4-(dichloroacetyl)-1-oxa-4-azospiro [4.5] decane (MON 4660) Pesticide Petition Filing 1/98
[Federal Register: January 28, 1998 (Volume 63, Number 18)]
[Notices]
[Page 4252-4259]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr28ja98-81]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-787; FRL-5763-6]
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-787, must
be received on or before February 27, 1998.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch, Information Resources and Services Division
(7502C), Office of Pesticides 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 to: opp-
docket@epamail.epa.gov. Follow 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
[[Page 4253]]
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: The product manager listed in the
table below:
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Office location/
Product Manager telephone number Address
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Amelia M. Acierto............. Rm. 4W60, 4th. floor, 2800 Crystal
CSI #2, 703-308-8377, Drive,
e- Arlington, VA
mail:acierto.amelia@e
pamail.epa.gov.
Adam Heyward.................. Rm. 206, CM #2, 703- 1921 Jefferson
305-5518, e-mail: Davis Hwy.,
heyward. Arlington, VA
adam@epamail.epa.gov.
Joseph Tavano................. Rm. 214, CM #2, 703- Do.
305-6411, e-mail:
tavano.joseph@epamail
.epa.gov.
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SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as
follows proposing the establishment and/or amendment of regulations for
residues of certain pesticide chemicals 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 these petitions
contain 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-787] (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 file format or ASCII
file format. All comments and data in electronic form must be
identified by the docket number [PF-787] and appropriate petition
number. Electronic comments on notice may be filed online at many
Federal Depository Libraries.
List of Subjects
Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated:January 20, 1998
James Jones,
Acting Director, Registration Division, Office of Pesticide Programs.
Summaries of Petitions
Petitioner summaries of the pesticide petitions are printed below
as required by section 408(d)(3) of the FFDCA. The summaries of the
petitions were prepared by the petitioners and represent the views of
the petitioners. 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.
2. Monsanto Company
PP 5E4503
EPA has received a pesticide petition (PP 5E4503) from Monsanto
Company, 700 14<SUP>th</SUP> St., NW., Washington, DC 20005, proposing
pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act,
21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance
for residues of the inert ingredient 4-(dichloroacetyl)-1-oxa-4-
azospiro [4.5] decane (MON 4660) in or on the raw agricultural
commodity, corn, resulting from early post-emergence applications. The
analytical method, which determines the residue by gas-liquid
chromatography using an electron-capture detector has been reviewed by
the Agency and accepted for enforcement purposes. 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.
A. Residue Chemistry
1. Plant metabolism. The metabolism of MON 4660 in corn was studied
with radiolabeled MON 4660 in the greenhouse and the field. Parent MON
4660 was not found in any of the corn samples. MON 4660 is rapidly and
extensively metabolized to a large number of highly polar metabolites
characterized as weak organic acids or residues conjugated to natural
sugars.
2. Analytical method. Monsanto has developed an analytical method
using gas liquid chromatography with electron capture detection that
has a verified limit of quantitation of 0.005 ppm for parent MON 4660
in all corn matrices. This method has been validated by the Agency.
3. Magnitude of residues. Monsanto has conducted 14 residue field
studies with MON 4660 applied pre-emergence to corn. Analysis of corn
forage, silage, fodder and grain showed no residues above the limit of
quantitiation of 0.005 ppm. Two residue field studies with MON 4660
applied pre-emergence to corn at rates 20 and 28 times the proposed
maximum use rate showed no measurable residues (<0.005 ppm) in corn
grain. Based on these results it was concluded that the potential for
measurable concentration of MON 4660 in processed commodities of corn
was very low. Eight residue field trials (2 samples per trial) were
conducted with MON 4660 applied early post-emergence with corn plants 6
to 11 inches tall. Analysis of corn forage, fodder and grain again
showed no measurable residues (<0.005 ppm). These residues, derived
from postemergence applications are below the established Sensitivity
of Method Tolerance for corn (0.005 ppm).
B. Toxicological Profile
The toxicology data considered in support of the revised tolerance
include the following:
1. Acute toxicity-- i. An acute oral toxicity study in the rat with
an LD<INF>50</INF> of 2,600 mg/kg. Toxicity Category III.
ii. An acute dermal toxicity study in the rabbit with an
LD<INF>50</INF> of > 5,000 mg/kg. Toxicity Category IV.
iii. An acute inhalation study in the rat with a 4-hour inhalation
LC<INF>50</INF> of 0.27 mg/L. Toxicity Category III.
iv. A rabbit eye irritation study in which 4-(dichloroacetyl)-1-
oxa-4-azospiro [4.5] decane is determined not to be an eye irritant.
