[Federal Register Volume 62, Number 29 (Wednesday, February 12, 1997)]
[Notices]
[Pages 6521-6524]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-3226]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
[PF-707; FRL-5587-2]
American Cyanamid Company; Pesticide Tolerance Petition Filing
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice of filing.
-----------------------------------------------------------------------
SUMMARY: This notice announces the initial filing of a pesticide
petition proposing the establishment of tolerances for residues of
dithianon (5,10-dihydro-5,10-dioxonaphtho[2,3-b]-1,4-dithiin-2,3-
dicarbonitrile) in or on pome fruits and dried hops. This notice
includes a summary of the petition that was prepared by the petitioner,
American Cyanamid Company.
DATES: Comments, identified by the docket number [PF-707], must be
received on or before, March 14, 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.
Comments and data may also be submitted electronically by sending
electronic mail (e-mail) to: opp-docket@epamail.epa.gov. 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 docket number [PF-707]. Electronic comments on this
notice of filing 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 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. 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: By mail: Cynthia Giles-Parker, Product
Manager (PM 22), Registration Division (7505C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington
DC 20460. Office location, telephone number, and e-mail address:
Crystal Mall #2, Room 229, 1921 Jefferson Davis Highway, Arlington, VA,
703-305-7740, e-mail: giles-parker.cynthia@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition (PP
6E4781) from American Cyanamid Company, P.O. Box 400, Princeton, NJ
08543, 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 the fungicide dithianon in
or on the raw agricultural commodity (RAC) pome fruits at 5 parts per
million (ppm) and dried hops at 100 ppm. The proposed analytical
methods are HPLC methods with UV detection for pome fruits (apples and
pears) and with electrochemical detection for quantitation for hops.
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
[[Page 6522]]
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.
As required by section 408(d) of the FFDCA, as recently amended by
the Food Quality Protection Act (FQPA) Pub. L. 104-170, American
Cyanamid 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 American Cyanamid. 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 this notice of filing. EPA has made
minor edits to the summary for the purpose of clarity.
I. Petition Summary
On August 20, 1996, American Cyanamid Company petitioned the EPA
for an import tolerance for dithianon residues on pome fruits (with
representative crops of apples and pears) and dried hops. This is the
first tolerance petition for dithianon fungicide in the United States.
Section 408(b)(2)(A) of the amended FFDCA allows the EPA to
establish a tolerance only if the Administrator determines that there
is a ``reasonable certainty that no harm will result from the aggregate
exposure to the pesticide chemical residue, including all anticipated
dietary exposures and all other exposures for which there is reliable
information.'' All of the studies required for the proposed import
tolerance have been completed and submitted to EPA for review. The
available information indicates there is a reasonable certainty that no
harm will result from various types of exposure to dithianon. The
following is a summary of the information submitted to the EPA to
support the establishment, under section 408(b)(2)(D) of the amended
FFDCA, of an import tolerance for dithianon on pome fruits and dried
hops.
A. Residue Chemistry
1. Plant metabolism. The qualitative nature of the residues of
dithianon in plants is adequately understood. Metabolism studies in
three diverse crops demonstrate a similar pattern of dithianon
metabolism with a significant amount of unchanged parent compound
remaining on the plant surfaces. The metabolism of dithianon in plants
results in a large number of fragments in only trace amounts. Hence,
parent dithianon is the only residue of concern.
2. Analytical method. Two practical analytical methods for
detecting and measuring levels of dithianon in pome fruits (apples and
pears) and in hops have been submitted to EPA. The analytical method
for apples and pears is an HPLC method with UV detection. For hops, an
HPLC method with electrochemical detection for quantitation was
submitted. Both methods are appropriate for enforcement purposes.
3. Magnitude of residues. Residue field trials were conducted in
representative countries exporting the majority of the RAC of this
petition to the United States. For the pome fruit crop group, field
residue trials on apples were conducted in France, New Zealand,
Germany, and Brazil and on pears in France, Australia, and New Zealand.
