[Federal Register Volume 65, Number 235 (Wednesday, December 6, 2000)]
[Notices]
[Pages 76253-76258]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-31056]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-983; FRL-6573-7]


Notice of Filing Pesticide Petitions to Establish and to Extend 
Tolerances for Certain Pesticide Chemicals in or on Food

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 docket control number PF-983, must be 
received on or before January 5, 2001.

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-983 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  For Pesticide Petition (PP 9F5079) 
contact: Cynthia Giles-Parker, Registration Division (7505C), Office of 
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington DC 20460; Telephone number: (703) 305-7740; e-
mail address: <a href="/cdn-cgi/l/email-protection#2d4a4441485e005d4c5f46485f034e54435945444c6d485d4c034a425b"><span class="__cf_email__" data-cfemail="b0d7d9dcd5c39dc0d1c2dbd5c29ed3c9dec4d8d9d1f0d5c0d19ed7dfc6">[email protected]</span></a>.
    For Pesticide Petitions (PP 8F3654 8F3674) contact: Mary Waller, 
Registration Division (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington DC 20460; Telephone number: (703) 308-9354; e-mail address: 
<a href="/cdn-cgi/l/email-protection#f780969b9b9285d99a96858eb7928796d9909881"><span class="__cf_email__" data-cfemail="5720363b3b3225793a36252e1732273679303821">[email protected]</span></a>.

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
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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'' 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-983. 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 (CM #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-983 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, CM#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: <a href="/cdn-cgi/l/email-protection#462936366b2229252d23320623362768212930"><span class="__cf_email__" data-cfemail="e58a9595c8818a868e8091a5809584cb828a93">[email protected]</span></a>, 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-983. 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.

[[Page 76254]]

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 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.

List of Subjects

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

    Dated: November 21, 2000.
James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Petitioner summaries of the pesticide petitions are printed below 
as required bysection 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. ISK Biosciences Corporation (PP 9F5079)

Summary of Petition

    EPA has received a pesticide petition (PP 9F5079) from ISK 
Biosciences Corporation, 5970 Heisley Road, Suite 200, Mentor, Ohio, 
44060, proposing, pursuant to section 408(d) of the Federal Food, Drug, 
and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 
by establishing a tolerance for residues of fluazinam in or on the raw 
agricultural commodities potato and peanut at 0.02 parts per million 
(ppm) and wine grapes at 3.0 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 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. The residue of concern is best defined as the 
parent, fluazinam. The metabolism of fluazinam in plants (potatoes, 
peanuts, and wine grapes) is adequately understood for the purposes of 
these tolerances. The metabolism of fluazinam involves initial 
reduction of the nitro groups, hydrolysis of the trifluoromethyl group 
as well as replacement of chlorine by glutathione with subsequent 
reactions along the glutathione pathway. Parent fluazinam is rapidly 
degraded and is either not found or barely detectable in peanuts and 
potatoes. Fluazinam parent was the major identifiable residue in a 
grape metabolism study. Identifiable residues in plant metabolism 
studies either closely resemble fluazinam in structure or are the 
result of re-incorporation of the fluazinam carbon pool into natural 
products.
    Ruminant and poultry metabolism studies demonstrated that the 
transmittal of residues from the feed of goats and hens through to 
meat, milk, and eggs was low. Total 14C residues were below 1 ppm in 
all tissues, milk and eggs. Identifiable residues were less than 2% of 
the administered dose in all matrices, except for chicken fat and 
liver.
    2. Analytical method. An analytical method using gas chromatography 
with electron capture detection (GC-ECD) for the determination of 
fluazinam residues on potatoes, peanuts, grapes and the processing 
fractions thereof has been developed and validated. The method involves 
solvent extraction followed by liquid-liquid partitioning and 
concentration prior to a final purification using column 
chromatography. The method has been successfully validated by an 
independent laboratory using peanut nutmeat as the matrix. The limit of 
quantitation of the method is 0.02 ppm in peanuts and 0.01 ppm in 
potatoes and grapes.
    3. Magnitude of residues--i. Potatoes. Data from 11 field trials in 
potatoes showed that mean fluazinam residues from duplicate samples 
were 0.01 ppm in the RAC commodity at all locations. The result of a 
processing study using a 3.5X application rate showed no concentration 
into the processing fractions dry peels, french fries and chips. A 
calculated processing factor of 2.4 for the animal feed commodity wet 
peels was determined based on residue levels just slightly above the 
limit of quantitation.
    ii. Peanuts. A total of 15 field trials were conducted over three 
growing seasons at nine sites representative of peanut production. 
Residues of fluazinam in nutmeat from all location were below 0.01 ppm. 
Residues in peanut hay, a grazing restriction commodity, ranged from 
0.16 to 10.2 ppm in the six locations where it was harvested. In a 
processing study, residues concentrated 3x in crude oil and 5x in 
soapstock, but did not concentrate in refined oil or presscake.
    iii. Wine grapes. A total of 20 field trials were conducted over 
three growing seasons in major wine grape growing regions worldwide. 
Residues of fluazinam in grapes ranged from 0.03 to 2.27 ppm. 
Vinification of grapes from two locations showed a reduction of 
fluazinam in wine to non-detectable levels.
    iv. Secondary residues. Since levels of fluazinam in potatoes and 
peanut nutmeat were below detectable levels

