dithianon (Delan) Pesticide Tolerance Petition Filing 2/97
[Federal Register: February 12, 1997 (Volume 62, Number 29)] [Notices]
ENVIRONMENTAL PROTECTION AGENCY
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: email@example.com. 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-
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
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
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
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,
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/
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
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
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
--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
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
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
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.
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: firstname.lastname@example.org
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]