[Federal Register Volume 61, Number 215 (Tuesday, November 5, 1996)]
[Notices]
[Pages 56954-56956]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-28551]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-672; FRL-5572-8]
Pesticide Tolerance Petition; Notice of Filing
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice of filing.
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SUMMARY: This notice is a summary of a pesticide petition proposing the
extension of time-limited tolerances for combined residues of 4-
(dichloroacetyl)-3,4-dihydro-3-methyl-2H-1,4-benzoxazine (benoxacor)
when used as an inert ingredient (safener) in pesticide formulations
containing metolachlor in or on raw agricultural commodities for which
tolerances have been established for metolachlor. This summary was
prepared by the petitioner.
DATES: Comments, identified by the docket number [PF-672], must be
received on or before December 5, 1996.
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 ASCII file format.
All comments and data in electronic form must be identified by the
docket number [PF-672]. Electronic comments on this notice may be filed
online at many Federal Depository Libraries. Additional information on
electronic submissions can be found below in 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). No 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 a.m. to 4:30 p.m., Monday through Friday,
excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: By mail, Kerry B. Leifer, Registration
Division (7505W), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St. SW, Washington, DC 20460. Office location
and telephone number: Rm. 6-F, Crystal Station #1, 2800 Jefferson Davis
Highway, Arlington, VA 22202, (703) 308-8811; e-mail:
leifer.kerry@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition (PP)
7E3489 from Ciba Crop Protection, Ciba-Geigy Corporation, P.O. Box
18300, Greensboro, NC 27419, proposing pursuant to section 408(d) of
the Federal Food, Drug and Cosmetic Act (FFDCA), 21 U.S.C section 346a
(d), to amend 40 CFR part 180 by extending a time-limited tolerance for
combined residues of 4-(dichloroacetyl)-3,4-dihydro-3-methyl-2H-1,4-
benzoxazine (benoxacor) when used as an inert ingredient (safener) in
pesticide formulations containing metolachlor in or on raw agricultural
commodities for which tolerances have been established for metolachlor
from December 1, 1996 to December 1, 1998. The proposed analytical
method is capillary gas chromatography using Nitrogen/Phosphorous (N/P)
detection.
Pursuant to section 408(d)(2)(A)(i) of the FFDCA, as amended, Ciba-
Geigy Corporation has submitted the following summary of information,
data and arguments in support of their pesticide petition. This summary
was prepared by Ciba-Geigy and EPA has not fully evaluated the merits
of the petition. EPA edited the summary to clarify that the conclusions
and arguments were the petitioner's and not necessarily EPA's and to
remove certain extraneous material.
I. Ciba-Geigy Petition Summary:
1. Residue Chemistry
A. Plant/Animal Metabolism
Ciba Crop Protection (Ciba) notes that the metabolism in plants and
animals (goat, hen, and rat) is well understood. Identified metabolic
pathways are similar in plants and animals.
B. Analytical Method
Ciba Analytical Method AG536(C) is available and involves
extraction, filtering, dilution, partitioning, and cleanup. Samples are
then analyzed by capillary gas chromatography using Nitrogen/
Phosphorous (N/P) detection. The limit of quantitation (LOQ) is 0.01
ppm.
C. Magnitude of the Residues
More than 30 residue trials were conducted in 19 states on a
variety of agricultural crops [corn (field and sweet); soybeans,
potatoes, green beans, radishes, sorghum, peanuts, head lettuce, peas].
There were no detectable residues of benoxacor at the limit of
quantitation (LOQ) of 0.01 ppm (many samples were analyzed at an LOQ of
0.005 ppm and no residues were detected) in any raw agricultural
commodity or processed commodity. No transfer of residue to animals is
expected through their diet. Benoxacor is stable for a minimum of 12
months at temperatures down to -15C.
2. Toxicological Profile
The following studies were submitted in support of this petition:
A. Acute toxicity
A rat acute oral study with an LD50 > 5000 mg/kg, a rabbit acute
dermal study with an LD50 > 2010 mg/kg, a rat inhalation study with an
LC50 > 2000 mg/liter, a primary eye irritation study in the rabbit
showing moderate eye
[[Page 56955]]
irritation, a primary dermal irritation study in the rabbit showing
benoxacor is not a skin irritant, and a skin sensitization study which
showed benoxacor to be a skin sensitizer in the Guinea pig. Results of
a dermal absorption study show a maximum of 55.7% of benoxacor is
absorbed by the rat following a 24 hour dermal exposure.
Benoxacor was applied to the shaved skin of 5 male and 5 female
New Zealand White rabbits at dose levels of 0, 1, 500, or 1010 mg/kg
for at least 22 consecutive days. This study showed benoxacor is not
dermally toxic at doses greater than the limit dose of 1000 mg/kg/
day.
