[Federal Register Volume 61, Number 57 (Friday, March 22, 1996)]
[Rules and Regulations]
[Pages 11994-12009]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-7026]
[[Page 11993]]
_______________________________________________________________________
Part V
Environmental Protection Agency
_______________________________________________________________________
40 CFR Part 185
Revocation of Pesticide Food Additive Regulations; Final Rule
Federal Register / Vol. 61, No. 57 / Friday, March 22, 1996 / Rules
and Regulations
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[[Page 11994]]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 185
[OPP-300335A; FRL-5357-7]
Revocation of Pesticide Food Additive Regulations
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: EPA has made a final determination regarding 26 food additive
regulations (FARs) for 7 pesticides that were previously proposed for
revocation on the grounds that the FARs violated the Delaney clause in
section 409 of the Federal Food, Drug and Cosmetic Act (FFDCA). Today,
EPA is revoking 13 FARs because they violate the Delaney clause and the
remaining 13 FARs because they are not needed to prevent adulterated
food.
EFFECTIVE DATE: This final rule is effective May 21, 1996.
ADDRESSES: Written objections, requests for a hearing, and/or requests
for stays identified by the document control number OPP-300335A (FRL-
5357-7), must be submitted by April 22, 1996, to the Hearing Clerk,
EPA, 401 M Street, SW., Washington, DC 20460, with a copy to the OPP
docket. Comments on objections, requests for a hearing, and/or requests
for stays must be submitted by May 6, 1996 to the OPP docket: Public
Response and Program Resources Branch, Field Operations Division
(7506C), Office of Pesticide Programs, Environmental Protection Agency,
401 M St. SW., Washington, DC 20460. Hand deliver to: Rm. 1132, CM 2,
1921 Jefferson Davis Hwy., Arlington, VA.
Information submitted as a filing concerning this document 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 filings 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 (non-CBI) filings will be available for public inspection in
Rm. 1132 at the address given above, from 8 a.m. to 4 p.m., Monday
through Friday, excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: By mail: Niloufar Nazmi, Special
Review Branch (7508W), Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. Office location and telephone number: Crystal
Mall #2, Room 1113, 1921 Jefferson Davis Highway, Arlington, VA (703)
308-8028; e-mail: [email protected].
SUPPLEMENTARY INFORMATION:
Table of Contents
I. Introduction
A. Statutory Background
B. Regulatory Background
C. Actions Since Proposed Rule
D. Today's Action
II. EPA's Policy Changes Since the Proposal
A. Concentration and Ready-to-Eat Policies
B. Updated Residue Chemistry Guidelines
C. RAC Interpretation
III. Decision Framework
IV. Analysis of the FARs
A. Is a FAR needed?
B. Induce Cancer Determination
V. EPA's Decisions
A. FARs That are Not Needed
B. Food Additive Regulations That Violate the Delaney Clause
VI. Consideration of Comments
VII. Procedural Matters
A. Filing of Objections and Requests for Hearings
B. Effective Date
C. Request for Stays of Effective Date
VIII. Regulatory Requirements
A. Executive Order 12866
B. Regulatory Flexibility Act
C. Paperwork Reduction Act
D. Unfunded Mandates Reform Act and Executive Order 12875
I. Introduction
A. Statutory Background
The Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 301 et
seq., authorizes the establishment by regulation of maximum permissible
levels of pesticides in foods. Such regulations are commonly referred
to as ``tolerances.'' Without such a tolerance or an exemption from the
requirement of a tolerance, a food containing a pesticide residue is
``adulterated'' under section 402 of the FFDCA and may not be legally
moved in interstate commerce. 21 U.S.C. 331, 342. EPA was authorized to
establish pesticide tolerances under Reorganization Plan No. 3 of 1970.
5 U.S.C. App. at 1343 (1988). Monitoring and enforcement of pesticide
tolerances are carried out by the U.S. Food and Drug Administration
(FDA) and the U.S. Department of Agriculture (USDA). EPA can establish
a tolerance in response to a petition (FFDCA section 408(d)(1),
409(b)(1)), or on its own initiative (FFDCA sections 408(e), 409(d)).
The FFDCA has separate provisions for tolerances for pesticide
residues on raw agricultural commodities (RACs) and tolerances on
processed food. For pesticide residues in or on RACs, EPA establishes
tolerances, or exemptions from tolerances when appropriate, under
section 408. 21 U.S.C. 346a. EPA regulates pesticide residues in
processed foods under section 409, which pertains to ``food
additives.'' 21 U.S.C. 348. Maximum residue regulations established
under section 409 are commonly referred to as food additive regulations
(hereafter referred to as ``FARs''). Section 409 FARs are needed,
however, only for certain pesticide residues in processed food. Under
section 402(a)(2) of the FFDCA, a pesticide residue in processed food
generally will not render the food adulterated if the residue results
from application of the pesticide to a RAC and the residue in the
processed food when ready to eat is below the RAC tolerance. This
exemption in section 402(a)(2) is commonly referred to as the ``flow-
through'' provision because it allows the section 408 raw food
tolerance to flow through to the processed food forms. Thus, a section
409 FAR is only necessary to prevent foods from being deemed
adulterated when the level of the pesticide residue in a processed food
when ready to eat is greater than the tolerance prescribed for the RAC,
or if the processed food itself is treated or comes in contact with a
pesticide.
If a food additive regulation must be established, section 409 of
the FFDCA requires that the use of the pesticide will be ``safe'' (21
U.S.C. 348(c)(3)). Relevant factors in this safety determination
include (1) the probable consumption of the pesticide or its
metabolites; (2) the cumulative effect of the pesticide in the diet of
man or animals, taking into account any related substances in the diet;
and (3) appropriate safety factors to relate the animal data to the
human risk evaluation. Section 409 also contains the Delaney clause,
which specifically provides that ``no additive shall be demed safe if
it has been found, after tests which are appropriate for the evaluation
of the safety of food additives, to induce cancer when ingested by man
or animal.''
B. Regulatory Background
1. Les v. Reilly
On May 25, 1989, the State of California, the Natural Resources
Defense Council, Public Citizen, the AFL-CIO, and several individuals
filed a petition requesting that EPA revoke several FARs. The
petitioners argued that these FARs should be revoked because they
violated the Delaney clause.
[[Page 11995]]
EPA responded to the petition by revoking certain FARs, but
retained several others on the grounds that the Delaney clause provides
an exception for pesticide residues posing de minimis risk; EPA denied
the petition with respect to the FARs determined to fall under this
exception. EPA's response was challenged by the petitioners in the U.S.
Court of Appeals, Ninth Circuit. On July 8, 1992, the court ruled in
Les v. Reilly, 968 F.2d 985 (9th Cir.), cert. denied, 113 S.Ct. 1361
(1993), that the Delaney clause barred the establishment of a FAR for
pesticides which ``induce cancer'' no matter how infinitesimal the
risk.
In response to the court's decision in Les v. Reilly, EPA has taken
steps to identify and revoke all section 409 FARs for pesticides which
``induce cancer.'' On March 30, 1994, EPA issued a list of pesticide
uses which potentially could be affected by the court's decision (59 FR
14980). (Note that, for the purpose of today's document, this list has
been superseded by appendices to the court-approved settlement in
California v. Browner, discussed below.)
After revoking certain FARs of six pesticides that were the subject
of the original NRDC petition, EPA decided to evaluate the remaining
pesticide uses in phases. The first phase of proposed revocations was
announced on July 1, 1994, and involved 26 FARs for seven pesticides
(59 FR 33941; July 1, 1994). In today's notice, EPA is making final
determinations regarding these 26 FARs.
2. California v. Browner
In a court-approved settlement, entered on February 9, 1995, in the
case of California v. Browner, EPA agreed to make decisions regarding
pesticides that may be affected by the Delaney clause. This settlement
agreement includes a timetable for making the decisions. This document
is consistent with the timeframes in that settlement.
C. Actions Since Proposed Rule
The National Food Processors' Association (NFPA) filed a petition
with the EPA in September 1993. This petition challenged a number of
policies under which EPA administers its tolerance-setting program. In
the Federal Register of June 14, 1995 (60 FR 31300), EPA issued a
partial response to the NFPA petition. In that document, EPA concluded
that some changes were warranted to its policies concerning application
of the Delaney clause, in particular the concentration and ``ready-to-
eat'' (RTE) policies. On January 25, 1996, EPA completed its response
to the NFPA petition by announcing its coordination policy and its
interpretation of what constitutes a RAC (61 FR 2378). Section II of
this preamble contains a summary of these policy changes.
D. Today's Action
The FAR revocations being made final in this notice were proposed
on July 1, 1994 (59 FR 33941), before EPA had responded to the NFPA
petition and adopted its new policies. In addition, EPA has received
many petitions from the registrants of these pesticides requesting
revocation of many of the FARs, on the basis that they are not needed.
For each of these petitions, EPA has published a ``Notice of
Availability and Request for Comments'', in the Federal Register.
Today's final rule is consistent with EPA's new policies and, where
appropriate, the decisions are based on the petitions rather than the
proposed rule of July 1, 1994.
II. EPA's Policy Changes Since the Proposal
A. Concentration and Ready-to-Eat Policies
To determine whether the use of a pesticide on a growing crop needs
a section 409 FAR in addition to a section 408 tolerance, EPA looks at
the likelihood that the residue levels in the processed food when ready
to eat will exceed the section 408 tolerance level. In the past, EPA
applied this policy focusing almost exclusively on the results of
processing studies using treated crops. In response to the NFPA
petition, EPA announced new policies on how it would determine whether
a pesticide needs a section 409 FAR (60 FR 31300, July 1, 1994). EPA
stated that it would consider a greater range of information in
determining the likelihood of residues in processed food exceeding the
section 408 tolerance. EPA also adopted a definition of RTE as it
applies to human food and animal feed. Whether a food is RTE or not is
critical to application of the concentration policy. If a food is not
RTE, EPA considers the degree of dilution that occurs in producing a
RTE food from the not-RTE food in determining the likelihood that
residues in RTE food will exceed the section 408 tolerance.
Perhaps the most significant new information that EPA stated it
would consider is information bearing on the average residue value from
crop field trials. The data from field residue trials show that it is
possible to obtain significantly different residue values from multiple
field trials. EPA's old policy was to use the highest field trial
sample value to calculate expected residues in the processed food.
However, in response to the NFPA petition, EPA concluded that where a
crop is mixed or blended during processing, it is appropriate to use an
average of the residue levels from field trials, rather than the
highest sample value in estimating the potential level of residue in
processed food. As EPA noted, EPA believes that generally the most
appropriate average value to use is the ``highest average field trial''
(HAFT) value, or the average of the highest values found in each of the
field trials. Consequently, EPA revised its procedures and is now using
the HAFT as the basis for determining whether a section 409 FAR is
needed. Use of the HAFT for food commodities that are likely to be
mixed or blended decreases the likelihood that residues in processed
food will exceed the section 408 tolerance.
In addition EPA has revised its policies for the use of multiple
processing studies. EPA may receive several processing studies for a
crop, with each showing a different concentration factor. When
different concentration factors result from multiple processing
studies, EPA will now use the average concentration factor to determine
the expected level of concentration. In addition, EPA is examining
processing studies to ensure that they reflect typical commercial
practices. If a study does not include a step (e.g., washing) that is
considered typical practice in processing a RAC, EPA may decide not to
include that study in the calculation of the average concentration
factor.
In response to the NFPA petition, EPA stated it would interpret the
phrase RTE food as meaning food ready for consumption ``as is'' without
further preparation. For instance, EPA has determined that cottonseed
oil is not RTE, while oat bran is.