These studies cover a wide range of geography with diverse climates and
growing conditions, as well as various cultural practices. The residue
values reported in the tolerance petition were all less than the
proposed tolerance of 5 ppm for pome fruits. Hop residue trials
conducted in Germany support the dried hop tolerance. Except for one
outlier, the field residue levels of dithianon in dried hops were less
than the proposed tolerance of 100 ppm.
Of the crops for which this tolerance is requested, only apples
have processed commodities. Apple processing studies submitted in this
petition indicate that dithianon does not concentrate in apple juice,
but does concentrate in the wet apple pomace. It is unlikely that apple
pomace will be imported into the United States. Therefore, an import
tolerance is not necessary for that processed commodity.
B. Toxicological Profile
A complete, valid and reliable database of mammalian toxicology
studies supports the tolerance for dithianon on pome fruits and dried
hops.
1. Acute toxicity. Dithianon has a low order of acute toxicity to
rats by the oral route of exposure with an LD50 (females) greater
than 678 milligram/kilogram (mg/kg) and LD50 (males) greater than
720 mg/kg. Since this petition is for an import tolerance, oral
toxicity data sufficiently assesses the risk of acute exposure for this
use.
2. Genotoxicity. The collective data from an extensive battery of
in vitro and in vivo tests covering all major genetic end-points,
including an in vivo chromosomal aberration assay, show that dithianon
does not pose a genotoxic risk and is not likely to be a genotoxic
carcinogen.
3. Reproductive and developmental toxicity. Results from a 2-
generation reproductive toxicity study in rats show that dithianon is
not a reproductive toxicant. Developmental toxicity studies in rats and
rabbits revealed no evidence of teratogenic effects for fetuses of
either species and no evidence of development effects in the absence of
maternal toxicity. The no observed effect levels (NOELs) for fetal/
developmental toxicity are established at 20 mg/kg/day in rats and 25
mg/kg/day in rabbits. The maternal NOELs are 20 mg/kg/day in rats and
10 mg/kg/day in rabbits. A 2-generation reproduction study in rats
supports a NOEL for fertility/reproductive toxicity of 600 ppm (highest
concentration tested) or 42 mg/kg/day. In the reproduction study, the
parental NOEL was 200 ppm or 15 mg/kg/day.
4. Subchronic toxicity. Short-term exposure of mice and rats to
dithianon technical resulted in slight anemia. Mice also exhibited
hemosiderin deposition in the liver, and rats showed increased kidney
and liver weights and histopathological findings in the kidney (females
only). Short-term exposure of dogs to dithianon resulted in decreased
body weight or weight gain, decreased food consumption, and increased
kidney weight. The NOEL in a 28-day oral study in mice was 100 ppm or
15 mg/kg/day and for rats the NOEL was 315 ppm or 31.5 mg/kg/day. In
90-day oral studies in rats and dogs the NOELs were 180 ppm or 15.5 mg/
kg/day and 200 ppm or 3.0 mg/kg/day, respectively.
5. Chronic toxicity. Findings similar to those observed in short-
term toxicity studies were also apparent in the long-term dietary
toxicity studies conducted in dogs, rats and mice. Pre-neoplastic and
neoplastic lesions were observed in the life-time rat dietary study in
females. However, the collective evidence from this study and special
mechanistic studies showed that these lesions occur due to a
regenerative response of the kidney basophilic tubules, which follow
persistent cellular damage to kidney proximal tubular epithelial cells.
Thus, a threshold for these lesions exists. Moreover, these lesions
were only noted following a 24-month dietary exposure to 600 ppm of
dithianon, a concentration that exceeded the Maximum Tolerated Dose
(MTD), as evidenced by markedly depressed body weight gains in females
as compared to controls. Pre-neoplastic or neoplastic lesions were not
observed in the life-time dietary study in mice, even at a
concentration of dithianon that exceeded the MTD.