B. Genotoxicity
Benoxacor did not induce point mutations in vitro at limit
(cytotoxic) concentrations in a Salmonella/mammalian microsome test or
show any mutagenic activity in the Chinese hamster V79 mammalian point
mutation test and is neither clastogenic nor aneugenic in the Chinese
hamster at doses up to the limit dose of 5000 mg/kg. Benoxacor did not
induce unscheduled DNA synthesis in isolated rat hepatocytes at
cytotoxic concentrations up to 20 g/ml.
C. Developmental and Reproductive Toxicity
A developmental toxicity study in the rat at doses of 0, 1, 100, or
400 mg/kg/day by gavage with maternal and developmental NOEL's of 1 mg/
kg/day. Maternal, embryo, and fetal toxicity were observed at doses >
100 mg/kg/day.
A developmental toxicity study in the rabbit at doses of 0, 0.5,
2.5, 12.5 or 62.5 mg/kg/day. Slight evidence of maternal and fetal
toxicity was observed at 62.5 mg/kg/day. The maternal and developmental
NOEL's were 12.5 mg/kg/day and 62.5 mg/kg/day, respectively.
A two-generation reproduction study in the rat at doses of 0, 10,
50, 500, or 1000 ppm with a NOEL of 50 ppm. No effects on fertility,
reproductive performance or development were seen in the rat at a
maximally-tolerated dose of 1000 ppm. Treatment related effects on body
weight at feeding levels of > 500 ppm were accompanied by marginally
reduced food intake only in the 1000 ppm group.
D. Subchronic Toxicity
Six groups of 15 male and 15 female Sprague Dawley rats were fed
benoxacor at dietary concentrations of 0, 10, 100, 300, 1000, or 6000
ppm for 13 weeks. The liver (pigmentation, karyomegaly, cytomegaly,
bile duct proliferation, portal mononuclear cell infiltration) and
stomach (pyloric gland degeneration and necrosis) were identified as
target organs in the 6000 ppm group. Based on a significant depression
of body weight gain at 1000 and 6000 ppm as well as hematology,
clinical chemistry and pathology findings, the NOEL was determined to
be 300 ppm.
A 90-day feeding study in the dog at doses of 0, 0.25, 1, 5, 50,
150, or 400 mg/kg/day. Liver, kidney, stomach, and thymus were
identified as target organs. The NOEL was 50 mg/kg/day. The maximum
tolerated dose was exceeded at > 150 mg/kg/day.
A 90-day feeding study in CD-1 mice at dietary concentrations of 0,
50, 500, 2000 or 6000 ppm for 90 days. Effects on survival, clinical
signs, body weight, food consumption, the hematological system, and
liver and kidney were seen at 6000 ppm and to a lesser extent at 2000
ppm. The NOEL was 500 ppm.
E. Chronic Toxicity
A 52-week feeding study in the dog at doses of 0, 1, 5, 40, or 80
mg/kg. Liver and kidney were identified as target organs and the NOEL
was established at 5 mg/kg.
An 18-month oncogenicity study in the mouse at doses of 0, 10, 30,
600, or 1200 ppm with a NOEL of 30 ppm (4.2 mg/kg/day) for both chronic
toxicity and tumors. Target organs were the liver and forestomach. A
carcinogenic response was noted in the forestomach and is likely to be
linked to a non-genotoxic mode of action involving direct irritation to
the epithelial lining of the forestomach and limiting ridge between the
non-glandular and glandular stomach.
A 24 month chronic feeding and oncogenicity study in the rat at
doses of 0, 10, 50, 500, or 1000 ppm. Liver and forestomach were
identified as target organs. A carcinogenic response was seen in the
forestomach and is likely linked to a non-genotoxic mode of action
involving direct irritation to the epithelial lining of the forestomach
and the limiting ridge. The NOEL for tumors was 500 ppm (25 mg/kg/day)
and the NOEL for chronic toxicity was 10 ppm (0.5 mg/kg/day).
Based on the available chronic toxicity data, Ciba Crop Protection
believes the RfD for benoxacor is 0.002 milligrams (mg)/kilogram(kg)/
day based on a 2-year feeding study in rats with a No-Observed Adverse
Effect Level (NOAEL) of 0.5 mg/kg/day and an uncertainty factor of 300.
For this action, Ciba has used the NOAEL instead of a NOEL because of
slight effects noted on target organs at the low dose of 0.5 mg/kg/day
used in the chronic rat study. The use of a 300-fold safety factor
takes into account these changes and the reference dose derived in this
manner will provide an adequate safety margin for human exposure.
