[Federal Register Volume 59, Number 126 (Friday, July 1, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-15925]
[[Page Unknown]]
[Federal Register: July 1, 1994]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR PART 185
[OPP-300335; FRL-4770-3]
RIN 2070-AC18
Pesticides; Proposed Rule Revoking Certain Food Additive
Regulations
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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SUMMARY: EPA is proposing to revoke certain food additive regulations
for several pesticides which EPA has determined ``induce cancer''
within the meaning of the Delaney Clause of section 409 of the Federal
Food, Drug and Cosmetic Act (FFDCA). The food additive regulations
being proposed for revocation include captan, ethylene oxide, mancozeb,
oxyfluorfen, propargite, propylene oxide, and simazine. As a result of
a 1992 court decision regarding the Delaney Clause, EPA recently
revoked food additive regulations for four pesticides found to ``induce
cancer'' that were subject to the litigation. This proposal continues a
series of actions revoking food additive regulations for additional
pesticides found to ``induce cancer'' within the meaning of the Delaney
Clause.
DATES: Written comments, identified by the document control number,
[OPP-300335], must be received on or before September 29, 1994.
ADDRESSES: By mail, submit comments to: Public Response Section, Field
Operations Division (7506C), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.
In person, bring comments to: OPP Docket, Public Information Branch,
Field Operations Division, Rm. 1132, Crystal Mall #2, 1921 Jefferson
Davis Hwy., Arlington, VA. The telephone number for the OPP docket is
(703)-305-5805.
Information submitted as a comment concerning this document may be
claimed confidential by marking any part or all of that information as
``Confidential Business Information'' (or CBI). Information so marked
will not be disclosed except in accordance with procedures set forth in
40 CFR part 2 and in section 10 of the Federal Insecticide, Fungicide
and Rodenticide Act (FIFRA). For questions related to disclosure of
materials, contact the OPP Docket at the telephone number given above.
A copy of the comment that does not contain CBI must be submitted for
inclusion in the public record. Information not marked confidential may
be disclosed publicly by EPA without prior notice. All written comments
will be available for public inspection in the OPP Docket, Rm. 1132 at
the Virginia 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 and Reregistration Division (7508W), Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. Office location and
telephone number: Crystal Station #1, 2800 Crystal Drive, Arlington,
VA. Telephone 703-308-8028.
SUPPLEMENTARY INFORMATION:
I. Introduction
A. Statutory Background
The Federal Food, Drug, and Cosmetic Act (FFDCA) (21 U.S.C. 301 et
seq.) authorizes the establishment of maximum permissible levels of
pesticides in foods, which are referred to as ``tolerances'' (21 U.S.C.
346(a), 348). Without such a tolerance or an exemption from 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. 342). Monitoring and enforcement of
pesticide residues are carried out by the U.S. Food and Drug
Administration (FDA) and the United States Department of Agriculture
(USDA).
The FFDCA governs tolerances for raw agricultural commodities
(RACs) and processed foods separately. For pesticide residues in or on
RAC's, EPA establishes tolerances, or exemptions from tolerances when
appropriate, under section 408 of the FFDCA. In processed foods, food
additive regulations setting maximum permissible levels of pesticide
residues are established under section 409 of the FFDCA. Section 409
tolerances are required, however, only for certain pesticide residues
in processed food. Under section 402(a)(2) of the FFDCA, no section 409
tolerance is required if the pesticide residue in a processed food,
when ready to eat, is equal to or below the tolerance for that
pesticide in or on the RAC from which it was derived. This exemption in
section 402(a)(2) is commonly referred to as the ``flow-through''
provision because it allows the section 408 raw food tolerance to flow
through to the processed food form. Thus, a section 409 tolerance is
only necessary to prevent foods from being deemed adulterated when the
concentration of the pesticide residue in a processed food is greater
than the tolerance prescribed for the raw agricultural commodity, 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 deemed 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.'' (21 U.S.C.348(c)(3)).
