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dimethomorph (Acrobat) Pesticide Petition Filing 2/99



[Federal Register: March 10, 1999 (Volume 64, Number 46)]
[Notices]               
[Page 11874-11879]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr10mr99-80]

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ENVIRONMENTAL PROTECTION AGENCY

[PF-862; FRL-6063-3]

 
Notice of Filing of Pesticide Petitions

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of pesticide 
petitions proposing the establishment of regulations for residues of 
certain pesticide chemicals in or on various food commodities. 
DATES: Comments, identified by the docket control number PF-862, must 
be received on or before April 9, 1999. 
ADDRESSES: By mail submit written comments to: Information and Records 
Integrity Branch, Public Information and Services Divison (7502C), 
Office of Pesticides Programs, Environmental Protection Agency, 401 M 
St., SW., Washington, DC 20460. In person bring comments to: Rm. 119, 
CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically by following 
the instructions under ``SUPPLEMENTARY INFORMATION.'' No confidential 
business information should be submitted through e-mail.
    Information submitted as a comment 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. 119 at the 
address

[[Page 11875]]

given above, from 8:30 a.m. to 4 p.m., Monday through Friday, excluding 
legal holidays.

FOR FURTHER INFORMATION CONTACT: Mary L. Waller, Fungicide Branch, 
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: Rm. 249, Crystal 
Mall #2, 1921 Jefferson Davis Highway, Arlington, VA 22202, (703) 305-
6117; e-mail:waller. mary@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition as 
follows proposing the establishment and/or amendment of regulations for 
residues of certain pesticide chemical in or on various food 
commodities under section 408 of the Federal Food, Drug, and Comestic 
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that this 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.
    The official record for this notice of filing, as well as the 
public version, has been established for this notice of filing under 
docket control number [PF-862] (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 official record is located at the address in 
``ADDRESSES'' at the beginning of this document.
    Electronic comments can 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. Comment and data 
will also be accepted on disks in Wordperfect 5.1/6.1 file format or 
ASCII file format. All comments and data in electronic form must be 
identified by the docket control number [PF-862] and appropriate 
petition number. Electronic comments on this notice may be filed online 
at many Federal Depository Libraries.

List of Subjects

    Environmental protection, Agricultural commodities, Food additives, 
Feed additives, Pesticides and pests, Reporting and recordkeeping 
requirements.

    Dated: February 22, 1999.

James Jones,

Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summaries of the pesticide petitions are printed 
below as required by section 408(d)(3) of the FFDCA. The summary of 
each petition was prepared by the petitioner and represents the views 
of the petitioner. EPA is publishing the petition summaries verbatim 
without editing them in any way. The petition summary announces the 
availability of a description of the analytical methods available to 
EPA for the detection and measurement of the pesticide chemical 
residues or an explanation of why no such method is needed.

1. American Cyanamid Company

PP 7F4816

    EPA has received a pesticide petition (PP 7F4816) from American 
Cyanamid Company, P.O. Box 400 Princeton, NJ 08543-0400 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 dimethomorph, (E,Z)4-[3-(4-chlorophenyl)-3-
(3,4-dimethoxyphenyl)-1-oxo-2-propenyl]morpholine in or on the raw 
agricultural commodity cereal grains (Crop Group 15) and forage of 
cereal grain crops (Crop Group 16) at 0.05 parts per million (ppm) and 
fodder and straw of cereal grain crops (Crop Group 16) at 0.10 ppm. 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.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of dimethomorph in plants is 
adequately understood for the purposes of these tolerances. A 
rotational crop study showed the potential for indirect or inadvertent 
residues of dimethomorph in or on commodities of cereal crops.
    2. Analytical method. There is a practical method for measuring 
0.050 ppm of dimethomorph in or on commodities of cereal crops. This 
gas chromatography method with nitrogen-phosphorus detection (M3112) is 
appropriate for enforcement purposes. Confirmation of residues is 
provided by liquid chromatography/mass spectroscropy of the final 
extract of this method.
    3. Magnitude of residues. The magnitude of residue studies were 
conducted for wheat as a rotational crop to potatoes treated at 1.4 x 
the maximum labeled rate. Residues found in these studies were below 
the level of quantitation (LOQ) in the forage and grain samples from 
all six trials and in the hay, and straw samples from four of the 
trials. The maximum observed residue (sample means) was 0.057 ppm for 
hay, and 0.086 ppm for straw for the other two trials. Therefore, at 
the maximum labeled rate, residues of dimethomorph in or on hay are 
expected to be below the LOQ (< 0.05 ppm) and residues in or on straw 
are expected to be less than 0.10 ppm.