Using the Guidelines for Carcinogenic Risk Assessment published
September 24, 1986 (51 FR 33992), Ciba believes the Agency will
classify benoxacor as a Group C carcinogen (possible human carcinogen)
based on findings of a carcinogenicity effect in the non-glandular
stomach of both rats and mice. Because this carcinogenic response was
only observed at high doses in the non-glandular stomach of the rodent,
an anatomical structure not found in humans, it is likely this response
occurred via a non-genotoxic, threshold based mechanism. Ciba believes
exposure to benoxacor should be regulated using a margin of exposure
approach where the carcinogenic NOEL established in the most sensitive
species, the mouse, was 4.2 mg/kg/day.
3. Aggregate Exposure
A. Dietary exposure
1) Food
For purposes of assessing the potential dietary exposure under the
proposed tolerances, Ciba has estimated aggregate exposure based on the
theoretical maximum residue contribution (TMRC) from the benoxacor
tolerance of 0.01 ppm in or on raw agricultural commodities for which
tolerances have been established for metolachlor. In conducting this
exposure assessment, Ciba has made very conservative assumptions--100%
of all raw agricultural products for which tolerances have been
established for metolachlor will contain benoxacor residues and those
residues would be at the level of the tolerance (0.01 ppm) -which
result in an overestimate of human exposure.
2) Drinking water
Although benoxacor is mobile and hydrolyzes slowly at low pHs, it
rapidly degrades in the soil (half-life of 49 days under aerobic
conditions and 70 days anaerobically). Based on this data, Ciba does
not anticipate exposure to residues of benoxacor in drinking water.
This is supported by extensive experience with metolachlor, where in
large scale ground water monitoring studies, metolachlor has been
detected in less than 4% of the samples with the typical value being 1
ppb or less. Since benoxacor is formulated as a 1 to 30 or 1 to 20
ratio with metolachlor and acetamide, respectively, (maximum of 0.2
pounds benoxacor per acre) the presence of benoxacor in groundwater is
highly unlikely. The EPA has not established a Maximum Concentration
Level for residues of benoxacor in drinking water.
B. Non-Dietary Exposures
[[Page 56956]]
Ciba has evaluated the estimated non-occupational exposure to
benoxacor and based on its low use rate concludes that the potential
for non-occupational exposure to the general population is unlikely
except for the potential residues in food crops discussed above.
Benoxacor is used only on agricultural crops and is not used in or
around the home.
4. Cumulative Effects
Ciba also considered the potential for cumulative effects of
benoxacor and other substances that have a common mechanism of
toxicity. Ciba concluded that consideration of a common mechanism of
toxicity is not appropriate at this time. Ciba does not have any
reliable information to indicate that toxic effects seen at high doses
of benoxacor (generalized liver toxicity, nephrotoxicity and the
occurrence of forestomach tumors in an organ not present in humans)
would be cumulative with those of any other chemical compounds; thus
Ciba is considering only the potential risks of benoxacor in its
aggregate exposure assessment.
5. Safety Determination
A. U.S. Population
Using the conservative exposure assumptions described above and
based on the completeness and reliability of the toxicity data base for
benoxacor, Ciba has calculated that aggregate exposure to benoxacor
will utilize 9.4% of the RfD for the U.S. population based on chronic
toxicity endpoints and only 0.4% based on a margin of exposure
assessment and a carcinogenic NOEL of 4.2 mg/kg/day. EPA generally has
no concern for exposures below 100 percent 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. Ciba
concludes that there is a reasonable certainty that no harm will result
from aggregate exposure to benoxacor residues.
B. Infants and Children
Using the same conservative exposure assumptions used for the
determination in the general population, Ciba has concluded that the
percent of the RfD that will be utilized by aggregate exposure to
residues of benoxacor is 10.5% for nursing infants less than 1 year
old, 40.4% for non-nursing infants, 23.8% for children 1-6 years old
and 15.4% for children 7-12 years old. These worst case estimates are
likely at least 4 times greater than actual values when considering
that benoxacor residues have not been detected at the limit of
quantitation of 0.005 ppm (tolerance is 0.01 ppm) and using a more
realistic market share of 50% rather than the conservative 100%.
Therefore, based on the completeness and reliability of the toxicity
data base and the conservative exposure assessment, Ciba concludes that
there is a reasonable certainty that no harm will result to infants and
children from aggregate exposure to benoxacor residues.
6. International Tolerances
A maximum residue level has not been established for benoxacor by
the Codex Alimentarius Commission.
II. Administrative Matters:
Interested persons are invited to submit comments on this notice of
filing. Comments must bear a notation indicating the document control
number, [PF-672].
A record has been established for this rulemaking under docket
number [PF-672] (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 a.m.
to 4:30 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 may 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
notice record which will also include all comments submitted directly
in writing. The official rulemaking record is the paper record
maintained at the address in ``ADDRESSES'' at the beginning of this
document.
List of Subjects
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: October 31, 1996.
Stephen L. Johnson,
Director, Registration Division, Office of Pesticide Programs.
[FR Doc. 96-28551 Filed 11-1-96; 1:38 pm]
BILLING CODE 6560-50-F
