as I Prepare My Comments for EPA?

    You may find the following suggestions helpful for preparing your 
comments:
    1. Explain your views as clearly as possible.
    2. Describe any assumptions that you used.
    3. Provide copies of any technical information and/or data you used 
that support your views.
    4. If you estimate potential burden or costs, explain how you 
arrived at the estimate that you provide.
    5. Provide specific examples to illustrate your concerns.
    6. Make sure to submit your comments by the deadline in this 
notice.
    7. To ensure proper receipt by EPA, be sure to identify the docket 
control number assigned to this action in the subject line on the first 
page of your response. You may also provide the name, date, and Federal 
Register citation.

II. What Action is the Agency Taking?

    EPA has received a pesticide petition as follows proposing the 
establishment and/or amendment of regulations for residues of a certain 
pesticide chemical in or on various food commodities under section 408 
of the Federal Food, Drug, and Cosmetic 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 support granting of the petition. Additional data 
may be needed before EPA rules on the petition.

List of Subjects

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

    Dated: August 15, 2000.
Peter Caulkins,
Acting 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 view of the 
petitioner. EPA is publishing the petition summary verbatim without 
editing it 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.

Rohm and Haas Company

PP 9F5058

    EPA has received a pesticide petition (PP 9F5058) from Rohm and 
Haas Company, 100 Independence Mall West, Philadelphia, PA proposing, 
pursuant to section 408(d) of the FFDCA, 21 U.S.C. 346a(d), to amend 40 
CFR part 180 by establishing a tolerance for residues of zoxamide (RH-
117281 Technical) benzamide-3,5-dichloro-N-(3-chloro-1-ethyl-1-methyl-
2-oxopropyl)-4-methyl in or on the raw agricultural commodity tomatoes 
and cucurbits at 2 parts per million (ppm). 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.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of zoxamide in plants (tomatoes 
and cucurbits) is adequately understood for the purposes of these 
tolerances. There were no significant metabolites other than the parent 
compound in either crop. Residues were surface residues of parent 
zoxamide and minor amounts of hydrolysis or photolysis degradates and a 
fairly large number of polar materials, each less than 2% of the total 
radioactive residue (TRR). No metabolites were present in excess of 5% 
of the total dosage. This is the same pattern seen in grapes, filed 
earlier.
    2. Analytical method. Tolerance enforcement methods using gas 
chromatography/electron capture detection (GC/ECD) with confirmation by 
gas chromatography/mass selective detection (GC/MSD), have been 
developed for zoxamide in cucurbits (cucumber, cantaloupe, zucchini), 
tomatoes, tomato paste, and tomato puree. The limit of quantitation is 
0.01 ppm for all matrices. Average recoveries are 89.3  
9.71% for cucurbits, 93.8  10.1% for tomatoes, 94.1 
 9.3% for tomato paste, and 90.7  13.7% for 
tomato puree, over the range of fortifications. The methods involve 
extraction with solvent, filtration, liquid-liquid partition, and final 
purification of the residues using solid phase column chromatography. 
The methods have been radiovalidated and an independent laboratory 
validation has been completed.
    3. Magnitude of residues--Cucurbits. Seventeen cucurbit field 
residue trials were conducted in nine states. There were 6 trials for 
cucumbers, 6 trials for cantaloupe, and 5 trials for zucchini. These 
trials will cover a cucurbit crop group tolerance. All studies were 
done with eight applications of 0.2 lb. active ingredient/acre (ai/
acre) (0.224 kg ai/ha) for a total seasonal use rate of 1.6 lb. ai/acre 
(1.8 kg ai/ha). In all trials, fruit was harvested on the day of the 
final application (0 day Pre-harvest interval (PHI)). This is the 
proposed maximum seasonal use rate and proposed PHI. In three trials, 
residue decline samples were taken over 6 or 7 days.
    Samples were analyzed for RH-117281. The average residue over all 
trials was 0.11 ppm (0.245 ppm for cantaloupe, 0.053 ppm for cucumbers 
and 0.115 ppm for zucchini). This single highest residue in any trial 
was 0.73 ppm. Residue declined from 0.12 to 0.04 ppm over 7 days in one 
trial and remained fairly constant at about 0.04 ppm in the other two 
residue decline trials.
    These data support the establishment of a permanent tolerance of 
2.0 ppm on cucurbits.
    Tomatoes. Sixteen field residue trials, including 2 decline 
experiments, 2 bridging trials, and one processing study were conducted 
in six states. The trials each consisted of eight applications of the 
80 W formulation of RH-117281 at

