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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:

------------------------------------------------------------------------
                                   Office location/                     
        Product Manager            telephone number          Address    
------------------------------------------------------------------------
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