[[Page 76255]]

(the fluazinam label includes a peanut hay grazing restriction, and 
only wine grapes which are imported are included in this tolerance 
petition), no residues of concern are expected on animal feed items. 
Furthermore, since animal metabolism studies do not show potential for 
significant residue transfer, detectable secondary residues in animal 
tissues, milk or eggs are not expected. Therefore, tolerances are not 
needed for these commodities.

B. Toxicological Profile

    1. Acute toxicity. A battery of acute toxicity studies was 
conducted which placed technical fluazinam in Toxicity Category III for 
oral LD<INF>50</INF>, dermal LD<INF>50</INF>, dermal irritation, 
Category II for inhalation LC<INF>50</INF> and Category I for eye 
irritation. Technical fluazinam showed potential for dermal 
sensitization.
    In an acute neurotoxicity study, the no observed affect effect 
level (NOAEL) for neurotoxicity was 2,000 milligram/kilogram (mg/kg) 
highest dose tested (HDT) and the NOAEL for systemic effects was 50 mg/
kg.
    2. Genotoxicty. A battery of tests has been conducted to assess the 
genotoxic potential of technical fluazinam. Assays conducted included 
two gene mutation tests in bacteria, a chromosomal aberration test in 
mammalian cells, a mouse micronucleus test and a DNA repair test in 
bacteria. Technical fluazinam did not elicit a genotoxic response in 
any of the studies conducted.
    3. Reproductive and developmental toxicity. In a 2-generation 
reproductive toxicity study, the NOAEL for reproductive effects was 100 
ppm (10.1 mg/kg/day). The NOAEL for parental toxicity was 20 ppm (2.1 
mg/kg/day).
    In a rat developmental study, there were no developmental effects 
observed at non-maternally toxic doses. The developmental NOAEL was 50 
mg/kg/day and the lowest observed adverse effect level (LOAEL) was 250 
mg/kg/day, based upon statistically significant decreased mean fetal 
body weight and other evidence suggestive of delayed fetal development 
related to maternal toxicity. The maternal NOAEL was shown to be 50 mg/
kg/day.
    In a rabbit developmental study, there were no developmental 
effects observed at non-maternally toxic doses. The developmental NOAEL 
was 7 mg/kg/day and the LOAEL was 12 mg/kg/day, based on increased 
incidence of total litter loss and possible slightly increased 
incidences of fetal findings at this dose. It was concluded that the 
maternal NOAEL was 4 mg/kg/day.
    4. Subchronic toxicity. The NOAEL for the 13 week feeding study in 
rats was 50 ppm (4.1 mg/kg/day). The LOAEL was 500 ppm (41 mg/kg/day), 
based on periacinar hepatocellular hypertrophy and sinusoidal chronic 
inflammation in males, increased liver weights in males and increased 
lung weights in females.
    In a 13 week dog study, the NOAEL was 10 mg/kg/day. The LOAEL was 
100 mg/kg/day, based on ocular change observed ophthalmoscopically and 
liver effects consisting of increased relative liver to body weight, 
bile duct hyperplasia with or without cholangiofibrosis and increased 
plasma phosphatase levels.
    In a 21 day dermal study, the NOAEL for systemic effects was 10 mg/
kg/day. The LOAEL was 100 mg/kg/day, based on hepatocelluar hypertrophy 
and increases in AST and cholesterol levels.
    In a subchronic neurotoxicity study, no effects considered to be 
indicative of neurotoxicity were observed at the highest dose tested, 
3,000 ppm (233 mg/kg/day). The NOAEL for systemic toxicity (body weight 
differences) was 1,000 ppm (74 mg/kg/day).
    5. Chronic toxicity. Fluazinam was not carcinogenic in rats. A 
NOAEL of 10 ppm (0.43 mg/kg/day) of fluazinam was established based on 
the following effects at 1,000 and/or 100 ppm: lower food consumption 