B. Regulatory Background
On May 25, 1989, the State of California, the Natural Resources
Defense Council, Public Citizen, the AFL-CIO, and several individuals
filed a petition requesting that EPA revoke several food additive
regulations and challenging EPA's de minimis interpretation of the
Delaney Clause. The petition, which sought a ``zero-risk''
interpretation of the Delaney Clause, requested that EPA revoke certain
food additive regulations. The petitioners argued that these food
additive regulations should be revoked because they are carcinogens and
therefore violate the Delaney Clause.
EPA responded to the petition by revoking certain food additive
regulations, but retained several others on the grounds that the
Delaney Clause provides an exception for pesticide residues posing de
minimis risk, and EPA denied the petition for the food additive
regulations 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 food additive
regulation for pesticides which ``induce cancer'' no matter how
infinitesimal the risk.
On July 14, 1993, EPA issued a revised response to the petition
taking into account the court's ruling. That revised response granted
the original petition and revoked the food additive regulations named
in the petition. Published elsewhere in this issue of the Federal
Register, EPA is issuing an Order denying all objections to the
revocation. Although the court's ruling dealt only with the pesticides
named in the lawsuit, EPA is proceeding with the revocation of other
food additive regulations for pesticides which EPA has determined
``induce cancer.''
In implementing the court's decision in Les v. Reilly, EPA has
taken steps to identify and revoke all section 409 tolerances for
pesticides which have been found to ``induce cancer.'' In February
1993, EPA issued two lists of pesticide uses which would likely be
affected by the court's decision. The first list contains affected food
and feed additive regulations, and the second identifies pesticide uses
where data show a food or feed additive regulation must be established,
but cannot because the pesticide has been found to ``induce cancer.''
Both lists are updated regularly to reflect changes in data reviews and
other regulatory actions.
II. Proposed Revocation of the Subject Section 409 Tolerances Which
are Inconsistent with the Delance Clause
EPA intends to revoke all food and feed additive regulations which
it finds are inconsistent with the Delaney Clause. To ensure an orderly
revocation, EPA will proceed in a phased manner. This document proposes
revocation of food additive regulations established for pesticides
classified as a Group ``B'' (probable human) carcinogens and those
Group ``C'' (possible human) carcinogens quantified by a linear low-
dose extrapolation model and found to ``induce cancer'' within the
meaning of the Delaney Clause. In the near future, EPA will be
proposing revocations of other section 409 tolerances affected by the
court's ruling.
A. Basis for Proposing Revocation
As a result of the court's 1992 decision, the only issue to be
considered for these proposed revocations is whether, under the Delaney
Clause, a pesticide chemical induces cancer in man or animals. If EPA
makes this determination, the Delaney Clause prohibits the food
additive regulation.
In construing the ``induce cancer'' standard as to animals, EPA
follows a weight- of-the-evidence approach, which is guided, where
appropriate, by the principles in EPA's Cancer Assessment Guidelines.
As regards animal carcinogenicity, EPA, in general, agrees with FDA's
explanation of the term ``induce cancer'':
The carcinogenicity of a substance in animals is established when
administration in adequately designed and conducted studies results
in an increase in the incidence of one or more types of malignant
(or, where appropriate, 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 conclusion, but a
biological conclusion is not determined by the statistical results.
(52 FR 49577, Dec. 31, 1987). Each of the pesticides subject to this
proposal qualifies as an animal carcinogen under this test.
Summarized below is the information supporting EPA's determination.
EPA has determined that each of these pesticides ``induces cancer'' in
animals within the meaning of the Delaney Clause. Full copies of each
of these reviews, as well as other references in this section, are
available in the OPP Docket, the location of which is given under
``ADDRESSES'' above in this document.
Captan
Based on several rodent studies, EPA has concluded that exposure to
captan results in an increased incidence of malignant tumors of the
small intestines in mice. The carcinogenic potential of captan is
supported by the increased incidence of other tumor types found outside
of historical control range. The direct-acting genotoxicity and
reactivity of captan support EPA's finding that captan ``induces
cancer'' within the meaning of the Delaney Clause.
