[Federal Register Volume 62, Number 88 (Wednesday, May 7, 1997)]
[Rules and Regulations]
[Pages 24835-24838]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-11901]
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ENVIRONMENTAL PROTECTION AGENCY
40 Part CFR 180
[OPP-300480; FRL-5713-5]
RIN 2070-AB78
Aminoethoxyvinylglycine; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final Rule.
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SUMMARY: This document establishes time-limited tolerances for residues
of the plant regulator aminoethoxyvinylglycine in or on the food
commodities apples and pears. The tolerances expire on and will be
revoked by EPA on April 1, 2001. Abbott Laboratories submitted a
petition to EPA under the Federal Food, Drug and Cosmetic Act as
amended by the Food Quality Protection Act of 1996 requesting the
tolerances. This regulation sets the permissible levels of this plant
regulator on apples and pears.
EFFECTIVE DATE: This regulation becomes effective May 7, 1997.
Objections and hearing requests must be filed by July 7, 1997.
ADDRESSES: Written objections and hearing requests, identified by the
document control number [OPP-300480], may be submitted to: Hearing
Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M St.,
SW., Washington, DC 20460. Fees accompanying objections and hearing
requests shall be labeled ``Tolerance Petition Fees'' and forwarded to
EPA Headquarters Accounting Operations Branch, OPP (Tolerance Fees),
P.O. Box 360277M, Pittsburg, PA 15251. A copy of any objections and
hearing requests filed with the Hearing Clerk should be identified by
the document control number and submitted 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 a copy of objections and hearing
requests to: Rm. 1132, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA
22202.
A copy of objections and hearing requests filed with the Hearing
Clerk may also be submitted electronically to the OPP by sending
electronic mail (e-mail) to: opp-docket@epa.gov. Copies of objections
and hearing requests must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption. Copies of
objections and hearing requests will also be accepted on disks in
Wordperfect in 5.1 file format or ASCII file format. All copies of
objections and hearing requests in electronic form must be identified
by the docket number [OPP-300480]. No Confidential Business Information
(CBI) should be submitted through e-mail. Electronic copies of
objections and hearing requests on this rule may be filed online at
many Federal Depository Libraries. Additional information on electronic
submissions can be found in Unit VII of this document.
FOR FURTHER INFORMATION CONTACT: By mail: Denise Greenway, c/o Product
Manager (PM) 90, Biopesticides and Pollution Prevention Division
(7501W), Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460. Office location and telephone number: Rm. 5-W57, CS #1, 2800
Crystal Drive, Arlington, VA 22202, (703) 308-8263; e-mail:
greenway.denise@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: In the Federal Register of February 20, 1997
(62 FR 7778), EPA issued a notice pursuant to section 408(d) of the
Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d),
announcing the filing of a pesticide tolerance petition by Abbott
Laboratories, 1401 Sheridan Road, North Chicago, IL 60064-4000. The
notice contained a summary of the petition prepared by the petitioner
and this summary contained conclusions and arguments to support its
conclusion that the petition complied with the Food Quality Protection
Act (FQPA) of 1996. The petition requested that 40 CFR part 180 be
amended by adding tolerances for residues of aminoethoxyvinylglycine,
in or on the following food commodities: apples at 0.08 part per
million (ppm), and pears at 0.08 ppm.
There were no comments or requests for referral to an advisory
committee received in response to the notice of filing.
The data submitted in the petition and other relevant material have
been evaluated. The toxicology data listed below were considered in
support of these tolerances.
I. Toxicological Profile
1. A battery of acute toxicity studies placing technical
aminoethoxyvinylglycine in Toxicity Categories III and IV.
2. A 13-week feeding study in rats at dietary intakes of 0, 0.45,
1.9 and 9.2 milligrams per kilogram per day (mg/kg/day) (males) and 0,
0.55, 2.2, and 9.4 mg/kg/day (females) with a no-observed-effect-level
(NOEL) of 9.2 mg/kg/day for male rats and 2.2 mg/kg/day for female
rats. The lowest-observed-effect-level (LOEL) was established at 9.4
mg/kg/day (the highest dose tested in females) based on reduced body
weight gain, food consumption and food efficiency; increased severity
and incidence of reversible kidney and liver effects; and discoloration
of the liver.
3. A developmental toxicity study in rats at 0, 0.4, 1.77, and 8.06
mg/kg/day. The maternal LOEL is 8.06 mg/kg/day (the highest dose
tested) based on decreased defecation, body weight gain, and food
consumption; and the presence of red material around the nose. The
developmental LOEL is also 8.06 mg/kg/day based on decreased mean fetal
body weight and increases (within historical ranges) in two
developmental skeletal variants (reduced ossification of the sternebrae
and vertebral arches). The NOEL for maternal and developmental toxicity
was established at 1.77 mg/kg/day.