B. Updated Residue Chemistry Guidelines
In a notice issued September 21, 1995 (60 FR 49150), EPA announced
the availability of its updated table II of the Pesticide Assessment
Guidelines, Subdivision O, Residue Chemistry. This table, commonly
referred to ``Residue Chemistry Table II'' provides a listing of all
significant food and feed commodities, both raw and processed, for
which residue data are collected and tolerances or FARs are
established. In the latest update of this table, criteria were
established for inclusion of feed items, and, based on those criteria,
a number of feed items were eliminated as significant animal feeds. If
a commodity is not listed in table II as a significant
[[Page 11996]]
food or feed, a tolerance is not necessary for pesticide residues in
that commodity.
C. RAC Interpretation
On January 25, 1996 (61 FR 2386), EPA published its interpretation
of the term RAC as applied to dried commodities under the FFDCA. This
notice explained EPA's interpretation of which dried commodities
qualify as RACs. EPA based its interpretation on the purpose of drying,
such that commodities dried for the purpose of creating a new
marketable commodity are treated as processed food, while those dried
for storage or transportation needs are treated as raw foods. This
interpretation is consistent with EPA's current practice and therefore
no commodities were reclassified as either RAC or processed as a result
of the interpretation.
III. Decision Framework
In analyzing whether the 26 FARs addressed in this document should
be revoked, EPA has used the following decision framework. First, EPA
determined whether a section 409 FAR was necessary to prevent
adulteration, given the revisions to the concentration, RTE, and RAC
policies as well as to table II. If application of new policies showed
no FAR was needed, this document revokes the FAR on that ground.
However, if the analysis showed that a FAR is still needed, then the
FAR's consistency with the Delaney clause was analyzed. Contrary to the
opinion expressed in some comments on the proposed rule (see comments
of American Crop Protection Association, and EPA's response in Unit VI
of this preamble), EPA does not believe that this approach is legally
required under the FFDCA. EPA has chosen this approach in its
discretion.
In examining whether a FAR was needed, EPA followed a stepwise
process involving a series of questions. In brief, the questions are:
1. Do processing data show that there is actual concentration of
residues during processing? If processing studies demonstrate that the
level of residues in the processed food is less than or equal to the
level of residues in the precursor crop (i.e., no ``concentration in
fact''), residues in the processed food would not be expected to exceed
the section 408 tolerance.
2. Does use of the average of concentration factors from multiple
processing studies show that there is concentration of residues during
processing?
3. Is the commodity mixed or blended during processing, such that
use of the HAFT value is appropriate?
4. Using the HAFT, do residues in processed food exceed the section
408 tolerance?
5. If a processed food item is not eaten ``as is,'' is the dilution
that occurs during preparation of RTE food sufficient to reduce
pesticide residues below the section 408 tolerance? EPA will evaluate
the expected residue level in RTE food containing the processed food
item. If the dilution of residues resulting from RTE food preparation
is greater than the concentration of residues resulting from processing
(the dilution factor is greater than the concentration factor), it is
likely that the residues in the finished RTE food will be less than the
section 408 tolerance. In this case, no FAR would be necessary for the
RTE food.
If, after consideration of the above factors, a FAR was determined
to be necessary, EPA then examined whether the existing FAR for the
pesticide chemical violates the Delaney clause.
IV. Analysis of the FARs
EPA originally proposed to revoke all 26 FARs on the basis that
they violate the Delaney clause. EPA has since determined that under
its revised concentration and RTE policies, 13 FARs are not needed to
prevent adulterated food. For the 13 FARs that are needed, EPA next
examined their consistency with the ``induce cancer'' standard of the
Delaney clause in section IV.B. of this preamble.
A. Is a FAR needed?
Under current policy, a FAR is needed when the appropriate field
trial residue value multiplied by the appropriate concentration factor
significantly exceeds the section 408 tolerance in the ready to eat
commodity. The extent to which EPA will allow residues in the processed
food to exceed the section 408 tolerance is determined on a case by
case basis, taking into account the sensitivity of the analytical
method used to detect the residues. In analyzing the need for section
409 FARs, EPA has taken into account not only existing section 408
tolerances but also available residue data bearing on whether the
current section 408 tolerance should be revised under existing
tolerance-setting policies. EPA has received large amounts of residue
data as part of the pesticide reregistration program of section 4 of
the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). Review
of these data in several instances shows that the existing section 408
tolerance is set either too high or too low. Tolerance adjustments
would normally be accomplished through the reregistration program.
EPA, however, sees no reason to wait until these tolerances are
formally revised to determine whether the pesticide concentrates for
the purpose of applying the coordination policy. EPA has decided that
it should base its concentration decision upon the most recent data on
residues in raw crops. If those data indicate that section 408
tolerances should be adjusted, EPA has used the adjusted section 408
tolerance level as the basis for its determination of whether a section
409 FAR is needed because the pesticide concentrates. The basis for
EPA's determination that a section 408 tolerance should be adjusted is
in the docket for this rulemaking.
Captan on raisins. EPA proposed to revoke FARs for captan both from
pre-harvest use on grapes and direct treatment to raisins.
On January 31, 1996, EPA published notice in the Federal Register
(61 FR 3401) of a petition filed by the Captan Task Force requesting
revocation of the section 409 FAR for raisins. The petition claims that
good manufacturing practice for producing raisins requires that the
raisins are washed before they are ready-to-eat and that washing
raisins substantially eliminates remaining captan residues. The
petition claims that because captan residues do not concentrate in
washed raisins above the established residue levels on treated grapes,
the FAR should be revoked.
EPA has reviewed the public comments and reconsidered the available
grape/raisin processing studies. EPA agrees that washing is standard
practice in raisin production, Accordingly, EPA has determined that
only those studies which involve washing the raisins reflect current
processing practices. When only those data which include a washing step
are used to evaluate the need for a section 409 FAR for raisins, the
average concentration factor for residues of captan per se on washed
raisins is less than one. Therefore, no section 409 FAR is needed for
residues from pre-harvest treatment.
In regard to direct post-harvest application to grapes (drying
raisins), the petition claims that the section 409 FAR is not needed
because there are no registered products containing captan which
include label directions for post-harvest use on raisins. EPA has
reviewed all labels of products containing captan, and agrees with the
petitioner that there are no labels which allow postharvest use of
captan on drying grapes/raisins. Therefore, the
[[Page 11997]]
section 409 FAR is not needed for residues resulting from post-harvest
treatment of the fruit.
Ethylene oxide on ground spices. Since ethylene oxide is directly
applied to processed ground spices, the existing section 409 FAR is
necessary to prevent adulterated food. EPA policies on concentration
and dilution in RTE foods are not relevant to a processed commodity
treated directly with a pesticide.
Mancozeb on brans of oats, barley and rye; flours of oats, barley,
rye and wheat. On May 19, 1993, EPA published notice in the Federal
Register (58 FR 29318) of a petition filed by the Mancozeb Task Force.
This petition sought the revocation of the section 409 FAR for the
flours and brans of barley, oats, rye and wheat. The petitioner argued
that residues do not concentrate in the brans and flours of these
grains over the section 408 RAC tolerances. EPA has reviewed the
available data in accordance with the new Agency policies and made the
following determinations in regard to the residues of Mancozeb on brans
of oats, barley and rye, and flours of oats, barley, rye and wheat.
Oat bran. The current section 408 tolerance for mancozeb on oat
grain is 5 ppm (40 CFR 180.176). Evaluation of new residue data
indicates that the tolerance should be reduced to 1 ppm. Based on the
HAFT of 0.98 ppm for oat grain and an average concentration factor of
2.0 in oat bran, the expected residue in oat bran is calculated as 2.0
ppm. The HAFT multiplied by the concentration factor is 0.98 X 2.0=2.0
ppm. (This calculation is used throughout the document to calculate
expected residue levels.) EPA believes that it is likely that some oat
bran will contain residues exceeding the adjusted RAC tolerance level
of 1 ppm. Oat bran is a RTE processed food and needs a section 409 FAR.
Barley and rye bran. The current section 408 tolerance for mancozeb
on barley and rye grains are 5 ppm (40 CFR 180.176). Evaluation of new
residue data indicate that this tolerance should be reduced to 1 ppm.
Based on the HAFT of 0.98 ppm for barley and rye grain and an average
concentration factor of 2.0 in the brans, the expected residues in
barley and rye brans are calculated as 2.0 ppm. EPA has determined that
both rye and barley bran are not RTE foods and that once they are
prepared to their RTE forms, mancozeb residues are unlikely to exceed
the adjusted section 408 tolerances of 1 ppm for rye and barley grains.
Therefore, the section 409 FARs for mancozeb on brans of barley and rye
are not needed and will be revoked on these grounds. EPA will propose
to establish a Maximum Residue Limit (MRL) under section 701 of FFDCA
in or on barley bran. Moreover, EPA has determined that rye bran is not
a significant human food and does not require pesticide residue
tolerances. A memo to this effect is in OPP docket 300415.
Flours of oat, barley, rye and wheat. The current FAR for flours of
oat, barley, rye and wheat is 1 ppm (40 CFR 185.6300). EPA has
determined that the average concentration factor for wheat flour is
less than one, and has used it for other grains. Residues in processed
flours are not expected to exceed the adjusted RAC tolerance of 1 ppm
for the grains. Therefore, no section 409 FAR is needed for the flours
of oat, barely, rye and wheat.
Oxyfluorfen on spearmint, peppermint, soybean and cottonseed oils.
On December 14, 1994, EPA published notice in the Federal Register (59
FR 64405) of a petition filed by the Rohm and Haas Company which sought
to revoke these section 409 FARs because they are not needed. The
petitioner claimed that all processed oil data from processing studies
show that residue levels in oils are below the section 408 tolerance
levels. The petitioner also argued that these oils are not RTE
commodities.
Spearmint and peppermint oils. The current section 408 tolerance
for oxyfluorfen on mint hay is 0.1 ppm (40 CFR 180.381). Evaluation of
new residue data indicates that the tolerance should be reduced to 0.05
ppm. Based on the HAFT of 0.03 ppm for mint hay, and an average
concentration factor of 2.4, the expected residues in mint oils are
calculated as 0.072 ppm. The residue level for mint oils is not
appreciably higher than the adjusted mint RAC tolerance of 0.05 ppm,
taking into account the sensitivity of the analytical method used to
detect oxyfluorfen residues. In addition, peppermint and spearmint oils
are not RTE commodities, and the Agency has determined that they are
diluted by a factor of 120 and 160 respectively in RTE foods.
Therefore, a section 409 FAR is not needed. EPA will propose to
establish Maximum Residue Limits under section 701 of FFDCA for
oxyfluorfen in or on mint oils.
Soybean oil. Dry soybean seeds treated at 5 times the maximum
application rate did not have quantifiable oxyfluorfen residues, thus
processing data are not able to show the degree of concentration in
soybean oil. The maximum theoretical concentration factor for soybean
oil is 5. Since this is the same as the application exaggeration in the
residue study, oxyfluorfen residues in soybean oil, are not expected to
exceed the section 408 tolerance of .05 ppm. Therefore, a section 409
FAR is not needed.
Cottonseed oil. The current section 408 tolerance for oxyfluorfen
on cottonseed is 0.05 ppm (40 CFR 180.381). Evaluation of new residue
data indicates that the tolerance should be reduced to .02 ppm. Based
on the HAFT of 0.01 ppm for cottonseed and a concentration factor of
3.3, the expected residue in cottonseed oil is .04 ppm. Cottonseed oil
is not a RTE processed food and once diluted by a factor of 11, which
accounts for the minimum level of dilution of cottonseed oil in
preparing RTE food, the residues in the RTE food items are not expected
to exceed the adjusted section 408 RAC tolerance of .02 ppm. Therefore
a section 409 FAR is not needed. EPA will propose to establish Maximum
Residue Limits under section 701 of FFDCA for oxyfluorfen in or on
cottonseed oil.