B. Toxicological Profile

    1. Acute toxicity. An acute oral toxicity study in the Sprague-
Dawley rat for dimethomorph technical with a LD<INF>50</INF> of 4,300 
milligram per kilogram bodyweight (mg/kg 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. Oral LD<INF>50</INF> studies were conducted on the two 
isomers (E and Z) alone: An acute oral toxicity study in the Wistar rat 
for the E-isomer with a LD<INF>50</INF> greater than 5,000 mg/kg bwt 
for males and approximately 5,000 mg/kg bwt for females. An acute oral 
toxicity study in the Wistar rat for the Z-isomer with a 
LD<INF>50</INF> greater than 5,000 mg/kg bwt for both males and 
females. An acute dermal toxicity study in the Wistar rat for 
dimethomorph technical with a dermal LD<INF>50</INF> 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. A 4-hour inhalation study in 
Wistar rats for dimethomorph technical with a LC<INF>50</INF> greater 
than 4.2 milligram per liter (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. Genotoxicty. Salmonella reverse gene mutation assays (2 studies) 
were negative up to a limit dose of 5,000 <greek-m>g/plate. Chinese 
hamster lung cells were negative in V79 cells up to toxic doses in 2 
studies. Two Chinese hamster lung structural chromosomal studies were

[[Page 11876]]