and efficiency of food utilization, slight anemia, elevated 
cholesterol, increased liver weights, an increased number of 
macroscopic liver and testes lesions and an increased incidence of 
microscopically observed lung, liver, pancreas, lymph node and testes 
lesions.
    An additional study was conducted to further define the NOAEL for 
long-term effects in the rat. In the second study, a NOAEL of 50 ppm 
(2.2 mg/kg/day) was established based on liver and testes effects.
    Two long-term feeding studies were conducted in mice. In the first, 
the NOAEL for all effects was 10 ppm (1.14 mg/kg/day) and the LOAEL was 
100 ppm (11.2 mg/kg/day) based on the treatment-related effects 
observed in the liver.
    A second oncogenicity study in mice was conducted at 1,000, 3,000 
and 7,000 ppm to ensure that an maximum tolerance dose (MTD) was 
studied. Findings included increased female mortality, reduced body 
weight gains, increased brain weights and/or liver weights. An impurity 
in the test material used in this study resulted in vacuolation of the 
white matter of the brain and cervical spinal cord in treated animals. 
A statistically significant higher incidence of hepatocellular adenomas 
was observed in the 3,000 ppm dose males. Hepatocellular adenomas are 
common tumors in male mice. There was no dose relationship in the 
induction of the adenoma and no increase in hepatocellular carcinomas. 
It was concluded that fluazinam is not carcinogenic in the mouse.
    In a chronic dog study, the NOAEL was determined to be 1 mg/kg/day. 
The LOAEL was 10 mg/kg/day based on generalized, nonspecific toxicity. 
No ocular effects were observed ophthalmoscopally at any dose in this 
study.
    6. Animal metabolism. After an oral dose of fluazinam the median 
peak time for blood concentration of radiolabel activity for both sexes 
was 6 hours. The major route of excretion was the feces with urine 
contributing as a minor route. Less than 1% of the administered dose 
was found in the terminated animals. The highest concentration was 
found in the liver. There were no major differences related to sex or 
dose level in the findings. It was concluded that fluazinam is 
metabolized by both reduction and glutathione and glucuronide 
conjugation and further metabolism.
    7. Metabolite toxicology. The same metabolic processes occur in 
plants and animals but metabolism in plants is more extensive than in 
animals. All of the major identified metabolites in both plants and 
animals retain the phenylpyridinylamine structure. Many of the 
metabolites resulting from fluazinam are similar in plants and animals 
and, therefore, have already been evaluated toxicologically.
    Because of the rapid and complete elimination (in animals) and re-
incorporation (in plants) of fluazinam, the toxicity of metabolites is 
expected to be similar to but lower than the toxicity of the parent 
compound. The residue of concern is parent fluazinam only.
    8. Endocrine disruption. The toxicological profile of fluazinam 
shows no evidence of physiological effects characteristic of the 
disruption of the hormone estrogen in mammalian chronic studies or in 
mammalian or avian reproduction studies. It is therefore considered 
that there is an adequate level of safety over the reference dose for 
possible endocrine effects and that an additional safety factor for 
possible endocrine effects is not warranted.

C. Aggregate Exposure

    1. Dietary exposure. An RfD of 0.01 mg/kg/day is proposed for 
humans, based on the NOAEL from the one year dog study (1 mg/kg/day) 
and dividing by an uncertainty factor of 100.
    i. Food--a. Acute risk. Tier 1 acute dietary exposure analyses were