Propargite on raisins, dried figs, and tea. On September 7, 1994,
EPA published a notice in the Federal Register (59 FR 46250) of a
petition filed by Uniroyal Chemical Company which sought to revoke the
section 409 FAR on raisins because it is not needed. The petitioner
claimed that propargite residues are susceptible to release through
mechanical or washing processes and therefore do not concentrate in
raisins.
Raisins. Based on the HAFT of 4.7 ppm for grapes and an average
concentration factor of 1.7, the expected residue in raisins is
calculated at 8.0 ppm, which is less than the established section 408
RAC tolerance of 10 ppm for grapes. Therefore, a section 409 FAR is not
needed for raisins.
Dried figs. Based on a HAFT of 1.8 ppm for figs and an average
concentration factor of 2.7 for dried figs, the expected residue level
in dried figs is 4.9 ppm. EPA believes that it is likely that some
dried figs will contain propargite residues exceeding the established
RAC tolerance level of 3 ppm. Since dried figs are RTE, a section 409
FAR is needed.
Dried tea. Tea is a processed food item even though it is not
considered a RTE food. EPA has determined that the degree of dilution
from dried tea to brewed RTE tea will exceed any concentration from
fresh green tea to dried tea.
Under the circumstances where: (1) There is a section 408 tolerance
for the RAC; and (2) residues in the RTE food are below the section 408
tolerance, EPA normally would determine that the
[[Page 11998]]
section 409 FAR is not necessary. Residues would be covered by the
section 408 tolerance under the flow-through provision of section 402,
and EPA would revoke the FAR on that ground.
Tea presents a unique situation, because the FAR is established
primarily for import purposes. However, because only the dried tea is
imported into the United States, there is no section 408 tolerance for
fresh tea. Without a section 408 tolerance, the flow-through provision
does not apply. Revocation of the section 409 FAR would leave no
tolerance to cover residues in tea, potentially resulting in
adulterated tea. Therefore, the section 409 FAR for dried tea is
necessary.
Propylene oxide on glace fruit, cocoa, gums, dried prunes,
processed nutmeats (except peanuts), starch and processed spices. Since
propylene oxide is directly applied to these commodities, the ``flow
through'' provision of section 402 does not apply and the existing
section 409 FAR is necessary to prevent adulterated food.
Simazine on Sugarcane molasses and syrup. Molasses is a RTE food
item. The average concentration factor in the processing of molasses is
10. A determination of the HAFT has not been made since the
concentration factor is so large that the HAFT multiplied by that
number is certain to appreciably exceed the section 408 tolerance (.25
ppm). EPA expects that in most cases the HAFT will not be lower than
the tolerance by a factor of two. This conclusion is based on EPA's
experience with setting 408 tolerances (i.e., how they are derived
based on the highest residue values) and with the relationships between
average residues in field trials and either tolerances or maximum field
trial residues, which are usually close to the tolerance. In most cases
average residues across all field trials for a given crop are 2-6 times
less than a tolerance or maximum field trial value. The highest average
field trial (HAFT) will be higher than the average residue across all
trials. Therefore, in this particular case the Agency is confident that
ten times the HAFT will be appreciably higher than the 408 tolerance.
Examples of the relationships between average residues and tolerances
or maximum field trial residues are available in the docket for this
notice. EPA's conclusion regarding the level of simazine residues in
sugarcane molasses is confirmed by a processing study in which
sugarcane treated at the maximum application rate showed total residues
of 0.63 ppm in molasses, well above the 0.25 ppm sugarcane tolerance.
Therefore, EPA believes that it is likely that some molasses will
contain residues exceeding the tolerance.
According to Residue Chemistry Table II, sugarcane syrup is not
considered a significant human food item. The Agency has determined
that no section 409 FAR is required.
Simazine in potable water. Even though EPA no longer sets section
409 FARs under the FFDCA for residues in potable water, this FAR for
simazine exists. Therefore, EPA will apply the same analysis to it as
to the other section 409 FARs addressed in this notice.
B. Induce Cancer Determination
If a FAR is necessary to prevent adulterated food, as in the case
of the 13 FARs of the five chemicals discussed above, EPA must
determine whether the pesticide induces cancer within the meaning of
the Delaney clause. In the proposal for this final rule (59 FR 33941;
July 1, 1994), EPA determined that all of the following five chemicals
``induce cancer'' within the meaning of the Delaney clause: Ethylene
oxide, mancozeb, propargite, propylene oxide and simazine. (OPP docket
300335.)
In construing the ``induce cancer'' standard as to animals, EPA
follows a weight-of-the-evidence approach. In regard to animal
carcinogenicity, EPA, in general, interprets ``induces cancer'' to
mean:
The carcinogenicity of a substance in animals is established when
administration in an adequately designed and conducted study or studies
results in an increase in the incidence of one or more types of
malignant (or, where appropriate, benign or a combination of benign and
malignant) neoplasms in treated animals compared to untreated animals
maintained under identical conditions except for exposure to the test
compound. Determination that the incidence of neoplasms increases as
the result of exposure to the test compound requires a full biological,
pathological, and statistical evaluation. Statistics assist in
evaluating the biological significance of the observed responses, but a
conclusion on carcinogenicity is not determined on the basis of
statistics alone. Under this approach, a substance may be found to
``induce cancer'' in animals despite the fact that increased tumor
incidence occurs only at high doses, or that only benign tumors occur,
and despite negative results in other animal feeding studies. (See 58
FR 37863, July 14, 1993; 53 FR 41108, October 19, 1988; and 52 FR
49577, December 31, 1987.)
EPA has considered the comments submitted on the proposed rule, and
has applied this interpretation to the 5 chemicals addressed above.
Based on this analysis, EPA concludes that ethylene oxide, mancozeb,
propargite, propylene oxide and simazine induce cancer within the
meaning of the Delaney clause. Because EPA has determined that the
section 409 FARs for captan and oxyfluorfen should be revoked on
grounds other than the Delaney clause, the Agency is not issuing a
final finding in this action that these chemicals induce cancer within
the meaning of the Delaney clause. Full copies of EPA's reviews of each
chemical and other references in this document are available in the OPP
docket 300335, the location of which is given in the ``ADDRESSES''
section of this preamble.
V. EPA's Decisions
A. FARs That Are Not Needed
Captan. EPA is revoking the FAR for the fungicide captan in or on
raisins (50 ppm). This FAR is codified at 40 CFR 185.500. EPA is
revoking this regulation because the Agency has determined that this
FAR is not needed to prevent adulterated food. This final rule is based
on the grounds discussed in the petition of January 31, 1996, discussed
in Unit IV of this preamble.
Mancozeb. EPA is revoking the FARs for mancozeb (expressed as the
zinc ion and maneb coordination product) for residues in the brans of
barley and rye (20 ppm) and in the flours of barley, oats, rye and
wheat (1 ppm). These FARs are codified at 40 CFR 185.6300. EPA is
revoking these FARs because they are not needed to prevent adulterated
food. This final rule is based on the grounds discussed in the petition
of May 19, 1993, discussed in Unit IV of this preamble.
Oxyfluorfen. EPA is revoking the FARs for residues of oxyfluorfen
on cottonseed oil, peppermint oil, spearmint oil and soybean oil (.25
ppm). These FARs are codified at 40 CFR 185.4600. EPA is revoking these
FARs because the Agency has determined that these FARs are not needed
to prevent adulterated foods. This final rule is based on the grounds
discussed in the petition of December 14, 1994, discussed in Unit IV of
this preamble.
Propargite. EPA is revoking the FAR for residues of propargite on
raisins (25 ppm). This FAR is codified at 40 CFR 185.5000. EPA is
revoking this FAR because the Agency has determined that it is not
needed to prevent adulterated food. This final rule is based on the
grounds discussed in the petition of September 7, 1994, discussed in
Unit IV of this preamble.
[[Page 11999]]
Simazine. EPA is revoking the FAR for residues of simazine in
sugarcane syrup (1 ppm). This FAR is codified at 40 CFR 185.5350. EPA
is revoking this FAR because EPA has determined that it is not needed
to prevent adulterated food. This final rule is based on updated Agency
guidelines which dictate when a FAR is needed.
Table 1.--13 FARs That Are Not Needed
----------------------------------------------------------------------------------------------------------------
Food additive
Pesticide CFR citation Commodity regulation level
----------------------------------------------------------------------------------------------------------------
Captan 185.500 raisins 50.0 ppm
Mancozeb 185.6300 bran of barley, rye 20 ppm
flours of oats, barley, 1 ppm
rye, wheat
Oxyfluorfen 185.4600 peppermint, spearmint, 0.25 ppm
soybean, and cottonseed
oils
Propargite 185.5000 raisins 25 ppm
Simazine 185.5350 sugarcane syrup 1 ppm
----------------------------------------------------------------------------------------------------------------
B. Food Additive Regulations That Violate the Delaney Clause
Ethylene oxide. EPA is revoking the FAR for residues resulting from
the direct application of ethylene oxide to ground spices (50 ppm).
This FAR is codified at 40 CFR 185.2850. Ethylene oxide has been found
to induce cancer in animals based on tests which are appropriate for
the evaluation of the safety of food additives. Thus, this regulation
violates the Delaney clause in section 409 of the FFDCA.
Mancozeb. EPA is revoking the FAR for mancozeb (expressed as the
zinc ion and maneb coordination product) for residues in oat bran (20
ppm). This FAR is codified at 40 CFR 185.6300. Since mancozeb induces
cancer when ingested by animals, this regulation violates the Delaney
clause in section 409 of the FFDCA.
Propargite. EPA is revoking the FARs for residues of propargite on
dried figs (9 ppm) and dried tea (10 ppm). These FARs are codified at
40 CFR 185.5000. Since propargite induces cancer when ingested by
animals, these regulations violate the Delaney clause in section 409 of
the FFDCA.
Propylene oxide. EPA is revoking the FARs for residues of propylene
oxide on cocoa (300 ppm), glace fruit (700 ppm), gums (300 ppm),
processed nutmeats (except peanuts) (300 ppm), dried prunes (700 ppm),
processed spices (300 ppm), and starch (300 ppm). These FARs are
codified at 40 CFR 185.5150. Since propylene oxide induces cancer in
animals in tests appropriate for the evaluation of the safety of food
additives, these regulations violate the Delaney clause in section 409
of the FFDCA.
Simazine. EPA is revoking the FARs for residues of simazine on
sugarcane molasses (1 ppm) and in potable water (.01 ppm). These FARs
are codified at 40 CFR 185.5350. Since simazine induces cancer when
ingested by animals, these FARs violate the Delaney clause in section
409 of the FFDCA.
Table 2.--13 FARs That Violate The Delaney Clause
----------------------------------------------------------------------------------------------------------------
Food additive
Pesticide CFR citation Commodity regulation level
----------------------------------------------------------------------------------------------------------------
Ethylene oxide 185.2850 ground spices 50 ppm
Mancozeb 185.6300 bran of oats 20 ppm
Propargite 185.5000 dried figs 9 ppm
dried tea 10 ppm
Propylene oxide 185.5150 glace fruit 700 ppm
cocoa 300 ppm
gums 300 ppm
processed nutmeats 300 ppm
(except peanuts)
dried prunes 700 ppm
starch 300 ppm
processed spices 300 ppm
Simazine 185.5350 sugarcane molasses 1 ppm
potable water .01 ppm
----------------------------------------------------------------------------------------------------------------
VI. Consideration of Comments
EPA's proposed revocation of these FARs was published prior to
EPA's response to the NFPA petition. Many comments that were submitted
in response to the proposed rule urged EPA to reconsider many of its
tolerance setting policies, including the coordination, concentration,
RTE and RAC policies. As explained in the earlier units of this notice,
EPA has adopted new policies and used them in making the determinations
for this final rule. Because of these new policies, only 13 of the 26
FARs which EPA proposed to revoke on July 1, 1994, are being revoked
because they violate the Delaney clause. In addition, most commenters
also raised chemical specific issues, primarily concerning whether the
chemical induces cancer within the meaning of the Delaney clause. EPA's
response to chemical specific comments is summarized below. Full
responses to comments are in the docket.
