[Federal Register Volume 65, Number 134 (Wednesday, July 12, 2000)]
[Notices]
[Pages 43004-43009]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-17356]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-949; FRL-6591-8]


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-949, must be 
received on or before August 11, 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-949 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT: By mail: Dani Daniel, Registration 
Division (7505C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; 
telephone number: (703) 305-5409; 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:

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                Categories                      NAICS            Examples of potentially affected entities
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Industry.................................             111  Crop production.
                                                      112  Animal Production.
                                                      311  Food manufacturing.
                                                    32532  Pesticide manufacturing.
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    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'' 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-949. 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-949 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 number PF-949. Electronic comments may 
also be filed online at many Federal Depository Libraries.

[[Page 43005]]

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 Comestic Act (FFDCA), 21 U.S.C. 346a. 
EPA has determined that this petition 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 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 
requiremements.

    Dated: June 29, 2000.
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 view of the 
petitioner. 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.

Aventis CropScience

0F6119

    EPA has received a pesticide petition 0F6119 from Aventis 
CropScience, 2 T.W. Alexander Drive, Research Triangle Park, Raleigh, 
NC, 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 clofentezine in or on the raw agricultural commodity grapes 
at 0.35 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.
    APOLLO(r) SC Ovicide/Miticide (active ingredient clofentezine) is 
registered for use on apples, pears, almonds, walnuts, apricots, 
cherries, nectarines, and peaches to control European red mites and 
several spider mite species. It is an environmentally-friendly, IPM-
compatible product used at low dose rates, and only once per season. 
Clofentezine has been shown to be relatively non-toxic in studies 
conducted on mammals, fish, birds, aquatic invertebrates, predacious 
and other beneficial mites, bees, algae, and plants by establishing a 
tolerance for residues of clofentezine in or on the raw agricultural 
commodity grapes at 0.026 ppm to 0.33 ppm.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of clofentezine has been 
studied in three crops representative of the use pattern for APOLLO SC: 
apples (pome fruit), peaches (stone fruit), and grapes (vines/small 
fruit). In each case, unchanged clofentezine was the major extractable 
residue present. Non-extractable residues (fiber-bound) were 
negligible. Minor amounts of 2-chlorobenzonitrile, the major photo-
degradation product, were detected, predominantly on the fruit surface. 
Dissipation of this component may be a significant route in the 
degradation of clofentezine on the surface of these crops. The nature 
of the residue in grapes, and in all the other registered crops, is 
therefore adequately understood. The residue of concern is the parent, 
clofentezine.
    2. Analytical method. EPA recently approved an analytical method 
for clofentezine on apples at a limit of quantitation (LOQ) of 0.01 
ppm. In support of that effort, Aventis submitted an independent 
laboratory validation of the method which involves organic extraction 
and then cleanup, followed by high-pressure liquid chromatography. This 
method is suitable for enforcement for the registration of APOLLO SC 
ovicide/miticide on apples.
    For the requested use on grapes, an analytical method similar to 
the above was previously submitted to the Agency. This method was 
deemed suitable for enforcement of the tolerances proposed in a 
previous tolerance petition. Similar analytical methods for enforcement 
purposes are available for all the other registered crops and relevant 
animal tissues/milk/fat.
    3. Magnitude of residues. Extensive field residue trials have been 
conducted with APOLLO SC on grapes throughout the major growing regions 
of the United States. Application at 21 days pre-harvest interval (PHI) 
at the maximum use rate resulted in residues of clofentezine on fresh 
grapes of 0.026 ppm to 0.33 ppm. In processing studies on grapes which 
had been treated with APOLLO SC, residues in the processed commodity 
grape juice were lower than those in the raw agricultural commodity 
grapes; and residues in raisins were shown to also be lower than those 
in the raw agricultural commodity.
    Residue trials were conducted for APOLLO SC on apples, pears, 
apricots, cherries, nectarines, peaches, almonds, and walnuts at the 
maximum use rates and minimum (PHIs) throughout the

