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pyridaben (Sanmite) Pesticide Tolerance Petition 3/97

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ENVIRONMENTAL PROTECTION AGENCY
[PF-721; FRL-5592-7]
BASF Corporation; Pesticide Tolerance Petition Filing
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice of filing.
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SUMMARY: This notice announces the filing of pesticide petitions proposing the
tolerances for residues of the pesticide pyridaben, [2- tert-butyl-5-(4-ter-
butylbenzylthio)-4-chloropyridazin-3(2H)-one] and its metabolites PB-7 (2-
tert-butyl-5-[4-(1-carboxy-1- methylethyl)benzylthio]-4-chloropyridazin-3(2H)-
one) and PB-9 (2-tert- butyl-4-chloro-5-[4-(1,1-dimethyl-2-
hydroxyethyl)benzylthio]- chloropyridazin-3(2H)-one). BASF is petitioning EPA
for the establishment of tolerances for use of pyridaben to control certain
pests on apples, pears, citrus, almonds, peaches (imported commodity), plums
(imported commodity), and grapes (imported commodity). The proposed tolerances
for pyridaben are: apples at 0.6 ppm, wet apple pomace at 1.0 ppm, pears at
0.75 ppm, citrus at 0.5 ppm, dried citrus pulp at 1.5 ppm, citrus oil at 10.0
ppm, almonds at 0.05 ppm, almond hulls at 4.0 ppm, peaches at 0.05 ppm, plums
at 0.05 ppm, and grapes at 0.75 ppm. The proposed tolerances for pyridaben and
its metabolites are: milk at 0.01 ppm, meat at 0.05 ppm, meat by-products at
0.05 ppm, and fat at 0.05 ppm. This summary was prepared by the petitioner.
DATES: Comments, identified by the docket control number [PF-721], must be
received on or before April 11, 1997.
ADDRESSES: By mail, submit written comments to: Public Response and Program
Resources Branch, Field Operations Division (7506C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW, Washington, DC
20460. In person, bring comments to: Rm. 1132 CM #2, 1921 Jefferson Davis
Highway, Arlington, VA 22202. Comments and data may also be submitted
electronically by sending electronic mail (e- mail) to: 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. Comments
and data will also be accepted on disks in WordPerfect 5.1 file format or in
ASCII file format. All comments and data in electronic form must be identified
by the docket control number [PF-721]. Electronic comments on this notice may
be filed online at many Federal Depository Libraries. Additional information
on electronic submissions can be found in Unit II. of this document.
Information submitted as comments concerning this notice may be claimed
confidential by marking any part or all of that information as "Confidential
Business Information" (CBI). The 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. 1132 at
the address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: Richard Keigwin, Product Manager (PM) 10,
Registration Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. Office location,
telephone number, and e-mail: Crystal Mall #2, Rm. 210, 1921 Jefferson Davis
Highway, Arlington, VA 22202, 703-305-6788, e-mail:
keigwin.richard@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions (PP) 5F4543
(on citrus), 4E4370 (on imported commodities) and 6F4651 (apples), 6F4741
(almonds), and 6F4721 (pears) from BASF Corporation, Agricultural Products, PO
Box 13528, Research Triangle Park, NC 27709. The petition proposes, pursuant
to section 408 of the Federal Food, Drug and Cosmetic Act (FFDCA), 21 U.S.C
section 346a, to amend 40 CFR part 180 to establish tolerances for the
pesticide pyridaben [2-tert- butyl-5-(4-ter-butylbenzylthio)-4-
chloropyridazin-3(2H)-one] in or on the raw agricultural commodities: apples,
wet apple pomace, pears, citrus, dried citrus pulp, citrus oil, almonds,
almond hulls, peaches, plums, and grapes, respectively. The petition also
proposes to establish tolerances for pyridaben and its metabolites PB-7 (2-
tert- butyl-5-[4-(1-carboxy-1-methylethyl)benzylthio]-4-chloropyridazin-
3(2H)-one) and PB-9 (2-tert-butyl-4-chloro-5-[4-(1,1-dimethyl-2-
hydroxyethyl)benzylthio]-chloropyridazin-3(2H)-one) in or on the raw
agricultural commodities: milk, meat, meat-by-products, and fat. EPA has
determined that the petitions contain 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 this petition. Additional data may be needed
before EPA rules on the petition.
