[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]


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ENVIRONMENTAL PROTECTION AGENCY
[PF-707; FRL-5587-2]


American Cyanamid Company; Pesticide Tolerance Petition Filing

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice of filing.

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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 protected]. 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: [email protected].

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:
    [email protected]


    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