[[Page 43006]]

major growing regions of the United States. Residues in apples ranged 
from 0.01 ppm to 0.44 ppm. Residues in pears ranged from 0.01 ppm to 
0.2 ppm. Residues in stone fruit ranged from 0.01 ppm to 0.66 ppm. 
Residues on almond hulls ranged from 0.93 ppm to 2.4 ppm, on almond nut 
meats from 0.05 ppm to 0.3 ppm, and on walnuts 0.02 ppm. Tolerances 
were therefore established on apples (0.5 ppm); pears (0.5 ppm); 
apricots, cherries, nectarines, and peaches (1.0 ppm); almond nutmeats 
(0.5 ppm); almond hulls (5.0 ppm); and walnuts (0.02 ppm).
    Ruminant feeding studies were conducted to determine the magnitude 
of the clofentezine-derived residues in the tissues and milk of cows. 
Four groups of three dairy cattle were fed technical clofentezine in 
the diet at dose levels of 0, 10, 30, and 100 ppm over a period of 28 
days. Daily milk samples were taken and at the termination of the study 
the following organs were analyzed: liver, kidney, heart, muscle, 
peritoneal fat, and subcutaneous fat. At the feeding level of 10 ppm, 
residues were 0.3 ppm in liver and 0.05 ppm in kidney, milk, and other 
tissues. EPA established tolerances for cattle, goats, hogs, horses, 
and sheep as follows: 0.05 ppm in meat, fat, and meat by-products 
except liver; 0.4 ppm in liver; and 0.01 ppm in milk.

