[Federal Register Volume 60, Number 11 (Wednesday, January 18, 1995)]
[Proposed Rules]
[Pages 3607-3611]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-1062]



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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 185

[OPP-300360; FRL-4910-8]
RIN 2070-AC18


Acephate, Triadimefon, Iprodione, and Imazalil; Revocation of 
Food Additive Regulations

AGENCY: Environmental Protection Agency (EPA).

ACTION: Proposed rule.

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SUMMARY: EPA is proposing to revoke food additive regulations for the 
pesticides acephate, triadimefon (1-(4-chlorophenoxy)-3,3-dimethyl-1-
(1H-1,2,4-triazol-1-yl)-2-butanone), iprodione, and imazalil, 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). As a result of a 1992 court decision regarding the Delaney 
clause, EPA has initiated the process of revoking those section 409 
tolerances for pesticides found to ``induce cancer.'' This proposed 
rule is the second in a series of proposals to revoke affected 
regulations under section 409 of the FFDCA.

DATES: Written comments, identified by the document control number 
[OPP-300360], must be received on or before April 18, 1995.

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 or Lisa 
Nisenson, 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 703-308-8010.

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. 
346a, 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 
RACs, EPA establishes tolerances, or exemptions from tolerances when 
appropriate, under section 408. In processed foods, food additive 
regulations setting maximum permissible levels of pesticide residues 
are established under section 409. Section 409 tolerances are needed, 
however, only for certain pesticide residues in processed food. Under 
section 402(a)(2) of the FFDCA, no section 409 tolerance is required if 
any pesticide residue in a processed food is equal to or below the 
tolerance for that pesticide in or on the RAC from which it was derived 
and all other conditions of section 402(a)(2) are met. 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 
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 RAC, or if [[Page 3608]] 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, with little exception, ``no additive 
shall be deemed safe if it has been found to induce cancer when 
ingested by man or animal'' (21 U.S.C. 348(c)(3)).
    Before a pesticide may be sold or distributed, it must be 
registered under the Federal Insecticide, Fungicide and Rodenticide Act 
(FIFRA). To qualify for registration, a pesticide must, among other 
things, perform its intended function without causing ``unreasonable 
adverse effects on the environment'' (7 U.S.C. 136a(c)(5)). The term 
``unreasonable adverse effects on the environment'' is defined as ``any 
unreasonable risk to man or the environment taking into account the 
economic, social and environmental costs and benefits of the use of any 
pesticide'' (7 U.S.C. 136(bb)).

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 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; 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. The food additive regulations for two of the four 
affected pesticides, benomyl and trifluralin, have been reinstated 
pending judicial review by the Court of Appeals, District of Columbia 
Circuit, of several registrants' challenge to the revocation.
    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.'' EPA has 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 uses for pesticides 
that have either been found to induce cancer or are likely to be so 
classified where data show a food or feed additive regulation needs to 
be established. Both lists have been updated to reflect changes in data 
reviews and other regulatory actions (see 59 FR 14980, March 30, 1994). 
The first proposed revocation, which included 26 food additive 
regulations for seven pesticides classified as ``B'', probable human 
carcinogens or ``C'', possible human carcinogens subject to 
quantification by a linear low-dose extrapolation model, was published 
in the Federal Register of July 1, 1994 (59 FR 33941).

II. Proposed Revocation of Section 409 Tolerances Which are 
Inconsistent with the Delaney Clause

    EPA intends to revoke all food and feed additive regulations which 
are inconsistent with the Delaney clause. This notice proposes 
revocation of all food additive regulations published in the March 30, 
1994 Federal Register notice which have not previously been proposed 
for revocation. EPA expects to publish additional proposed revocations 
for feed additive regulations in the near future.

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 acephate, 
triadimefon, imazalil, and iprodione qualify under the Delaney clause 
as having been ``found to induce cancer when ingested by man or 
animals, or 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). If EPA finds they are human or animal 
carcinogens within the meaning of the Delaney clause, the food additive 
regulations must be revoked.
    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. 
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 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).

    Acephate, triadimefon, imazalil, and iprodione all qualify as 
animal carcinogens under this test.
    Summarized below is the information supporting EPA's determination 
that these pesticides ``induce cancer.'' Full copies of each of these 
reviews and other references in this notice are available in the OPP 
Docket, the location of which is given under ADDRESSES above.