[[Page 76256]]

conducted for fluazinam in/on peanuts, potatoes and imported wine 
grapes to determine the exposure contribution of these commodities to 
the diet and to ascertain the acute risk potential. The estimates were 
based on proposed tolerance level residues for all three crops, peanut 
and potato processing studies, market share assumptions of 100% crop 
treated, and consumption data from the 1994 through 1996 USDA 
continuing survey of food intake.
    Even using all of the worst case exposure scenarios listed above, 
the Tier 1 acute assessment for the U.S. population resulted in a 
margin of safety (MOS) of 270,507 at the 95th percentile. This 
corresponded to an estimated exposure of 0.000185 mg/kg/day. The 
highest acute exposure estimate (95th percentile) was observed in the 
seniors (55 years and over) subpopulation: 0.001285 mg/kg/day. This 
correlates to an MOE of 38,908.
    b. Chronic risk. Tier 1 dietary exposure analyses were conducted 
for fluazinam in/on peanuts, potatoes and imported wine grapes to 
determine the exposure contribution of these commodities to the diet 
and to ascertain the chronic risk potential. The estimates were based 
on proposed tolerance level residues for all three crops, peanut and 
potato processing studies, market share assumptions of 100% crop 
treated, and consumption data from the 1994 through 1996 USDA 
continuing survey of food intake.
    Even using all of the worst case exposure scenarios listed above, 
the Tier 1 chronic dietary exposure estimates resulted in an estimated 
exposure for the U.S. population of 0.000104 mg/kg/day. This exposure 
corresponds to 1.0% of the reference dose (RfD) of 0.01mg/kg/day. The 
highest exposure estimate was calculated for the Females 20+ years 
(non-pregnant/non-nursing) population subgroup. This exposure was 
determined to be 0.000156 mg/kg/day (1.6% of the RfD).
    It can be concluded that acute or long-term dietary exposure to 
fluazinam through residues on treated peanuts, potatoes and imported 
wine grapes should not be of cause for concern.
    ii. Drinking water. Since fluazinam is intended for application 
outdoors to field grown peanut and potato crops, the potential exists 
for parent and or metabolites to reach ground or surface water that may 
be used for drinking water. The calculated drinking water levels of 
concern (DWLOC) for chronic exposure for adult males, adult females and 
toddlers were estimated to be 355 parts per billion (ppb), 296 ppb, and 
149 ppb, respectively. The calculated DWLOCs for acute exposure for all 
adults, adult females and toddlers were estimated to be 17,943 ppb, 
14,993 ppb, and 7,497 ppb, respectively. The chronic and acute DWLOC 
values are well above the modeled chronic and acute DWECs of 0.17 ppb 
(GENEEC 56-day/3) and 15.1 ppb (GENEEC instantaneous value), 
respectively. Therefore, there is comfortable certainty that no harm 
will result from combined dietary (food and water) exposure due to the 
use of fluazinam on peanuts, potatoes and imported wine grapes.
    2. Non-dietary exposure. No petition for registration of fluazinam 
is being made for either indoor or outdoor residential use. Non-
occupational exposure of fluazinam to the general population is 
therefore not expected and is not considered in aggregate exposure 
estimates.

D. Cumulative Effects

    Fluazinam is a phenylpyridinylamine fungicide. Since there are no 
other members of this class of fungicides, it is considered unlikely 
that fluazinam would have a common mechanism of toxicity with any other 
pesticide in use at this time.

E. Safety Determination

    1. U.S. population. Based on a NOAEL of 1 mg/kg bwt/day from a one 
year feeding study in dogs, and using an uncertainty factor of 100, a 
reference dose of 0.01 mg/kg bwt/day is proposed for assessment of 
long-term risk. The estimate of dietary intake was based on proposed 
tolerance level residues for all three crops, peanut and potato 
processing studies, market share assumptions of 100% crop treated and 
consumption data. Even using those conservative intake estimates, the 
proposed tolerances will utilize only 1% of the RfD for the U.S. 
population. The estimated exposure of fluazinam from drinking water, 
0.17 ppb is at least three orders of magnitude below the calculated 
drinking water level of concern, 355 ppb.
    2. Infants and children. Data from developmental toxicity studies 
in the rat and rabbit and a 2-generation reproduction study were 
considered. These studies which were described earlier, demonstrated no 
increased sensitivity of rats or rabbits to in utero exposure to 
fluazinam. In addition, the multigeneration reproductive toxicity study 
did not identify any increased sensitivity of rats to in utero or 
postnatal exposure. For all three studies, parental NOAELs were lower 
than or equivalent to the developmental or offspring NOAELs. It is 
concluded that the standard margin of safety will protect the safety of 
infants and children and that an additional safety factor is not 
warranted.
    The dietary exposure of fluazinam to infants and children is 
estimated to be much lower than adults because 80% to 90% of the 
exposure is expected from sherry and wine. The proposed tolerances will 
utilize 0.5% of the RfD for infants and children. The estimated 
exposure of fluazinam from drinking water, 0.17 ppb is three orders of 
magnitude below the calculated drinking water level of concern, 149 
ppb.

