[Federal Register Volume 62, Number 34 (Thursday, February 20, 1997)]
[Notices]
[Pages 7778-7780]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-4114]


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ENVIRONMENTAL PROTECTION AGENCY
[PF-714; FRL-5589-4]


Abbott Laboratories; Pesticide Tolerance Petition Filing

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice of filing.

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SUMMARY: This notice announces the filing of a pesticide petition 
proposing regulations establishing tolerances for residues of the 
biochemical pesticide aminoethoxyvinylglycine in or on apples and 
pears. This notice includes a summary of the petition that was prepared 
by the petitioner, Abbott Laboratories.

DATES: Comments, identified by the docket control number [PF-714], must 
be received on or before March 24, 1997.

ADDRESSES: By mail, submit written comments to: Public Response and 
Program Resources Branch, Field Operations Division (7506C), Office of 
Pesticide Programs, Environmental Protection Agency, 401 M St. SW., 
Washington, DC 20460. In person, bring comments to: Rm. 1132, Crystal 
Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA.
    Comments and data may also be submitted electronically by sending 
electronic mail (e-mail) to: [email protected] or by 
submitting disks. Electronic comments must be submitted either in ASCII 
format (avoiding the use of special characters and any form of 
encryption) or in WordPerfect in 5.1 file format. All comments and data 
in electronic form must be identified by docket control number [PF-
714]. Electronic comments on this notice may be filed online at many 
Federal Depository Libraries. The official record for this rulemaking, 
as well as the public version described above, will be kept in paper 
form. Accordingly, EPA will transfer all comments received 
electronically into printed, paper form as they are received and will 
place the paper copies in the official rulemaking record, which will 
also include all comments submitted directly in writing.
    Information submitted as a comment concerning this notice may be 
claimed confidential by marking any part or all of that information as 
``Confidential Business Information'' (CBI). Information so marked will 
not be disclosed except in accordance with procedures set forth in 40 
CFR part 2. No CBI should be submitted through e-mail. 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.

FOR FURTHER INFORMATION CONTACT: Denise Greenway, Regulatory Action 
Leader, Biopesticides and Pollution Prevention Division (7501W), 
Environmental Protection Agency, Washington, DC 20460, Office location, 
telephone number, and e-mail address: Crystal Station I, 2800 Crystal 
Dr., Arlington, VA 22202. (703) 308-8263; e-mail: 
[email protected].
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition (PP-
6F4632) from Abbott Laboratories, 1401 Sheridan Road, North Chicago, IL 
60064-4000. The petition proposes, pursuant to section 408 of the 
Federal Food, Drug and Cosmetic Act (FFDCA), 21 U.S.C. 346a, to amend 
40 CFR part 180 to establish tolerances for residues of the biochemical 
pesticide aminoethoxyvinylglycine (AVG) in or on apples and pears at 
0.08 part per million (ppm). EPA has determined that the 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 support granting 
of the petition. Additional data may be needed before EPA rules on the 
petition. The proposed analytical method is high pressure liquid 
chromatography (HPLC).
    As required by section 408(d) of the FFDCA, as recently amended by 
the Food Quality Protection Act (FQPA) (Pub. L. 104-170), Abbott 
Laboratories included in the petition a summary of the petition and 
authorization for the summary to be published in the Federal Register 
in a notice of receipt of the petition. The summary represents the 
views of Abbott Laboratories; EPA, as mentioned above, is in the 
process of evaluating the petition. As required by section 408(d)(3), 
EPA is including the summary as a part of this notice of filing. EPA 
may have made minor edits to the summary for the purpose of clarity.

I. Abbott Laboratories' Petition Summary

A. Residue Chemistry

    1. Plant metabolism. AVG signifies the active ingredient L-alpha-
(2-aminoethoxyvinyl)glycine hydrochloride in its pure form. An 
alternative nomenclature for AVG is [S]-trans-2-amino-4-[2-
aminoethoxy]-3-butanoic acid hydrochloride. N-acetyl AVG is the primary 
metabolite of AVG in apples.
    2. Analytical method. Abbott Laboratories has determined that 
residues of AVG are not expected in/on apples and pears at detectable 
levels when orchards are treated at the label use rate and pre-harvest 
interval. The Limit of Quantitation (LOQ) is 0.075 ppm and the Limit of 
Detection (LOD) is 0.03 ppm by HPLC analysis. There is no concentrating 
of residues in the processed commodities (i.e., apple juice or wet 
apple pomace).
    3. Magnitude of the residue. In the magnitude of the residue study 
in apples, the maximum residue at day 0 following treatment at the 
label use rate was 0.131 ppm. By day 21, there were no quantifiable 
residues present. The exposure assessments (below) indicate that there 
will be large margins of exposure (MOEs) from aggregate exposure to 
AVG. The proposed HPLC method used is deemed adequate by Abbott 
Laboratories to measure residues and the company argues that no 
additional analytical method for detecting and measuring residue levels 
is needed.

