FLUORIDE ACTION NETWORK PESTICIDE PROJECT
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Oxyfluorfen (Rohm & Haas). March 22, 1996. Final Rule exempting Oxyfluorfen from FOOD ADDITIVE REGULATION (FAR). Federal Register.
http://www.epa.gov/docs/fedrgstr/EPA-PEST/1996/March/Day-22/pr-616DIR/pr-616.txt.html
[Federal Register: March 22, 1996 (Volume 61, Number 57)] [Rules and Regulations]
[Page 11993-12009]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[[Page 11993]]
Part V
Environmental Protection Agency
40 CFR Part 185
Revocation of Pesticide Food Additive Regulations; Final Rule
[[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.
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: nazmi.niloufar@epamail.epa.gov.
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 ``flowthrough'' 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
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-toeat'' (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:
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
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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
f 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 thyroidpituitary 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 midand 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 midand 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 SpragueDawley 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:
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