As required by section 408(d) of the FFDCA, as recently amended by the Food
Quality Protection Act (FQPA), Pub. L. 104-170, BASF included in the petition
a summary of the petition and authorization for the summary to be published in
the Federal Register in a notice of receipt of the petition. The summary
represents the views of BASF. EPA is in the process of evaluating the
petition. As required by section 408(d)(3) of the FFDCA, EPA is including the
summary as a part of the notice of filing. EPA may have made minor edits to
the summary for the purpose of clarity.
I. Petition Summary
A. Plant and Animal Metabolism
BASF Corporation notes that metabolism in plants and animals is understood.
B. Analytical Method
The proposed analytical method involves extraction, partition, clean-up and
detection of residues by gas chromatography/electron capture detector
(gc/ecd).
C. Magnitude of the Residues
Nine pear residue trials were conducted in six states. Residues of pyridaben
were measured by gc/ecd. The method of detection had a limit of detection of
0.05 parts per million (ppm). Residues ranged from 0.07 to 0.58 ppm.
Twelve apple residue trials were conducted in six states. Residues of
pyridaben were measured by gc/ecd. The method of detection had a limit of
detection of 0.05 ppm. Residues ranged from 0.08 to 0.44 ppm.
Nineteen citrus residue trials were conducted in four states. Residues of
pyridaben were measured by gc/ecd. The method of detection had a limit of
detection of 0.05 ppm. Residues ranged from 0.05 to 0.42 ppm.
Eight almond residue trials were conducted in California. Residues of
pyridaben were measured by gc/ecd. The method of detection had a limit of
detection of 0.05 ppm. Residues were <0.05 ppm in all trials.
Eight peach residue trials were conducted in Chile. Residues of pyridaben were
measured by gc/ecd. The method of detection had a limit of detection of 0.05
ppm. Residues were <0.05 ppm in all trials.
Six plum residue trials were conducted in Chile. Residues of pyridaben were
measured by gc/ecd. The method of detection had a limit of detection of 0.05
ppm. Residues were <0.05 ppm in all trials.
Eight grape residue trials were conducted in Chile. Residues of pyridaben were
measured by gc/ecd. The method of detection had a limit of detection of 0.05
ppm. Residues ranged from <0.05 to 0.22 ppm.
D. Toxicological Profile
1. Acute toxicity testing. a. Acute oral toxicity (rat): LD50 = 1100
milligrams/kilogram (mg/kg) in males; 570 mg/kg in females. Tox Category: III
b. Acute oral toxicity (mouse): LD50 = 424 mg/kg in males; 383 mg/kg in
females. Tox Category: II
c. Acute dermal toxicity (rat): LD50 = > 2000 mg/kg in males and females. Tox
Category: III
d. Acute inhalation toxicity (rat): LC50 = 0.66 mg/l in males; 0.62 mg/l in
females. Tox Category: III
e. Primary eye irritation (rabbit): Pyridaben is a slight ocular irritant. Tox
Category: III
f. Primary dermal irritation (rabbit): Pyridaben is not a dermal irritant. Tox
Category: IV
g. Dermal sensitization (guinea pig): Pyridaben is not a dermal sensitizer.
2. Acute neurotoxicity (rat): Rats were dosed once with 0, 50, 100 and 200
mg/kg. The no observed effect level (NOEL) for systemic toxicity was
determined to be 50 mg/kg for both males and females. The lowest observed
effect level (LOEL) for systemic effects was determined to be 100 mg/kg in
both sexes based on decreased food consumption, decreased body weight gain and
increased clinical signs. The LOEL for neurobehavioral effects was determined
to be 200 mg/kg in males and >200 mg/kg in females.