Toxicity Category III.
v. A dermal irritation study which exhibited slight skin
irritation. Toxicity Category IV.
vi. A guinea pig dermal sensitization study in which 4-
(dichloroacetyl)-1-oxa-4-azospiro [4.5] decane is determined to be a
skin sensitizer.
2. Genotoxicity. Mutagenicity studies including Salmonella
typhimurium/mammalian plate incorporation (Ames) assay, CHO/HGPRT gene
mutation assay, DNA repair studies (rat hepatocytes), and Salmonella/
mammalian activation gene mutation (Ames) assay were negative with and
without activation.
3. Reproductive and developmental toxicity-- i. A rat developmental
effects study with a NOEL for maternal toxicity of 10 mg/kg/day and
developmental toxicity of 75 mg/kg/day.
ii. A rabbit developmental effects study with a NOEL for maternal
toxicity of 10 mg/kg/day and developmental toxicity of 30 mg/kg/day.
iii. A 2-generation reproduction study in the rat fed diet levels
of 0, 10, 100, and 1,000 ppm. There were no treatment-related effects
on mating, fertility or offspring survival in this study. The NOEL for
toxicity in parental animals and offspring was 100 ppm (6 to 7 mg/kg/
day). As there were no adverse effects on reproductive performance, the
NOEL for reproductive toxicity was 1,000 ppm (57 to 72 mg/kg/day).
4. Subchronic toxicity-- i. A 90-day oral toxicity study in the rat
with a NOEL of 120 parts per million (ppm) or 12 mg/kg/day.
ii. A 90-day oral (gavage) study in the dog with a NOEL of 30 mg/
kg/day, the highest dose tested.
5. Chronic toxicity-- i. A mouse oncogenicity study in which 5
groups of 60 male and 60 female CD-1 mice were administered diets
containing 4-(dichloroacetyl)-1-oxa-4-azospiro [4.5] decane at
concentrations 0, 5, 80, 800 or 2,500 ppm for approximately 18 months.
These concentrations corresponded to 0, 0.7, 10.7, 108 and 350 mg/kg/
day in males and 0, 1, 16.8, 167 and 556 mg/kg/day in females. The
primary target organs were liver, lung and stomach. The NOEL for both
oncogenic and non-oncogenic effects was considered to be 10.7 mg/kg/day
in males and 116.8 mg/kg/day in females.
ii. A chronic toxicity/oncogenicity study in rats in which 5 groups
of 60 male and 60 female rats were administered diets containing 4-
(dichloroacetyl)-1-oxa-4-azospiro [4.5] decane for approximately 23
months. Target concentrations were 0, 5, 50, 500, or 1,600 ppm for
males and, 0, 5, 50, or 1,200 ppm for females. These concentrations
correspond to 0, 0.2, 2.2, 22 and 71 mg/kg/day in males and 0, 0.3,
2.8, 29 and 69 mg/kg/day in females. The primary effects in this study
occurred in the liver and stomach. The NOEL for oncogenic effects is 22
mg/kg/day in males and 29 mg/kg/day in females. The NOEL for non-
[[Page 4256]]
oncogenic effects is 2.2 mg/kg/day in males and 2.8 mg/kg/day in
females.
6. Animal metabolism. Because field trial residue data showed non-
detectable residues of MON 4660 in corn, neither animal metabolism nor
residue transfer studies with livestock were required. It is considered
likely that metabolism will be similar to that of other
dichloroacetamide safeners in mammals which are characterized by
extensive metabolism and elimination of most of the residue from the
body with very low levels of parent safener, if any, retained in the
tissues. The major route of metabolism is typically glutathione
conjugation followed by formation of an aldehyde intermediate which is
then either oxidized to an oxamic acid or reduced to the corresponding
alcohol.
7. Metabolite toxicology. The metabolism of MON 4660 is extensive
and results in a large number of polar metabolites each of which is
present in soil or corn plants in very low concentrations. These
metabolites have not been identified as being of toxic concern.
Based on the available toxicity data, Monsanto believes the RfD for
MON 4660 will be 0.02 mg/kg/day based on a 2-year feeding study in rats
with a NOEL of 2.2 mg/kg/day and application of an uncertainty factor
of 100. For cancer risk assessment for MON 4660, Monsanto believes that
margin of exposure assessment should be calculated using the
carcinogenic NOEL of 10.7 mg/kg/day observed in the mouse, which was
the most sensitive species.