B. Toxicological Profile

    1. Acute toxicity. The acute mammalian toxicological data 
considered in this proposed tolerance for AVG include: an acute oral 
toxicity study in rats, an acute dermal toxicity study in rabbits, an 
acute inhalation toxicity study in rats, a primary eye irritation study 
in rabbits, a dermal irritation study in rabbits, and a dermal 
sensitization study in guinea pigs.
    The results of these studies indicate that AVG has an acute oral 
LD50 of 6,400

[[Page 7779]]

milligrams active ingredient per kilogram of body weight (mg a.i./kg 
bwt) in rats, an acute dermal LD50 greater than 2,000 mg a.i./kg 
bwt in rabbits, an acute inhalation LD50 of 1,130 mg/m3 in 
rats, causes slight eye and dermal irritation in rabbits, and is not a 
dermal sensitizer in guinea pigs.
    2. Genotoxicity. Abbott Laboratories concludes that AVG was not 
mutagenic in an Ames Salmonella gene mutation assay with or without 
metabolic activation. The company maintains that there was no mutagenic 
activity associated with AVG in cultures of mouse lymphoma cells 
(L5178Y tk ) with or without metabolic activation. In a rat 
bone marrow cell micronucleus test in vivo, Abbott Laboratories reports 
that there was no indication that AVG was genotoxic.
    3. Developmental toxicity. In a developmental toxicity study in 
rats by oral gavage, a no observable effect level (NOEL) of 1.77 mg 
a.i./kg bwt/day was determined for both developmental and maternal 
toxicity.
    4. Subchronic toxicity. A Reference Dose (RfD) of 0.002 mg a.i./kg 
bwt/day was derived from a 90-day feeding study in rats in which there 
was decreased food consumption, body weight and food efficiency (body-
weight gain/food consumption), and fatty changes in kidney and liver at 
dosage levels of 9 mg a.i./kg bwt/day or higher. The NOEL in this study 
was 2.2 mg a.i./ kg bwt/day.
    In a 21-day dermal toxicity study in rats, the NOEL was greater 
than 1,000 mg a.i./kg/day.
    In a 28-day dietary immunotoxicity study in rats with a NOEL of 5 
mg a.i./kg/day, decreases in several immune response parameters are 
considered secondary to the decreased food consumption, body weight, 
and food efficiency in the treated rats.
    5. Reproductive toxicity; chronic toxicity; animal metabolism; 
metabolite toxicity. AVG is classified as a biochemical due to its 
proposed use pattern, its low use rate, and its natural occurrence. Due 
to the nature of this biochemical pesticide, the requirements for 
reproductive and chronic toxicity studies as well as animal metabolism 
and metabolite toxicity have not been triggered in the Tier Toxicity 
Testing approach.