F. International Tolerances

    There are presently no Codex maximum residue levels established for 
residues of fluazinam on any crop.

2. Novartis Crop Protection, Inc.,

Summary of Petitions:

    EPA has received two pesticide petitions (PP 8F3654, PP 8F3674) 
from Novartis Crop Protection, Inc., P.O. Box 18300, Greensboro, NC 
27419 proposing,pursuant to section 408(d) of the FFDCA, 21 U.S.C. 
346a(d), to amend 40 CFR part 180 by extending the expiration date for 
tolerances for residues of propiconazole in or on the raw agricultural 
commodities corn, field, stover (12.0 parts per million (ppm)); corn, 
field, forage (12.0 ppm); corn, field, grain (0.1 ppm); corn, sweet 
(0.1 ppm); pineapple (0.1 ppm); pineapple, fodder (0.1 ppm) (PP 
8F3674); peanut (0.2 ppm); peanut, hay (20 ppm); and peanut, hulls (1.0 
ppm) (PP 8F3654). EPA has determined that the petition contains data or 
information regarding the elements set forth in section 408(d)(2) of 
the FFDCA; however,EPA has not fully evaluated the sufficiency of the 
submitted data at this time or whether the data supports granting of 
the petition. Additional data may be needed before EPA rules on the 
petition.

A. Residue Chemistry

    1. Plant metabolism. Novartis believes the studies supporting 
propiconazole adequately characterize metabolism in plants and animals. 
The metabolism profile supports the use of an analytical enforcement 
method that accounts for combined residues of propiconazole and its 
metabolites which contain the 2,4-dichlorobenzoic acid (DCBA) moiety.
    2. Analytical method. Novartis has submitted a practical analytical 
method involving extraction, filtration, conversion, partition, 
derivitization, and solid phase cleanup with analysis by confirmatory 
gas chromatography using electron capture detection (ECD). The total 
residue method is used for

[[Page 76257]]

determination of propiconazole and its metabolites. The limit of 
quantitation (LOQ) for the method is 0.05 ppm.
    3. Magnitude of residues. Field residue trials have been conducted 
at various rates, timing intervals, and applications methods to 
represent the use patterns which would most likely result in the 
highest residues. For all samples, the total residue method was used 
for determination of the combined residues of parent and its 
metabolites which contain the DCBA moiety.