Three mouse studies demonstrated positive carcinogenic results. In
one study, captan was fed to CD-1 male and female mice. Initial dosing
of 0, 2,000, 6,000 and 10,000 parts per million (ppm) was administered,
but was increased after 4 weeks to 0, 6,000, 10,000 and 16,000 ppm.
Marked increases in adenomas and carcinomas of the small intestine were
found by pair-wise comparison between all dose groups and controls. A
positive dose-related trend for carcinomas, the malignant component of
the induced tumors, was found in both sexes. While the highest dose
tested (HDT) appears excessive, it does not diminish the biological
significance of the tumors which were seen at lower doses and which
continued to increase at the HDT. In another 2-year study, B6C3F1 mice
were fed 0, 6,000, and 16,000 ppm of captan for 80 weeks. At the HDT,
the combined incidence of adenomas/polyps and carcinomas was increased
by pairwise comparison with control animals in male mice; no compound-
related increase in tumors occurred in female mice. A special study was
performed in CD-1 mice (at 0 or 600 ppm for 3, 6, 9, 12, or 18 to 20
months) to examine the relationship between the hyperplastic and
neoplastic epithelial lesions produced by captan in the small
intestine. The fact that a significant increase in tumors was seen
during the recovery period following captan administration supports the
decision that, although intestinal hyperplasia may regress after
removal of captan, the potential for progression to benign and
malignant neoplasia remains.
In a 2-year male and female CR CD rat study at 0, 500, 2,000, or
5,000 ppm, a dose-related trend for combined renal tubular cell
adenomas/carcinomas was found for male rats. The combined incidence of
tumors induced by captan exceeded the testing laboratory's historical
control range. In another study, male and female Wistar Cpb : WU rats
were fed captan at 0, 125, 500 or 2,000 ppm for 30 months. The
incidence of uterine sarcomas was increased by pair-wise comparison to
the HDT with control animals in female rats, but no compound-related
increase in tumors was observed in male rats.
A range of studies demonstrate that captan is a genotoxic agent. It
is positive in almost all in vitro studies for gene mutations,
structural chromosomal aberrations, and induction of DNA repair.
The direct acting genotoxicity and reactivity of captan would
suggest a likely mechanism for carcinogenicity. Structural analogues
closely related to captan are also carcinogenic and induce cancer at
similar sites as captan (small intestine and renal cells). Based on
these results, EPA has determined that captan induces cancer in
animals. Additional information is included in the December 5, 1988 HED
Peer Review document.
Ethylene Oxide (EtO)
Based on several rodent studies, EPA has concluded that exposure to
EtO results in the induction of benign and malignant tumors in multiple
sites in both sexes of test animals. The carcinogenicity of EtO is
supported by its DNA reactivity, genotoxic properties, and structural
relation to other carcinogenic compounds. Two studies administered by
the inhalation route to Fischer 344 rats demonstrate positive
carcinogenic results. In the first 2-year bioassay administered as 0,
10, 33, or 100 ppm EtO vapor, six types of carcinogenic responses were
considered treatment related. There were statistically significant
increases in mononuclear cell leukemia (spleen) in females at the HDT
and tumors of the pancreas (males at the HDT), skin (males at the HDT),
and brain (both sexes at the HDT and also in males at the middle dose).
There were also treatment-related increases in the peritoneal
mesothelioma (males in all treatment groups) and pituitary gland
adenomas (males at the highest two doses). In a second 2-year study
using male Fischer 344 rats at 0, 50, or 100 ppm EtO vapor, there were
dose-related increases in the incidences of peritoneal mesotheliomas
and brain tumors, which were statistically significant at the HDT. A
significantly increased incidence of mononuclear cell leukemia was seen
at the low dose; the absence of a dose-related effect was attributed to
mortality at the HDT. Although both rat tests were disrupted by non-
treatment related infections, these infections do not appear to have
affected the tumor induction described above.