B. Toxicological Profile

    The toxicology of clofentezine has been thoroughly evaluated by EPA 
as part of previous regulatory actions. The studies are considered to 
be valid, reliable and adequate for the purposes of evaluating 
potential health risks and for establishing tolerances. The primary 
studies submitted in support of the registration of clofentezine are 
summarized below.
    1. Acute toxicity. A relatively low degree of acute toxicity and 
irritation potential. It is classified as toxicity category III for 
oral, dermal and inhalation toxicity, and toxicity category IV for eye 
and skin irritation. The acute oral LD50 of clofentezine was 
determined to be >5,2000 milligrams/kilograms (mg/kg) in rats and mice, 
>3,200 mg/kg in hamsters, and >2,000 mg/kg in beagle dogs. The acute 
rate dermal LD50 was >2,100 mg/kg. Clofentezine is 
considered to be practically non-irritating to eyes and skin but is 
considered to be a week skin sensitizer in the guinea pig maximization 
assay.
    APOLLO SC is classified as toxicity category IV for oral toxicity 
and skin irritation, and as toxicity category III for dermal toxicity 
and eye irritation. The acute oral LD50 of APOLLO SC was 
determined to be >5,000 mg/kg in rats; the acute dermal LD50 
in rats was >2,400 mg/kg. APOLLO SC is considered slightly irritating 
to eyes and skin.
    2. Genotoxicty. No evidence of genotoxicity was noted in a battery 
of in vitro and in vivo studies. Studies submitted included Ames 
Salmonella and mouse lymphoma gene mutation assay, a mouse micronucleus 
assay, a rat dominant lethal assay, and a gene conversion and mitotic 
recombination assay in yeast.
    3. Reproductive and developmental toxicity. A multigeneration rate 
reproduction study was conducted a dietary concentrations of 0, 4, 40, 
and 400 ppm. The parental no observed adverse effect level (NOAEL) was 
40 ppm based on slightly reduced body weights (bwt), increased liver 
weights and hepatocellular hypertrophy at 400 ppm. No treatment-related 
reproductive effects were noted at any dose level.
    In a rate developmental toxicity study, clofentezine was 
administered by gavage at dose levels of 0, 320, 1, 280 and 3,2000 mg/
kg/day during gestation days 6 to 20. Evidence of maternal toxicity was 
noted at 3,200 mg/kg/day and consisted of decreased weight gain, 
increased liver weights and centrilobular hepatocellular enlargement. 
No developmental effects were observed at any dose level.
    In a rabbit developmental toxicity study, clofentezine was 
administered by gavage at dose levels of 0, 250, 1,000 and 3,000 mg/kg/
day during gestation days 7 to 28. Slight maternal toxicity (decreased 
maternal food consumption and weight gain) and a slight decrease in 
fetal weight were noted at 3,000 mg/kg/day. Thus, the NOAEL was 
considered to be 1,000 mg/kg/day for both maternal and developmental 
effects.
    4. Subchronic toxicity. In a preliminary 90-day feeding study 
designed to select a suitable high dose level for a subsequent chronic 
rate study, clofentezine was administered to rats at dietary 
concentrations of 0, 3,000, 9,000 and 27,000 ppm. A significant 
reduction in weight gain was noted at 9,000 and 27,000 ppm. In 
addition, a marked, dose-related hepatomegaly and centrilobular 
hepatocyte enlargement was noted in all treatment groups. In a 
subsequent 90-day feeding study, clofentezine was administered to rats 
at dietary concentrations of 0, 40, 400, and 4,000 ppm. Slightly 
reduced weight gain, alterations in serveral clinical pathology 
parameters, increased liver, kidney and spleen weights, and 
centrilobular hepatocyte enlargement were noted at 400 and/or 4,000 
ppm. Thus, 40 ppm ( 2.8 mg/kg/day) was considered to be the 
NOAEL for this study.
    Clofentezine was administered to beagle dogs for 90 days at dietary 
concentrations of 0, 3,200, 8,000 and 20,000 ppm. Increased liver 
weights were noted at all dose levels but no histopathological changes 
nor any other treatment-related effects were observed.
    5. Chronic toxicity. In a 12-month feeding study, clofentezine was 
administered to beagle dogs at dietary concetrations of 0, 50, 1,000, 
and 20,000 ppm. An increase in adrenal and thyroid weights, as well as 
moderate hepatotoxicity consisting of minimal periportal hepatocyte 
enlargement with cytoplasmic eosinophilia, hepatomegaly and increased 
plasma cholesterol, triglycerides and alkaline phosphatase levels, were 
noted at 20,000 ppm. Evidence of slight hepatotoxicity was also noted 
at 1,000 ppm. Thus, the NOAEL for this study was considered to be 50 
ppm (1.25 mg/kg/day).
    In a 27-month feeding study, clofentezine was administered to rats 
at dietary concentrations of 0, 10, 40, and 400 ppm. Effects noted at 
400 ppm were limited to the liver and thyroid, primarily of males, and 
consisted of increased liver weights, a variety of microscopic liver 
lesions (centrilobular hepatocyte hypertrophy and vacuolation, focal 
cystic hepatocellular degeneration and diffuse distribution of fat 
deposits), increased serum thyroxine levels, and a slight but 
statistically significant increase in the incidence of thyroid 
follicular cell tumors. The NOAEL was considered to be 40 ppm 
(2 mg/kg/day).
    Clofentezine was not oncogenic to mice when administered for 2 
years at dietary concentrations of 0, 50, 500, and 5,000 ppm. Decreased 
weight gain, increased liver weights, and increased mortality were 
noted at 5,000 ppm. An increased incidence of eosinophilic or 
basophilic hepatocytes was noted at 5,000 ppm, and possibly 500 ppm.
    Numerous studies were conducted to investigate the mechanism for 
the increased incidence of male thyroid follicular tumors that was 
observed in the chronic rat study. These studies suggest that the 
tumors may have been caused by increased thyroid stimulating hormone 
(TSH) levels, which, in turn, resulted from clofentezine's liver 
toxicity.
    6. Animal metabolism. The metabolism, tissue distribution and 
excretion of clofentezine have been evaluated in a number of species. 
In all species, almost all of the administered dose was recovered 
within 24 to 48 hours after treatment, primarily via the feces. The 
major route of metabolism

[[Page 43007]]