Acephate

    After a full evaluation of all the data and supporting information 
regarding animal carcinogenicity, EPA has concluded that exposure to 
acephate results in the induction of malignant hepatocellular 
carcinomas in female CD-1 mice.
    Male and female CD-1 mice were fed 0, 50, 250, or 1,000 parts per 
million (ppm) of acephate for 105 weeks. Although fewer low-dose and 
mid-dose female mice survived to the end of the study compared with 
controls, the survival of the highest dose tested (HDT) female mice and 
all male mice was higher than that with the controls. Decreases in body 
weight gain ranged [[Page 3609]] from 8 to 11 percent for males and 6 
to 14 percent for females at the mid-dose, and about 24 percent for 
males and 29percent for females at the HDT. Dose-related increasing 
levels of liver toxicity, including regenerative changes, were 
observed. In the female mice at the HDT, the incidence of malignant 
hepatocellular carcinomas and hyperplastic nodules was significantly 
increased in comparison with controls. The increased incidence of 
carcinomas exceeds the testing laboratory's historical control range. 
There were no increases in tumors in the two lower dosed female groups 
or any of the male groups.
    Male and female Charles River (CD) Sprague-Dawley rats were fed 0, 
5, 50, and 700 ppm of acephate for 28 months. There was no dose-related 
effect on mortality, although there was significant cholinesterase 
inhibition in the mid- and high-dose male and female rats. There was a 
4 to 8 percent weight loss in the HDT males.
    Acephate has been tested in a wide array of genotoxicity assays. 
The evidence indicates that acephate produced positive responses in 
gene mutation in vitro assays with Salmonella, E. coli, and S. 
cerevisiae. Acephate has been reported to produce mutations in mouse 
lymphoma cells, sister chromatid exchanges (SCEs) in Chinese hamster 
ovary (CHO) cells, and mitotic recombination in Saccharomyces. Several 
in vivo assays for SCEs and cytogenetic endpoints have been negative.
    Based on this information regarding animal carcinogenicity, the 
Agency concludes that exposure to acephate results in the induction of 
malignant hepatocellular carcinomas in female CD-1 mice. The incidence 
exceeded the historical control range of the testing laboratory. There 
is evidence that acephate is genotoxic based on in vitro studies, but 
this activity may be difficult to detect in vivo. The relevance of 
these data to an evaluation of acephate's potential for human 
carcinogenicity is discussed in the Peer Review document of Acephate 
(May 8, 1985).