B. Toxicological Profile

    1. Acute toxicity. Propiconazole exhibits low toxicity. Data 
indicated the following: a rat acute oral LD<INF>50</INF> of 1,517 
milligrams/kilograms (mg/kg); a rabbit acute dermal LD<INF>50</INF> > 
6,000 mg/kg; a rat inhalation LC<INF>50</INF> >5.8 g/liter air; minimal 
skin and slight eye irritation; and nonsensitization.
    2. Genotoxicty. Propiconazole exhibits no mutagenic potential based 
on the following data: In vitro gene mutation test (Ames assay, rat 
hepatocyte DNA repair test, (human fibroblast DNA repair test), In 
vitro chromosome test, (human lymphocyte cytogenetic test), In vivo 
mutagenicity test, (Chinese hamster bone marrow cell nucleus anomaly 
test, Chinese hamster bone marrow cell micronucleus test, mouse 
dominant lethal test), and other mutagenicity test (BALB/3T3 cell 
transformation assay).
    3. Reproductive and developmental toxicity. In an oral teratology 
study in the rabbit, a maternal no observed adverse effect level 
(NOAEL) of 30 mg/kg was based on reduced food intake but without any 
fetotoxicity even at the top dose of 180 mg/kg. In an oral teratology 
study in the rabbit, a maternal NOAEL of 100 mg/kg was based on 
reductions in body weight gain and food consumption and a fetal NOAEL 
of 250 mg/kg was based on increased skeletal variations at 400 mg/kg. 
In an oral teratology study in the rat, a maternal and fetal NOAEL of 
100 mg/kg was based on decreased survival, body weight gain, and food 
consumption in the dams and delayed ossification in the fetuses at 300 
mg/kg. In a second teratology study in the rat, a maternal and fetal 
NOAEL of 30 mg/kg was based on reductions in body weight gain and food 
consumption in the dams and delayed development in the fetuses at 90 
and 360/300 mg/kg. A supplemental teratology study in the rat involving 
eight times as many animals per group as usually required showed no 
teratogenic potential for the compound. A 2-generation reproduction 
study in the rat showed excessive toxicity at 5,000 ppm without any 
teratogenic effects. A 2-generation reproduction study in the rat 
showed no effects on reproductive or fetal parameters at any dose 
level. Postnatal growth and survival were affected at the top dose of 
2,500 ppm, and parental toxicity was also evident. The NOAEL for 
development toxicity is 500 ppm.
    4. Subchronic toxicity. In a 21 day dermal study in the rabbit, a 
NOAEL of 200 mg/kg was based on clinical signs of systemic toxicity. In 
a 28 day oral toxicity study in the rat, a NOAEL of 50 mg/kg was based 
on increased liver weight. In a subchronic feeding study in the mouse, 
a NOAEL of 20 ppm (3 mg/kg) was based on liver pathologic changes. In a 
13 week feeding study in the male mouse, a NOAEL of 20 ppm (3 mg/kg) 
was based on liver pathologic changes. In a 90 day feeding study in 
rats, the NOAEL was 240 ppm (24 mg/kg) based on a reduction in body 
weight gain. In a 90 day feeding study in dogs,the NOAEL was 250 ppm 
(6.25 mg/kg) based on reduced food intake and stomach histologic 
changes.
    5. Chronic toxicity. In a 12 month feeding study in the dog, a 
NOAEL of 50 ppm (1.25 mg/kg) was based on stomach histologic changes. 
In a 24 month oncogenicity feeding study in the mouse, the NOAEL was 
100 ppm (15 mg/kg). The MTD was exceeded at 2,500 ppm in males based on 
decreased survival and body weight. Increased incidence of liver tumor 
was seen in these males but no evidence of carcinogenicity was seen at 
the next lower dose of 500 ppm in either sex. In a 24 month chronic 
feeding/oncogenicity study in the rat, a NOAEL of 100 ppm (5 mg/kg) was 
based on body weight and blood chemistry. The MTD was 2,500 ppm based 
on reduction in body weight gain and no evidence of oncogenicity was 
seen. Based on the available chronic toxicity data, Novartis believes 
the Reference dose (RfD) for propiconazole is 0.0125 mg/kg/day. This 
RfD is based on a 1 year feeding study in dogs with a NOAEL of 1.25 mg/
kg/day (50 ppm) and an uncertainly factor of 100. No additional 
modifying factor for the nature of effects was judged to be necessary 
as stomach mucous hyperemia was the most sensitive indicator of 
toxicity in that study.
    Using the Guidelines for Carcinogenic Risk Assessment published on 
September 24, 1986 (51 FR 33992), the USEPA has classified 
propiconazole in group C for carcinogenicity (evidence of possible 
carcinogenicity for humans). The compound was tested in 24 month 
studies with both rats and mice. The only evidence of carcinogenicity 
was an increase in liver tumor incidence in male mice at a dose level 
that exceeded the maximum tolerated dose (MTD). Dosage levels in the 
rat study were appropriate for identifying a cancer risk. The Cancer 
Peer Review Committee recommended the RfD approach for quantitation of 
human risk. Therefore, the RfD is deemed protective of all chronic 
human health effects, including cancer.