Carcinogenic effects were also induced during tests when B6C3F1
mice were exposed by inhalation to EtO (at 0, 50 or 100 ppm EtO vapor).
The incidences of alveolar/bronchiolar adenomas, carcinomas, and
combined adenomas/carcinomas in the HDT for each sex (except for
adenomas in male mice) were significantly greater than in control mice.
There were also significant positive trends in lung tumors in each sex.
Malignant lymphomas of the hematopoietic system occurred with a
positive trend in female mice with the incidence at the HDT higher than
in controls. The incidence of mammary gland adenocarcinomas or
adenosqamous carcinomas (combined) in low-dose females was greater than
that in controls. The incidence of hepatocellular adenomas in low dose
females was also greater than that in controls.
In addition to the inhalation studies, there is a gavage study
which showed forestomach tumors (primarily squamous cell carcinomas)
and a subcutaneous study in mice which showed tumors at the site of
injection. Other studies show induction of gene mutations in bacteria,
fungi, higher plants and Drosophila. EtO has been shown to be a direct-
acting mutagen, inducing dominant lethal effects and heritable
translocation in rodents and chromosomal aberrations in both higher
plants and rodents.
Although the majority of carcinogenicity studies involved routes of
exposure other than ingestion, because tumors were produced distant
from the site of administration, e.g., brain tumors, the data show that
ethylene oxide has tumor-inducing potential independent of the route of
exposure, and thus EPA concludes that these tests are appropriate for
evaluating the safety of ethylene oxide in the diet. EPA also
considered the gavage study in making the decision that ethylene oxide
induces cancer. A more complete evaluation of the carcinogenicity of
EtO may be found in EPA's Office of Research and Development document
entitled ``Health Assessment Document for Ethylene Oxide'' (EPA/600/8-
84/009F, 1985). Also, the National Toxicology Program has published a
Technical Report (No. 326, 1987) on its inhalation study in mice, which
is described above. Although the Office of Pesticide Programs has not
conducted a Peer Review on the carcinogenicity of EtO, the program
agrees with the analyses found in these documents and has determined
that EtO induces cancer in animals.
Mancozeb
As made clear in an Order published in the Federal Register on June
30, 1994, EPA has previously determined that mancozeb induces cancer in
animals within the meaning of the Delaney Clause. Information relevant
to that determination is laid out below. Any commenter who seeks
reconsideration of that determination must submit new evidence
demonstrating that reconsideration of the previous determination is
warranted or otherwise explain why reconsideration is appropriate.
EPA has concluded that exposure to mancozeb results in an increased
incidence of cancer in animals, namely benign and malignant thyroid
tumors in rodents. In a study using male Sprague-Dawley rats, the
incidences of thyroid follicular cell adenomas, carcinomas, and
combined adenomas/carcinomas at the HDT was significantly increased in
pair-wise comparison to controls; female rats had a significant
increase for combined thyroid tumors. Mancozeb was also associated with
increasing trends in thyroid follicular cell adenomas, carcinomas and
combined adenomas/carcinomas. A study in mice was also conducted;
however, the HDT was considered inadequate to assess carcinogenic
potential.
EPA also has concluded that mancozeb is carcinogenic because of the
presence of ethylene thiourea (ETU), a metabolite, contaminant and
degradation product present in mancozeb products. A 2-year bioassay in
mice showed statistically significant increases in combined
hepatocellular liver adenomas/carcinomas in both sexes at two doses, as
well as significant positive (increasing) trends in tumors. EPA
believes that summing of adenomas and carcinomas is appropriate for
this type of tumor, but notes the study also showed that hepatocellular
liver carcinomas alone were statistically increased at both doses in
females and at the high dose in males. This study also showed increased
incidences of thyroid follicular cell adenomas and carcinomas. In rat
studies, exposure to ETU was related to increased incidences of thyroid
follicular cell adenomas and carcinomas in both sexes (note the same
tumor type as the mancozeb studies).