In a 1-year chronic toxicity study in dogs, the NOEL was 40 ppm or
1.6 mg/
[[Page 6523]]
kg/day. The NOEL for chronic effects in mice from the 18-month
combined chronic toxicity and oncogenicity study was 20 ppm or 3.0 mg/
kg/day, while the NOEL for potential oncogenic effects was 500 ppm or
75 mg/kg/day, which is the highest concentration tested. In the 24-
month combined chronic toxicity and oncogenicity study in rats, the
NOEL for chronic effects was 20 ppm or 1.0 mg/kg/day. The
carcinogenicity NOEL was 120 ppm for females or 6.0 mg/kg/day.
6. Animal metabolism. The rat and goat metabolism studies indicate
that the qualitative nature of the residues of dithianon in animals is
adequately understood. Elimination of dithianon via excreta is rapid.
The metabolism data suggests that unabsorbed dithianon is broken down
in the gastrointestinal tract, since only very low concentrations of
the unaltered parent were identified in the fecal excreta. A hen
metabolism study is not required, because pome fruits (represented by
apples and pears) and hops are not used as significant feedstuff for
poultry.
In the metabolism studies using radio labeled dithianon,
examination of organs, tissues, and milk indicated that accumulation is
not of concern. Additionally, repeated dosing did not result in the
accumulation of total radioactive residues.
7. Metabolite toxicology. No toxicologically significant
metabolites were detected in plant or animal metabolism studies.
Therefore, toxicology studies with metabolites are not required.
8. Endocrine effects. Collective organ weights and
histopathological findings from the 2-generation rat reproductive
study, as well as from the subchronic and chronic toxicity studies in
three different animal species, demonstrate no apparent estrogenic
effects or treatment-related effects on the endocrine system.
C. Aggregate Exposure
1. Dietary Exposure--i. Food. The Theoretical Maximum Residue
Concentrations (TMRC) of dithianon on or in pome fruits, dried hops,
and processed commodities (apple juice/cider, dried apples and pears,
apple juice concentrate) are:
--0.003419 mg/kg body weight (b.w.)/day for the general U.S.
population.
--0.006417 mg/kg b.w./day for non-nursing infants.
--0.007479 mg/kg b.w./day for children 1 to 6 years of age.
--0.005147 mg/kg b.w./day for children 7 to 12 years of age.
The TMRC for the non-nursing infants group is based on the
assumption that apple sauce, rather than unprocessed apples, would be
eaten by this subpopulation. For the 7 to 12 year old age group, no
consumption data was available for dried pears, so the values for dried
pears from the 1 to 6 year old age group were used for the calculation.
These TMRC values are calculated from the proposed tolerances of 5 ppm
on pome fruits (with a 0.12 ppm residue level calculated for apple
juice), 100 ppm on dried hops, and from food consumption data obtained
from the Agriculture Department's (USDA) Continuing Survey of Food
Intake by Individuals (CSFII) conducted from 1989 to 1992. These
chronic dietary exposure estimates are very conservative, because they
assume that 100% of all apples, pears, and hops for human consumption
are imported. The estimates also assume that all apples, pears, and
hops that are imported are treated with dithianon and that the levels
of residues on the RAC are at the tolerance level.
Dietary exposure to residues of dithianon will be limited to
residues on imported pome fruits, in apple and pear processed
commodities, and in beer. Wet apple pomace is considered as a
significant ruminant feed item, but it is unlikely that apple pomace
would be imported for this use. Apple pomace is not a poultry feed
item. Thus, no residues are expected in poultry or eggs. There are no
other established tolerances for dithianon in the United States, and
there are no registered uses for dithianon on food or feed crops in the
United States.
ii. Drinking water. This proposed tolerance is for imported pome
fruits and dried hops. Since there are no approved uses for dithianon
in the United States, the potential exposure from drinking water is not
relevant to this petition.
2. Non-dietary exposure. This petition is for a tolerance on
imported pome fruits and dried hops. There is no approved use for
dithianon in the United States and none is being sought. Therefore, the
potential for non-dietary exposure is not pertinent to this petition.
D. Cumulative Effects
We are aware of no information to indicate or suggest that any
toxic effects produced by dithianon would be cumulative with those of
any other chemical.
