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Propiconazole - Pesticide Petition Filing 11/98

[Federal Register: November 20, 1998 (Volume 63, Number 224)]
[Notices]
[Page 64498-64502]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr20no98-53]
[[Page 64498]]

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ENVIRONMENTAL PROTECTION AGENCY
[PF-842; FRL-6042-1]
Notice of Filing of Pesticide Tolerance Petitions
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of pesticide
petitions proposing the establishment of regulations for residues of
certain pesticide chemicals in or on various food commodities.
DATES: Comments, identified by the docket control number PF-842, must
be received on or before December 21, 1998.
ADDRESSES: By mail submit written comments to: Information and Records
Integrity Branch, Public Information and Services Divison (7502C),
Office of Pesticides Programs, Environmental Protection Agency, 401 M
St., SW., Washington, DC 20460. In person bring comments to: Rm. 119,
CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically by following
the instructions under "SUPPLEMENTARY INFORMATION." No confidential
business information should be submitted through e-mail.
    Information submitted as a comment concerning this document may be
claimed confidential by marking any part or all of that information as
"Confidential Business Information" (CBI). CBI should not be
submitted through e-mail. Information marked as CBI will not be
disclosed except in accordance with procedures set forth in 40 CFR part
2. A copy of the comment that does not contain CBI must be submitted
for inclusion in the public record. Information not marked confidential
may be disclosed publicly by EPA without prior notice. All written
comments will be available for public inspection in Rm. 119 at the
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: Mary L. Waller, Registration Support
Branch, Registration Division (7505W), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW, Washington, DC 20460.
Office location, telephone number, and e-mail address: Rm. 247, Crystal
Mall #2, 1921 Jefferson Davis Highway, Arlington, VA 22202, (703) 308-
9354; e-mail: waller.mary@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as
follows proposing the establishment and/or amendment of regulations for
residues of certain pesticide chemicals in or on various food
commodities under section 408 of the Federal Food, Drug, and 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 supports
granting of the petition. Additional data may be needed before EPA
rules on the petition.
    The official record for this notice of filing, as well as the
public version, has been established for this notice of filing under
docket control number [PF-842] (including comments and data submitted
electronically as described below). A public version of this record,
including printed, paper versions of electronic comments, which does
not include any information claimed as CBI, is available for inspection
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal
holidays. The official record is located at the address in
"ADDRESSES" at the beginning of this document.
    Electronic comments can be sent directly to EPA at:
    opp-docket@epamail.epa.gov

    Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption. Comment and data
will also be accepted on disks in Wordperfect 5.1/6.1 file format or
ASCII file format. All comments and data in electronic form must be
identified by the docket control number (PF-842) and appropriate
petition number. Electronic comments on this notice may be filed online
at many Federal Depository Libraries.

List of Subjects

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

    Dated: November 10, 1998.

James Jones,

Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    Petitioner summaries of the pesticide petitions are printed below
as required by section 408(d)(3) of the FFDCA. The summaries of the
petitions were prepared by the petitioners and represent the views of
the petitioners. EPA is publishing the petition summaries verbatim
without editing them in any way. The petition summaries announce 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. Novartis Crop Protection, Inc.

PP 8F3654 PP 8F3674

    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 Federal Food, Drug,
and Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR part 180 by
establishing tolerances for residues of propiconazole (1-[2-(2,4-
dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl-1H-1,2,4-triazole) in
or on the raw agricultural commodities corn, fodder (12.0 parts per
million (ppm)); corn, forage (12.0 ppm); corn, grain (0.1 ppm); corn,
sweet (0.1 ppm); pineapples (0.1 ppm); pineapples, fodder (0.1 ppm) (PP
8F3674); peanuts (0.2 ppm); peanuts, hay (20 ppm); and peanuts, 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/animal 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 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

[[Page 64499]]

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 LD50 of 1,517
milligrams/kilograms (mg/kg); a rabbit acute dermal LD50 >
6,000 mg/kg; a rat inhalation LC50 > 5.8 mg/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 mucosa 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.
    2. Food--i. 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
overestimate 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 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

[[Page 64500]]

(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 October
31, 1998).
    Additional uses of propiconazole have been requested in several
pending petitions. Proposed tolerances include: PP 5F4424 for use of
propiconazole on drybean 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).
    3. 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 (T1/2 >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.
    4. 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. 98-31069 Filed 11-19-98; 8:45 am]
BILLING CODE 6560-50-F