Triadimefon

    After a full evaluation of all the data and supporting information 
regarding animal carcinogenicity, EPA has concluded that exposure to 
triadimefon results in the induction of hepatocellular adenomas in both 
male and female NMRI mice. Male and female NMRI mice were fed 0, 50, 
300, or 1,800 ppm of triadimefon for 21 months. At the HDT, the 
incidence of hepatocellular adenomas was increased in both male and 
female mice by pair-wise comparison between the HDT and controls. A 
positive dose-related significant trend for adenomas was found in both 
sexes. The incidence of hepatocellular adenomas for each sex exceeded 
the testing laboratory's historical control range for adenomas in NMRI 
mice.
    In another study, male and female CF1-W74 mice were fed 0, 50, 300, 
or 1,800 ppm of triadimefon for 24 months. The HDT was considered 
appropriate for assessing carcinogenicity based on increased 
hematological changes; statistically significant increases in liver 
weights accompanied by histopathological changes and weight gains at 
the HDT were significantly lower than in controls.
    Initially, the tumor profile was thought to provide no indication 
that triadimefon had an influence on total tumor incidence, on the 
number of mice with tumors or on incidence of single tumor types; 
however, the pathology report indicated that more mice had hyperplastic 
liver nodules at the HDT than mice in the other treated groups or the 
controls. The Peer Review Committee recommended that in light of the 
NMRI study results outlined above, and that the original analysis of 
the study results was performed before the current criteria were put 
into place, the liver nodules should be re-read with updated criteria.
    The new histopathological information for the CF1-W74 mouse study 
was submitted subsequent to the completion of the latest Triadimefon 
Peer Review document. Only a small number of slides were available for 
reexamination, and the results were deemed inconclusive. However, they 
are suggestive of an effect on tumor incidence in the liver and are 
consistent with the findings in the NMRI study that the liver is a 
principal site for tumor induction. Lesions which were originally 
classified as hyperplastic or regenerative nodules were reclassified as 
either hepatocellular adenomas or carcinomas. In males, 3, 3, 2, and 3 
adenomas and 1, 4, 4, and 4 carcinomas were found out of 6, 8, 7, and 
13 liver samples examined at doses of 0, 50, 300, and 1,800 ppm, 
respectively. This suggests that triadimefon may contribute to the 
induction of liver tumors and there may be a carcinoma component.
    In a 104-week study, male and female Wistar rats were fed 0, 50, 
300, or 1,800 ppm of triadimefon. Triadimefon induced a positive dose-
related trend in the incidence of thyroid follicular cell adenomas/
adenomas multiple in male Wistar rats. Positive dose-related trends 
were achieved in both sexes for combined incidences of thyroid 
follicular cell cystic hyperplasia and adenomas/adenomas multiple.
    Hepatocellular adenomas are considered to be evidence of cancer 
because hepatocellular adenomas can progress to hepatocellular 
carcinomas. Malignancy (carcinoma) implies a more extensive disease 
process. Thus, hepatocellular adenomas represent an earlier stage than 
carcinomas in the progression of cancer induction. This is one of the 
major reasons that the National Toxicology Program (NTP) has used to 
justify combining these two tumor types for an overall analysis of 
carcinogenicity (in addition to analyzing them separately). For 
triadimefon, the possible progression to carcinoma was suggested in the 
CF1-W74 mouse study and is strongly supported by carcinoma induction in 
close structural analogues, e.g., etaconazole, uniconazole, 
cyproconazole, tebuconazole, and fenbuconazole.
    Based on the above data and supporting information regarding animal 
carcinogenicity, it is concluded that exposure to triadimefon results 
in the induction of hepatocellular adenomas in both male and female 
NMRI mice. A positive dose-related significant trend for adenomas was 
also found in both sexes. This conclusion is bolstered by the extensive 
structural activity support from closely structurally related triazole 
compounds tested in many mouse studies that showed increased incidences 
of not only adenomas but carcinomas as well. It is also noted that 
although the analysis was inconclusive, there was a carcinoma response 
by triadimefon in the CF1-W74 mouse study. In addition, triadimefon 
induced a positive dose-related trend in the incidence of thyroid 
follicular cell adenomas/adenomas multiple in male Wistar rats. 
Positive dose-related trends were achieved in both sexes for combined 
incidences of thyroid follicular cell cystic hyperplasia and adenomas/
adenomas multiple.
    The relevance of these data to an evaluation of triadimefon's 
potential for human carcinogenicity is discussed in the Peer Review 
document of Triadimefon (September 26, 1990).

