dimethomorph (Acrobat) Pesticide Petition Filing 2/00
[Federal Register: March 8, 2000 (Volume 65, Number 46)]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
ENVIRONMENTAL PROTECTION AGENCY
Notice of Filing a Pesticide Petition to Establish a Tolerance
for Certain Pesticide Chemicals in or on Food
AGENCY: Environmental Protection Agency (EPA).
SUMMARY: This notice announces the initial filing of a pesticide
petition proposing the establishment of regulations for residues of a
certain pesticide chemical in or on various food commodities.
DATES: Comments, identified by docket control number PF-918, must be
received on or before April 7, 2000.
ADDRESSES: Comments may be submitted by mail, electronically, or in
person. Please follow the detailed instructions for each method as
provided in Unit I.C. of the ``SUPPLEMENTARY INFORMATION.'' To ensure
proper receipt by EPA, it is imperative that you identify docket
control number PF-918 in the subject line on the first page of your
FOR FURTHER INFORMATION CONTACT: By mail: Mary Waller, Product Manager
(21), Registration Division (7505C), Office of Pesticide Programs,
Environmental Protection Agency, Ariel Rios Bldg., 1200 Pennsylvania
Ave., NW., Washington, DC 20460; telephone number: (703) 308-9354; e-
mail address: email@example.com.
I. General Information
A. Does this Action Apply to Me?
You may be affected by this action if you are an agricultural
producer, food manufacturer or pesticide manufacturer. Potentially
affected categories and entities may include, but are not limited to:
Categories NAICS potentially
Industry 111 Crop production
112 Animal production
311 Food manufacturing
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in the table could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether or not this action might apply to certain entities. If you have
questions regarding the applicability of this action to a particular
entity, consult the person listed under ``FOR FURTHER INFORMATION
B. How Can I Get Additional Information, Including Copies of this
Document and Other Related Documents?
1. Electronically. You may obtain electronic copies of this
document, and certain other related documents that might be available
electronically, from the EPA Internet Home Page at http://www.epa.gov/.
To access this document, on the Home Page select ``Laws and
Regulations'' and then look up the entry for this document under the
``Federal Register--Environmental Documents.'' You can also go directly
to the Federal Register listings at http://www.epa.gov/fedrgstr/.
2. In person. The Agency has established an official record for
this action under docket control number PF-918. The official record
consists of the documents specifically referenced in this action, any
public comments received during an applicable comment period, and other
information related to this action, including any information claimed
as confidential business information (CBI). This official record
includes the documents that are physically located in the docket, as
well as the documents that are referenced in those documents. The
public version of the official record does not include any information
claimed as CBI. The public version of the official record, which
includes printed, paper versions of any electronic comments submitted
during an applicable comment period, is available for inspection in the
Public Information and Records Integrity Branch (PIRIB), Rm. 119,
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
PIRIB telephone number is (703) 305-5805.
C. How and to Whom Do I Submit Comments?
You may submit comments through the mail, in person, or
electronically. To ensure proper receipt by EPA, it is imperative that
you identify docket control number PF-918 in the subject line on the
first page of your response.
1. By mail. Submit your comments to: Public Information and Records
Integrity Branch (PIRIB), Information Resources and Services Division
(7502C), Office of Pesticide Programs (OPP), Environmental Protection
Agency, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW., Washington, DC
2. In person or by courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Information Resources
Division (7502C), Office of Pesticide Programs (OPP), Environmental
Protection Agency, Rm. 119, Crystal Mall #2, 1921 Jefferson Davis
Highway, Arlington, VA. The PIRIB is open from 8:30 a.m. to 4 p.m.,
Monday through Friday, excluding legal holidays. The PIRIB telephone
number is (703) 305-5805.
3.Electronically. You may submit your comments electronically by e-
mail to: ``firstname.lastname@example.org,'' or you can submit a computer disk as
described above. Do not submit any information electronically that you
consider to be CBI. Avoid the use of special characters and any form of
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be
identified by docket control number PF-918. Electronic comments may
also be filed online at many Federal Depository Libraries.
D. How Should I Handle CBI That I Want to Submit to the Agency?
Do not submit any information electronically that you consider to
be CBI. You may claim information that you submit to EPA in response to
this document as CBI by marking any part or all of that information as
CBI. Information so marked will not be disclosed except in accordance
with procedures set forth in 40 CFR part 2. In addition to one complete
version of the comment that includes any information claimed as CBI, a
copy of the comment that does not contain the information claimed as
CBI must be submitted for inclusion in the public version of the
official record. Information not marked confidential will be included
in the public version of the official record without prior notice. If
you have any questions about CBI or the procedures for claiming CBI,
please consult the person identified under ``FOR FURTHER INFORMATION
E. What Should I Consider as I Prepare My Comments for EPA?
You may find the following suggestions helpful for preparing your
1. Explain your views as clearly as possible.
2. Describe any assumptions that you used.
3. Provide copies of any technical information and/or data you used
that support your views.
