[Federal Register Volume 62, Number 58 (Wednesday, March 26, 1997)]
[Notices]
[Pages 14418-14421]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-7494]


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ENVIRONMENTAL PROTECTION AGENCY
[PF-724; FRL-5594-7]


American Cyanamid Company; Pesticide Tolerance Petition Filing

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the filing of a pesticide petition 
proposing the establishment of a tolerance for residues of dimethomorph 
[(E,Z)4-[3-(4-chlorophenyl)-3-(3,4-dimethoxyphenyl)-1-oxo-2-propenyl]-
morpholine] in or on the raw agricultural commodity potatoes and grape 
commodities. This notice contains a summary of the petition that was 
prepared by the petitioner, American Cyanamid Company.

DATES: Comments, identified by the docket control number [PF-724], must 
be received on or before April 25, 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 be sending 
electronic mail (e-mail) to: [email protected]. 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 
docket control number [PF-724]. 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 a 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: Connie B. Welch, Product 
Manager (PM) 21, Registration Division (7505W), Office of Pesticide 
Programs, Environmental Protection Agency, 401 M St., SW., Washington, 
DC 20460. Office location, telephone number, and e-mail address: Rm. 
227, CM #2, 1921 Jefferson Davis Highway, Arlington, VA, (703) 305-
6226; e-mail: [email protected].

SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition (PP 
7F4816) from American Cyanamid Company, Agricultural Products Research 
Division, P.O. Box 400 Princeton, NJ 08543-0400 proposing pursuant to 
section 408(d) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 
section 346a, to amend 40 CFR part 180 by establishing tolerances for 
residues of the fungicide, dimethomorph [(E,Z)4-[3-(4-chlorophenyl)-3-
(3,4-dimethoxyphenyl)-1-oxo-2-propenyl]-morpholine] in or on the raw 
agricultural commodity potato at 0.05 parts per million (ppm) and a 
time-limited tolerance for residues of dimethomorph in or on the raw 
agricultural commodity grape at 2.0 ppm. The proposed analytical method 
for determining residues is a High Performance Liquid Chromatography 
(HPLC) method (FAMS 002-04). A confirmatory method (FAMS 022-03) also 
is available which provides for analysis by either Gas Chromatography/
Nitrogen-Phosphorus Detection or by HPLC/UV Detection. EPA has 
determined that the petition contains data or information regarding the 
elements set forth in section 408(d)(2); 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, (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), 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.

[[Page 14419]]

I. Petition Summary Prepared by American Cyanamid Company

A. Residue Chemistry

    1. Plant metabolism. American Cyanamid believes that the results of 
the potato metabolism study show only negligible residues in tubers, 
0.01-0.02 ppm total radioactive residues (TRR). This is in contrast to 
the aerial portions of the plant which were found to have up to 23.5 
parts per million (ppm) TRR, thus demonstrating that translocation of 
dimethomorph within the plant was not significant. Almost all of the 
radioactive residue (97.8%) was extractable from the plant at harvest. 
In the aerial portion of the plant, approximately 70% of the TRR was 
identified as dimethomorph. No metabolites were identified that require 
regulation. There was no concentration of residue in the peel or tuber. 
The latter point indicates that during processing dimethomorph is not 
expected to concentrate to a level greater than that of the proposed 
tolerance for the raw agricultural commodity, potato tubers.
    The results of the grape metabolism study showed that the TRR in/on 
grapes harvested 35 days following the last of four applications (0.8 
lb active ingredient/application (ai/A) for 4 consecutive weeks) for a 
total rate of 3.2 lb ai/A (3x the proposed maximum seasonal rate) was 
14.6 ppm. Unmetabolized dimethomorph accounted for 87.3% of the TRR 
(12.7 ppm). No metabolites were identified that require regulation.
    2. Analytical method. A reliable method for the determination of 
dimethomorph residues in potatoes and grapes exists. This method (FAMS 
002-04) is appropriate for enforcement purposes. FAMS 002-04 is a HPLC 
method. A confirmatory method (FAMS 022-03) also is available which 
provides for analysis by either Gas Chromatography with Nitrogen-
Phosphorus Detection or by HPLC with UV Detection.
    3. Magnitude of residues. The residue data for potato submitted to 
support this tolerance petition were collected from studies conducted 
in several European countries; these countries are representative of 
potato growing regions of the U.S. Dimethomorph residues observed in 
these field residue studies ranged from <0.01 ppm (the Limit of 
Quantitation of the method) to 0.04 ppm; however, most residues were 
<0.01 ppm. These trials were conducted using multiple applications (5-
12) with a maximum seasonal rate of up to 2.56 lb ai/A. The proposed 
U.S. use pattern is five applications at a maximum treatment rate of 
0.203 lb ai/A and a maximum seasonal use rate of 1.015 lb ai/A. Residue 
levels in domestic potatoes would be expected to be similar or lower (< 
0.01 ppm) than that observed in the European trials. Therefore, a 
tolerance of 0.05 ppm is appropriate.
    The residue data for grape submitted to support this tolerance 
petition were collected from studies conducted in various regions of 
France; these sites are representative of grape growing regions of 
Europe. Dimethomorph residues observed in these field residue studies 
ranged from <0.01 ppm (the Limit of Quantitation of the method) to 1.81 
ppm. These trials were conducted using multiple applications (3-11) 
with a maximum seasonal rate of up to 2.94 lb ai/A. In six studies 
conducted on the magnitude of residue in grape processed commodities, 
residues of dimethomorph did not concentrate in grape juice or wine. 
Therefore, a time-limited tolerance of 2.0 ppm in/on grape commodities 
is appropriate.