American Crop Protection Association (ACPA)
Comments: ACPA submitted extensive comments on the proposal.
[[Page 12000]]
Many of ACPA's comments seem to suggest that EPA has incorrectly
applied the legal standard ``induce cancer'' because EPA failed to
duplicate prior FDA practice. ACPA admits that EPA announced it would
use FDA's ``induce cancer'' standard and would follow the weight of the
evidence approach used by FDA but ACPA contends that EPA's application
of the standard was not sufficiently thorough and that EPA has failed
to consider various categories of relevant evidence. ACPA alleges that
one particular type of evidence ignored by EPA is biologic and
mechanistic data. Further, ACPA argues that EPA has wrongly interpreted
the Delaney clause because EPA has failed to take into account the
relevance of the results of animal studies to humans. ACPA also asserts
that EPA failed to take account of the fact that an ``induce cancer''
finding is appropriate only where the evidence is ``conclusive.''
Finally, ACPA argues that EPA is legally required to determine whether
a section 409 FAR is legally necessary to prevent the adulteration of
food before revoking it on Delaney clause grounds.
EPA's response: EPA believes its application of the ``induce
cancer'' standard and the weight of the evidence approach has
sufficiently addressed all relevant evidence. Where ACPA or other
commenters have raised questions concerning how specific data were
considered for specific chemicals, EPA has in this notice or in the
docket responded to those comments. ACPA's comments regarding the role
of the relevance of animal studies to humans under the Delaney clause,
the relevance of biologic and mechanistic data, the degree of certainty
required for a Delaney clause finding, and the need for a determination
as to the necessity of a FAR are addressed below.
Relevance to humans. ACPA asserts that a substance does not induce
cancer within the meaning of the Delaney clause even if it produces
cancer when fed to experimental animals if the results of the
experiment are not relevant to human carcinogenicity. To support this
conclusion, ACPA first notes that the Delaney clause contains two
clauses separated by the conjunction ``or.''
[N]o additive shall be deemed to be safe if it is found to
induce cancer when ingested by man or animal or if it is found,
after tests which are appropriate for the evaluation of the safety
of food additives, to induce cancer in man or animal * * *.
21 U.S.C. 348(c)(3)(A) (emphasis added). According to ACPA, the first
clause is limited to evidence gathered through epidemiological studies
on humans or animals and the second clause addresses evidence gathered
from experiments. ACPA bases this conclusion on the inclusion of the
word ``tests'' in the second clause but not in the first. Further, ACPA
argues that the requirement that the tests be ``appropriate for the
evaluation of the safety of food additives'' mandates that EPA must
consider the relevance of both the test design and the test results to
human carcinogenicity. For example, ACPA asserts that if the test
produces cancer in the animals but that cancer would not be produced in
humans then the substance does not induce cancer in animals under the
Delaney clause because the test was inappropriate for an evaluation of
human carcinogenicity. A failure to consider the relevance of test
results to humans, ACPA contends, would make the focus of the Delaney
clause protection of the health of experimental animals, not humans.
EPA disagrees with each step of ACPA's analysis. First, EPA
believes that the feeding studies with experimental animals fall within
the first clause of the Delaney clause. It is a difficult stretch to
suggest that a substance that has produced cancer in an animal feeding
study has not been ``found to induce cancer when ingested by * * *
animal[s].'' This is especially the case when the alternative
interpretation is that this phrase refers to a type of study--an
epidemiological study of animals--which is rarely if ever used to
evaluate carcinogenicity.
Moreover, the legislative history refutes ACPA's proposed
interpretation. The second half of the Delaney clause concerning
appropriate tests was included in the anti-cancer provision because of
a concern that tests other than feeding studies might be deemed
controlling under the Delaney clause. At the same time the
``appropriate'' tests clause was added, the original clause was amended
to add a reference to ingestion, thus signaling a special status for
ingestion studies.
Congressman Delaney's anti-cancer clause as initially drafted
stated: ``The Secretary shall not approve for use in food any chemical
additive found to induce cancer in man, or, after tests, found to
induce cancer in animals.'' H.R. 7798, 85th Cong., 1st Sess., section
409 (d), reprinted in XIV A Legislative History of the Federal Food,
Drug, and Cosmetic Act at 97 [hereinafter cited as Leg. Hist.]. At
first, the Department of Health, Education and Welfare (HEW) objected
to a specific mention of cancer in the Food Additive Amendments but
relented and proposed the anti-cancer language which was enacted. HEW
explained in detail the reason for revising the initial anti-cancer
clause:
It would be important, also to use language that would provide
the intended safeguards without creating unintended and unnecessary
complications. For example, the language suggested by some to bar
carcinogenic additives would, if read literally, forbid the approval
for use in food of any substance that causes any type of cancer in
any test animal by any route of administration. This could lead to
undesirable results which obviously were not intended by those who
suggested the language. Concentrated sugar solution, lard, certain
edible vegetable oils, and even cold water have been reported to
cause a type of cancer at the site of injection when injected
repeatedly by hypodermic needle into the same spot in a test animal.
But scientists have not suggested that these same substances cause
cancer when swallowed by mouth.
The enactment of a law which would seem to bar such common
materials from the diet would place the agency that administered it
in an untenable position. The agency would either have to try to
enforce the law literally so as to keep these items out of the
diet--evidently an impossible task--or it would have to read between
the lines of the law an intent which would make the law workable,
without a clear guide from Congress as to what was meant.
This difficulty could readily be avoided, if there is still a
desire to make specific mention of cancer in the bill, by providing
that ``no additive shall be deemed to be safe if it is found to
induce cancer when ingested by man or animal, or if it is found,
after tests which are appropriate to the evaluation of the safety of
food additives, to induce cancer in animals.''
104 Cong. Rec. 17415 (1958), XIV Leg. Hist. at 869 (reprinting a letter
from Elliot L. Richardson, Assistant Secretary, Department of HEW). If
HEW had intended that HEW be granted discretion to decide whether any
test was appropriate for evaluating the safety of food additives, even
ingestion studies, the word ``appropriate'' could have simply been
inserted before ``tests'' in Congressman Delaney's draft. However, the
proposed revision not only added language modifying the word ``test''
but rewrote the opening language of the anticancer provision by
inserting a reference to ingestion and animals. This creates the clear
inference that the appropriateness of ingestion studies was not open to
question.
This was certainly the contemporaneous interpretation of the
Delaney clause. In 1960, when the addition of a Delaney clause to the
Color Additive Amendments was fully debated in Congress, the House
Report on the Amendments described the Delaney clause as follows:
This clause provides that a color additive shall be deemed
unsafe and shall not be
[[Page 12001]]
listed for any use which will or may result in ingestion of any part
of such additive, if the additive is found to induce cancer when
ingested by man or animal, or if it is found to induce cancer in man
or animal by other tests, not involving ingestion, which are
considered to be appropriate for the evaluation of the safety of
additives for use in food.
H. Rep. No. 1761, 86th Cong., 2d Sess. 11 (1960), XVI Leg. Hist. at
680. Similarly, the Secretary of HEW indicated at hearings on the Color
Additive Amendments that HEW interpreted the ``ingestion'' part of the
Delaney clause as requiring the use of scientific tests:
The conclusion that an additive ``is found to induce cancer when
ingested by man or animal'' is a scientific one. The conclusion is
reached by competent scientists using widely accepted scientific
testing methods and critical judgment.
Color Additives: Hearings on H.R. 7624 and S. 2197 Before the Comm. on
Interstate and Foreign Commerce, 86th Cong., 2d Sess. 62 (1960), XVI
Leg. Hist. at 67 (statement of HEW Secretary Flemming). Finally, that
the ``ingestion'' half of the Delaney clause was interpreted as
covering feeding studies and thus as being the principal operative
phrase in the Delaney clause is confirmed by HEW's reaction to a
proposal to delete the first half of the Delaney clause. HEW objected
arguing that this change ``is obviously designed to weaken the
anticancer clause and to allow room for the contention that our
Department should establish tolerances to permit chemicals in food even
though they had been found to induce cancer when fed.'' H. Rep. No.
1761, 86th Cong., 2d Sess. 83 (1960), XVI Leg. Hist. at 752 (reprinting
letter to the Committee from HEW Secretary Flemming) (emphasis added).
Following HEW's objections, this amendment was not further pursued.\1\
\1\ To the extent any statement in the notice published at 58 FR
37862 (July 14, 1993) implies that ingestion studies fall within the
``appropriate tests'' half of the Delaney clause, that implication
was inadvertent and is inconsistent with the statute and with prior
EPA precedent (50 FR 20373, May 15, 1985).
---------------------------------------------------------------------------
Second, even assuming for the sake of argument that feeding studies
only fall within the second half of the Delaney clause, EPA still does
not accept ACPA's suggestion that the ``appropriate'' tests language
allows or requires EPA to consider the relevance to humans of the
results of an animal study in determining whether a pesticide induces
cancer in animals. Just as in the first half of the Delaney clause, the
second half requires a finding of whether a substance induces cancer
``in man or animal.'' The appropriate tests language does not override
the clear intent of the statutory ``or'' but merely insures that the
tests relate to the safety of food additives. As the legislative
history quoted above shows, the appropriate tests language was designed
to give the government the discretion to take into account the ``route
of administration'' in determining whether the substance would cause
cancer when ``swallowed by mouth.'' Accordingly, EPA believes an
``appropriate'' test for the evaluation of the safety of food additives
is one that yields information bearing on whether the substance will
induce cancer in humans or animals when ingested. Clearly, an animal
feeding study meets this criterion in all regards as to animals.
Indeed, it would be strange to suggest otherwise. The very stimulus for
the Delaney clause was that ``[l]aboratory experiments have shown that
a number of substances when added to the diet of test animals have
produced cancer.'' H. Rep. No. 1761, 86th Cong., 2d Sess. 11 (1960),
XVI Leg. Hist. at 680.
Contrary to ACPA's contention, a focus on the potential of a
substance to cause cancer in animals without considering the relevance
of this cancer to humans does not make the goal of the Delaney clause
the protection of laboratory animals. The underlying rationale of the
Delaney clause is that science cannot establish for humans a safe dose
of a substance that induces cancer in animals. As explained by HEW:
[The Delaney clause] allows the Department and its scientific
people full discretion and judgment in deciding whether a substance
has been shown to produce cancer when added to the diet of test
animals. But once this decision is made, the limits of judgment have
been reached and there is no reliable basis on which discretion
could be exercised in determining a safe threshold dose for the
established carcinogen.
H. Rep. No. 1761, 86th Cong., 2d Sess. 14 (1960), XVI Leg. Hist. at 683
(the Committee report adopted the statement of HEW Secretary Flemming).
Thus, by enacting the Delaney clause, Congress concluded that barring
substances based on findings in animals alone was the most practicable
way to protect humans. ACPA may find this approach misguided but that
does not make it not the law.
At bottom, ACPA's argument seeks to give EPA the discretion to set
safe doses for substances found to induce cancer when fed to animals.
That discretion, however, was removed by the Delaney clause. Les v.
Reilly, 968 F.2d 985, 988 (9th Cir. 1992), cert. denied, 113 S.Ct. 1361
(1993). Once a finding of animal carcinogenicity is made, the operation
of the Delaney clause is ``automatic.'' Public Citizen v. Young, 831
F.2d 1108, 1121 (D.C. Cir. 1987), cert. denied, 485 U.S. 1006 (1988).
The D.C. Circuit has previously concluded that the Delaney clause
indicates that ``Congress did not intend the FDA to be able to take a
finding that a substance causes only trivial risk in humans and work
back from that to a finding that the substance does not `induce cancer
in * * * animals.''' Id. Similarly, EPA may not work back from a
conclusion that the results of an animal study are irrelevant to humans
to a finding that the substance does not induce cancer in animals.