C. Aggregate Exposure

    1. Dietary exposure. The RfD for propiconazole is 0.0125 mg/kg/day 
and is based on a 1 year feeding study in dogs with a NOAEL of 1.25 mg/
kg/day (50 ppm) and an uncertainly factor of 100.
    i. Food--Acute risk. The risk from acute dietary exposure to 
propiconazole is considered to be very low. The lowest NOAEL in a short 
term exposure scenario, identified as 30 mg/kg in the rat teratology 
study, is 24-fold higher than the chronic NOAEL. Based on worst-case 
assumptions, the chronic exposure assessment did not result in any 
margin of exposure (MOE) less than 150 for even the most impacted 
population subgroup. Novartis believes that the MOE for acute exposure 
would be more than 100 for any population groups; MOE of 100 or more 
are considered satisfactory.
    ii. Chronic risk. For the purposes of assessing the potential 
dietary exposure under the existing, pending, and proposed tolerances 
for the residue of propiconazole and its metabolites determined as 2,4-
dichlorobenzoic acid, Novartis has estimated aggregate exposure based 
upon the Theoretical Maximum Residue Concentration (TMRC). The TMRC is 
a ``worst case'' estimate of dietary exposure since it assumes 100% of 
all crops for which tolerances are established are treated and that 
pesticide residues are at the tolerance levels, resulting in an 
overestimation of human exposure.
    Currently established tolerances range from 0.05 ppm in milk to 60 
ppm in grass seed screenings and include: apricots (1.0 ppm); bananas 
(0.2 ppm); barley grain (0.1 ppm); barley straw (1.5 ppm); cattle 
kidney and liver (2.0 ppm); cattle meat, fat, and meat by products 
except kidney and liver (0.1 ppm); celery (5.0 ppm); corn forage and 
fodder (12.0 ppm); corn grain and sweet (0.1); eggs (0.1 ppm); goat 
kidney and liver (2.0 ppm); goat meat, fat, and meat by products except 
kidney and liver (0.1 ppm); grass forage (0.5 ppm); grass hay/straw 
(40.0 ppm); grass seed screenings (60.0 ppm); hogs kidney and liver 
(2.0 ppm); hog meat, fat, and meat by products except kidney and liver 
(0.1 ppm); horses kidney and liver (2.0 ppm); horse meat, fat, and meat 
by

[[Page 76258]]

products except kidney and liver (0.1 ppm); milk (0.05 ppm); mint tops 
(0.3 ppm - regional tolerance west of Cascade Mountains); mushrooms 
(0.1 ppm); nectarines (1.0 ppm); oat forage (10.0 ppm); oat grain (0.1 
ppm); oat hay (30.0 ppm); oat straw (1.0 ppm); peaches (1.0 ppm); 
peanut hay (20.0 ppm); peanut hulls (1.0 ppm); peanuts (0.2 ppm);, 
pecans (0.1 ppm); pineapple (0.1 ppm); pineapple fodder (0.1 ppm); 
plums (1.0 ppm); poultry liver and kidney (0.2 ppm); poultry meat, fat, 
and meat by products except kidney and liver (0.1 ppm); prunes, fresh 
(1.0 ppm); rice grain (0.1 ppm); rice straw (3.0 ppm); wild rice (0.5 
ppm regional tolerance Minnesota); rye grain (0.1 ppm); rye straw (1.5 
ppm); sheep kidney and liver (2.0 ppm); sheep meat, fat, and meat by 
products except kidney and liver (0.1 ppm); stone fruit crop group 12 
(1.0 ppm); wheat grain (0.1 ppm); and wheat straw (1.5 ppm). In 
addition, time-limited regional tolerances for sorghum grain and stover 
at 0.1 ppm and 1.5 ppm, respectively were established to support a 
section 18 Crisis exemption in Texas (expiration date December 31, 
2000) and Nebraska, Kansas, and Oklahoma (expiration date September 30, 
2000).
    Additional uses of propiconazole have been requested in several 
pending petitions. Proposed tolerances include: PP 5F4424 for use of 
propiconazole on dry bean and soybean - dry bean forage (8.0 ppm); dry 
bean hay (8.0 ppm); dry bean vines (0.5 ppm); dry bean (0.5 ppm), 
soybeans (0.5 ppm); soybean fodder (8.0 ppm); soybean forage (8.0 ppm); 
soybean hay (25.0 ppm); and soybean straw (0.1 ppm); PP 5F4591 for use 
of propiconazole on berries, carrots and onions - berry crop grouping 
(1.0 ppm); dry bulb onion (0.3 ppm); green onion (8.0); PP 5F3740 - 
tree nut crop grouping (0.1 ppm); PP 5F4498 - inadvertent/rotational 
crop tolerances for alfalfa forage (0.1 ppm), alfalfa hay (0.1 ppm), 
grain sorghum fodder (0.3 ppm), grain sorghum forage (0.3 ppm) and 
grain sorghum grain (0.2 ppm).
    ii. Drinking water. Other potential sources of exposure of the 
general population to residues of propiconazole are residues in 
drinking water and exposure from non-occupational sources. Review of 
environmental fate data by the Environmental Fate and Effects Division 
of USEPA indicates that propiconazole is persistent and moderately 
mobile to relatively immobile in most soil and aqueous environments. No 
Maximum Concentration Level (MCL) currently exists for residues of 
propiconazole in drinking water and no drinking water health advisory 
levels have been established for propiconazole.
    The degradation of propiconazole is microbially mediated with an 
aerobic soil metabolism half-life of 70 days. While propiconazole is 
hydrolytically and photochemically stable (T 1/2 >100 days), it binds 
very rapidly and tightly to soil particles following application. 
Adsorption/desorption and aged leaching data indicate that 
propiconazole and its degradates will primarily remain in the top 0-6 
inches of the soil. It has been determined that under field conditions 
propiconazole will degrade with a half-life of approximately 100 days.
    2. Non-dietary exposure. Propiconazole is registered for 
residential use as a preservative treatment for wood and for lawn and 
ornamental uses. At this time, no reliable data exist which would allow 
quantitative incorporation of risk from these uses into a human health 
risk assessment. The exposure to propiconazole from contacting treated 
wood products is anticipated to be very low since the surface of wood 
is usually coated with paint or sealant when used in or around the 
house. The non-occupational exposure from lawn and ornamental 
applications is also considered to be minor. It is estimated that less 
than 0.01% of all households nationally use propiconazole in a 
residential setting.