Oxyfluorfen
EPA has concluded that exposure to oxyfluorfen results in an
increased incidence of hepatocellular adenomas and carcinomas in mice.
In a 20-month study, CD-1 mice were fed oxyfluorfen with doses ranging
from 0 (as well as an additional control group fed ethanol) to 200 ppm.
During weeks 57 and 58 of the testing, the HDT was increased to 800
ppm. Upon final examination of the mice, there were significant
positive dose-related trends for hepatocellular adenomas, carcinomas,
and combined adenomas/carcinomas in males. The incidences of these
tumors exceeded the historical controls for carcinomas at the two
highest doses tested and for adenomas at the HDT. There were no
compound-related increases in tumors observed in the female mice. The
HDT was assessed to be inadequate for maximal dosing to assess the full
carcinogenic potential of oxyfluorfen. A rat study was also conducted;
however, errors during the test resulted in a dose range deemed
insufficient to assess the carcinogenicity of oxyfluorfen.
Oxyfluorfen is structurally related to four other diphenyl ether
herbicides that have also induced the tumors types similar to those
noted in the oxyfluorfen mouse study (liver tumors). Several studies
provide evidence that oxyfluorfen has mutagenic activity, namely gene
mutations in Salmonella and mouse lymphoma assays.
In 1989, an EPA Carcinogenicity Peer Review convened to assess the
carcinogenicity studies of oxyfluorfen. Although the mouse test may not
have achieved the maximum tolerated dose for a full assessment of
carcinogenicity, the liver tumors observed were dose related. The
occurrence of these tumors was not significant by pair-wise comparison
to concurrent controls; however, the Peer Review committee noted that
if a maximum dose actually had been administered, the incidences of
both benign and malignant tumors would have likely been statistically
significant. In addition, the incidences, even at less than maximal
appropriate dose, exceeded the historical control range. The supporting
evidence on oxyfluorfen's mutagenicity and structural similarity to
other chemicals which also induce liver tumors has led EPA to conclude
that oxyfluorfen induces cancer in animals. The Peer Review committee's
document (dated September 29, 1989) contains more discussion on the
studies and supporting evidence.
Propargite
EPA has concluded that exposure to propargite results in an
increased incidence of undifferentiated sarcoma of the jejunum (a tumor
in the gastrointestinal tract) in both sexes of rats. Male and female
Sprague-Dawley rats were fed 0, 50, 80, 400, or 800 ppm of propargite
for 2-years. Both sexes had a significant increasing trend for this
malignant tumor type with dose increments of propargite as well as a
pair-wise difference from controls. Undifferentiated sarcoma of the
gastrointestinal tract is a rare tumor in rats. In the historical
control data, no tumors of the jejunum were noted. Propylene oxide, a
known carcinogen, was used as a stabilizer in early batches of
propargite. However, EPA has concluded that since the tumors were
mesodermal in origin, they were unlikely to have been due to the
presence of propylene oxide. In another study male and female mice were
fed 0, 50, 160, 500, or 1,000 ppm propargite for 18 months. There were
no apparent increases in tumors associated with increases in the dose
level of propargite. These tests, however, were considered to be
inadequate for judging carcinogenicity since the dose levels were too
low owing to lack of systemic effects and to the older age of the mice
at the time dosing was initiated.
Propargite was demonstrated to be mutagenic in a Chinese hamster
ovary cell gene mutation study in the absence of metabolic activation,
which indicates that propargite is a direct-acting mutagen. Overall
these data provide evidence for a mutagenicity concern that would
support a carcinogenicity concern.
Exposure to propargite results in an increased incidence of
undifferentiated sarcoma of the jejunum in both sexes of Sprague-Dawley
rats. This malignant tumor was produced with a high incidence at an
unusual site. Based on these results, EPA has determined that
propargite induces cancer in animals. Full details and references can
be found in the report from the February 12, 1992 Peer Review Committee
meeting.