``[T]he agency may not, once a color [or food] additive is found to
induce cancer in test animals in the conventional sense of the term,
undercut the statutory consequence.'' Id. at 1122.
Mechanistic and biologic information. EPA believes that mechanistic
and biologic information is relevant to the Delaney clause
determination on animal carcinogenicity to the extent such information
bears on the question of whether a substance induces cancer in the test
animal. Mechanistic and biologic information may have particular
relevance to the issue of causation. However, having said that, EPA
recognizes that proper evaluation under the Delaney clause of
mechanistic and biologic information poses difficult questions. For
example, ACPA contends that if a substance induces cancer through a
secondary mechanism (e.g., the substance causes the growth of urinary
tract stones and the stones irritate the urinary tract causing cancer),
then the substance does not induce cancer within the meaning of the
Delaney clause.
EPA does not believe that EPA or FDA has ever squarely decided this
legal question in taking final action on a substance under the Delaney
clause. Nor does EPA believe that question needs to be addressed in
this notice. Although secondary mechanism arguments have been raised as
to several of the pesticides at issue in this notice, as discussed
elsewhere in this notice, EPA has decided either as a factual matter
that those arguments are not adequately supported or that there exists
other evidence showing cancer induction independent from any cancer
produced through a secondary mechanism.
``Conclusive'' evidence of carcinogenicity. Citing a prior FDA
decision involving cyclamates and the Delaney clause, ACPA has
contended that findings of carcinogenicity under
[[Page 12002]]
the Delaney clause must meet some unusually high level of certainty.
Other commenters also made this argument. EPA disagrees. Neither the
statute, nor FDA precedent for that matter, support using any other
than the general administrative standard of proof which is generally
described as a preponderance of the evidence. The relevant words of the
statute bar the establishment of a regulation for a food additive
``found to induce cancer when ingested by man or animal * * *.'' The
straightforward requirement to make a finding certainly does not impose
some extraordinary level of proof.
Further, EPA does not believe the FDA decision on cyclamates
requires a higher standard of proof. That decision does use the word
``conclusive'' in connection with the Delaney clause, but that is a
factor of FDA having classified the studies involved in that case into
one of three categories: (1) Conclusive or positive; (2) inconclusive
but suggestive; or (3) negative (45 FR 61474, 61481-61482, September
16, 1980). This breakdown was made so as to explicate whether the
proper showing of safety could be made under the section 409 safety
standard excluding the requirements of the Delaney clause. FDA
concluded that inconclusive but suggestive studies would have to be
addressed by a petitioner attempting to show a compound was ``safe''
(45 FR 61477). FDA described a positive study as a study which
``contains results that establish that a test substance causes cancer''
(45 FR 61481). EPA has found nothing in this precedent to suggest that
any standard other than a preponderance of the evidence applies to the
Delaney clause finding.
Determination on the need for section 409 FARs. ACPA as well as
several other commenters argued that EPA is legally required to
determine if a section 409 FAR is necessary to prevent the adulteration
of food prior to revoking such a FAR on Delaney clause grounds. Where
there are grounds for revocation of a section 409 FAR unconnected to
safety, EPA generally would, as a policy matter, rely on those grounds
to revoke the FAR prior to revoking finally under the Delaney clause.
However, as EPA has recently explained in the Coordination Policy
statement (61 FR 2377, January 31, 1996), EPA is under no legal
obligation to subordinate the Delaney clause to other grounds in a
revocation proceeding.
EtO
Comment: The American Spice Trade Association (ASTA) submitted a
panel report which concluded that EtO is not likely to induce cancer in
animals or humans when ingested as a residue on spices. The panel
contends that it is inappropriate to conclude that EtO causes cancer
through ingestion based on inhalation data. Therefore the revocation of
the section 409 FAR because of the Delaney clause is inappropriate.
EPA's response: EPA has concluded that it is appropriate to use
inhalation data to evaluate the safety of EtO as a food additive. This
conclusion is based on the finding of multiple benign and malignant
tumors distant from the site of exposure, which suggests that EtO has
tumor inducing potential independent of route of administration.
Inhalation exposure to EtO was associated with multiple benign and
malignant tumors in F344 rats and B6C3F1 mice. EtO was also associated
with tumor formation following oral gavage administration to Fischer
rats and subcutaneous administration to NMRI mice. In addition, EtO is
a genotoxic agent in vivo and in vitro. The large in vivo genetic
toxicity database shows that EtO produces effects distant from the site
of exposure. Genetic effects noted in vivo include micronuclei, sister
chromatid exchange, germ cell effects (dominant lethal), and heritable
translocations; these effects were associated with intravenous or
intraperitoneal injection and inhalation exposure (Dellarco et al.
1990). These genetic toxicity data provide further support for the
conclusion that EtO induces cancer.
Comment: ASTA had a number of comments regarding exposure. These
comments claim that:
(1) EtO is unstable in the acid pH of the stomach based on in vitro
hydrolysis data.
(2) Ingested EtO is likely to be detoxified by glutathione present
in the gastric mucosa and epithelial cells.
(3) EtO exposure via ingestion of treated spices is expected to be
significantly lower than levels associated with tumors in rodents.
(4) Consumers are unlikely to be exposed to EtO via consumption of
treated spices based on residue persistence studies submitted to EPA.
The study allegedly showed EtO levels in spices at or below the limit
of quantification within 60 days.
EPA's response: The issue central to the Delaney clause is whether
EtO induces cancer in man or animals when ingested or in a study which
is appropriate to evaluate the safety of a food additive. EtO is
associated with cancer in animals following inhalation, oral, and
subcutaneous administration. As explained above, EPA has determined
that these studies are appropriate for the evaluation of the safety of
EtO as a food additive. No data have been submitted which would
establish affirmatively that all EtO residues in food would break down
or be ``detoxified'' in the stomach. Therefore, EPA does not believe
that it should reconsider the determination that inhalation data are
appropriate for evaluating EtO as a food additive on these grounds.
Further, as explained above, EtO is associated with genetic toxicity,
including heritable mutation, in vivo following oral, inhalation,
intraperitoneal, and intravenous administration.
The level of human exposure to EtO residues in treated spices is
not relevant to the Delaney clause. As stated above, the critical issue
is that EtO has been found to induce cancer in animals. The Delaney
clause does not allow EPA to consider exposure levels. Although residue
chemistry data submitted to the Agency show that EtO residues in spices
dissipate over time, the data also show that sufficient residues remain
so that a tolerance is needed for spices treated with EtO.
Comment: ASTA commented that the EPA Office of Pesticide Programs
(OPP) should conduct a peer review of the carcinogenicity of EtO, and
should not rely on a Health Assessment Document developed by the EPA
Office of Research and Development (ORD) to establish the
carcinogenicity of EtO.
EPA's response: The ORD Health Assessment Document cited in the
proposal for this rule is an EPA document which reflects the position
of the Agency on the carcinogenicity of EtO. This document was
subjected to peer review, both internal and external, prior to
publication. In addition, the content of the document was independently
peer-reviewed in a public session by the Environmental Health Committee
of EPA's Science Advisory Board. Therefore, the Agency does not believe
that additional peer review of this finding is needed at this time.
Comment: ASTA stated its position that revocation of the FAR for
EtO is a de facto cancellation of EtO's registration under FIFRA, and
that therefore due process requires that FIFRA section 6 procedures be
followed in this action. ASTA also suggested that EPA refer the matter
of whether EtO induces cancer to the Scientific Advisory Panel (SAP).
EPA's response: EPA has clearly stated its policy on coordination
between FFDCA and FIFRA. Congress has charged EPA with administering
two statutes with different procedural schemes. As discussed in EPA's
[[Page 12003]]
Coordination Policy, EPA has taken an approach which harmonizes the two
statutory standards to the extent possible. FIFRA does not require EPA
to take action under FIFRA before acting under the FFDCA. EPA does not
believe that the rulemaking procedures in the FFDCA violate
Constitutional due process. With respect to ASTA's suggestion that EPA
consult the SAP, there is no requirement that EPA refer FFDCA tolerance
revocations to the SAP prior to taking action. The Agency has reviewed
all the available information on EtO and has made its determination
that EtO induces cancer within the meaning of the Delaney Clause. In
addition, as noted above, the EPA Health Assessment Document for EtO,
which included an evaluation of the chemical's carcinogenicity, was
peer-reviewed in a public session by the Environmental Health Committee
of EPA's Science Advisory Board.
Comment: The National Food Processors' Association (NFPA) and
Grocery Manufacturers Association (GMA) commented that EPA should
withdraw the proposed section 409 revocation of EtO pending a detailed
reexamination of the data.
EPA's response: EPA has made the findings in this notice with
respect to EtO after reviewing all available information, and sees no
reason to withdraw the proposal based on the speculation that other
information might become available someday which would disprove this
finding. If interested persons submit new information on the
carcinogenicity of EtO in the future, EPA will review it and consider
then whether additional regulatory action is warranted.
Mancozeb
Comment: The Mancozeb Task Force (MTF) objected to EPA's
conclusions that exposure to mancozeb causes an increased incidence of
benign and malignant thyroid tumors in rats and an increasing trend of
tumors at the highest dose tested (HDT). The MTF believes that these
tumors resulted from exposure to ETU formed metabolically from
mancozeb.
EPA's response: The Agency is aware that ETU is a contaminant and
degradation product present in mancozeb, and that ETU is a plant and
animal metabolite of mancozeb which is present in food treated with
mancozeb. Exposure to either mancozeb or ETU results in induction of
the same tumor type (thyroid tumors) in rats (ETU also induced thyroid
and liver tumors in mice). Consistent with prior FDA decisions, EPA
believes that the Delaney clause applies to metabolites of a food
additive as well as the parent compound. (See, e.g., 56 FR 41902,
41909, August 23, 1991.)
Comment: The MTF also argued that the rat thyroid lesions resulted
from overstimulation of the thyroid and the development of
proliferative lesions when the threshold for thyroid-pituitary feedback
is exceeded on a chronic basis.
EPA's response: This may be a plausible mechanism for the thyroid
tumors in rats. However, EPA has not received sufficient evidence to
show the mechanism through which mancozeb induces cancer. Moreover, as
noted in EPA's response to ACPA's comments, EPA has not determined the
legal relevance of secondary mechanism claims to the Delaney clause
finding.
In the Agency's Draft Policy Document on Thyroid Follicular
Carcinogenesis: Mechanistic and Science Policy Considerations, SAB
Review Draft, May 1988, EPA explained a mechanism through which a
substance could cause thyroid cancer:
Studies over the last several decades in multiple laboratories
and using a number of different treatment regimens (e.g., iodine
deficiency) have demonstrated the significance of long-term thyroid-
pituitary hormonal imbalance in thyroid carcinogenesis. A consistent
progression of events is noted: reduction in thyroid hormone
concentrations, elevation in thyroid stimulating hormone (TSH)
levels, cellular hypertrophy and hyperplasia, nodular hyperplasia,
and neoplasia. Hyperplasia and sometimes neoplasia of the pituitary
may also be seen * * *. A block in any of the early steps act as a
block for subsequent steps including tumor development, and
cessation of treatment at an early stage in the progression results
in regression toward normal thyroid structure and function.
Two basic questions must be addressed before this draft policy is
applied. The MTF has not submitted data establishing that the neoplasms
found in the mancozeb studies are due to thyroid-pituitary imbalance,
or that other carcinogenic mechanisms can be discounted. Specifically,
the MTF has not submitted data to demonstrate any of the following six
points:
(a) Goitrogenic activity in vivo;
(b) Clinical chemistry changes (e.g., reduced thyroid hormone and
increased TSH serum concentrations);
(c) Specific evidence of reduced hormone synthesis (e.g., inhibited
iodine uptake) or increased thyroid hormone clearance (e.g., enhanced
biliary excretion);
(d) Evidence of progression (e.g., hypertrophy/hyperplasia, nodular
hyperplasia-neoplasia);
(e) Reversibility of effects after exposure is terminated; and
(f) Structure Activity Relationships (SAR) to other thyroid
tumorigens.