3. Subchronic toxicity testing. a. 21-Day dermal (rat): Rats were repeatedly
dosed with pyridaben at 0, 30, 100, 300 and 1000 mg/kg/day for 21 days. The
NOEL was determined to be 100 mg/kg/day and the LOEL 300 mg/kg/day based on
decreased body weight gain in females.
b. 90-Day rodent (rat): CD rats were dosed with pyridaben at 0, 30, 65, 155
and 350 ppm in the diet for 13 weeks. The NOEL was determined to be 65 ppm
(4.94 mg/kg/day) for males and 30 ppm (2.64 mg/kg/day) in females. The LOEL
for males was determined to be 155 ppm (11.55 mg/kg/ day) based on reduced
body weight gain, reduced food consumption, reduced food efficiency, and
altered clinical pathology parameters. The LOEL for females was determined to
be 65 ppm (5.53 mg/kg/day) based on reduced body weight gain and reduced food
efficiency.
c. 90-Day non-rodent (dog): Beagle dogs were dosed with pyridaben at 0, 0.5,
1, 4, and 16 mg/kg/day in the diet for 13 weeks. The NOEL was determined to be
1 mg/kg/day and the LOEL determined to be 4 mg/kg/ day based on reduced body
weight gain and an increase in clinical signs in both sexes.
d. 90-Day neurotoxicity (rat): Rats were dosed with pyridaben at 0, 30, 100,
and 350 ppm in the diet for 13 weeks. The systemic NOEL was determined to be
100 ppm (equivalent to 8.5 mg/kg/day in males and 9.3 mg/kg/day in females).
The systemic LOEL was determined to be 350 ppm (equivalent to 28.8 mg/kg/day
in males and 31.1 mg/kg/day in females) based on decreased body weight gain,
decreased food consumption and decreased food efficiency. No neuropathological
effects were noted in the study.
4. Chronic toxicity testing. a. 1-Year non-rodent (dog): Two studies were run.
In the first, beagle dogs were dosed with pyridaben at 0, 1, 4, 16 and 32
mg/kg/day in the diet for one year. In the second, beagle dogs were dosed with
pyridaben at 0 and 0.5 mg/kg/day in the diet for 1 year. The NOEL was
determined to be <0.5 ppm and LOEL determined to be 0.5 mg/kg/day based on
increased clinical signs and decreased body weight gain in both sexes.
b. Combined rodent chronic toxicity/carcinogenicity (rat): Wistar rats were
fed 0, 4, 10, 28 and 80 ppm pyridaben in the diet to assess carcinogenicity
and 0, 4, 10, 28 and 120 ppm in the diet to assess chronic toxicity for 104
weeks. The NOEL was determined to be 28 ppm in both sexes (equivalent to 1.13
mg/kg/day in males and 1.46 mg/kg/day in females). The LOEL was determined to
be 120 ppm in both sexes (equivalent to 5.0 mg/kg/day in males and 6.52
mg/kg/day in females) based on decreased body weight gain in both sexes and
decreased alanineamino transferase (ALT) levels in males. Pyridaben was not
carcinogenic under the conditions of the test.
c. Carcinogenicity in the rodent (mouse): CD-1 mice were fed 0, 2.5, 8.0, 25
and 80 ppm pyridaben in the diet for 78 weeks. The NOEL was determined to be
25 ppm in both sexes (equivalent to 2.78 mg/kg/day in both sexes). The LOEL
was determined to be 80 ppm in both sexes (equivalent to 8.88 mg/kg/day in
males and 9.74 mg/kg/day in females) based on decreased body weight gain,
decreased food efficiency and changes in organ weights and histopathology.
Pyridaben was not carcinogenic under the conditions of the test.
5. Developmental toxicity testing. a. Developmental toxicity (rat): Sprague-
Dawley rats were dosed with 0, 2.5, 5.7, 13 and 30 mg/kg/day pyridaben in the
diet from days 6 through 15 of gestation. The maternal NOEL was determined to
be 4.7 mg/kg/day and the maternal LOEL was determined to be 13 mg/kg/day based
on decreased body weight gain, and decreased food consumption during the
dosing period. The developmental NOEL was determined to be 13 mg/kg/day and
the developmental LOEL was determined to be 30 mg/kg/day based on decreased
fetal body weight and an increase in incomplete ossification in selected
bones.