4. If you estimate potential burden or costs, explain how you
arrived at the estimate that you provide.
5. Provide specific examples to illustrate your concerns.
6. Make sure to submit your comments by the deadline in this
7. To ensure proper receipt by EPA, be sure to identify the docket
control number assigned to this action in the subject line on the first
page of your response. You may also provide the name, date, and Federal
II. What Action is the Agency Taking?
EPA has received a pesticide petition as follows proposing the
establishment and/or amendment of regulations for residues of a 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.
List of Subjects
Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
Dated: February 21, 2000.
Director, Registration Division, Office of Pesticide Programs.
Summary of Petition
The petitioner summary of the pesticide petition is printed below
as required by section 408(d)(3) of the FFDCA. The summary of the
petition was prepared by the petitioner and represents the view of the
petitioner. EPA is publishing the petition summary verbatim without
editing it 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.
American Cyanamid Company
EPA has received a pesticide petition (8F4946) 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 imported
raw agricultural commodities (RAC) of dried hops cones at 45 parts per
million (ppm); and on the RAC of tomato fruit at 0.50 ppm and in or on
the processed commodities of tomato puree at 0.50 ppm and tomato paste
at 1.50 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
A. Residue Chemistry
1. Plant metabolism. American Cyanamid believes that the nature of
the residues in hops and tomatoes is considered to be understood. This
belief is based upon the results of the metabolism studies conducted on
potato, grape, and lettuce. 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 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.
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 per acre (ai/acre) per application for four
consecutive weeks for a total rate of 3.2 lb ai/acre (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.
The results of the lettuce metabolism study showed that the TRR in/
on lettuce leaves harvested 4 days following the last of four
applications approximately 1.0 lb ai/acre per application with a 9 to
11-day spray interval, for a total rate of 4.1 lb ai/acre, was 102 ppm.
Of this total residue, 98.5% was extractable and unmetabolized
dimethomorph accounted for greater than 93% of the extractable TRR. No
metabolites were identified that require regulation.
2. Analytical method. A reliable method for the determination of
dimethomorph residues in hops and
tomatoes exists; this method is the FDA Multi-Residue Method, Protocol
D, as published in the Pesticide Analytical Manual I.
3. Magnitude of residues. The residue data for hops submitted to
support this tolerance petition were taken from studies conducted in
Germany. Dimethomorph residues observed in dried hops cones collected
from these field studies ranged from 4.3 ppm to 42.0 ppm. These trials
were conducted using four applications of dimethomorph with a maximum
seasonal rate of 1.82 lb ai/acre. Therefore, a tolerance of 45.0 ppm is
The residue data for tomatoes submitted to support this tolerance
petition were collected from 16 studies conducted in tomato-producing
regions of the United States. Trials were conducted using multiple
applications (6-7) of dimethomorph with a maximum seasonal rate of up
to 1.4 lb ai/acre (1.4x the proposed label rate). Dimethomorph residues
observed in these field trials ranged from 0.05 ppm to 0.55 ppm
immediately after harvest. In a study on the magnitude of residue in
tomato processed commodities, residues of dimethomorph did not
concentrate in any fraction except in paste (3x). Therefore, tolerances
of 0.50 ppm in/on tomato fruit, 0.50 ppm in/on tomato puree, and 1.50
ppm in/on tomato paste are proposed.
B. Toxicological Profile
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 body weight (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
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
iii. An acute dermal toxicity study in the Wistar rat for
dimethomorph technical with 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 milligrams/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. Genotoxicity--i. Salmonella reverse gene mutation assays (2
studies) were negative up to a limit dose of 5,000 g/plate.
Chinese hamster (CH) lung V79 cells were negative up to toxic doses in
ii. Two CH 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 lymphocytic cultures, but only in S9 activated cultures
treated at 422 g/mL HDT, which was strongly cytotoxic. No
increase in chromosomal aberrations was observed in the absence of S9
activation at all doses. Furthermore, the positive clastogenic response
observed under the in vitro conditions was not confirmed in two in vivo
iv. Micronucleus assay (two 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
(UDS), 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 lowest observed adverse effect level (LOAEL) for
maternal toxicity of 160 mg/kg/day and a no observed adverse effect
level (NOAEL) for maternal toxicity of 60 mg/kg/day. The NOAEL for
developmental toxicity is 60 mg/kg/day. Dimethomorph is not teratogenic
in the Sprague-Dawley rat.
ii. A rabbit developmental toxicity study with a LOAEL for maternal
toxicity of 650 mg/kg/day and a NOAEL for maternal toxicity of 300 mg/
kg/day. The NOAEL for developmental toxicity is 650 mg/kg/day HDT.