C. Aggregate Exposure
1. Dietary exposure-- i. Food. Monsanto has used the Theoretical
Maximum Residue Contribution as a conservative estimate of the
potential dietary exposure for MON 4660. This approach assumes that
100% of all raw agricultural commodities for which tolerances have been
established for acetochlor, bear tolerance-level (0.005 ppm) residues
of MON 4660. This over-estimate of actual dietary exposure provides a
quite conservative basis for risk assessment.
ii. Drinking water. Although MON 4660 is stable to hydrolyis and
shows only a small amount of photodegradation in soil and in water, it
is rapidly degraded in the soil. The aerobic soil half-life is
approximately 18 days. This low persistence in the environment combined
with the low application rate (maximum of 0.4 pound per acre) indicates
that MON 4660 is not likely to be present in groundwater. Based on
these considerations, Monsanto does not anticipate exposure to residues
of MON 4660 in drinking water. The EPA has not established a Maximum
Concentration Level or a health advisory level for residues of MON 4660
in drinking water.
2. Non-dietary exposure. MON 4660 is used only as a safener or
antidote to the effects of acetochlor herbicide on corn seed or
seedlings. It is sold only as part of acetochlor herbicide end-use
products which are classified as Restricted Use by EPA which means they
are used only by certified applicators and are not available to the
general public. Herbicide products containing MON 4660 are not
registered for residential, home owner, or other non-crop uses. They
are thus not used in parks, school grounds, public buildings, roadsides
or rights-of-way or other public areas. Commercial cornfields are
generally located well away from public areas where incidental contact
could occur. Therefore, the general public is very unlikely to have any
non-dietary exposure to MON 4660.
D. Cumulative Effects
Monsanto has no reliable data or information to suggest that MON
4660 has toxic effects that arise from toxic mechanisms that are common
to other substances. Therefore, a consideration of common toxic
mechanism and cumulative effects with other substances is not
appropriate for MON 4660, and Monsanto is considering only the
potential effects of MON 4660 in this exposure assessment.
E. Safety Determination
1. U.S. population-- i. Chronic risk. The conservative estimate of
aggregate chronic exposure is 2.0 x 10<SUP>-6</SUP> mg/kg/day. This
potential exposure represents only 0.01% of the RfD of 0.02 mg/kg/day
and provides a Margin of Exposure of 5,350,000 when compared to the
10.7 mg/kg/day carcinogenic reference point. EPA generally has no
concern for exposures below 100% of the RfD and there are adequate
margins of safety for cancer. Monsanto concludes there is a reasonable
certainty of no harm resulting from exposure to MON 4660.
ii. Acute risk. The acute toxicity of MON 4660 is low, and there
are no concerns for acute dietary, occupational or non-occupational
exposures to MON 4660.
2. Infants and children. Employing the same conservative TMRC
estimates of exposure used in the risk assessment for the general
population, Monsanto has calculated that the aggregate exposures for
nursing infants, non-nursing infants, children age 1-6 and children age
7-12 are less than one-tenth of 1% of the RfD for each group.
Monsanto notes the developmental toxicity NOELs for rats (75 mg/kg/
day) and rabbits (30 mg/kg/day) are 34-fold and 14-fold higher than the
NOEL of 2.2 mg/kg/day in the chronic rat study on which the RfD is
based. This indicates that the RfD is adequate for assessing risk to
children. Also, the developmental toxicity NOELs for rats and rabbits
are higher than the NOELs for maternal toxicity (10 mg/kg/day in each
specie) indicating that the offspring were no more sensitive to MON
4660 than were the parents.
In the 2-generation reproduction study in rats, the NOEL for pup
toxicity (57-72 mg/kg/day) was higher than the NOEL for parental or
systemic effects (6-7 mg/kg/day) indicating that offspring were no more
sensitive to MON 4660 than were the parents. Also, the NOEL for pup
toxicity (57-72 mg/kg/day) was 25 to 33-fold higher than the NOEL for
chronic toxicity upon which the RfD is based.
Monsanto believes that these data do not indicate an increased pre-
natal or post-natal sensitivity of children and infants to MON 4660
exposure and concludes that the 100-fold uncertainty factor used in the
RfD is adequate to protect infants and children.
F. International Tolerances
The Codex Alimentarius Commission has not established a maximum
residue level for MON 4660. (Amelia Acierto)
[FR Doc. 98-2088 Filed 1-27-98; 8:45 am]
BILLING CODE 6560-50-F
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