[[Page 51614]]

0.02 lb. ai/acre (0.224 kg ai/ha), for a total seasonal rate of 1.6 lb 
ai/acre (1.8 kg ai/ha). The bridging trials had a separate treated plot 
which received 10 applications of the 2F formulation at the same rate. 
Three of the trials, including the processing study trial, had 1 to 3 
additional applications in order to ensure that the commercial quality 
fruit could be harvested at the appropriate preharvest interval. In all 
of the trials, fruit was harvested 5 days after the final application. 
In two of the trials, samples were taken at 0, 3, 5, and 7 days after 
the final application to determine residue decline.
    Samples were analyzed for residues of RH-117281. The average 
residue over all trials was 0.21 ppm. This single highest residue in 
any trial was 1.18 ppm.
    Tomato puree and tomato paste were generated from one residue 
trial. Washing removed about 80% of the residue from the tomato RAC. 
There was no concentration of residue in either tomato puree or tomato 
paste.
    These data support the establishment of a permanent tolerance of 
2.0 ppm on tomatoes and tomato processed fractions.

B. Toxicological Profile

    1. Acute toxicity. Zoxamide has low acute toxicity. Zoxamide was 
practically non-toxic by ingestion of a singe oral dose in rats and 
mice (LD50 >5,000 milligrams/kilograms (mg/kg), practically 
non-toxic by dermal application to rats (LD50 > 2,000 mg/
kg), and practically non-toxic to rats after a 4-hr inhalation exposure 
with an LC50 value of > 5.3 mg/L (highest attainable 
concentration), is not considered to be a primary eye irritant or a 
skin irritant and is not a dermal sensitizer. The technical material 
was nonirritating to skin after single applications and moderately 
irritating to eyes. Zoxamide produced delayed contact hypersensitivity 
in the guinea pig at concentrations of 2,500 ppm and higher. An acute 
neurotoxicity study in rats did not produce any neurotoxic or 
neuropathologic effects with a NOAEL > 2,000 mg/kg.
    2. Genotoxicity. Zoxamide was nonmutagenic in a standard battery of 
tests. In in vitro assays, zoxamide showed no evidence of mutagenic 
activity in an Ames and CHO/HGPRT assays for gene mutation, and no 
evidence of structural chromosomal aberrations in the CHO in vitro 
cytogenetic study. As predicted by its antibulin mode of action, 
mitotic accumulation and polyploidy were noted at cytotoxic doses in 
the in vitro chromosomal assay. However, there was no evidence of 
structural or numerical chromosomal aberrations when zoxamide was 
tested in vivo in the mouse micronucleus test.
    3. Reproductive and developmental toxicity-- i. No observable 
adverse effects levels (NOAELs) for developmental and maternal toxicity 
to zoxamide were established at 1,000 mg/kg/day highest dose tested 
(HDT) in both the rat and rabbit. No signs of developmental toxicity 
were exhibited.
    ii. In a 2-generation reproduction study in the rat, zoxamide had a 
no adverse effect on reproductive performance or pup development at 
doses up to an exceeding 1,471 mg/kg/day, the limit dose tested. This 
NOAEL was 20-fold higher than the NOAEL for adult toxicity of 71 mg/kg/
day. A delay in periweaning weight gain and associated spleen effects 
in the F1 and F2a litters were shown in the F2b litters to be a 
secondary effect related to feed refusal due to palatability of the 
treated diets, and not to a systemic toxic effect. The consequences of 
feed refusal due to palatability do not constitute an adverse effect 
relevant to human health risk assessment.
    4. Subchronic toxicity. The NOAEL in a 90-day rat subchronic 
feeding and neurotoxicity study was 1,500 mg/kg/day in males and 1,622 
mg/kg/day in females HDT. Zoxamide did not produce neurotoxic or 