B. Toxicological Profile

    American Cyanamid believes that the toxicity of dimethomorph has 
been studied extensively and there is a complete data base to address 
the acute and chronic effects, effects on genetic material, the 
potential for carcinogenicity or teratogenicity, and effects on 
reproductive performance or growth of offspring.
    The toxicological data submitted to support the petition for a 
tolerance for dimethomorph on potatoes and for a time-limited tolerance 
on grape include:
    1. Acute toxicity. i. An acute oral toxicity study in the Sprague-
Dawley rat for dimethomorph technical with a LD50 of 4,300 
milligrams/kilograms (mg/kg) body weight (bwt) for males and 3,500 mg/
kg bwt for females. Based upon EPA toxicity criteria, the acute oral 
toxicity category for dimethomorph technical is Category III or 
slightly toxic.
    ii. Oral LD50 studies were conducted on the two isomers (E and 
Z) alone:
    a. An acute oral toxicity study in the Wistar rat for the E-isomer 
with a LD50 greater than 5,000 mg/kg bwt for males and 
approximately 5,000 mg/kg bwt for females.
    b. An acute oral toxicity study in the Wistar rat for the Z-isomer 
with a LD50 greater than 5,000 mg/kg bwt for both males and 
females.
    iii. An acute dermal toxicity study in the Wistar rat for 
dimethomorph technical with a dermal LD50 greater than 5,000 mg/kg 
bwt for both males and females. Based on the EPA toxicity category 
criteria, the acute dermal toxicity category for dimethomorph is 
Category IV or relatively non-toxic.
    iv. A 4-hour inhalation study in Wistar rats for dimethomorph 
technical with a LC50 greater than 4.2 mg/L for both males and 
females. Based on the EPA toxicity category criteria, the acute 
inhalation toxicity category for dimethomorph technical is Category IV 
or relatively non-toxic.
    2. Genotoxicity. i. Salmonella reverse gene mutation assays (2 
studies) were negative up to a limit dose of 5,000 g/plate. 
Chinese hamster lung cells were negative in V79 cells up to toxic doses 
in 2 studies.
    ii. Two Chinese hamster lung structural chromosomal studies were 
reportedly positive for chromosomal aberrations at the highest dose 
tested (HDT) (160 g/ml/-S9; 170 g/ml/+S9). 
Dimethomorph induced only a weak response in increasing chromosome 
aberrations in this test system. These results were not confirmed in 
two micronucleus tests under in vivo conditions.
    iii. Structural Chromosomal Aberration studies were weakly 
positive, in human lymphocyte cultures, but only in S9 activated 
cultures treated at the HDT (422 g/ml) which was strongly 
cytotoxic. Dimethomorph was negative in the absence of activation at 
all doses. Furthermore, the positive clastogenic response observed 
under the in vitro conditions was not confirmed in two in vivo 
micronucleus assays.
    iv. Micronucleus assay (2 studies) indicated that dimethomorph was 
negative for inducing micronuclei in bone marrow cells of mice 
following i.p. administration of doses up to 200 mg/kg or oral doses up 
to the limit dose of 5,000 mg/kg. Thus, dimethomorph was found to be 
negative in these studies for causing cytogenic damage in vivo.
    v. Dimethomorph was negative for inducing unscheduled DNA 
synthesis, in cultured rat liver cells, at doses up to 250 g/
ml, a weakly cytotoxic level.
    vi. Dimethomorph was negative for transformation in Syrian hamster 
embryo cells treated, in the presence and absence of activation, up to 
cytotoxic concentrations (265 g/ml/+S9; 50 g/ml/-S9).
    3. Reproductive and developmental toxicity. i. A rat developmental 
toxicity study with a maternal toxicity Lowest-Observed-Effect Level 
(LOEL) of 160 mg/kg/day and a maternal toxicity No-Observed-Effect 
Level (NOEL) of 60 mg/kg/day. The NOEL for developmental toxicity is 60 
mg/kg/day. Dimethomorph is not teratogenic in the Sprague-Dawley rat.
    ii. A rabbit development toxicity study with maternal toxicity LOEL 
of 650 mg/kg/day and a NOEL of 300 mg/kg/day. The NOEL for 
developmental

