dimethomorph (Acrobat) Pesticide Petition Filing 2/99
[Federal Register: March 10, 1999 (Volume 64, Number 46)]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
ENVIRONMENTAL PROTECTION AGENCY
Notice of Filing of Pesticide Petitions
AGENCY: Environmental Protection Agency (EPA).
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
given above, from 8:30 a.m. to 4 p.m., Monday through Friday, excluding
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. email@example.com.
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:
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
Dated: February 22, 1999.
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
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-
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
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
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
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
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