Dimethomorph is not teratogenic in the New Zealand white rabbit.
iii. A 2-generation rat reproduction study with a LOAEL for
parental systemic toxicity of 1,000 ppm (80 mg/kg/day) and a NOAEL for
parental systemic toxicity of 300 ppm (24 mg/kg/day). The NOAEL for
fertility and reproductive function was 1,000 ppm (80 mg/kg bwt/day)
4. Subchronic toxicity--i. A 90-day dietary study in Sprague-Dawley
rats with a NOAEL of greater than or equal to 1,000 ppm HDT (73 mg/kg/
day) for males and 82 mg/kg/day for females.
ii. A 90-day dog dietary study with a NOAEL 450 ppm (15 mg/kg/day)
and a LOAEL 1,350 ppm (43 mg/kg/day).
5. Chronic toxicity--i. A 2-year chronic toxicity study in Sprague-
Dawley rats with a NOAEL of 200 ppm (9 mg/kg/day for males and 12 mg/
kg/day for females). The LOAEL for systemic toxicity is 750 ppm (36 mg/
kg/day for males and 58 mg/kg/day for females).
ii. A 1 year chronic toxicity study in dogs with a NOAEL of 450 ppm
(14.7 mg/kg/day) and a LOAEL of 1,350 ppm (44.6 mg/kg/day).
iii. A 2-year oncogenicity study in Sprague-Dawley rats with a
NOAEL for systemic toxicity of 200 ppm (9 mg/kg/day for males and 11
mg/kg/day for females). The LOAEL for systemic toxicity was 750 ppm (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 2,000 ppm (95 mg/kg/day for
males and 132 mg/kg/day for females) HDT.
iv. A 2-year oncogenicity study in mice with a NOAEL for systemic
toxicity of 100 mg/kg/day and a 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 HDT.
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
plant or animal commodities which require regulation.
8. Endocrine disruption. Collective organ weights and
histopathological findings from the 2-generation reproduction study in
rats, as well as
from the subchronic and chronic toxicity studies in two or more animal
species, demonstrate no apparent estrogenic effects or effects on the
endocrine system. There is no information available which suggests that
dimethomorph technical would be associated with endocrine effects.
C. Aggregate Exposure
1. Dietary exposure--i. Food. For purposes of assessing the
potential dietary exposure, a Theoretical Maximum Residue Contribution
(TMRC) has been calculated from the tolerance of dimethomorph technical
in or on hops at 45 ppm, whole tomatoes at 0.50 ppm, tomato puree at
0.50 ppm, and tomato paste (including tomato juice and catsup) at 1.50
ppm. This exposure assessment is based on very conservative
assumptions, namely, 100% of all hops and tomato commodities consumed
is treated with dimethomorph technical and that the residues of
dimethomorph technical in hops and tomato commodities are equal to the
tolerance. Although there are no other established United States
permanent tolerances for dimethomorph technical, petitions for a
permanent tolerance of 0.05 ppm in or on potatoes and for a time-
limited tolerance of 2.0 ppm in or on imported grapes are pending at
the Agency. Therefore, the dietary exposures to residues of
dimethomorph technical in or on food will be limited to residues in
hops, tomatoes, potatoes and grapes. For the overall population, the
contribution of the tolerances for hops and tomato commodities to daily
consumption uses only 0.05% and 0.58%, respectively, of the Reference
Dose (RfD). The combined contributions of the hops, tomato and pending
potato and grapes tolerances to the daily consumption uses only 1.58%
of the RfD for the overall U.S. population, less than 5% for infants
and non-nursing infants (2.38% and 2.60%, respectively) and less than
5% for children ages 1-6 and 7-12 (4.39% and 1.81%, respectively).
Therefore, American Cyanamid concludes that the chronic dietary
exposure to dimethomorph from all current and pending tolerances is
less than 10% of the PAD for the U.S. population and for population
subgroups (e.g., for children 1-6 years, 4.3% plus 4.39%).
ii. Drinking water. Currently, the only federally-registered food/
feed use of dimethomorph in the United States is on potato crops. For
this use, the Drinking Water Level of Concern from chronic exposure was
estimated by the EPA to be 3,400 parts per billion (ppb) for the U.S.
population and for males 13 years and older, 2,900 ppb for females 13
years and older, and 960 ppb for children (1-6 years). These levels are
all much greater than that calculated from the Generic Estimated
Environmental Concentration (GENEEC); 24 ppb for 56-days which
simulates the residues in surface water. Dimethomorph residues in
ground water were also estimated using the Screening Concentration in
Ground Water Model (SCI-GRO), but these estimates were significantly
lower than those obtained from the GENEEC model. Given the low levels
of dimethomorph residues as estimated by the GENEEC model, the large
margin of exposure (40x-142x), and the similarity in use pattern on
potato and tomato, the additional use of dimethomorph on tomatoes is
not expected to reach a level of concern for residues in drinking
water. Potential exposure in drinking water in the U.S. for the
proposed tolerance on imported hops is not relevant to this petition.