4. A 21-day repeated dose dermal toxicity study in rats at 0, 100,
500, and 1,000 mg/kg/day. The NOEL is 1,000 mg/kg/day; a LOEL was not
determined.
5. An immunotoxicity study in rats at 0, 1.25, 2.5, 5 and 15 mg/kg/
day with a NOEL of 5 mg/kg/day based on the decreased primary antibody
(IgM) response to sheep red blood cells; decreased absolute and
relative thymus weights; decreased body weight, food consumption and
food efficiency at the high-dose level. The LOEL is 15 mg/kg/day. The
study did not fully meet the requirements outlined in the Pesticide
Assessment Guidelines Subdivision M OPPTS Series 152-18. However,
because a NOEL and LOEL were determined, and found to be consistent
with those from other repeat-dose studies, the study need not be
repeated.
6. An acceptable Ames study for inducing reverse mutation in
Salmonella strains of bacteria exposed with or without activation at
doses up to 5,000 micrograms per plate. The study showed negative
results.
7. An acceptable study for inducing micronuclei in bone marrow
cells of rats treated up to the maximum dose tested of 6,200 mg/kg. The
study showed negative results.
8. A mutagenicity study with mouse lymphoma cells with or without
activation to doses up to 5,000 micrograms/mL. Aminoethoxyvinylglycine
is not mutagenic or cytotoxic when tested against mouse lymphoma cells
strain L5178Y at a concentration of 5,000 micrograms/mL.
[[Page 24836]]
9. Additional data (a two-generation reproduction study in the rat)
is being required by the Agency.
II. Aggregate Exposures
1. From food and feed uses. The primary source for human exposure
to aminoethoxyvinylglycine will be from ingestion of both raw and
processed food commodities as proposed in the February 20, 1997 Notice
of Filing cited above. Based on tolerances of 0.08 ppm in or on apples
and pears, the Theoretical Maximum Residue Contributions (TMRC) for the
U.S. adult population and for U.S. children (1 to 6 years of age) were
determined. In deriving the dietary exposure to
aminoethoxyvinylglycine, EPA assumed that 100% of the apple and pear
crops were cultured with the aid of this plant regulator. A subchronic
exposure was used to estimate the TMRC. The TMRC for the U.S.
population was estimated to be 0.000069 mg/kg/day. The TMRC for non-
nursing infants less than 1 year old was 0.000722 mg/kg/day. The TMRC
for nursing infants less than 1 year old was 0.000552 mg/kg/day. The
TMRC for children 1 to 6 years old was 0.000224 mg/kg/day. The TMRC for
children 7 to 12 years old was 0.000092 mg/kg/day.
2. From potable water. In examining aggregate exposure, FQPA
directs EPA to consider available information concerning exposures from
the pesticide residue in food and all other non-occupational exposures.
The primary non-food sources of exposure the Agency looks at include
drinking water (whether from groundwater or surface water), and
exposure through pesticide use in gardens, lawns, or buildings
(residential and other indoor uses).
Because the Agency lacks sufficient water-related exposure data to
complete a comprehensive drinking water risk assessment for many
pesticides, EPA has commenced and nearly completed a process to
identify a reasonable yet conservative bounding figure for the
potential contribution of water-related exposure to the aggregate risk
posed by a pesticide. In developing the bounding figure, EPA estimated
residue levels in water for a number of specific pesticides using
various data sources. The Agency then applied the estimated residue
levels, in conjunction with appropriate toxicological endpoints
(Reference Doses (RfDs) or acute dietary NOELs) and assumptions about
body weight and consumption, to calculate, for each pesticide, the
increment of aggregate risk contributed by consumption of contaminated
water. While EPA has not yet pinpointed the appropriate bounding figure
for consumption of contaminated water, the ranges the Agency is
continuing to examine are all below the level that would cause
aminoethoxyvinylglycine to exceed the RfD if the time-limited
tolerances being considered in this document were granted. The Agency
has therefore concluded that the potential exposures associated with
aminoethoxyvinylglycine in water, even at the higher levels the Agency
is considering as a conservative upper bound, would not prevent the
Agency from determining that there is a reasonable certainty of no harm
if the time-limited tolerances are granted.
3. From non-dietary uses. There is a proposed non-dietary use for
aminoethoxyvinylglycine as a commercial plant regulator to be applied
to certain ornamentals. There are no proposed home and garden uses. The
exposure from this commercial use is expected to be dermal in nature.