Comment: The MTF also commented that the FAR for mancozeb in or on
brans and flours is not necessary because residues do not concentrate
in RTE foods above the level of the RAC tolerance, and that EPA should
complete action on the Task Force's petition to revoke the FAR for
brans and flours on that basis.
EPA's response: As discussed above in EPA's coordination policy,
EPA does not have any obligation to determine whether or not a FAR is
necessary before proceeding to revoke it. However, EPA has reviewed the
Task Force's petition, and, as discussed in Unit V.A. of this preamble,
where EPA agrees with the petition, EPA is revoking the FAR on grounds
that the residues do not concentrate above the level of the RAC
tolerance. The FARs for mancozeb in or on flours of oat, barley, rye
and wheat, and for brans of barley and rye are not needed, and are
being revoked on that basis. EPA did not agree with the petition with
respect to oat bran, which is a RTE food. Therefore, the FAR for oat
bran is being revoked because it violates the Delaney clause.
Propargite
Comment: Uniroyal Chemical Co., Inc. commented that the Agency has
not performed a weight of the evidence review of all available data and
information on propargite, including mechanistic considerations.
Uniroyal also asserted that EPA's ``induces cancer'' determination does
not reflect that one mutagenic study was negative and ignores all other
mutagenicity studies. Based on one negative mutagenicity study and
strong evidence for a secondary mechanism for tumors in rats, Uniroyal
argued that propargite cannot be said to induce cancer.
EPA's response: After a full evaluation of all the data and
supporting information regarding animal carcinogenicity, EPA concludes
that exposure to propargite results in an increased incidence of
undifferentiated sarcoma of the jejunum in both sexes of Sprague-Dawley
rats. This rare (unusual site) and malignant tumor was produced with a
high incidence and is fatal. The mutagenicity data support the
carcinogenicity of propargite.
The commenter argues that the jejunal tumors were caused by a
secondary mechanism involving cell proliferation. In support, the
commenter submitted a study purporting to show that propargite only
causes cell proliferation at high doses. The theory that cancer can be
caused by cell proliferation, and that proliferation is subject to a
[[Page 12004]]
threshold, is just that--a theory. The Agency has yet to validate the
cell proliferation model as it tentatively has done with regard to the
mechanism involving thyroid-pituitary hormonal imbalance in thyroid
carcinogenicity (see EPA's response to secondary mechanism comment on
mancozeb, above). Important basic science data are needed, like those
developed for the thyroid, before EPA can even consider this model.
With respect to the comment regarding mutagenicity data, propargite
was demonstrated to be mutagenic in a Chinese hamster ovary cell gene
mutation study in the absence, but not presence of metabolic
activation; this indicates that propargite is a direct-acting mutagen.
Propargite produced positive and negative results in two replicate
experiments for micronuclei in mouse bone marrow. Propargite was
negative in an older, unclassified Salmonella gene mutation assay and
for unscheduled DNA synthesis. Overall, these data provide evidence for
mutagenicity that would support a finding of carcinogenicity.
Comment: Uniroyal also commented that revocation of the FARs for
propargite may increase dietary risk to consumers and raise the cost
and lower the quality of food. Finally, Uniroyal commented that raisins
and dried tea should be classified as RACs rather than as processed
foods.
EPA's response: The concerns raised by Uniroyal regarding relative
dietary risks and cost or quality of food are not relevant to the
analysis of FARs under the Delaney clause. The Delaney clause contains
no provision for consideration of exposure levels, relative risks, or
cost impacts. See Les v. Reilly, 968 F.2d 985 (9th Cir. 1992), cert.
denied, 113 S.Ct. 1361 (1993).
With regard to whether raisins and dried tea are RACs or processed
foods, EPA recently issued an interpretive ruling defining RACs. Under
this ruling, commodities which are routinely dried for storage or
transportation purposes are considered RACs, while commodities which
are dried for the purpose of creating a distinct commodity are
considered processed. As specifically discussed in that ruling, raisins
are produced by a drying process that converts one distinct commodity
(i.e. grapes) into another distinct commodity (i.e. raisins).
Therefore, raisins are a processed food.
EPA has found that dried tea is also a processed food, but for a
slightly different reason. Tea leaves are not only dried prior to
storage and transport; some varieties constituting a significant
amount, if not the majority, of tea imported into this country, are
fermented to various degrees prior to drying. Fermenting is certainly
within the meaning of ``processing,'' therefore the status of dried tea
as a processed food was not affected by the RAC interpretation of
drying. Although there are some varieties of tea which are not
fermented prior to the drying process, the propargite tea FAR applies
to dried tea generally, and thus must be revoked.
Propyline Oxide
Comment: The Warren Chemical Co. (Warren) commented that inhalation
studies should not be used to determine carcinogenicity because
propylene oxide converts to propylene glycol in the stomach.
EPA's response: The Agency believes that inhalation studies are
appropriate for evaluating the safety of propylene oxide due to the
appearance of tumors in both mice and rats at a site distant (e.g. in
the mammary gland) from the route of exposure (inhalation). EPA does
not have sufficient data to establish that ingestion of propylene oxide
residues in foods would only result in exposure to propylene glycol, as
the commenter asserts. Therefore, the Agency believes that the
inhalation data are appropriate for the evaluation of propylene oxide.
Comment: Warren also commented that EPA's finding that female mice
showed a significant dose related trend of mammary gland
adenocarcinomas relative to controls did not consider a statement in
the study report. The authors of the study stated that the tumor
incidence was within the range found in historical untreated controls,
and that they did not consider the incidence of this tumor to be
related to exposure to propylene oxide.
EPA's response: For comparisons of tumor incidence in treated and
control animals, it is the concurrent control which is the primary
reference. The following excerpt is from EPA's ``Guidelines for
Carcinogen Risk Assessment'' (51 FR 33992-34003, September 24, 1986)
To evaluate carcinogenicity, the primary comparison is tumor
response in dosed animals as compared with that in contemporary
matched control animals. Historical control data are often valuable,
however, and could be used along with concurrent control data in the
evaluation of carcinogenicresponses.
Thus, comparisons with historical controls are secondary to those with
concurrent controls. Historical control data when it is from the same
laboratory and same time period as that in which the study was
performed may be used to determine if the concurrent control response
is within the normal range. EPA often disagrees with authors of studies
regarding the significance of certain observations. In this case, the
EPA review considered the concurrent controls a more appropriate
reference for comparing the tumor incidence in treated animals. In any
event, there were tumors found in the rat study as well, which fact
also forms part of the basis for EPA's finding that propylene oxide
induces cancer.
Comment: Warren also commented that EPA should not consider
fibroadenomas when applying the Delaney clause because a fibroadenoma
could possibly disappear without becoming malignant.
EPA's response: A fibroadenoma is a benign neoplastic lesion.
Adenocarcinomas are malignant and can arise within fibroadenomas. A
fibroadenoma may or may not progress to a carcinoma. As discussed
above, an increase in the incidence of malignant tumors or, where
appropriate, benign tumors or a combination of benign and malignant
tumors, satisfy the ``induce cancer'' standard under the Delaney
clause. In any event, adenocarcinomas were also found in the study
where fibroadenomas occurred.
Comment: Warren also argued that EPA should not rely on the rat
gavage study for each of the following reasons:
(a) It showed tumors only in the forestomach, an organ humans do
not have.
(b) EPA's peer review did not take into account the fact that
propylene oxide converts in the stomach to propylene glycol.
(c) The study went on for three years instead of two, which is
improper because older rats are more susceptible to cancer.
(d) Human stomachs have a protective lining which rat forestomachs
do not have.
(e) Gavage, or pipetting substance into an animal's stomach, is not
what ``ingested'' means in the context of the Delaney clause.
EPA's response: (a) The commenter points out that humans do not
have forestomachs, and argues that tumors in this organ should be
disregarded by EPA in assessing the carcinogenicity of propylene oxide.
However, it is not always possible to draw a direct site to site
correlation between tumors in different species. Just because humans do
not have forestomachs does not mean that there could not be any
tumorigenic response in another organ. In any event, the absence of a
forestomach in humans does not affect the fact that cancer was induced
in the rat forestomach.
(b) EPA addressed the issue of conversion of propylene oxide to
[[Page 12005]]
propylene glycol in the stomach in its response to a prior comment
above.
(c) The commenter argues that because the study lasted three years
instead of two, the Q* or cancer potency factor assigned to propylene
oxide should have been revised. The fact that the study lasted three
years instead of two does not necessarily mean that its findings were
not valid. Although older rats may tend to get more cancer than younger
rats, the concurrent control animals also aged, and their chance of
developing tumors increased with that of the treated animals. Whether
or not the Q* should account for this element of the study is not
relevant to the determination that tumors were produced in the study,
and therefore propylene oxide induces cancer. An ``induces cancer''
finding under the Delaney clause does not depend on relative potency.
(d) The commenter speculates that the protective lining of the
human stomach would protect it from any tumor-causing effects of
exposure to propylene oxide, therefore rat forestomach tumors cannot be
relevant to whether propylene oxide residues in food would cause cancer
in humans. However, there is no data to support the commenter's theory
that such a protective lining would have prevented the forestomach
tumors in the rat study. As noted above, there is not necessarily a
direct site to site correlation between species. EPA does not believe
that this speculation forms any basis to disregard the rat gavage
study.
(e) The Agency believes that studies where test compounds are
administered to treated animals by gavage are ``ingestion'' studies
within the meaning of the Delaney clause. EPA also believes that gavage
studies are generally appropriate for the evaluation of the safety of
food additives. See EPA's response to comments of Grocery
Manufacturers' Association, below.
Comment: Finally, Warren commented that there is no alternative
sterilant for cocoa or for nutmeats. The commenter noted that
irradiation is not appropriate for treatment of cocoa powder because
irradiated cocoa tends to turn rancid. The commenter also noted that
irradiation is not a viable alternative for all spices because it
degrades the oils and flavor of some spices (like chili powder).
Finally, the commenter stated that irradiation would impose high costs
on production of these commodities.
EPA's response: As noted earlier regarding costs of food,
availability of pesticide alternatives is not relevant to the Agency's
decisions on FARs under the Delaney clause. EPA can only consider
whether the substance at issue induces cancer when ingested by man or
animals, or when tested in a test which is appropriate for evaluating
the safety of a food additive.
Comment: John A. Todhunter commented on behalf of Aberco, Inc., a
registrant of pesticides containing propylene oxide. With regard to
cocoa, Dr. Todhunter commented that there will be no propylene oxide
residues in foods made with treated cocoa powder because the cocoa is
incorporated into foods which are processed at high temperatures (i.e.
baked or cooked foods). With regard to gums and spices, Dr. Todhunter
commented that propylene oxide is not a pesticide under the FFDCA when
it is used to sterilize gums and spices. The commenter argued that FDA
has listed gums and spices as ``generally regarded as safe'' (GRAS),
and that therefore anything which becomes a constituent of a GRAS
substance through good manufacturing practices (GMP) cannot be
regulated under section 409. The commenter cited FDA regulations at 21
CFR 182.10 (spices) and 184.1330 through 184.1351 (gums). With regard
to starch, Dr. Todhunter commented that propylene oxide is not a
pesticide under the FFDCA when it is used to sterilize starch because
starch is not a RAC. The commenter also stated that there will be no
propylene oxide residues on foods made with treated starch because the
starch is later incorporated into foods and beverages which are all
processed at high temperatures. Dr. Todhunter also recommended that EPA
establish tolerances for propylene oxide on cocoa powder, gums and
starch under section 406 of the FFDCA. Dr. Todhunter further commented
that the nuts on which propylene oxide is used are not ``processed
nutmeats'' but are RACs, and therefore propylene oxide should be
regulated under FFDCA section 408 rather than 409.