Propylene Oxide
EPA has concluded that exposure to propylene oxide results in the
induction of benign and malignant tumors in the nasal cavity of mice
and rats. In a 2-year inhalation study at 0, 200, or 400 ppm using
B6C3F1 mice, hemangiomas and hemangiosarcomas of the nasal cavity were
statistically increased both individually and when the two tumor types
were combined in male mice at the HDT. In addition there were
significant positive (increasing) trends for both benign and malignant
tumors of this type. In female mice, the incidence of combined
hemangiomas/hemangiosarcomas was also statistically significant at the
HDT. The female mice also showed a significant dose-related trend of
mammary gland adenocarcinomas relative to controls. In a 2-year
inhalation study, Cpb:WU Wistar rats were exposed to propylene oxide at
doses of 0, 30, 100, or 300 ppm. A statistically significant increase
in mammary gland fibroadenomas and adenocarcinomas was found in the
high-dose females when compared to controls. The number of mammary
tumors per rat was also significantly increased. While there was no
increase in tumors of the nasal cavity, a statistically significant
increase in nonneoplastic alterations (degenerative changes and
hyperplasia) of the olfactory and respiratory epithelium was observed
in each sex in each exposure group. In addition to the inhalation
studies, there is a gavage study, which showed forestomach tumors
(primarily squamous cell carcinomas), and a subcutaneous study in mice,
which showed tumors at the site of injection.
Like other epoxides, propylene oxide is DNA-reactive. It is a
direct-acting mutagen with positive results in bacterial, yeast,
Drosophila, and cultured mammalian cells. Propylene oxide is a clear
alkylating agent and is mutagenic.
Although the majority of carcinogenicity studies involved routes of
exposure other than ingestion, because tumors were produced distant
from the site of administration (e.g., mammary gland tumors), the data
shows that propylene oxide has tumor-inducing potential independent of
the route of exposure and thus EPA concludes that these tests are
appropriate for evaluating the safety of propylene oxide in the diet.
(EPA also considered the gavage study in making its induce cancer
call.) Details on the studies related to the carcinogenicity and
supporting information can be found in EPA's Integrated Risk
Information System (IRIS) prepared by the Agency's Carcinogenicity Risk
Assessment Verification Endeavor (CRAVE) group. Based on the positive
response in the carcinogenicity studies, propylene oxide's structural
similarity to other known animal carcinogens (epichlorohydrin and
ethylene oxide), and its genotoxic potential, EPA has determined that
in appropriate tests propylene oxide induces cancer in animals.
Simazine
EPA has concluded that exposure to simazine results in increased
incidents of malignant mammary gland carcinomas and malignant pituitary
gland carcinomas in female Sprague-Dawley rats at the HDT. Male and
female Sprague-Dawley rats were fed simazine for 2 years at doses of 0
ppm (as controls), 10 ppm, 100 ppm, or 1,000 ppm. Due to excessive
mortality and significant decreased weight gain in female rats at the
HDT (1,000 ppm), this dose appeared excessive for testing
carcinogenicity. However, when the shortened lifespan in the females
was considered in the statistical analysis, the incidence of malignant
mammary gland carcinoma at both the 100 and 1,000 ppm doses was
statistically significant compared to controls. There was a
statistically significant increase in the combined mammary gland
adenoma/carcinoma compared to control incidence as well. These and
other dose-related trends suggest that the mammary gland carcinomas
contributed to the increased mortality at the HDT. There were no dose-
related adverse effects seen in the male rats tested.
Male and female CD-1 mice were fed simazine for 95 weeks at levels
ranging from 0 to 4000 ppm. There was no increased incidence of tumors
associated with simazine exposure.
Simazine is structurally related to other S-triazine herbicides.
Studies involving several of these compounds show that exposure leads
to an increased incidence of mammary gland tumors. Simazine was found
to be negative for gene mutations in the Salmonella assay, but positive
in the mouse lymphoma assay, the Drosophila assay and plant cytogenic
assays.