C. Aggregate Exposure

    Dietary exposure--food and drinking water/non-dietary exposure. 
Expected dietary exposures from residues of AVG would occur through 
apples, pears, and processed apples and pears. Spray drift may lead to 
exposure to residues in drinking water. There are no proposed home and 
garden uses for AVG. AVG is used in a commercial floral preservative. 
There is no exposure to infants and children through this floral 
preservative. The only potential exposure from this floral preservative 
would be dermal exposure.
    For estimations of maximum anticipated residues, non-detectable 
residues were assigned a value one half of the LOD. For the two 
instances in which residues were detectable on one of the replicates, 
the full LOD was used. The maximum anticipated residues of AVG were 
calculated to be 0.018 ppm in the apple raw agricultural commodity.
    The processed commodities examined were apple juice and wet apple 
pomace. Processing factors were calculated from apples without washing 
prior to processing to provide the highest possible estimate of 
anticipated residues in the juice and pomace. The mean apple juice 
processing factor was determined to be 0.8; for wet apple pomace the 
processing factor was 0.9.
    A chronic dietary exposure analysis was conducted for AVG using the 
anticipated residues in apples for both apples and pears. Residues were 
rarely detected in field trials conducted at the maximum rate and 
minimum interval between application and harvest. The anticipated 
residue of 0.018 ppm represents about half of the LOD.
    Low residues are expected in wet apple pomace, so finite residues 
of AVG are not expected in meat and milk; therefore, these foods were 
not included in the exposure analysis.
    Tap water, non-tap water, and water in commercially prepared food 
were also included in the analysis. Residue levels in water were 
assumed to be 0.0012 ppm. This was based upon calculations for airblast 
application of AVG onto late season trees. It is estimated that a 
negligible amount of the applied dose could drift into nearby drinking 
water sources. The following table summarizes the results from the 
chronic aggregate exposure analysis based upon anticipated residues for 
the overall U.S. population and the five most highly exposed population 
subgroups. The exposure estimate was compared against the RfD of 0.002 
mg a.i./kg bwt/day:

------------------------------------------------------------------------
                                   Exposure mg a.i./                    
       Population subgroup              kg bwt          Percent of RfD  
------------------------------------------------------------------------
U.S. Population.................  0.000055..........  2.5               
All Infants.....................  0.000206..........  10.3              
Non-nursing Infants < 1 yr......  0.000258..........  12.9              
Children 1-6 yrs................  0.000099..........  5.0               
Children 7-12 yrs...............  0.000077..........  3.8               
Females 13-50 yrs...............  0.000040..........  2.0               
------------------------------------------------------------------------

    As seen in the above table, even for the most highly exposed 
population subgroup, less than 13% of the RfD was used.
    Chronic aggregate exposure to AVG also was estimated using proposed 
tolerance-level residues. Exposure was estimated using the same 
consumption data that were used for the anticipated residue exposure 
calculation.
    The following table summarizes results of the chronic exposure 
analyses using proposed tolerances for the overall U.S. population and 
the five most highly exposed population subgroups.

------------------------------------------------------------------------
                                   Exposure mg a.i./                    
       Population subgroup              kg bwt          Percent of RfD  
------------------------------------------------------------------------
U.S. Population.................  0.000111..........  5.6               
All Infants.....................  0.000538..........  26.9              
Non-nursing Infants < 1 yr......  0.000638..........  31.9              
Children 1-6 yrs................  0.000324..........  16.2              
Children 7-12 yrs...............  0.000173..........  8.7               
Females 13+/nursing.............  0.000133..........  6.7               
------------------------------------------------------------------------

    An examination of the summary table demonstrates that chronic 
aggregate exposure represents no more than 32% of the chronic RfD for 
any population subgroup. These calculations were performed assuming 
that 100% of the apple and pear crops in the United States would 
contain AVG residues at tolerance levels. Assuming that 100% of all 
apple products consumed would contain tolerance-level residues is the 
worst-case scenario and yields a gross overestimate of dietary 
exposure.
    An acute exposure analysis based upon anticipated residues was 
conducted using EPA's Tier 2 method with anticipated residues. For 
blended commodities (e.g., apple juice and pear nectar), the mean 
anticipated residue level was used. For single serving commodities 
(e.g., raw apples and pears), the LOQ of 0.075 ppm was used as a worst-
case estimate of high end exposure because AVG residues were not 
quantifiable in the few samples in which residues were detected.
    A separate exposure analysis was conducted for infants because baby 
foods are blended commodities. For these analyses, only raw forms of 
apples and pears were assumed to be consumed as single servings 
containing the high-end residue value of 0.075

[[Page 7780]]

ppm. All prepared and processed foods were assumed to be blended foods 
containing the mean anticipated residue of 0.018 ppm. The following 
table summarizes the exposure analysis at the 95th percentile:

------------------------------------------------------------------------
                                   Exposure mg a.i./                    
       Population subgroup              kg bwt                MOE       
------------------------------------------------------------------------
U.S. Population.................  0.000276..........  6,510             
All Infants.....................  0.000598..........  3,009             
Non-nursing Infants < 1 yr......  0.000551..........  3,269             
Children 1-6 yrs................  0.000756..........  2,381             
Children 7-12 yrs...............  0.000448..........  4,022             
Females 13-50 yrs...............  0.000198..........  9,091             
------------------------------------------------------------------------

    The MOE of the most highly exposed population subgroup, children 1 
to 6 years old, is more than 23-fold higher than a level considered to 
provide adequate protection.
    The acute exposure summary (below) in which proposed tolerance-
level residues were used shows that estimated exposures provide 
adequate MOEs, even at the 95th percentile of exposure. In this 
analysis, acute exposure was calculated for the entire population 
rather than for consumers only, a procedure recommended by the EPA in 
their proposed method for acute dietary risk assessment.