was found to be ring hydroxylation, sometimes preceded by the 
replacement of a chlorine atom with a methyl-thio group. Blood and 
tissue levels in the fetuses of pregnant rats that had been treated 
with clofentezine were much lower than the levels found in the mother, 
indicating that clofentezine does not readily pass across the placenta. 
In addition, less than 1% of the administered dose was absorbed through 
the skin of rats following a 10-hour exposure to a 50 SC (50% 
suspension concentrate) formulation of clofentezine.
    Following oral dosing of a cow and three goats with 14C-labeled 
clofentezine, the residue in milk was identified as a single 
metabolite, 4-hydroxyclofentezine. Similarly, 4-hydroxyclofentezine has 
been shown to be the only metabolite present in fat, liver, and kidney. 
No unchanged clofentezine or other metabolites were found. Therefore, 
the nature of the residue in animals is adequately understood. The 
residues of concern are the combined residues of the parent, 
clofentezine, and the 4-hydroxyclofentezine metabolite.
    7. Endocrine disruption. Except for the thyroid mechanistic studies 
mentioned above, no special studies have been conducted to investigate 
the potential of clofentezine to induce estogenic or other endocrine 
effects. However, the standard battery of required toxicity studies has 
been completed. These studies include an evaluation of the potential 
effects on reproduction and development, and an evaluation of the 
pathology of the endocrine organs following repeated or long-term 
exposure. These studies are generally considered to be sufficient to 
detect any endocrine effects. However, with the exception of a slightly 
increased incidence of thyroid tumors in male rats, no such effects 
were noted in any of the studies with clofentezine. The male rat is 
known to be much more susceptible than humans to the carcinogenic 
effects resulting from thyroid hormone imbalance and/or increased 
levels of TSH. Therefore, the alterations in thyroid hormone and 
subsequent thyroid pathological changes, which have been noted 
following administration of high doses of clofentezine, are considered 
to be of minimal relevance to human risk assessment, particularly 
considering the low levels of clofentezine to which humans are likely 
to be exposed.

C. Aggregate Exposure

    1. Dietary exposure. Clofentezine is a miticide used on apples, 
pears, almonds, walnuts, apricots, cherries, peaches, and nectarines. 
Clofentezine has also been registered recently for use on ornamental 
plants, however, the product (OVATION (miticide/insecticide) is not 
being marketed at this time. There are no other non-crop uses. Thus, 
potential sources of non-occupational exposure to clofentezine would 
consist only of any potential residues in food and drinking water. 
There are no acute toxicity concerns with clofentezine. Therefore, only 
chronic exposures are addressed here.
    i. Food. A worst case dietary exposure assessment was performed for 
clofentezine using the dietary exposure evaluation model (DEEM) 
software (Novigen Sciences, Inc.) and 1994-1996 United States 
Department of Agriculture (USDA) consumption data. This assessment 
assumed that 100% of all grapes, apples, pears, almonds, walnuts, 
apricots, cherries, nectarines, peaches, milk, and the fat, meat, and 
meat by-products of cattle, goats, horses, sheep, and hogs contained 
residues at the established and proposed tolerance levels. A more 
realistic assessment was also conducted using estimates of market 
share.
    ii. Drinking water. All EPA environmental fate data requirements 
have been satisfied. The potential for clofentezine to leach into 
ground water was assessed in terrestrial field dissipation studies 
conducted in several locations and in varying soil types. Half-lives 
ranged from 32.4 to 83 days. No evidence of leaching of parent or 
degradation products was observed. Based upon these and other studies, 
EPA concluded that ``clofentezine is a relatively short-lived, non-
mobile compound which does not pose a risk to ground water, and will 
not be expected to accumulate in rotational crops.'' Thus, the 
potential for finding significant clofentezine residues in drinking 
water is minimal and the contribution of any such residues to the total 
dietary intake of clofentezine will be negligible. No maximum 
contaminant level for clofentezine has been established.
    Sufficient ground or surface water monitoring data are not 
available to perform a quantitative risk assessment for clofentezine at 
this time. However, EPA previously determined estimated drinking water 
environmental concentrations (DWECs) in ground and surface water using 
available environmental fate data and the screening model for ground 
water (SCI-GROW) and the generic expected environmental concentration 
(GENEEC) model for surface water. The DWEC of clofentezine in ground 
water was estimated to be 0.04 parts per billion (ppb) using SCI-GROW, 
and the DWECs for surface water were estimated to be 6.5 ppb (acute 
DWEC) and 0.3 ppb (chronic DWEC) using GENEEC. EPA policy allows the 
90/56-day GENECC value to be divided by 3 to obtain a value for chronic 
risk assessment calculations. Therefore, a surface water estimate of 
0.1 ppb was used in the chronic risk assessment.
    iii. Chronic exposure. EPA uses the drinking water level of 
comparison (DWLOC) as a theoretical upper limit on a pesticide's 
concentration in drinking water when considering total aggregate 
exposure to a pesticide in food, drinking water, and through 
residential uses. DWLOCs are not regulatory standards for drinking 
water; however, EPA uses DWLOCs in the risk assessment process as a 
surrogate measure of potential exposure from drinking water. In the 
absence of monitoring data for pesticides, it is used as a point of 
comparison against conservative model estimates of a pesticide's 
concentration in water. Calculated DWLOCs for chronic risks are listed 
in the following Table 1.