[[Page 14420]]

toxicity is 650 mg/kg/day, the highest dose tested. Dimethomorph is not 
teratogenic in the New Zealand white rabbit.
    iii. A multi-generational rat reproduction study with parental LOEL 
for systemic toxicity of 80 mg/kg/day and a NOEL of 24 mg/kg/day. The 
NOEL for fertility and reproductive function was 80 mg/kg/day, the 
highest dose tested.
    4. Subchronic toxicity. i. A 90-day dietary study in Sprague-Dawley 
rats with a NOEL of greater than or equal to 73 mg/kg/day in males and 
82 mg/kg/day in females, the highest doses tested.
    ii. A 90-day dog dietary study with a NOEL 15 mg/kg/day and a LOEL 
43 mg/kg/day.
    5. Chronic toxicity. i. A 2-year chronic toxicity study in Sprague-
Dawley rats with a NOEL 9 mg/kg/day for males and 12 mg/kg/day for 
females. The LOEL for systemic toxicity is 36 mg/kg/day for males and 
58 mg/kg/day for females.
    ii. A 1-year chronic toxicity study in dogs with a NOEL of 14.7 mg/
kg/day and a LOEL of 44.6 mg/kg/day.
    iii. A 2-year oncogenicity study in Sprague-Dawley rats with a NOEL 
for systemic toxicity of 9 mg/kg/day for males and 11 mg/kg/day for 
females. The LOEL for systemic toxicity was 34 mg/kg/day for males and 
46 mg/kg/day for females. There was no evidence of increased incidence 
of neoplastic lesions in treated animals. The NOEL for oncogenicity is 
95 mg/kg/day for males and 132 mg/kg/day for females, the highest dose 
tested.
    iv. A 2-year oncogenicity study in mice with a NOEL for systemic 
toxicity of 100 mg/kg/day and a LOEL of 1,000 mg/kg/day. There was no 
evidence of increased incidence of neoplastic lesions in treated 
animals. The NOEL for oncogenicity is 1,000 mg/kg/day, the highest dose 
tested.
    6. Animal metabolism. Results from the livestock and rat metabolism 
studies show that orally administered dimethomorph was rapidly excreted 
by the animals. The principal route of elimination is the feces.
    7. Metabolite toxicology. There were no metabolites identified in 
potatoes or animal commodities which require regulation.
    8. Endocrine effects. There is no evidence of effects of 
dimethomorph on the endocrine system. There were no changes noted in 
organ weights for the pituitary, thyroid, ovaries or testes. There was 
no increased incidence of mammary tumors observed. No effects on 
fertility or reproduction were noted and there was no evidence of 
related histopathological changes in reproductive or endocrine system 
organs.