An acute dermal toxicity study yielded an LD50 of > 2 g/kg.
A 21-day repeated dose dermal toxicity study resulted in no significant
treatment-related effects at 1,000 mg/kg/day, the highest dose tested.
4. Cumulative exposure to substances with common mechanism of
toxicity. Section 408(b)(2)(D)(v) requires that, when considering
whether to establish, modify, or revoke a tolerance, the Agency
consider ``available information'' concerning the cumulative effects of
a particular pesticide's residues and ``other substances that have a
common mechanism of toxicity.'' The Agency believes that ``available
information'' in this context might include not only toxicity,
chemistry, and exposure data, but also scientific policies and
methodologies for understanding common mechanisms of toxicity and
conducting cumulative risk assessments. For most pesticides, although
the Agency has some information in its files that may turn out to be
helpful in eventually determining whether a pesticide shares a common
mechanism of toxicity with any other substances, EPA does not at this
time have the methodologies to resolve the complex scientific issues
concerning common mechanism of toxicity in a meaningful way. EPA has
begun a pilot process to study this issue further through the
examination of particular classes of pesticides. The Agency hopes that
the results of this pilot process will increase the Agency's scientific
understanding of this question such that EPA will be able to develop
and apply scientific principles for better determining which chemicals
have a common mechanism of toxicity and evaluating the cumulative
effects of such chemicals. The Agency anticipates, however, that even
as its understanding of the science of common mechanisms increases,
decisions on specific classes of chemicals will be heavily dependent on
chemical-specific data, much of which may not be presently available.
Although at present the Agency does not know how to apply the
information in its files concerning common mechanism issues to most
risk assessments, there are pesticides as to which the common mechanism
issues can be resolved. These pesticides include pesticides that are
toxicologically and structurally dissimilar to existing chemical
substances (in which case the Agency can conclude that it is unlikely
that a pesticide shares a common mechanism of activity with other
substances) and pesticides that produce a common toxic metabolite (in
which case common mechanism of activity will be assumed).
EPA does not have, at this time, available data to determine
whether aminoethoxyvinylglycine has a common mechanism of toxicity with
other substances or how to include this pesticide in a cumulative risk
assessment. Unlike other pesticides for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity,
aminoethoxyvinylglycine does not appear to produce a toxic metabolite
produced by other substances. For the purposes of this tolerance
action, therefore, EPA has not assumed that aminoethoxyvinylglycine has
a common mechanism of toxicity with other substances.
III. Determination of Safety for U.S. Population and Non-nursing
Infants
1. The U.S. population. Based on a NOEL of 2.2 milligrams per
kilogram of bodyweight per day (mg/kg bwt/day) from a subchronic
toxicity study that demonstrated reduced body weight gain, food
consumption, and food efficiency; increased severity and incidence of
reversible kidney and liver effects; and discoloration of the liver;
and using an uncertainty factor of 1,000 the Agency has set a RfD of
0.0002 mg/kg bwt/day for this assessment of risk. Based on the
available toxicity data and the available exposure data identified
above, the proposed tolerances will utilize 3.4% of the RfD for the
U.S. population.
2. Non-nursing infants. Exposure to non-nursing infants as a
result of the use of aminoethoxyvinylglycine in the culture of apples
and pears will result in the use of 36.1% of the RfD.
3. From nonfood uses. Exposure from nonfood uses of
aminoethoxyvinylglycine and from
[[Page 24837]]
contaminated potable water sources have not been precisely addressed in
this assessment. However, the EPA does not foresee that these exposures
will result in a cumulative level that exceeds the RfD. EPA concludes
that there is reasonable certainty that no harm will result from the
aggregate exposures to residues of aminoethoxyvinylglycine.
IV. Determination of Safety for Infants and Children
Risk to infants and children was determined by the use of a
developmental study in rats that had a NOEL for developmental toxicity
of 1.77 mg/kg/day, based on decreased mean fetal body weight and
increases (within historical ranges) in two developmental skeletal
variants (reduced ossification of the sternebrae and vertebral arches),
and a maternal NOEL of 1.77 mg/kg/day based on decreased defecation,
body weight gain, and food consumption; and the presence of red
material around the nose.
FFDCA section 408 provides that EPA may apply an additional tenfold
margin of exposure (safety) for infants and children in the case of
threshold effects to account for pre- and post-natal toxicity and the
completeness of the data base unless EPA determines that a different
margin of exposure (safety) will be safe for infants and children.