EPA's response: EPA disagrees with most of these comments. First,
propylene oxide, when used to sterilize these processed foods, is a
pesticide as defined under FIFRA because it is used to destroy or
mitigate pests. See 7 U.S.C. 136(u). Cocoa powder is a processed food
which is treated before it moves in commerce, therefore propylene oxide
is a food additive when used to treat cocoa powder. Whether residues
would remain in the cocoa after it is incorporated into other foods is
not relevant to whether or not a FAR is necessary for propylene oxide
residues on cocoa powder.
Edible gums and spices are processed foods which are treated with
propylene oxide before they move in commerce, therefore propylene oxide
is a food additive when used to sterilize them. Whether or not use of
propylene oxide is part of GMP for production of these foods is not
relevant to whether or not a FAR is necessary for propylene oxide
residues. The regulations cited are simply the FDA's listing of the
gums and spices themselves as GRAS. The FDA regulations are not
intended to make anything which may become part of the foods (such as a
sterilant) GRAS.
Starch is a processed food which is treated before it moves in
commerce, therefore propylene oxide is a food additive when used to
treat starch. Whether residues would remain in a food made from treated
starch after it is incorporated into other foods is not relevant to
whether or not a FAR is necessary for propylene oxide residues on
starch.
The notion that EPA should regulate pesticides in processed foods
under FFDCA section 406 was raised by NFPA in their second petition
submitted in July 1995. EPA responded to this issue in the notice
issuing the Coordination Policy (61 FR 2377, January 25, 1996). To the
extent that Congress left EPA with discretion to regulate pesticides
under either sections 406 or 409, EPA has declined to change from its
current practice.
With regard to nutmeats, EPA agrees that nutmeats per se are a RAC
that should have a raw food tolerance established under FFDCA section
408. See Pesticide Assessment Guidelines, Subdivision O: Residue
Chemistry Table II (October 1982, amended September 1995).
The current FAR for propylene oxide on processed nutmeats was
established more than 25 years ago. EPA determined in 1982 that nuts
were a RAC, and since then, has established raw food tolerances for
nuts under FFDCA section 408. Although the FAR was established for
``processed'' nutmeats, it has been viewed by the industry as covering
the current use of propylene oxide on nutmeats, regardless of whether
they were considered raw or processed.
EPA has not yet reviewed propylene oxide in its pesticide
reregistration program, at which time the discrepancy in the tolerance
situation would have been addressed routinely. In light of the strict
standard of the Les v. Reilly court decision, however, EPA has focused
its attention more carefully on each of the statutory provisions
affecting its decisions relating to tolerances. For instance, EPA has
articulated or refined its policies in a number of areas, including its
concentration, ready-to-eat
[[Page 12006]]
and raw/processed policies, discussed in Unit II of this preamble.
EPA has received a petition from SRS International corporation, on
behalf of Aberco, Inc., to establish a 408 tolerance for propylene
oxide on raw nutmeats. A notice of filing of this petition was
published in the Federal Register on February 1, 1996 (61 FR 3696). The
Agency is currently reviewing the petition and the toxicology and
residue databases for propylene oxide, and will act on the petition as
soon as practicable.
Simazine
Comment: Ciba-Geigy Corp. (Ciba) commented that the results of
studies relied upon by EPA for its determination that simazine induces
cancer are not appropriate for evaluation of the human safety of
simazine as a food additive and do not demonstrate that simazine
``induces cancer'' within the meaning of Delaney Clause. Ciba's first
argument for this premise was based on the fact that no increased
incidence of any tumor type was observed in male or female mice which
were fed simazine.
EPA's response: EPA has found that simazine induces cancer in
animals when ingested within the meaning of the Delaney clause. As
such, EPA was precluded from considering relevance of this finding to
humans. (See response to ACPA's comments.) In construing the ``induce
cancer'' standard as to animals, EPA follows a weight-of-the-evidence
approach. After a full evaluation of all the data and supporting
information regarding animal carcinogenicity, EPA concluded that
exposure to simazine by ingestion results in increased incidence of
malignant mammary gland carcinomas and malignant pituitary gland
carcinomas in female Sprague-Dawley rats. The study's tumor incidence
results were statistically significant when compared with concurrent
controls and exceeded the upper limit of the historical control range
of the testing laboratory. The pituitary tumors were fatal with a
possibly accelerated onset at both the mid- and highest dose, and the
mammary tumors also contributed to the increased mortality at the
highest dose. There was equivocal evidence of kidney tubule tumors (an
uncommon tumor type) in both sexes. The structural analogs are strongly
supportive as these compounds mostly induced malignant mammary gland
tumors in Sprague-Dawley rats. There was some evidence of genotoxicity
for simazine, as well as for some of the analogs.
The Agency agrees that there was no increased incidence of tumors
associated with Simazine exposure in the CD-1 mouse study. However,
this negative study in mice does not convince EPA that simazine did not
induce cancer in the study on rats.
Comment: Ciba also argued that the mid-dose level (100 ppm) in the
Sprague-Dawley rat study exceeded the Maximum Tolerated Dose (MTD),
based on significant reductions in survival at this dose. Based on this
argument, Ciba asserted that increased incidence of mammary gland
carcinomas resulted only at doses that exceeded the MTD, i.e., the mid-
and high doses.
EPA's response: The Agency is not convinced that the mid-dose in
female rats exceeded the MTD, because the pituitary tumors contributed
to the mortality. There were statistically significant increases in
mammary gland carcinomas and in pituitary adenomas and combined
adenoma/carcinoma at both the mid-and highest-doses.
The study authors reported that the pituitary tumors (adenomas and
carcinomas) in female rats were considered to be fatal ``by virtue of
their size and compression of the mid-brain'' and thus contributed to
the decreased survivability of both the mid- and highest-dose group
females. In addition, their onset was 4-15 weeks earlier in the mid-
and highest-dose groups as compared to the control and low dose groups.
Comment: Ciba also commented that atrazine, a structurally similar
compound, while displaying a similar oncogenic profile in S-D rats and
in mice, did not induce mammary tumors in the Fisher 344 female rat.
EPA's response: Simazine is one of several s-triazine compounds
used in agriculture as herbicides. It is structurally related to
atrazine, cyanazine, and propazine, among others. Although atrazine did
not induce mammary tumors in Fisher 344 female rats, these structural
analogs provide much evidence from other studies to support EPA's
finding regarding simazine. Atrazine was associated with increased
mammary gland tumors (primarily malignant tumors) in female Sprague-
Dawley rats; early onset of mammary tumors was also observed. Cyanazine
was also associated with increased mammary gland tumors (primarily
malignant tumors in female Sprague-Dawley rats.) Propazine was
associated with increased mammary gland tumors (primarily benign) in
female Sprague-Dawley rats. The structural analogs are strongly
supportive as these compounds mostly induced malignant mammary gland
tumors in Sprague-Dawley rats.
Comment: Ciba asserted that simazine is not genotoxic, although the
commenter admitted that a few positive genotoxicity results have been
reported in the public literature. Ciba argued that potent genotoxic
oncogens usually induce mammary tumors in almost one hundred percent of
animals, while mammary tumor incidence with simazine was far short of
one hundred percent.
EPA's response: Simazine was found negative in the Salmonella assay
for gene mutations; this is consistent with other tested s-triazines.
However, it is reported that simazine is positive for gene mutations in
the mouse lymphoma assay, the Drosophila sex-linked recessive lethal
assay, the cell transformation assay in Syrian hamster embryo cells,
and plant cytogenetic assays. Simazine is also reported negative in
several other assays including yeast assays, unscheduled DNA synthesis
(UDS), sister chromatid exchanges, and for aneuploidy. Overall, these
data suggest a possible mutagenic action for simazine. The Agency
believes that the evidence of simazine's genotoxicity provides
additional support for the finding that it induces cancer.
In addition, structural analogs of simazine have shown genotoxic
actions as well. For example, cyanazine has evidence of positive
genotoxic activity in the mouse lymphoma assay for gene mutations and
for UDS in rat hepatocytes, and propazine induces gene mutations in the
cultured V79 cell assay for gene mutations.
Comment: Ciba argued that Sprague-Dawley rats have a high
spontaneous background rate of mammary tumors, and that any mammary
tumors induced by simazine are hormonally-mediated and therefore have a
threshold. Ciba asserted that therefore simazine's carcinogenicity
should be regulated qualitatively with a safety factor and not
quantitatively.
EPA's response: Simazine induced increased incidence of malignant
mammary gland carcinomas and malignant pituitary gland carcinomas in
female Sprague-Dawley rats. Mammary tumor incidence was as high as 78%,
and was outside the historical control incidence of the testing
laboratory. The pituitary and mammary tumors also contributed to the
observed increased mortality. There was equivocal evidence of kidney
tubule tumors (an uncommon tumor type) in both sexes. The structural
analogs are strongly supportive as these compounds mostly induced
malignant mammary gland
[[Page 12007]]
tumors in Sprague-Dawley rats. There was some evidence of genotoxicity
for Simazine as well as for some of the analogs.
Although a hormonal mechanistic argument for the mammary tumors was
proposed by the commenter, neither the Agency nor the scientific
community at large has yet developed or identified protocols which
could provide data to demonstrate such a mechanism. No agreed upon
experimental model has been identified, and the critical step
associated with the mode of action has not been identified. As
discussed with respect to cell proliferation and jejunal tumors in
EPA's response to comments on propargite, important basic science data
must be developed, as were developed for the thyroid mechanism, before
the Agency can evaluate the validity of the claim that simazine induces
cancer through a hormonal mechanism. (See also EPA's response to ACPA
regarding secondary mechanisms in general.)
Other Comments
Comment: GMA commented that FDA determined in 1974 that the term
``ingestion'' in the Delaney clause does not include gavage studies,
and therefore the results of a gavage study would invoke the Delaney
clause only if this type of study is found to be scientifically
``appropriate'' as a model for dietary exposure. The commenter
submitted an excerpt of FDA's ``Study of the Delaney Clause and Other
Anti-Cancer Clauses,'' (Agriculture, Environmental and Consumer
Protection Appropriations for 1975: Hearings before a Subcommittee on
Appropriations, House of Representatives, 93rd Cong., 2nd Sess., part
8, 1974).
EPA's response: EPA disagrees with this comment. Gavage is merely
one of several different techniques for administering a test compound
to animal orally. Gavage is sometimes used instead of incorporating the
substance into an animal's food because a more precise dose can be
given by gavage. EPA could not find any reference, other than the
report cited, where FDA stated that a gavage study must be evaluated
under the ``appropriate test'' prong of the Delaney clause rather than
the ``ingestion'' prong. Moreover, there is no explanation in the
report as to why a gavage study should not be considered an ingestion
study. In any event, it is not necessary to determine whether gavage is
ingestion for purposes of this notice because EPA believes that gavage
studies are generally appropriate for the evaluation of the safety of a
food additive because they involve dietary exposure to the test
substance, albeit by forced feeding.
VII. Procedural Matters
A. Filing of Objections and Requests for Hearings
Any person adversely affected by this final rule may file written
objections to the final rule, and may include with any such objection a
written request for an evidentiary hearing on the objection. Such
objections must be submitted to the Hearing Clerk on or before April
22, 1996. A copy of the objections and hearing requests filed with the
Hearing Clerk shall be submitted to the Office of Pesticide Programs
Docket Room. Regulations applicable to objections and requests for
hearings are set out at 40 CFR parts 178 and 179. Those regulations
require, among other things, that objections specify with particularity
the provisions of the final rule objected to, the basis for the
objections, and the relief sought. Additional requirements as to the
form and manner of the submission of objections are set out at 40 CFR
178.25. The Administrator will respond as set forth in 40 CFR 178.30,
178.35 and/or 178.37 to objections that are not accompanied by a
request for evidentiary hearing.