                      Table 1.--Summary of DWLOC Calculations-Chronic (Non-Cancer Scenario)
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                                                            Chronic (non-cancer) scenario
                                   -----------------------------------------------------------------------------
                                                                Maximum
      Population subgroup \1\        RfD mg/kg/      Food        water       SCI-GROW      GENEEC
                                        day      exposure mg/ exposure mg/  (ppb) \3\      (ppb)     DWLOC (ppb)
                                                    kg/day     kg/day \2\
----------------------------------------------------------------------------------------------------------------
U.S. population \1\...............        0.013     0.000346      0.01265         0.04          0.1          442
Northeast region \1\..............        0.013     0.000380      0.01262         0.04          0.1          441
Non-hispanic other than black or          0.013     0.000386      0.01261         0.04          0.1          441
 white \1\........................
Non-nursing infants \2\...........        0.013     0.001295      0.01171         0.04          0.1          117

[[Page 43008]]

 
Children (1-6 yrs) \3\............        0.013     0.001333      0.01167         0.04          0.1          233
All infants (1 yr) \2\............        0.013     0.001114      0.01189         0.04          0.1         117
----------------------------------------------------------------------------------------------------------------
\1\ Assume 70 kg bodyweight.
\2\ Assume 10 kg bodyweight.
\3\ Assume 20 kg bodyweight.

    To calculate the DWLOC for chronic (non-cancer) exposure relative 
to a chronic toxicity endpoint, the chronic dietary food exposure (from 
DEEM) was subtracted from the RfD to obtain the acceptable chronic 
(non-cancer) exposure to clofentezine in drinking water. DWLOCs were 
then calculated using default body weights and drinking water 
consumption figures.
    The estimated average concentration of clofentezine in surface 
water is 0.1 ppb. This value is less than EPA's DWLOCs for clofentezine 
as a contribution to chronic aggregate exposures (454 ppb). Therefore, 
taking into account the present uses and the proposed new use, residues 
of clofentezine in drinking water (when considered along with other 
sources of exposure for which reliable data are available) will not 
result in unacceptable levels of aggregate human health risk.

D. Cumulative Effects

    The primary effects observed in the toxicity studies conducted with 
clofentezine appear to be a result of its potency as an enzyme inducer. 
Although many other chemicals are also known to induce microsomal 
enzymes, insufficient information is available at this time to 
determine whether or not the potential toxic effects from these 
chemicals are cumulative. Furthermore, realistic estimates of potential 
non-occupational exposure to clofentezine indicate that such exposures 
are minimal and far below the levels that might be expected to produce 
any effects. Thus, any contribution of clofentezine to cumulative risk 
will not be significant. Therefore, only exposure from clofentezine is 
being addressed at this time.