Available data indicate that maternal and developmental toxicity
were observed in the developmental toxicity study in rats at the
highest dose tested (8.06 mg/kg/day). Maternal toxicity was observed in
the rat in the 8.06 mg/kg/day dose group as decreased defecation, body
weight gain, and food consumption; and the presence of red material
around the nose. Developmental toxicity was observed in the high dose
group (8.06 mg/kg/day) as decreased mean fetal body weight and
increases (within historical ranges) in two developmental skeletal
variants (reduced ossification of the sternebrae and vertebral arches).
Due to the incompleteness of the data, the Agency used a thousandfold
uncertainty factor in the RfD calculations, and has imposed a
requirement for a two-generation reproduction study in rats. The
thousandfold uncertainty factor includes an additional uncertainty
factor of 10 to protect infants and children.
The percent of the RfD that will be utilized by the aggregate
exposure to aminoethoxyvinylglycine will range from 4.6% for children 7
to 12 years old, up to 36.1% for non-nursing infants less than 1 year
old. Therefore, EPA concludes that there is a reasonable certainty that
no harm will result to infants and children from aggregate exposure.
V. Other Considerations
A. Endocrine Effects
Currently, EPA does not have any data indicating that
aminoethoxyvinylglycine has endocrine effects. The Agency is not
requiring information on the endocrine effects of this biochemical
plant regulator at this time; Congress has allowed 3 years after FQPA
was signed into law on August 3, 1996, for the Agency to implement a
screening and testing program with respect to endocrine effects.
B. Metabolism in Plants and Animals
The metabolism of aminoethoxyvinylglycine in plants and animals is
adequately understood for the purposes of these time-limited
tolerances. A study designed to determine whether uptake, translocation
and metabolism of aminoethoxyvinylglycine occurs in apples identified
seven minor metabolites in addition to the primary metabolite, N-acetyl
aminoethoxyvinylglycine. The study was not meant as a measure of the
amount of aminoethoxyvinylglycine residues and metabolites found in
apples under normal field conditions. The only significant
incorporation of aminoethoxyvinylglycine in apple tissues, following
brush-on application at high rates, resulted from absorption from the
peel rather than translocation from the leaves. Aminoethoxyvinylglycine
is also metabolized in the tissues to form N-acetyl
aminoethoxyvinylglycine and several other minor metabolites, and is
partially degraded on the apple surface to water-soluble products that
may be formed due to microbial and/or photodegradative action.
C. Analytical Method
There is a practical method for detecting and measuring levels of
aminoethoxyvinylglycine in or on food with a limit of detection that
allows monitoring of food with residues at or above the levels set in
these time-limited tolerances. The proposed analytical method for
determining residues is high-pressure liquid chromatography (HPLC). The
HPLC/fluorescence detector analytical method used by the registrant has
been validated by an independent laboratory (ABC Laboratories), as
required by PR Notice 88-5, and is sufficient for these time-limited
tolerances. Validation by an EPA laboratory is a condition of
registration for aminoethoxyvinylglycine, and upon such validation
information on this method will be provided to FDA. In the interim, the
registrant-submitted method is available to anyone interested in
pesticide enforcement when requested by mail from: Calvin Furlow,
Public Response Branch. Field Operations Division (7506C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. Office location and telephone number: Rm. 1130A,
CM #2, 1921 Jefferson Davis Hwy., Arlington, VA 22202 (703) 305-5937.
D. International Tolerances
There are no Codex Alimentarius Commission (Codex) Maximum Residue
Levels (MRLs) for residues of aminoethoxyvinylglycine on apples or
pears, or on any other crops.
E. Data Gaps
A data gap currently exists for a rat two-generation reproduction
study. All tolerances are time-limited because of this data gap. The
time limitation allows for development and review of the data. The
study, imposed by EPA to augment the results of the developmental
toxicity study, is expected to be submitted and reviewed prior to the
expiration date of these tolerances. Based on the available
toxicological data, the thousandfold uncertainty factor, and the levels
of exposure, the EPA has determined that the proposed time-limited
tolerances have a reasonable certainty of no harm from aggregate
exposure to the pesticide and its residues.
F. Summary of Findings
The analysis for aminoethoxyvinylglycine using tolerance level
residues shows that the proposed uses in the culture of apples and
pears will not cause exposure to exceed the levels at which the Agency
believes there is an appreciable risk. All population subgroups
examined by EPA are exposed to aminoethoxyvinylglycine residues at
levels below 100 percent of the RfD for chronic effects.
Based on the information cited above, the Agency has determined
that the establishment of the time-limited tolerances by adding a new
section to 40 CFR part 180 will be safe; therefore the time-limited
tolerances are established as set forth below.