neuropathologic effects.
    A 90-day feeding study with mice, the NOAEL was 436 mg/kg/day in 
males and 574 mg/kg/day in females based on a slight decrease in weight 
gain among the females only at the LOAEL of 1,666 mg/kg/day.
    A 90-day dog feed study gave a NOAEL of 55 mg/kg in males and 62 
mg/kg/day in females based on increased liver weights without a 
corresponding clinical or histopathologic change in females only at 322 
mg/kg/day.
    No signs of systemic toxicity were observed when zoxamide was 
administered dermally to rats for 28 days at a limit dose of 1,000 mg/
kg/day. This occurred despite skin irritation at all doses tested (150, 
400, and 1,000 mg/kg/day). Similarly, in vivo dermal absorption was 
shown to be low regardless of concentration or formulation type (i.e., 
1-6% of the administered dose was systemically absorbed after 24 hrs.)
    5. Chronic toxicity. In a combined rat chronic/oncogenicity study, 
the NOAEL for chronic toxicity was 51 mg/kg/day in males an 65 mg/kg/
day in females based on an equivocal increase in relative liver weight 
at a LOAEL of 328 mg/kg/day in females at the interim sacrifice only. 
The NOAEL was considered to be 1,058 mg/kg/day in males and 1331 mg/kg/
day in females (HDT, limit dose). No carcinogenicity was observed.
    An 18-month mouse carcinogenicity study showed no signs of 
carcinogenicity or of any other compound-related effect at dosage 
levels up to 1021 mg/kg/day in males and 1,289 mg/kg/day in females 
(HDT, limit dose).
    The NOAEL in a 1-year feeding study in dogs was 255 mg/kg/day in 
males and 48 mg/kg/day in females based on minimal effects on body 
weight and body weight gain and increased liver weights in females only 
at a LOAEL of 278 mg/kg/day.
    6. Animal metabolism. In pharmacokinetic and metabolism studies in 
the rat, zoxamide was rapidly and extensively absorbed, metabolized and 
excreted following oral exposure. A total of approximately 60% of the 
administered dose was systemically absorbed. Plasma levels peaked 
within 8 hours of dosing, and declined with a half-life of 12-14 hours, 
consistent with the nearly complete excretion within 48 hours. No 
evidence of accumulation of the parent compound or its metabolites was 
observed. The predominant route of excretion was hepatobiliary. 
Metabolism was found to occur through multiple pathways involving 
primary hydrolysis, glutathione-mediated reactions, and reductive 
dehalogenation; secondary oxidation on both the aromatic methyl and the 
aliphatic side-chain; and terminal glucuronic acid and ammo acid 
conjugation. Altogether, 32 separate metabolites were identified; no 
single metabolite other than parent zoxamide accounted for more than 
10% of the administered dose. The rapid metabolism and excretion of 
zoxamide is a major factor explaining the compound's overall remarkably 
low toxicity profile in animals.
    7. Metabolite toxicology. There were no significant metabolites 
other than the parent zoxamide in tomatoes or cucurbits.
    8. Endocrine disruption. Based on structure-activity and mode of 
action information as well as the lack of developmental and 
reproductive toxicity, zoxamide is unlikely to exhibit endocrine 
activity. There was no evidence of a functional or histopathologic 
change in the male or female reproductive tract, and no indicators of 
an endocrine effect of any kind below limit doses in mammalian 
subchronic or chronic studies or in mammalian and avian reproduction 
studies. A slight thyroid effect at the limit dose (994-1139 mg/kg/day) 
in the subchronic and chronic dog studies was secondary to liver 
hypertrophy and

[[Page 51615]]

enlargement at that dose. Collectively, the weight of evidence provides 
no indication of an endocrine effect of zoxamide.