Studies showing statistically significant increases in malignant
mammary gland tumors and pituitary gland carcinomas, together with the
structural similarity with other S-triazine compounds, lead EPA to
conclude that simazine induces cancer in female rats. Discussions of
the various studies on the carcinogenicity of simazine can be found in
the Health Effects Division (HED) Peer Review of simazine (July 31,
1989).
B. Proposed Food Additive Revocations
Captan
EPA is proposing to revoke the food additive regulation for the
fungicide captan (or N-trichloromethylmercapto-4-cyclohexene-1,2-
dicarboximide) in or on washed raisins. This food additive regulation,
set at 50 ppm, is codified at 40 CFR 185.500. EPA is proposing
revocation of this regulation because the Agency has determined that
captan induces cancer in animals. Thus the regulation violates the
Delaney Clause in section 409 of the FFDCA.
Ethylene Oxide
EPA is proposing to revoke the food additive regulations permitting
the direct application of ethylene oxide to ground spices. This food
additive regulation is codified at 40 CFR 185.2850. EPA is proposing
revocation of this food additive regulation because, based on tests
which are appropriate for the evaluation of the safety of food
additives, ethylene oxide has been found to induce cancer in animals.
Thus the regulation violates the Delaney Clause in section 409 of the
FFDCA.
The American Spice Trade Association (ASTA) has submitted a letter
challenging the applicability of the inhalation studies described in
section II. A of this notice to the conclusion that EtO induces cancer
within the meaning of the Delaney Clause. ASTA refers to section 409,
which prohibits the approval of a food additive (including pesticide
residues) 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 food additives, to induce cancer in man or animals. ASTA
does not believe that the inhalation studies are appropriate for
assessing whether EtO induces cancer when ingested. A copy of this
letter is available for inspection and comment through the OPP docket
at the location and telephone number listed under ``ADDRESSES'' above
in this document
Mancozeb
EPA is proposing to revoke the food additive regulations for
mancozeb (expressed as the coordination product of zinc ion and maneb
(or manganous ethylenebisdithiocarbamate)) for residues in the brans of
barley, oats, and rye (20 ppm) and in the flours of barley, oats, rye,
and wheat (1 ppm). These food additive regulations are codified at 40
CFR 185.6300. EPA is proposing to revoke this food additive regulation
because the Agency has determined that mancozeb induces cancer in
animals. Thus the regulation violates the Delaney Clause in section 409
of the FFDCA.
Oxyfluorfen
EPA is proposing to revoke the food additive regulations for
residues of oxyfluorfen on cottonseed oil, peppermint oil, spearmint
oil, and soybean oil. These food additive regulations, set at 0.25 ppm,
are codified at 40 CFR 185.4600. EPA is proposing to revoke these food
additive regulations because the Agency has determined that oxyfluorfen
induces cancer in animals. Thus the regulation violates the Delaney
clause in section 409 of the FFDCA.
Propargite
EPA is proposing to revoke the food additive regulations for
residues of propargite on dried figs (9 ppm), raisins (25 ppm), and
dried tea (10 ppm), which are codified at 40 CFR 185.5000. EPA is
proposing to revoke these food additive regulations because the Agency
has determined that propargite induces cancer in animals. Thus the
regulation violates the Delaney Clause in section 409 of the FFDCA.
It should be noted that this proposed revocation of the section 409
tolerances for propargite does not affect hops. EPA recently announced
a change in its policy with respect to the classification of dried hops
under the Federal Food, Drug and Cosmetic Act (FFDCA) (PR Notice 93-12,
December 23, 1993). Under this revision, hops are considered for
regulatory purposes as a raw agricultural commodity in both the fresh
(green) and dried forms. EPA has reclassified dried hops as a raw
agricultural commodity consistent with recent legislative directives on
this subject.