VI. Objections and Hearing Requests
The new FFDCA section 408(g) provides essentially the same process
for persons to ``object'' to a tolerance regulation issued by EPA under
new section 408(e) and (1)(6) as was provided in the old section 408
and in
[[Page 24838]]
section 409. However, the period for filing objections is 60 days,
rather than 30 days. EPA currently has procedural regulations which
govern the submission of objections and hearing requests. These
regulations will require some modification to reflect the new law.
However, until those modifications can be made, EPA will continue to
use those procedural regulations with appropriate adjustments to
reflect the new law.
Any person may, by July 7, 1997, file written objections to any
aspect of this regulation and may also request a hearing on those
objections. Objections and hearing requests must be filed with the
Hearing Clerk, at the address given above (40 CFR 178.20). A copy of
the objections and/or hearing requests filed with the Hearing Clerk
should be submitted to the OPP docket for this rulemaking. The
objections submitted must specify the provisions of the regulation
deemed objectionable and the grounds for the objections (40 CFR
178.25). Each objection must be accompanied by the fee prescribed by 40
CFR 180.33(i). If a hearing is requested, the objections must include a
statement of the factual issue(s) on which a hearing is requested, the
requestor's contentions on such issues, and a summary of any evidence
relied upon by the objector (40 CFR 178.27). A request for a hearing
will be granted if the Administrator determines that the material
submitted shows the following: There is a genuine and substantial issue
of fact; there is a reasonable possibility that available evidence
identified by the requestor would, if established, resolve one or more
of such issues in favor of the requestor, taking into account
uncontested claims or facts to the contrary; and resolution of the
factual issue(s) in the manner sought by the requestor would be
adequate to justify the action requested (40 CFR 178.32). Information
submitted in connection with an objection or hearing request 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. A copy of the information 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.
VII. Public Docket
EPA has established a record for this rulemaking under docket
number [OPP-300480] (including any comments and data submitted
electronically). 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 may 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.
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 any copies of objections and hearing requests
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.
VIII. Regulatory Assessment Requirements
Under Executive Order 12866 (58 FR 51735, Oct. 4, 1993), this
action is not a ``significant regulatory action'' and since this action
does not impose any information collection requirements subject to
approval under the Paperwork Reduction Act, 44 U.S.C. 3501 et seq., it
is not subject to review by the Office of Management and Budget. In
addition, this action does not impose any enforceable duty, or contain
any ``unfunded mandates'' as described in Title II of the Unfunded
Mandates Reform Act of 1995. (Pub. L. 104-4), or require prior
consultation as specified by Executive Order 12875 (58 FR 58093, Oct.
28, 1993), or special considerations as required by Executive Order
12898 (59 FR 7629, February 16, 1994).
Because tolerances established on the basis of a petition under
section 408(d) of FFDCA do not require issuance of a proposed rule, the
regulatory flexibility analysis requirements of the Regulatory
Flexibility Act (RFA), 5 U.S.C. 604(a), do not apply. Prior to the
recent amendment of the FFDCA, EPA had treated such rulemakings as
subject to the RFA; however, the amendments to the FFDCA clarify that
no proposal is required for such rulemakings and hence that the RFA is
inapplicable. Nonetheless, the Agency has previously assessed whether
establishing tolerances or exemptions from tolerance, raising tolerance
levels, or expanding exemptions adversely impact small entities and
concluded, as a generic matter, that there is no adverse impact (46 FR
24950, May 4, 1981).
Pursuant to 5 U.S.C. 801(a)(1)(A), EPA submitted a report
containing this rule and other required information to the U.S. Senate,
the U.S. House of Representatives and the Comptroller General of the
General Accounting Office prior to publication of the rule in today's
Federal Register. This rule is not a major rule as defined by 5 U.S.C.
804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and Pests, Reporting and
recordkeeping requirements.
Dated: April 24, 1997.
Daniel M. Barolo,
Director, Office of Pesticide Programs.
Therefore, 40 CFR part 180 is amended as follows:
PART 180--[AMENDED]
1. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 346a and 371.
2. By adding Sec. 180.502 to read as follows:
Sec. 180.502 Aminoethoxyvinylglycine; tolerances for residues.
(a) General. Tolerances are established for residues of
aminoethoxyvinylglycine in or on the following food commodities:
------------------------------------------------------------------------
Parts per Revocation/
Commodity million Expiration Date
------------------------------------------------------------------------
Apples.................................. 0.08 April 1, 2001
Pears................................... 0.08 4April 1, 2001
------------------------------------------------------------------------
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 97-11901 Filed 5-6-97; 8:45 am]
BILLING CODE 6560-50-F