C. Aggregate Exposure

    1. Dietary exposure-- i. Food. Tolerances are proposed in the 
present or preceding summaries for the residues of zoxamide in or on 
tomatoes (2 ppm), cucurbits (2 ppm), potatoes (0.1 ppm), grapes (5 
ppm), and raisins (15 ppm). There is no reasonable expectation of 
transfer of residues of zoxamide into meat or milk from potatoes. There 
are no tomato, cucurbit or grape feed commodities fed to livestock, and 
none of these commodities is fed to poultry. There are no other 
established or proposed U.S. tolerances for zoxamide, and no currently 
registered uses in the United States. Risk assessments were conducted 
by Rohm and Haas to assess dietary exposures and risks from zoxamide as 
follows:
    Acute exposure and risk. No acute endpoint was identified for 
zoxamide, and no acute risk assessment is required.
    ii. Chronic exposure and risk. For chronic dietary risk assessment, 
the proposed tolerance values, as well as anticipated (average) 
residues and processing factors were used and the assumption that 100% 
of all tomatoes, cucurbits, potatoes, and grapes will contain residues 
of zoxamide at the tolerance or anticipated residue levels. Potential 
chronic exposures were estimated using USDA food consumption data from 
the 1989-1992 survey. With the proposed tolerances and anticipated 
residue levels for zoxamide, the percentage of the 0.5 mg/kg/day RfD 
utilized is as follows:

------------------------------------------------------------------------
                                                 Tolerance   Anticipated
                                                   Levels      Residues
                                                Total % RfD  Total % RfD
------------------------------------------------------------------------
U.S. Population--48 States....................          1.3          0.1
Nursing Infants  1 year old...................          1.3          0.2
Non-Nursing Infants  1 year old...............          2.4          0.1
Children 1-6 years old........................          3.5          0.2
Children 7-12 years old.......................          1.8          0.1
------------------------------------------------------------------------

    The chronic dietary risks from these uses do not exceed EPA's level 
of concern.
    iii. Drinking water. No direct information is available on 
potential for exposure to zoxamide from drinking water. However, 
exposure from drinking water is unlikely to occur as a result of the 
uses on treated crops. Submitted environmental fate studies indicate 
that zoxamide dissipates rapidly from the environment under all 
conditions tested, and it is not mobile and poses no threat to 
groundwater. Furthermore, its environmental metabolites are very short-
lived and also have no potential to leach.
    There is no established Maximum Concentration Level (MCL) for 
residues of zoxamide in drinking water, and no drinking water health 
advisory levels have been established. There is no entry for zoxamide 
in the ``Pesticides in Groundwater Database'' (EPA 734-122-92-001, 
September 1992).
    2. Chronic exposure and risk. Nevertheless, to assess an upper 
bound on the potential for exposure from drinking water, chronic 
exposure to zoxamide in drinking water was estimated using the generic 
expected environmental concentration (GENEEC) V1.2 model, as directed 
in OPP's Interim Approach for Addressing Drinking Water Exposure. 
GENEEC is a highly conservative model used to estimate residue 
concentrations in surface water. As indicated in EPA's drinking water 
exposure guidance, a very small percentage of people in the U.S. would 
derive their drinking water from such sources. GENEEC (56 Day average) 
water exposure values utilize substantially less than 1% of the RfD for 
adults and children.
    3. Non-dietary exposure. Zoxamide is not currently registered for 
any indoor or outdoor residential or structural uses and no application 
is pending; therefore, no non-dietary non-occupational exposure is 
anticipated.
    4. Aggregate exposure and risk. The anticipated aggregate exposure 
from food and drinking water combined is 4% of the RfD, and there is no 
expectation of other non-occupational exposure. Thus, aggregate 
exposure to zoxamide does not exceed EPA's level of concern.

D. Cumulative Effects

    At this time, no data are available to determine whether zoxamide 
has a common mechanism of toxicity with other substances. Thus, it is 
not appropriate to include this fungicide in a cumulative risk 
assessment. Unlike other pesticides for which EPA has followed a 
cumulative risk approach based on a common mechanism of toxicity, 
zoxamide does not appear to produce a toxic metabolite produced by 
other substances. In addition, the toxicity studies submitted to 
support this petition indicate that zoxamide has only limited toxic 
potential. No toxic endpoints of potential concern were identified. For 
the purposes of this tolerance action, therefore, zoxamide [benzamide-
3,5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-methyl] is 
assumed not to have a common mechanism of toxicity with other 
substances.