Propylene Oxide
EPA is proposing to revoke the food additive regulations 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). The
food additive regulations are codified at 40 CFR 185.5150. EPA is
proposing revocation since the Agency has determined that propylene
oxide induces cancer in animals and induces cancer in tests appropriate
for the evaluation of the safety of food additives. Thus the regulation
violates the Delaney Clause in section 409 of the FFDCA.
Simazine
EPA is proposing to revoke the food additive regulations for
simazine, codified at CFR 185.5350, for residues on sugarcane molasses
(1 ppm), potable water (0.01 ppm) and sugarcane syrup (1 ppm). EPA is
proposing revocation of the food additive regulations because EPA has
determined that Simazine induces cancer in animals. Thus the regulation
violates the Delaney Clause in section 409 of the FFDCA.
Table 1--Food Additive Regulations Proposed for Revocation
------------------------------------------------------------------------
CFR Commodity and food additive
Pesticide Citation regulation level (ppm)
------------------------------------------------------------------------
Captan....................... 185.500 Raisins (50.0)
Ethylene oxide............... 185.2850 Ground spices (50.0)
Mancozeb..................... 185.6300 Bran of oats, barley, rye
(20); flours of oats,
barley, rye, wheat (1.0)
Oxyfluorfen.................. 185.4600 Peppermint, spearmint,
soybean, and cottonseed
oils (0.25)
Propargite................... 185.5000 Dried tea (10), raisins
(25), and dried figs (9)
Propylene oxide.............. 185.5150 Glace fruit (700), cocoa
(300), gums (300),
processed nutmeats (except
peanuts) (300), dried
prunes (700), starch (300),
processed spices (300)
Simazine..................... 185.5350 Sugarcane molasses (1.0),
potable water (0.1),
sugarcane syrup (1.0)
------------------------------------------------------------------------
C. Consideration of Comments
Any interested person may submit comments on this proposed action
on or before September 29, 1994 at the address given in the section
entitled ``ADDRESSES.'' Before issuing final actions, EPA will consider
all relevant comments, which should be limited only to the pesticides
and food additive regulations subject to this proposed notice, as well
as comments that have already been submitted in response to a February
5, 1993 notice which asked for comments on various EPA, FDA, and USDA
policies for regulating pesticide residues in foods and feeds (58 FR
7470). That notice requested comments on the following areas:
coordination of section 408 and 409; concentration of residues;
classification of foods as ``ready-to-eat''; the fate of affected FIFRA
registrations; the DES proviso; section 18 emergency exemptions; and
regulatory impacts.
III. Executive Order 12866
The Agency has not completed an evaluation of the economic impacts
of this regulatory action because an evaluation of benefits is
irrelevant to action under the Delaney Clause. The Agency is compelled
to take this action without regard to the cost-benefit relationship.
However, the Agency welcomes any comments and information which would
contribute to an analysis of the impacts of this action and similar
future actions.
IV. 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. As explained above, the Agency is compelled to
take this action without regard to the economic impacts. Again, EPA
welcomes any information on impacts to small businesses, governments,
and organizations.
V. 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.
List of Subjects in 40 CFR Part 185
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Food additives, Pesticides and pests,
Reporting and recordkeeping requirments.
Dated: June 18, 1994.
Lynn R. Goldman,
Assistant Administrator for Prevention, Pesticides and Toxic
Substances.
Therefore, it is proposed that 40 CFR part 185 be amended as
follows:
1. 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 Captan.
Sec. 185.2850 [Removed]
3. By removing Sec. 185.2850 Ethylene oxide.
Sec. 185.4600 [Removed]
4. By removing Sec. 185.4600 Oxyfluorfen.
Sec. 185.5000 [Amended]
5. By amending Sec. 185.5000 Propargite by removing from the table
therein the entries for dried tea, raisins, and dried figs.
Sec. 185.5150 [Removed]
6. By removing Sec. 185.5150 Propylene oxide.
Sec. 185.5350 [Removed]
7. By removing Sec. 185.5350 Simazine.
[FR Doc. 94-15925 Filed 6-28-94; 4:15 pm]
BILLING CODE 6560-50-F