2. Non-dietary exposure. The proposed tolerances are for imported
hops and, there are no residential uses for dimethomorph in the United
States; therefore, non-dietary exposure in the United States is not
relevant to this petition.
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
E. Safety Determination
1. U.S. population. The proposed RfD is 0.1 mg/kg bwt/day, based on
a NOAEL of approximately 10 mg/kg bwt/day (200 ppm) from a 2-year
dietary toxicity study in rats that demonstrated decreased body weight
and liver foci in females at 750 ppm. Because American Cyanamid Company
believes that dimethomorph technical is not genotoxic, carcinogenic, or
teratogenic and is not a reproductive toxicant, the proposed RfD is
calculated using an uncertainty factor of 100. The TMRC for imported
hops is estimated at 0.0000515 mg/kg bwt/day for the general
population. This represents a dietary exposure to the general U.S.
population which is 0.05% of the RfD. Similarly, the TMRC for all
tomato commodities is estimated at 0.0005818 mg/kg bwt/day for the
general U.S. population. This represents a dietary exposure to the
general U.S. population which is 0.58% of the RfD. No population
subgroup is more highly exposed to hops than the general population.
Children ages 1-6 and 7-12 are more highly exposed to tomato
commodities than the general population. The TMRC values for tomato
commodities are estimated at 0.0011050 and 0.0008449 mg/kg bwt/day for
children ages 1-6 and 7-12, respectively. The dietary exposure to
children ages 1-6 is 1.10% of the RfD, and the dietary exposure to
children ages 7-12 is 0.84% of the RfD. The combined TMRC for all
current and proposed dimethomorph tolerances in hop, tomatoes, cereal
grain commodities, cantaloupe, cucumber, squash, watermelon, potatoes,
and grapes will utilize less than 10% of the RfD for the general U.S.
population. Since EPA generally has no concern for exposures below 100%
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 commodities of the cited crops.
2. Infants and children. The TMRC for hops consumed by infants,
non-nursing infants, children ages 1-6 and children ages 7-12 is
minimal. For all population subgroups, consumption of residues of
dimethomorph in or on hops will use 0.00% of the RfD. The TMRC for
tomato commodities consumed by infants, non-nursing infants, children
ages 1-6 and children ages 7-12 is also minimal. The consumption of
residues of dimethomorph on tomato commodities will use 0.17%, 0.25%,
1.10%, and 0.84% of the RfD for infants, non-nursing infants, children
ages 1-6 and children ages 7-12, respectively. The combined TMRC values
for the proposed dimethomorph tolerances in/on hops, tomatoes, potatoes
and grapes in infants and non-nursing infants are 0.0023770 mg/kg bwt/
day and 0.0026026 mg/kg bwt/day, respectively. The combined tolerances
will use less than 5% of the RfD for infants and non-nursing infants
(2.38% and 2.60%, respectively). The combined TMRC values for the
proposed dimethomorph tolerances in/on hops, tomatoes, potatoes and
grapes consumed by a child 1-6 years of age is 0.0043911 mg/kg bwt/day,
which is less than 5% (actual 4.39%) of the RfD. The
combined TMRC values for the proposed dimethomorph tolerances in/on
hops, tomatoes, potatoes and grapes consumed by a child 7-12 years of
age is 0.0018062 mg/kg bwt/day, which is also less than 5% (actual
1.81%) of the RfD. Moreover, the combined TMRC values for all current
and proposed dimethomorph tolerances will utilize less than 10% of the
RfD for each of these subgroups. American Cyanamid Company 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 used to establish the proposed RfD (10 mg/kg bwt/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. Therefore, American Cyanamid believes that the results of
the toxicology and metabolism studies support both the safety of
dimethomorph technical to humans based on the intended use as a
fungicide on hops, tomatoes, potatoes and grapes and the granting of
the requested tolerances for hops, tomato, potato and grape
F. International Issues
No Codex maximum residue levels have been established for
dimethomorph to date.
[FR Doc. 00-5632 Filed 3-7-00; 8:45 am]
BILLING CODE 6560-50-F