D. Cumulative Effects

    Consideration of a common mechanism of toxicity is not appropriate 
at this time since there is no reliable information to indicate that 
toxic effects produced by propiconazole would be cumulative with those 
of any other types of chemicals. While other triazoles are available on 
the commercial or consumer market, sufficient structural differences 
exist among these compounds to preclude any categorical grouping for 
cumulative toxicity. Consequently, Novartis is considering only the 
potential risks of propiconazole in its aggregate exposure assessment.

E. Safety Determination

    1. U.S. population--Reference dose. Using the conservative exposure 
assumptions described above (100% stone fruit acres treated and 
tolerance level residues) and based on the completeness and reliability 
of the toxicity data base for propiconazole, Novartis has calculated 
aggregate exposure levels for this chemical. The calculation shows that 
only 16% of the RfD will be utilized for the U.S. population based on 
chronic toxicity endpoints. 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. Novartis concludes that there is a 
reasonable certainty that no harm will result from aggregate exposure 
to propiconazole residues.
    2. Infants and children. Developmental toxicity (e.g., reduced pup 
weight and ossification) was observed in the rat teratology studies and 
2-generation rat reproduction studies at maternally toxic doses. Some 
of these findings are judged to be nonspecific, secondary effects of 
maternal toxicity. The lowest NOAEL for developmental toxicity was 
established in the rat teratology study at 30 mg/kg, a level 24-fold 
higher than the NOAEL of 1.25 mg/kg on which the RfD is based.
    3. Reference dose. Using the same conservative exposure assumptions 
as employed for the determination in the general population, Novartis 
has calculated that the percent of the RfD that will be utilized by 
aggregate exposure to residues of propiconazole is 26% for nursing 
infants less than 1 year old, 65% for non-nursing infants less than 1 
year old, 35% for children 1-6 years old, and 23% for children 7-12 
years old. Therefore, based on the completeness and reliability of the 
toxicity data base and the conservative exposure assessment, Novartis 
concludes that there is a reasonable certainty that no harm will result 
to infants and children from aggregate exposure to propiconazole 
residues.

F. International Tolerances

    International CODEX values are established for almond, animal 
products, bananas, barley, coffee, eggs, grapes, mango, meat, milk, 
oat, peanut-whole, peanut grains, pecans, rape, rye, stone fruit, sugar 
cane, sugar beets, sugar beet tops, and wheat. The U.S. residue 
definition includes both propiconazole and metabolites determined as 
2,4-dichlorobenzoic acid (DCBA), while the CODEX definition is for 
propiconazole, per se, i.e. parent only. This difference results in 
unique tolerance expressions with the U.S. definition resulting in the 
higher tolerance levels.
[FR Doc. 00-31056 Filed 12-5-00; 8:45 am]
BILLING CODE 6560-50-S


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