E. Safety Determination

    1. U.S. population. The toxicity and residue data bases for 
clofentezine are considered to be valid, reliable, and essentially 
complete. Although clofentezine has been classified by EPA as category 
C for oncogenicity, quantitative oncogenic risk assessment was 
considered inappropriate for the following reasons:
    a. Evidence of tumors was limited to a single site in one sex of 
one species and occurred only at the high-dose level.
    b. The increased incidence of thyroid follicular tumors was only 
marginally increased above both concurrent and historical control 
levels.
    c. No evidence of genotoxicity has been observed.
    d. Mechanistic data indicate that the thyroid tumors were likely a 
secondary, threshold-medicated effect associated with clofentezine's 
liver toxicity. Furthermore, humans are believed to be much less 
susceptible to this effect than rats. Therefore, no effect on the 
thyroid pituitary axis or oncogeni response would be expected at 
exposure levels which did not affect the liver.
    e. Clofentexine was recommended as a category D by EPA's scientific 
advisory panel (SAP) in 1988. Thus, a standard margin of safety 
approach is considered appropriate to assess the potential for 
clofentezine to produce both oncogenic and non-oncogenic effects. Based 
on the previously described data, EPA has adopted an RfD value for 
clofentezine of 0.0125 mg/kg/day, which was calculate using the NOAEL 
of 1.25 mg/kg/day from the 1-year dog feeding study and a 100-fold 
safety factor.
    Using the worst-case assumptions of 100% of crop treated and that 
all crops and animal commodities contain residues of clofentezine at 
the current tolerance levels, the aggregate exposure of the general 
population to clofentezine from the established and proposed tolerances 
utilizes about 9% of the RfD. Using more realistic estimates of percent 
crop treated, this decreases to less than 3% of the RfD. There is 
generally no concern for exposures which utilize less than 100% of the 
RfD because the RfD represents the level at or below which daily 
aggregate exposure over a lifetime would not pose significant risks to 
human health. Therefore, there is a reasonable certainty that no harm 
will result to the general population from aggregate exposure to 
clofentezine residues.
    2. Infants and children. Data from rat and rabbit developmental 
toxicity studies and rat multigeneration reproduction studies are 
generally used to assess the potential for increased sensitivity of 
infants and children. The developmental toxicity studies are designed 
to evaluate adverse effects on the developing organism resulting from 
pesticide exposure during prenatal development. Reproduction studies 
provide information relating to reproductive and other effects on 
adults and offspring from prenatal and postnatal exposure to the 
pesticide.
    No indication of increased sensitivity to infants and children was 
noted in any of the studies with clofentezine. No developmental effects 
were noted in rats, even at a dose level (3,200 mg/kg/day) that 
exceeded the 1,000 mg/kg/day limit dose and produced maternal toxicity. 
In addition, no evidence of reproductive toxicity was noted in the rat 
multigeneration reproduction study. Slight developmental toxicity 
(decreased fetal weights) was noted in rabbits, but only at a dose 
level (3,000 mg/kg/day) that exceeded the EPA limit dose and also 
produced maternal toxicity.
    FFDCA section 408 provides that EPA may apply an additional safety 
factor for infants and children to account for prenatal and postnatal 
toxicity and the completeness of the data base. The toxicology data 
base for clofentezine regarding potential prenatal and postnatal 
effects in children is complete according to existing Agency data 
requirements and does not indicate any developmental or reproductive 
concerns. Furthermore, the existing RfD is based on a NOAEL of 1.25 mg/
kg/day (from the 1-year dog study) which is already more than 800-fold 
lower than the NOAEL in the rabbit developmental toxicity study. Thus, 
the existing RfD of 0.0125 mg/kg/day is considered to be appropriate 
for assessing potential risks

[[Page 43009]]

to infants and children and an additional uncertainty factor is not 
warranted.
    Using the conservative exposure assumptions described above 
(proposed and current tolerances, 100% crop treated, and no adjustments 
for percent contribution from livestock diet), aggregate exposure to 
residues of clofentezine are expected to utilize about 48% of the RfD 
in non-nursing infants, 20% of the RfD in nursing infants, and 36% of 
the RfD in children aged 1 to 6 years old. Using more realistic 
estimates of percent crop treated, the percent of RfD utilized is less 
than or equal to 10% for these population subgroups. These numbers 
would be lowered further if anticipated residues and/or an adjustment 
for percent contribution from livestock diet were utilized rather than 
tolerance values. Therefore, there is a reasonable certainty that no 
harm will result to infants or children from aggregate exposure to 
clofentezine residues.

F. International Tolerances

    Codex tolerances have been established for clofentezine on a wide 
variety of crops, including apples. The following maximum residue 
levels (MRLs) were adopted by the Codex Committee on Pesticide Residues 
(CCPR) in April 1988, except as noted in parentheses:

------------------------------------------------------------------------
               Commodity                           MRL  (mg/kg)
------------------------------------------------------------------------
 Cattle meat...........................  0.05
Cattle, edible offal...................  0.1
Cattle, milk...........................  0.01
Citrus fruits..........................  0.5 (1995)
Cucumber...............................  1.0 (1991)
Currants...............................  0.01 (1993)
Eggs (poultry).........................  0.05
Grapes.................................  1.0 (1995)
Pome fruits............................  0.5
Poultry, edible offal..................  0.05
Poutry meat............................  0.05
Stone fruits...........................  0.2
Strawberry.............................  2.0
------------------------------------------------------------------------

    This value, 1.25 mg/kg/day, was calculated by EPA using their 
standard conversion factor for food consumption. The NOAEL based upon 
actual food consumption in the study is 1.7 mg/kg/day.

[FR Doc. 00-17356 Filed 7-11-00; 8:45 am]
BILLING CODE 6560-50-M