b. Developmental toxicity (rabbit): New Zealand white rabbits were dosed with
0, 1.5, 5, and 15 mg/kg/day pyridaben in the diet from days 6 through 19 of
gestation. The maternal NOEL was determined to be 5 mg/ kg/day and the
maternal LOEL was determined to be 15 mg/kg/day based on decreased body weight
gain, and decreased food consumption during the dosing period. The
developmental NOEL was determined to be <15 mg/kg/ day and the developmental
LOEL was determined to be <15 mg/kg/day.
c. Developmental toxicity (rabbit): Himalayan rabbits were dosed, by dermal
application, with 0, 70, 170 and 450 mg/kg/day pyridaben from days 6 through
19 of gestation. The maternal systemic NOEL was determined to be 70 mg/kg/day
and the maternal LOEL was determined to be 170 mg/kg/day based on decreased
body weight gain, and decreased food consumption during the dosing period. The
developmental NOEL was determined to be 170 mg/kg/day and the LOEL determined
to be 450 mg/kg/day based on decreased ossification of the skull.
6. Reproductive toxicity testing. Multi-generation reproduction (rat): CD rats
were dosed with 0, 10, 28 and 80 ppm pyridaben in the diet. The
parental/systemic NOEL was determined to be 28 ppm in both sexes (equivalent
to 2.20 mg/kg/day in males and 2.41 mg/kg/day in females). The
parental/systemic LOEL was determined to be 80 ppm (equivalent to 6.31
mg/kg/day in males and 7.82 mg/kg/day in females) based on decreased body
weight, decreased body weight gain and decreased food efficiency. The
reproductive NOEL and LOEL were both determined to be >80 ppm in males and
females.
7. Mutagenicity testing. a. Ames Testing: Negative b. In vitro cytogenicity
(Chinese hamster lung cells): Negative c. In vivo micronucleus assay (mouse):
Negative d. DNA damage/repair (E. coli): Negative
E. Threshold Effects
Based on the available chronic toxicity data, EPA has established the
Reference Dose (RfD) for pyridaben at 0.005 mg/kg/day. The RfD for pyridaben
is based on a 1-year feeding study in dogs with a threshold LOEL of 0.5
mg/kg/day based on increased clinical signs and decreased body weight gain in
both sexes and an uncertainty factor of 100.
F. Non-Threshold Effects
Using its Guidelines for Carcinogenic Risk Assessment, EPA has classified
pyridaben as Group "E " for carcinogenicity (no evidence of carcinogenicity)
based on the results of carcinogenicity studies in two species. There was no
evidence of carcinogenicity in an 18-month feeding study in mice and a 2-year
feeding study in rats at the dosage levels tested. The doses tested were
adequate for identifying a cancer risk. Thus, a cancer risk assessment is not
necessary.
G. Aggregate Exposure
1. Dietary exposure. Since pyridaben is regulated based upon non- carcinogenic
chronic toxicity, BASF conducted a DRES analysis based on anticipated residue
levels determined by EPA. The anticipated residue levels were derived from the
average residue levels from field trials conducted at the maximum proposed use
rate and minimum pre-harvest interval, and a correction factor of 2.3 to
account for all organosoluble residues as determined by EPA. This analysis
demonstrates that the exposure to non-nursing infants < 1 year, the most
sensitive subpopulation is approximately 73.4 percent of the RfD and to the
general population exposure is approximately 11.3 percent of the RfD.
2. "Other" exposure. Other potential sources of exposure of the general
population to residues of pesticides are residues in drinking water and
exposure from non-occupational sources. Based on the studies submitted to EPA
for assessment of environmental risk, BASF does not anticipate exposure to
residues of pyridaben in drinking water. There is no established maximum
concentration level for residues of pyridaben in drinking water under the Safe
Drinking Water Act. BASF has not estimated non-occupational exposure for
pyridaben since the current registration for pyridaben is limited to
commercial greenhouse use for non-food ornamental plants and the only other
domestic use will be for commercial apple, pear, citrus and almond production.
The potential for non-occupational exposure to the general population is
considered to be insignificant.
3. Cumulative exposure. BASF also considered the potential for cumulative
effects of pyridaben and other substances that have a common mechanism of
toxicity. BASF has concluded that 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 pyridaben would be
cumulative with those of any other chemical compounds.