C. Aggregate Exposure

    1. Dietary (food) exposure. Dietary exposure should be based solely 
upon the Theoretical Maximum Residue Concentration (TMRC) from the 
tolerance of 0.05 ppm dimethomorph in or on potato and the time-limited 
tolerance of 2.0 ppm dimethomorph in or on grape. The goat metabolism 
study demonstrates that there is no reasonable expectation of transfer 
of residues of dimethomorph to meat or milk from potatoes or from 
grapes. There are no potato or grape feed commodities fed to poultry. 
Therefore, no consumption data associated with meat, milk, poultry or 
eggs should be included in the calculation of the TMRC. There are no 
other established U.S. tolerances for dimethomorph, and there are no 
registered uses for dimethomorph on food or feed crops in the United 
States.
    2. Dietary (drinking water) exposure. There is no available 
information about dimethomorph exposure via drinking water. However, 
exposure to dimethomorph from drinking water is not likely to occur as 
a result of use on potatoes. Dimethomorph dissipated fairly rapidly 
under field conditions with half lives ranging from 14 to 57 days. 
Laboratory and field studies demonstrate that dimethomorph is not 
mobile in soil. No movement below the top 4 inches was observed in the 
field studies. Laboratory leaching studies result in the classification 
of dimethomorph as having medium to high adsorption onto soil.
    3. Non-dietary exposure. There are no other registered uses of 
dimethomorph in the U.S. Thus, there is no potential for non-dietary 
exposure.

D. Cumulative Effects

    There is no information to indicate that any toxic effects produced 
by dimethomorph would be cumulative with those of any other chemical. 
The fungicidal mode of action of dimethomorph is unique; dimethomorph 
inhibits cell wall formation only in Oomycete fungi. The result is 
lysis of the cell wall which kills growing cells and inhibits spore 
formation in mature hyphae. This unique mode of action and limited pest 
spectrum suggest that there is little or no potential for cumulative 
toxic effects in mammals. In addition, the toxicity studies submitted 
to support this petition do not indicate that dimethomorph is a 
particularly toxic compound. No toxic end-points of potential concern 
were identified.

E. Safety Determination

    1. U.S. population. The proposed reference dose (RfD) is 0.1 mg/kg 
bwt/day, based on a NOEL of 10 mg/kg bwt/day from a 2-year dietary 
toxicity study in rats that demonstrated decreased body weight and 
liver foci in females. The proposed RfD is also based on an uncertainty 
factor of 100. For potatoes, the TMRC from this proposed action is 
estimated at 0.000057 mg/kg bwt/day. This represents an aggregate 
exposure to the general population of the United States of 0.063 
percent of the RfD. The TMRC for the most highly exposed group, 
children ages 1 to 6 is estimated at 0.000113 mg/kg bwt/day. This 
represents 0.125 percent of the RfD. Establishment of a tolerance for 
residues in/on grape commodities is not expected to significantly 
change the exposure estimate to the most highly exposed group since the 
commodity which is most extensively imported is wine. Since EPA 
generally has no concern for exposures below 100 percent of the RfD, 
EPA should conclude that there is a reasonable certainty that no harm 
will result from aggregate exposure to dimethomorph residues in or on 
potato and grape commodities.
    2. Infants and children. American Cyanamid believes that the 
results of the studies submitted to support this package provide no 
evidence that dimethomorph caused reproductive, developmental or 
fetotoxic effects. No such effects were noted at dose levels which were 
not maternally toxic. The NOELs observed in the developmental and 
reproductive studies were 6 to 65 times higher than the NOEL used to 
establish the proposed RfD (10 mg/kg bw/day). There is no evidence to 
indicate that children or infants would be more sensitive than adults 
to toxic effects caused by exposure to dimethomorph.

F. International Issues

    No Codex maximum residue levels (MRLs) have been established for 
dimethomorph to date.

II. Public Record

    A record has been established for this notice under docket control 
number [PF-724] (including comments and data submitted electronically 
as described below). A public version of the 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

[[Page 14421]]

Public Response and 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 an ASCII file avoiding the 
use of special characters and any form of encryption.
    The official record for this rulemaking, 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 rulemaking 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.

    Dated: March 18, 1997.
Stephen L. Johnson,
Director, Registration Division, Office of Pesticide Programs.

[FR Doc. 97-7494 Filed 3-25-97; 8:45 am]
BILLING CODE 6560-50-F