A person may include with any objection a written request for an
evidentiary hearing on the objection. A hearing request must include a
statement of the factual issues on which a hearing is requested, the
requestor's contentions on each such issue, and a summary of any
evidence relied upon by the requestor. Additional requirements as to
the form and manner of submission of requests for an evidentiary
hearing are set out at 40 CFR 178.27. Under 40 CFR 178.32(c), the
Administrator, where appropriate, will make rulings on any issues
raised by an objection if such issues must be resolved prior to
determining whether a request for an evidentiary hearing should be
granted. The Administrator will respond to requests for evidentiary
hearings as set forth in 40 CFR 178.30, 178.32, 178.35, 178.37, and/or
179.20. Under 40 CFR 178.32(b), a request for an evidentiary hearing on
an objection will be granted if the objection and request have been
properly submitted and if the Administrator determines that the
material submitted show:
(1) There is a genuine and substantial issue of fact for resolution
at a hearing.
(2) 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.
(3) Resolution of one or more of the factual issues in the manner
sought by the person requesting the hearing would be adequate to
justify the action requested.
Any person wishing to comment on any objections or requests for a
hearing may submit such comments to the Hearing Clerk on or before May
6, 1996.
B. Effective Date
EPA is making this final rule effective May 21, 1996. In addition,
if EPA does not receive objections to this order, this order and the
factual and legal basis for this order, become final and are not
judicially reviewable. See section 409(g)(1), 21 U.S.C. 348 (g)(1) and
Nader v. EPA: 859 F.2d 747 (9th Cir. 1988), cert. denied, 490 U.S. 1931
(1989). For example, if an interested person disagrees with a necessary
finding in this order but agrees with the outcome, that person must
file timely objections to that finding in this order; if no objection
to the finding is made, the finding will become final for purposes of
any future proceedings to which that finding is relevant.
C. Request for Stays of Effective Date
A person filing objections to this final rule may submit with the
objections a petition to stay the effective date of this final rule.
Such stay petitions must be submitted to the Hearing Clerk on or before
April 22, 1996. A copy of the stay request filed with the Hearing Clerk
shall be submitted to the Office of Pesticide Programs Docket Room. A
stay may be requested for a specific time period or for an indefinite
time period. The stay petition must include a citation to this final
rule, the length of time for which the stay is requested, and a full
statement of the factual and legal grounds upon which the petitioner
relies for the stay. In determining whether to grant a stay, EPA will
consider the criteria set out in the Food and Drug Administration's
regulations regarding stays of administrative proceedings at 21 CFR
10.35. Under those rules, a stay will be granted if it is determined
that:
(1) The petitioner will otherwise suffer irreparable injury.
(2) The petitioner's case is not frivolous and is being pursued in
good faith.
(3) The petitioner has demonstrated sound public policy grounds
supporting the stay.
(4) The delay resulting from the stay is not outweighed by public
health or other public interests.
Under FDA's criteria, EPA may also grant a stay if EPA finds such
action is
[[Page 12008]]
in the public interest and in the interest of justice.
Any person wishing to comment on any stay request may submit such
comments and objections to a stay request, to the Hearing Clerk, on or
before May 6, 1996. Any subsequent decisions to stay the effect of this
order, based on a stay request filed, will be published in the Federal
Register, along with EPA's response to comments on the stay request.
VIII. Regulatory Requirements
A. Executive Order 12866
EPA submitted this action to the Office of Management and Budget
(OMB) for review and any changes made during that review have been
documented in the public record.
EPA has estimated the following economic impacts on the affected
pesticide use sites:
1. Spices
EtO may currently be used either on whole spices under its raw food
tolerance (40 CFR 180.151), which are then ground (processed), or
directly on ground spices under the processed food tolerance being
revoked today. Sixty to eighty percent of the American spice supply is
imported, and an estimated 22% of those imported spices are treated
with EtO.
EPA does not have information on what portion of EtO treatments are
made to whole as opposed to ground spices. If EtO were unavailable for
use on all spices (both whole and ground), there would be an estimated
impact of $18 million to $27 million per year in increased costs of
alternative treatments and loss of some untreated product. Impacts are
unlikely to be this high, because only the tolerance on ground spices
is being revoked. The section 408 tolerance will remain, thus allowing
continued use of EtO on whole spices. To the extent that spices are
currently treated whole, a portion of the above estimated impacts will
not be incurred.
Moreover, EPA believes that some portion, possibly a substantial
portion, of spices currently treated in ground form can be shifted to
treatment in whole form. If a change to treating them whole would cost
less than substitution of alternatives, impacts would be further
reduced.
Alternatives to EtO treatment are limited to irradiation treatment
and heat-based technologies, both of which have practical limitations.
There is currently insufficient capacity of contract irradiation
facilities to handle all spices currently treated with EtO. The
majority of these facilities' business comes from the sterilization of
medical devices which have rigorous hygienic specifications causing
most facilities to not accept spices. Current heat-based technologies
have an adverse effect on the color and flavor of some spices. However
these limitations are expected to be reduced over time by the industry.
Only about one percent of the total U.S. spice supply is treated
with propylene oxide and its loss is not expected to cause significant
economic impacts.
2. Nutmeats
Propylene oxide is used to reduce microbial contamination of raw
nutmeats (except peanuts) which are to be used in other food products
such as ice cream, cheese, ready-to-eat cereals, some baked goods and
some confections. It is used because these foods are not processed at
high enough temperatures to reduce microbial contamination to
acceptable levels. There appear to be no viable alternatives to
propylene oxide for nutmeats used in these foods.
The section 409 FAR being revoked today does not authorize
propylene oxide residues in raw nutmeats, only processed nutmeats. At
the time of proposal there was no section 408 tolerance covering use of
propylene oxide on raw nutmeats. The proposed revocation of the
processed nutmeat tolerance would have left no tolerance covering any
use of propylene oxide on nutmeats. As a result, EPA received
considerable comment on the potential economic impacts of the loss of
propylene oxide.
Information on the impacts of the loss of propylene oxide for
nutmeats is limited, and quantifying these impacts is complicated. U.S.
nut production is nearly 1 billion pounds annually. According to
commenters, about 10 to 20 percent of all nutmeats are currently
treated with propylene oxide. At a value of approximately $1.60 per
pound, the farm value of the 10-20% of nutmeats that are treated is
$160-320 million. Commenters suggested that this 10-20 percent segment
of the nutmeat industry would be a total loss if propylene oxide became
unavailable for use. EPA believes that this estimate is high because it
assumes that there are no alternative uses of the nuts.
Untreated nuts currently are roasted or salted or added to other
foods that are processed under conditions that effectively reduce
microbial contaminants to acceptable levels. EPA believes that nuts
that cannot be treated with propylene oxide will not be a total loss,
but will be diverted into alternative uses. EPA cannot estimate with
current information how much this would reduce the overall impacts on
the nutmeat industry, nor can EPA estimate the impacts on the food
industries whose nut supply could be severely curtailed. EPA believes
that there would be substantial incentive for the affected industries
to develop alternative practices or treatments to reduce microbial
contamination in raw nutmeats.
EPA has received a petition to establish a section 408 raw food
tolerance for propylene oxide on nutmeats. If a section 408 tolerance
is granted, propylene oxide could continue to be used on nutmeats, and
there would be no impacts.
3. Cocoa
Impacts to the cocoa industry of losing the use of propylene oxide
are expected to be minor or insignificant. There are no chemical
alternatives to propylene oxide for use on cocoa. However, with proper
handling and processing techniques cocoa powder can be safely produced
without propylene oxide. The U.S. imports all of its cocoa, and
generally, only that cocoa which comes from relatively unsanitary
processing plants (50 percent or less) is treated with propylene oxide.
Without propylene oxide, switching to markets with higher quality cocoa
beans and better processing plant management techniques may cause
slightly higher prices to consumers for products containing cocoa
powder. In 1994, the U.S. imported over 650,000 metric tons of cocoa,
valued at $1 billion.
4. Dried Tea
Insignificant impacts are expected on the dried tea industry from
the loss of the propargite FAR. Propargite is not registered for use in
the U.S. on dried tea and is not the miticide of choice in tea
exporting countries. Dicofol is the preferred miticide on tea and its
FAR currently remains in effect.
5. No impacts
No impacts are expected from revocation of the FARs for the
following processed foods:
Propylene oxide is no longer registered for use on the following:
Glace fruit, gums, dried prunes, and starch.
EPA no longer establishes FARs in potable water. Therefore, no
impact is expected due to this FAR revocation.
For the 13 FARs that are not needed (listed in table I) the section
408 tolerances and registered uses will remain effective. Therefore, no
impact is expected.
[[Page 12009]]
Three of the section 409 FARs being revoked today also have section
408 tolerances which were proposed for revocation in the Federal
Register on March 1, 1996 (61 FR 8174). The estimated impacts from the
loss of these three pesticide uses are included in that notice. These
FARs are mancozeb/oat bran, propargite/dried figs, and simazine/
sugarcane molasses.
B. Regulatory Flexibility Act
The Regulatory Flexibility Act of 1980 (Pub. L. 96-354; 94 Stat.
1164, 5 U.S.C. 601 et seq.) requires EPA to analyze regulatory options
to assess the economic impact on small businesses, small governments
and small organizations.
In general, regulating pesticide residues and FARs in food is
indiscriminate with respect to the size of the farm or business that
was the source or processor of the food. The existence or absence of
FARs, and the levels at which FARs are set must logically apply to all
food available to U.S. consumers. In this instance, there is unlikely
to be a regulatory option that would treat small businesses differently
than large businesses with respect to pesticide FARs. In any event,
under the Delaney clause, the Agency is compelled to take this action
without regard to the economic impacts on either large or small
entities.
C. Paperwork Reduction Act
This order does not contain any information collection requirements
subject to review by Office of Management and Budget under the
Paperwork Reduction Act of 1980, 44 U.S.C. 3501 et seq.
D. Unfunded Mandates Reform Act and Executive Order 12875
Under Title II of the Unfunded Mandates Reform Act of 1995 (Pub. L.
104-4), this action does not result in the expenditure of $100 million
or more by any State, local or tribal governments, or by anyone in the
private sector, and will not result in any ``unfunded mandates'' as
defined by Title II. The costs associated with this action are
described in the Executive Order 12866 section of this preamble.
Under Executive Order 12875 (58 FR 58093, October 28, 1993), EPA
must consult with representatives of affected State, local, and tribal
governments before promulgating a discretionary regulation containing
an unfunded mandate. This action does not contain any mandates on
States, localities or tribes and is therefore not subject to the
requirements of Executive Order 12875.
List of Subjects in 40 CFR Part 185
Environmental protection, Food additives, Pesticides and pests.
Dated: March 15, 1996.
Lynn R. Goldman,
Assistant Administrator for Prevention, Pesticides and Toxic
Substances.
Therefore, 40 CFR part 185 is amended as follows:
PART 185--[AMENDED]
l. The authority citation for part 185 continues to read as
follows:
Authority: 2l U.S.C. 346a and 348.
Sec. 185.500 [Removed]
2. By removing Sec. 185.500.
Sec. 185.2850 [Removed]
3. By removing Sec. 185.2850.
Sec. 185.4600 [Removed]
4. By removing Sec. 185.4600.
Sec. 185.5000 [Amended]
5. By removing from the table in Sec. 185.5000 the entries for
``Figs, dried'', ``Raisins'' and ``Tea, dried.''
Sec. 185.5150 [Removed]
6. By removing Sec. 185.5150.
Sec. 185.5350 [Removed]
7. By removing Sec. 185.5350.
Sec. 185.6300 [Removed]
8. By removing Sec. 185.6300.
[FR Doc. 96-7026 Filed 3-21-96; 8:45 am]
BILLING CODE 6560-50-F