------------------------------------------------------------------------
                                   Exposure mg a.i./                    
       Population subgroup              kg bwt                MOE       
------------------------------------------------------------------------
U.S. Population.................  0.000406..........  4,432             
All Infants.....................  0.002188..........  823               
Non-nursing Infants < 1 yr......  0.002191..........  822               
Children 1-6 yrs................  0.001384..........  1,301             
Children 7-12 yrs...............  0.000663..........  2,845             
Females 13-50 yrs...............  0.000245..........  7,336             
------------------------------------------------------------------------

    The most highly exposed population subgroup, non-nursing infants, 
has an estimated MOE of 822, greater than 8-fold higher than a level 
considered to provide adequate protection.

D. Cumulative Effects

    AVG is a structurally unique biochemical pesticide and is a 
naturally occurring L--amino acid. Its proposed mode of action 
for mammalian toxicity is the inhibition of the enzyme-
cystathionase. Other agents which inhibit this enzyme include naturally 
occurring amino acids such as alanine, cysteine, glutamic acid, and 
homoserine. Given the expected exposure, Abbott Laboratories maintains 
that inhibition of this enzyme would not occur at levels that would 
pose a human health risk.

E. Endocrine Effects

    Abbott Laboratories reports that there have been no indications of 
treatment-related effects from AVG to suggest that the pesticide may 
have an endocrine disruption activity.

F. Safety Determination

    1. U.S. population. AVG is a naturally occurring amino acid. Based 
upon expected residues in apples, pears, and water, Abbott Laboratories 
concludes that there is a reasonable certainty of no harm resulting 
from aggregate exposure of AVG to the general population.
    2. Infants and children. The effects demonstrated in the 
developmental and immune toxicity studies are considered secondary to 
the adverse effects upon body weight gain, food consumption and food 
efficiency in the treated rats. These data indicate to Abbott 
Laboratories that AVG is not a developmental or immunological toxicant, 
and that infants and children are not sensitive subpopulations. The 
company concludes that there is a reasonable certainty that no harm 
will result from aggregate exposure of AVG to infants and children.

G. International Tolerances

    There are no Codex maximum residue levels established for residues 
of AVG on apples or pears.
    Therefore, based on the completeness and reliability of the 
toxicity data and the conservative exposure assessment, Abbott 
Laboratories concludes that there is a reasonable certainty that no 
harm will result from aggregate exposure to residues of AVG, including 
all anticipated dietary exposure and all other non-occupational 
exposures.

II. Public Record

    EPA invites interested persons to submit comments on this notice of 
filing. Comments must bear a notation indicating the docket control 
number [PF-714].
    A record has been established for this notice under docket control 
number [PF-714] (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 
public record is located in Room 1132 of the Public Response and 
Program Resources Branch, Field Operations Division (7506C), Office of 
Pesticide Programs, Environmental Protection Agency, Crystal Mall #2, 
1921 Jefferson Davis Highway, Arlington, VA.
    Electronic comments can be sent directly to EPA at:
    [email protected]

    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption.
    The official record for this rulemaking, as well as the public 
version, as described above, will be kept in paper form. Accordingly, 
EPA will transfer all comments received electronically into printed, 
paper form as they are received and will place the paper copies in the 
official rulemaking record which will also include all comments 
submitted directly in writing. The official rulemaking record is the 
paper record maintained at the address in ``ADDRESSES'' at the 
beginning of this document.

List of Subjects

    Environmental protection, Agricultural commodities, Pesticides and 
pests, Reporting and recordkeeping.
    Authority: 21 U.S.C. 346a.

    Dated: February 10, 1997.

Janet L. Anderson,
Director, Biopesticides and Pollution Prevention Division, Office of 
Pesticide Programs.

[FR Doc. 97-4114 Filed 2-19-97; 8:45 am]
BILLING CODE 6560-50-F