E. Safety Determination

    1. U.S. population-- i. Acute exposure and risk. Since no acute 
endpoint was identified for zoxamide, no acute risk assessment is 
required.
    ii. Chronic exposure and risk. Using the conservative exposure 
assumptions described above and taking into account the completeness 
and reliability of the toxicity data, the percentage of the RfD that 
will be utilized by dietary (food only) exposure to residues of 
zoxamide from the proposed tolerances is 1.3% (tolerance levels) and 
0.1% (anticipated residues) for the U.S. population. Aggregate exposure 
(food and water) are expected to be 1.37% RfD. 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. Rohm and Haas 
concludes that there is a reasonable certainty that no harm will result 
from aggregate exposure to zoxamide residues to the U.S. population.
    2. Infants and children-- i. In general. The potential for 
additional sensitivity of infants and children to residues of zoxamide 
is assessed using data from developmental toxicity studies in the rat 
and rabbit and 2-generation reproduction studies 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.
    ii. Developmental toxicity studies--Rats. In a developmental 
toxicity study in rats, the maternal NOAEL was 1,000 mg/kg/day (highest 
dose tested, HDT), and the developmental (pup) NOAEL was 1,000 mg/kg/
day HDT.
    iii. Rabbits. In a developmental toxicity study in rats, the 
maternal NOAEL was 1,000 mg/kg/day HDT, and the developmental (pup) 
NOAEL was 1,000 mg/kg/day HDT.
    iv. Reproductive toxicity study--Rats. In a multigeneration 
reproductive toxicity study in rats, the parental (systemic) NOAEL was 
71 mg/kg/day, based on an equivocal liver effect at the LOAEL of 360 
mg/kg/day. The NOAEL for reproductive and developmental

[[Page 51616]]

effects was 1,471 mg/kg/day HDT. No adverse reproductive or 
developmental effects were observed.
    3. Prenatal and postnatal sensitivity. No developmental or 
reproductive effects were demonstrated for zoxamide as a result of 
systemic exposures at up to limit doses of 1,000 and 1,471 mg/kg/day. 
Additionally, these NOAELs are greater than 20-fold higher than the 
NOAELs of 48-51 mg/kg/day from the dog and rat chronic studies which 
are the basis of the RfD. These developmental and reproductive studies 
indicate that developing and maturing animals are not more sensitive 
either pre or postnatally than other age groups to zoxamide; i.e., 
zoxamide does not exhibit additional prenatal or postnatal sensitivity. 
Thus, reliable data indicate that an additional Food Quality Protection 
Act uncertainty factor is not necessary to insure an adequate margin of 
safety for protection of infants and children.
    4. Acute exposure and risk. No acute endpoint was identified for 
zoxamide, and therefore no acute risk assessment is required.
    5. Chronic exposure and risk. Using the conservative exposure 
assumptions described above and taking into account the completeness 
and reliability of the toxicity data, the percentage of the RfD that 
will be utilized by dietary (food only) exposure to residues of 
zoxamide from the proposed tolerances is 2.4% (tolerance levels) and 
0.2% (anticipated residues) for children, 1-6 years old, the most 
highly exposed subgroups. Aggregate exposure (food and water) are 
expected to be 4% RfD. 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. Rohm and Haas concludes that there 
is a reasonable certainty that no harm will result from aggregate 
exposure to zoxamide residues to the U.S. population.

F. International Tolerances

    There are currently no CODEX, Canadian or Mexican maximum residue 
levels established for zoxamide in tomatoes, processed tomato products, 
or cucurbits. Thus, no harmonization issues are required to be resolved 
for this action.
[FR Doc. 00-21674 Filed 8-23-00; 8:45 am]
BILLING CODE 6560-50-F