H. Determination of Safety for U.S. Population
Using the exposure assumptions described in Unit I.G. of this document, BASF
concludes that aggregate exposure to pyridaben will utilize approximately 11.3
percent of the RfD for the U.S. population. EPA generally has no concern for
exposures below 100 percent of the RfD. Therefore, based on the completeness
and reliability of the toxicity data and the conservative exposure assessment,
BASF concludes that there is a reasonable certanity that no harm will result
from aggregate exposure to residues of pyridaben, including all anticipated
dietary exposure and all other non-occupational exposures.
I. Determination of Safety for Infants and Children
Developmental toxicity (delayed ossification) was observed in developmental
toxicity studies using rats and rabbits. The NOEL's for developmental effects
were established at 13 mg/kg/day in the rat study and 15 mg/kg/day in the
rabbit study. The developmental effect observed in these studies is believed
to be a secondary effect resulting from maternal stress (decreased body weight
gain and food consumption).
In a 2-generation reproduction study in rats, pups from the high dose group,
which were fed diets containing 80 ppm (equivalent to 6.31 and 7.82 mg/kg/day
in male and females, respectively) gained less weight beginning on lactation
day 14. Parental/systemic toxicity including decreased body weights, body
weight gains and food efficiency in males, and slightly decreased body weights
and body weight gains in females during lactation was also observed in the
high dose group. The results of this study indicate that the loss in weight
gain in pups from the high dose group was affected by nursing.
No clear scientific consensus yet exists to determine the most appropriate
endpoints for assessing risk in children. However, in consideration of the
data that show both developmental and reproductive toxicity were effects
secondary to parental toxicity, BASF believes that the established RfD of
0.005 mg/kg/day is the most conservative approach for assessing risk in
children. Using the exposure assumptions described in Unit I.G. of this
document, BASF has concluded that the percent of the RfD that will be utilized
by aggregate exposure to residues of pyridaben from the proposed use in
citrus, apples, pears, almonds, peaches, plums, and grapes is approximately
73.4 percent for non-nursing infants (<1 year), the most sensitive sub-
population. Based on the completeness and reliability of the toxicity data and
the conservative exposure assessment, BASF concludes that there is a
reasonable certainty that no harm will result in infants and children from
aggregate exposure to the residues of pyridaben, including all anticipated
dietary exposure and all other non-occupational exposures.
J. Other Considerations
The qualitative nature of the residues in plants and animals is adequately
understood. Residues of the parent molecule, pyridaben are the only residues
of concern. Residues of pyridaben do not concentrate in the processed
commodities apple and citrus juice. There is a practical analytical method for
detecting and measuring levels of pyridaben in or on food with a limit of
detection that allows monitoring of food with residues at or above the levels
set in these tolerances.
K. International Tolerances
A maximum residue level has not been established for pyridaben by the Codex
Alimentarius Commission.
II. Public Record
EPA invites interested persons to submit comments on this notice of filing.
Comments must bear a notification indicating the docket control number [PF-
721]. All written comments filed in response to this petition will be
available, in the Public Response and Program Resources Branch, at the address
given above from 8:30 a.m. to 4 p.m., Monday through Friday, except legal
holidays. A record has been established for this notice under docket control
number [PF-721] (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 public record is located in Rm.
1132 of the Public Response and Program Resources Branch, Field Operations
Division (7506C), Office of Pesticide Programs, Environmental Protection
Agency, Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA.
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. The official record for this
notice, as well as the public version, as described above, will be kept in
paper form. Accordingly, EPA will transfer all comments received
electronically into printed, paper form as they are received and will place
the paper copies in the official record which will also include all comments
submitted directly in writing. The official record is the paper record
maintained at the address in "ADDRESSES" at the beginning of this document.
Authority: 21 U.S.C. 346a.
List of Subjects
Environmental protection, Administrative practice and procedure, Agricultural
commodities, Pesticides and pests, Reporting and recordkeeping requirements.
Dated: March 6, 1997.
Peter Caulkins,
Acting Director, Registration Division, Office of Pesticide Programs.
[FR Doc. 97-6209 Filed 3-11-97; 8:45 am]