reportedly positive for chromosomal aberrations at the highest dose 
tested (HDT) (160 <greek-m>g/ml/-S9; 170 <greek-m>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. Structural Chromosomal 
Aberration studies were weakly positive, in human lymphocyte cultures, 
but only in S9 activated cultures treated at the HDT (422 <greek-m>g/
ml) which was strongly cytotoxic. Dimethomorph was negative in the 
absence of activation at all doses and the positive in human lymphocyte 
cultures was only in S9 activated cultures treated at the HDT (422 
<greek-m>g/ml) which was strongly cytotoxic. Dimethomorph was negative 
in the absence of activation at all doses and the positive clastogenic 
response observed under the in vitro conditions was not confirmed in 
two in vivo micronucleus assays. 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. Dimethomorph was negative for inducing 
unscheduled DNA synthesis in cultured rat liver cells at doses up to 
250 <greek-m>/ml, a weak cytotoxic level. Dimethomorph was negative for 
transformation in Syrian hamster embryo cells treated in the presence 
and absence of activation up to cytotoxic concentrations (265 
<greek-m>g/ml/+S9; 50 <greek-m>g/ml-S9).
    3. Reproductive and developmental toxicity. A rat developmental 
toxicity study with a maternal toxicity lowest-observed-adverse-effect 
Level (LOAEL) of 160 mg/kg/day and a maternal toxicity no-observed 
adverse-effect level (NOAEL) of 60 mg/kg/day. The NOAEL for 
developmental toxicity is 60 mg/kg/day. Dimethomorph is not teratogenic 
in the Sprague-Dawley rat. A rabbit development toxicity study with 
parental LOAEL for systemic toxicity of 80 mg/kg/day, and a NOAEL of 24 
mg/kg/day. The NOAEL for fertility and reproductive function was 80 mg/
kg/day, the HDT.
    4. Subchronic toxicity A 90-day dog dietary study in Sprague-Dawley 
rats with a NOAEL of greater than or equal to 73 mg/kg/day in males and 
82 mg/kg/day in females, the HDT. A 90-day dog dietary study with a 
NOAEL 15 mg/kg/day, and a LOAEL of 43 mg/kg/day.
    5. Chronic toxicity. A 2-year oncogenicity study in Sprague-Dawley 
rats with a NOAEL for systemic toxicity of 9 mg/kg/day for males and 12 
mg/kg/day for females. The LOAEL for systemic toxicity is 36 mg/kg/day 
for males and 58 mg/kg/day for females. A 1-year chronic toxicity study 
in dogs with a NOAEL of 14.7 mg/kg/day and a LOAEL of 44.6 mg/kg/day. A 
2-year oncogenicity study in Sprague-Dawley rats with a NOAEL for 
systemic toxicity of 9 mg/kg/day for males and 11 mg/kg/day for 
females. The LOAEL for system 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 NOAEL for oncogenicity is 
95 mg/kg/day for males and 132 mg/kg/day for females, the HDT. A 2-year 
oncogenicity study in mice with a NOAEL for systemic toxicity of 100 
mg/kg/day, and LOAEL of 1,000 mg/kg/day. There was no evidence of 
increased incidence of neoplastic lesions in treated animals. The NOAEL 
for oncogenicity is 1,000 mg/kg/day, the HDT.
    6. Animal metabolism. Results from 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 
plant or animal commodities which require regulation.
    8. Endocrine disruption. 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 exposure. Dietary exposure should be based upon the 
Theoretical Maximum Residue Concentration (TMRC) from the established 
tolerances for residues of dimethomorph at 0.05 ppm in or on potato; 
for the proposed tolerances for residues of dimethomorph at 2.0 ppm in 
or on grapes; and 0.15 ppm on potatoes wet peel; for the proposed 
tolerances for indirect and inadvertent residues of dimethomorph at 
0.05 ppm in or on cereal grains, and in or on fodder and straw of 
cereal grain crops, and from the time-limited tolerances (i.e. at 1.0 
ppm for cantaloupes, cucumbers, squash, and watermelons) which were 
established under Section 18 emergency exempt ions and which are not 
due to expire at or near completion of this regulatory action.
    i. Food. The goat and poultry metabolism studies demonstrate that 
there is no reasonable expectation of transfer of residues to meat, 
milk, poultry, or eggs from potato, grape, and cereal crop commodities. 
Therefore, no consumption data associated with meat, milk, poultry or 
eggs should be included in the calculation of the TMRC. Except for the 
permanent tolerances on potato tubers, there are no other permanent 
U.S. tolerances for dimethomorph.
    ii. Drinking water. The predicted dimethomorph surface and ground 
water concentrations are well below the drinking water level of 
concern. Using the SCI-GROW model to generate the Estimated 
Environmental Concentration (EEC) of dimethomorph residues in ground 
water, the projected EEC is 0.26 parts per billion (ppb). Using the 
Generic Estimated Environmental Concentration (GENEEC) model to 
estimate acute and chronic EECs of dimethomorph residues in surface 
water, the projected EEC ranged from a peak of 28 ppb to a 56 day 
concentration of 24 ppb. The level of concern for chronic exposure to 
residues of dimethomorph range from 960 ppb for children 1-6 years old 
to 3,400 ppb for the U.S. population and males 13 years and older. 
Therefore, American Cyanamid believes that exposure from water is below 
the level of concern for all of the populations examined. In addition, 
American Cyanamid believes that the aggregate (food, and water) chronic 
exposure for infants, children, and adults does not exceed the level of 
concern and adverse health effects from chronic exposure to 
dimethomorph in food, and water are not expected in these populations.
    2. Non-dietary exposure. In the United States, dimethomorph is 
registered only for use on potatoes. 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

[[Page 11877]]

petition do not indicate that dimethomorph is a particularly toxic 
compound.

E. Safety Determination

    1. U.S. population. The established reference dose (RfD) is 0.1 mg/
kg bwt/day, based on a NOAEL of 10 mg/kg bwt/day from a 2-year dietary 
toxicity study in rats that demonstrated decreased bwt, and liver foci 
in females. The established RfD is also based on an uncertainty factor 
of 100. The TMRC from the established tolerances for residues in or on 
potato along with the current Section 18 time-limited tolerances 
(cantaloupes, watermelons, cucumbers, and squash, as well as expiring 
tolerances for tomato commodities) utilizes less than 4% of the RfD for 
all population subgroups. The TMRC for grapes and cereal grains is not 
expected to cause the RfD to be exceeded.
    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 NOAELs observed in the developmental and 
reproductive studies were 6 to 65 times higher than the NOAEL (10 mg/kg 
bwt/day) used to establish the RfD. 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 Tolerances

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

 [FR Doc. 99-5823 Filed 3-9-99; 8:45 am]
BILLING CODE 6560-50-F