E. Safety Determination
1. U.S. population. The RfD represents the level at or below which
daily aggregate dietary exposure over a lifetime will not pose
appreciable risks to human health. For dithianon, the RfD of 0.01 mg/
kg/b.w./day is based on a NOEL of 20 ppm or 1 mg/kg b.w./day from the
24-month chronic toxicity study in rats and a safety (uncertainty)
factor of 100. A 100-fold safety factor is supported by a threshold
level for the proliferative effects in the kidney, which were only
observed in females following long-term administration of an
excessively toxic dietary concentration of dithianon. Thus, a
quantitative cancer risk assessment is not required.
The chronic dietary exposure of 0.003419 mg/kg b.w./day for the
general U.S. population will utilize 34.2% of the RfD. EPA generally
has no concern for exposures below 100% of the RfD. American Cyanamid
concludes that there is a ``reasonable certainty of no harm'' from
aggregate exposure to dithianon residues. The complete and reliable
toxicity data and the conservative chronic exposure assumptions support
this conclusion.
2. Infants and children. The chronic dietary exposure estimates
presented in Unit C of this document will utilize approximately 64.2%
of the RfD for non-nursing infants less than 1 year old, approximately
74.8% of the RfD for children 1 to 6 years of age, and approximately
51.5% of the RfD for children 7 to 12 years of age. Thus, the
conservative exposure estimates for the subpopulations of infants and
children are all well below the RfD for dithianon.
A 2-generation reproductive toxicity study in rats showed that
dithianon is not a reproductive toxicant. Moreover, no treatment-
related effects on pup development were noted in this study, supporting
a NOEL for developmental effects of 600 ppm (the highest concentration
tested) or approximately 42 mg/kg b.w./day. Results of developmental
toxicity studies in rats and rabbits revealed no evidence of
teratogenic effects for fetuses of either species and no evidence of
development effects in the absence of maternal toxicity, indicating
that dithianon is not selectively toxic to the fetus. These studies
support maternal NOELs of 20 and 10 mg/kg b.w./day for the rat and
rabbit studies, respectively, and developmental NOELs of 20 and 25 mg/
kg b.w./day for the rat and rabbit studies, respectively.
The NOEL used to calculate the RfD for the general U.S. population
is 1 mg/kg b.w./day derived from the 24-month chronic toxicity study in
rats. A NOEL of 1 mg/kg b.w./day is 20 to 42 times lower than the NOELs
for developmental effects from the developmental toxicity and
reproductive toxicity studies.
[[Page 6524]]
Based on the current toxicological data requirements, the database
relative to pre-and post-natal effects for children is complete, valid
and reliable. Collective results from the 2-generation and teratology
studies show no increased sensitivity to developing offspring. Thus, no
increased sensitivity of infants and children to dithianon residues is
anticipated. Therefore, American Cyanamid concludes that an additional
safety (uncertainty) factor is not warranted and the RfD of 0.01 mg/kg
b.w./day, which utilizes a 100-fold safety factor, is appropriate to
ensure a reasonable certainty of no harm to infants and children.
F. International Tolerances
A Maximum Residue Limit (MRL) for dithianon at the level of 5 mg/kg
was established for pome fruits by the 1992 WHO/FAO Joint Meeting on
Pesticide Residues (JMPR). The MRL for pome fruits was raised to step 8
at the Codex Committee on Pesticide Residues (CCPR) meeting in 1996 and
will be approved by the Codex Alimentarius Commission in 1997 for Codex
Maximum Residue Limit (CXL) (final). The 1992 JMPR established an MRL
for dithianon in dried hops of 100 mg/kg. This MRL for dried hops is a
CXL (final).
II. Public Record
EPA invites interested persons to submit comments on this notice of
filing. Comments must bear a notation indicating the docket number [PF-
707].
A record has been established for this notice of filing under
docket number [PF-707] 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 Room 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 ASCII file avoiding the
use of special characters and any form of encryption.
The official record for this notice of filing, 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.
List of Subjects
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: February 3, 1997.
Stephen L. Johnson,
Director, Registration Division, Office of Pesticide Programs.
[FR Doc. 97-3226 Filed 2-11-97; 8:45 am]
BILLING CODE 6560-50-F