Iprodione

    After a full evaluation of the data and supporting information 
regarding animal carcinogenicity, EPA concludes that exposure to 
iprodione resulted in an increased incidence of hepatocellular 
malignant carcinomas in male mice and combined hepatocellular adenomas/
carcinomas in both sexes of mice, ovarian lutenomas in female mice, and 
[[Page 3610]] testicular interstitial cell tumors in male rats.
    Iprodione was administered to CD-1 mice (50/sex/group) at levels of 
0, 160, 800, or 1,400 ppm for at least 99 weeks (or until the 52-week 
interim sacrifice of 15 additional mice/sex/group). At the terminal 
sacrifice, there was a significantly increased incidence of benign and 
malignant liver cell tumors in both sexes compared to the control. 
Analysis indicates that male mice had significant difference in the 
pair-wise comparisons of the 1,400-ppm dose group with the controls for 
liver adenomas, carcinomas and combined adenomas and/or carcinomas. 
Female mice had significant increasing trends in liver adenomas, 
carcinomas, and combined adenomas and/or carcinomas. All males in all 
dose groups (including concurrent controls) displayed a higher 
incidence of carcinomas than observed in historical controls. Although 
there was no increase in the incidence of testicular tumors in the male 
mice, there was a dose-related increase in the incidence of 
interstitial cell hyperplasia at the 800- and 1,400-ppm dose levels.
    In female mice, iprodione was associated with significant dose-
related increasing trends in liver adenomas, carcinomas and combined 
adenomas and/or carcinomas; there were significant differences in pair-
wise comparisons with the high-dose level with controls for liver 
adenomas and combined adenomas and/or carcinomas. The increased 
incidences of hepatocellular tumors at the 1,400-ppm level generally 
exceeded the available historical control data for these tumor types in 
mice of this strain. Additionally, iprodione was associated with a 
significant increasing trend in ovarian lutenomas, and there was a 
significant difference in the pair-wise comparison of the 1,400-ppm 
dose group with the control group and historical controls. EPA 
considers the dose levels used in this study to be adequate for testing 
the carcinogenicity of iprodione in mice.
    Iprodione was administered in the diet to 60 Sprague-Dawley rats/
sex/group for 2 years at dose levels of 0, 150, 300, or 1,600 ppm. 
There was a 52-week interim sacrifice of 10 additional rats/sex/group. 
At the interim sacrifice, males at the high-dose level displayed an 
increase in the incidence of lesions in the adrenals, and there was an 
increase in the incidence of centrilobular hepatocyte enlargement in 
males at the 300 and 600 dose levels; females displayed an increased 
incidence of centrilobular hepatocyte enlargement at the highest dose 
tested.
    In male rats fed iprodione for 2 years, there was a significant 
dose-related increasing trend and a significant difference in the pair-
wise comparison of the 1,600-ppm dose group with the controls for 
testicular interstitial cell benign tumors. The incidence of both 
unilateral and bilateral benign interstitial cell tumors was increased 
at this dose level compared to historical control data. In addition to 
the neoplastic lesions, interstitial cell hyperplasia in the testes, 
reduced spermatozoa in the epididymis, and absent/empty secretory 
colloid cells or reduced secretion in the seminal vesicles were 
observed at the 300- and 1,600-ppm dose levels. Atrophy of the 
seminiferous tubules in the testes, with atrophy of the prostate and 
absence of spermatozoa in the epididymis, were observed at 1,600 ppm. 
Centrilobular hepatocyte enlargement was increased in males at the 
high-dose level. Adrenal lesions were observed in both sexes at the 
300- and 1,600- ppm dose levels, although males displayed more lesions 
than females.
    In females rats fed iprodione at the high-dose level for 2 years, 
there were no significant compound-related tumors observed, although 
there was an increased incidence of tubular hyperplasia in the ovaries 
and increased sciatic nerve fiber degeneration compared to the 
controls. The dose levels chosen for this study were considered 
appropriate for assessing the carcinogenicity of iprodione in rats.
    Iprodione is structurally related to vinclozolin and procymidone. 
Procymidone has been associated with the appearance of tumors in both 
sexes in the reproductive organs and the liver, but did not have 
mutagenic activity in several tests. Vinclozolin, which is currently 
being tested for its carcinogenic potential, has been associated with 
adverse effects on the reproductive organs and liver. With the 
exception of the mouse lymphoma (forward mutation) assay, vinclozalin 
was negative for mutagenicity. In mutagenicity studies, iprodione was 
not mutagenic in the Ames assay, the CHO/HGPRT mammalian cell forwarded 
mutation assay, the in vitro chromosome aberration assay in CHO cells, 
the in vitro sister chromatid exchange assay in CHO cells and the 
dominant-lethal test in mice. However, iprodione was positive in the 
Bacillus subtilis assay for DNA damage without metabolic activation.

Imazalil

    After a full evaluation of the data and supporting information 
regarding animal carcinogenicity, EPA concludes that exposure to 
imazalil is associated with an increased incidence of adenomas and 
combined adenomas/adenocarcinomas of the livers of male Swiss mice and 
with a significant dose-related increasing trend in hepatocellular 
adenomas and combined adenomas and/or carcinomas.
    Imazalil base was administered in the diet to groups of 50 male and 
50 female Swiss mice and treated for 100 to 101 weeks at levels of 0, 
50, 200, or 600 ppm. Male mice had a significant dose-related 
increasing trends in hepatocellular adenomas and/or carcinomas. There 
was a significant difference in the pair-wise comparison of the 200-ppm 
dose group with the controls for hepatocellular adenomas. There were 
also significant differences in the pair-wise comparisons of the 600-
ppm dose group with the controls for hepatocellular adenomas and 
combined adenomas and/or carcinomas. EPA has concluded that the 
malignant carcinoma response at the 600-ppm dose level was biologically 
relevant and related to imazalil exposure despite the lack of pair-wise 
statistical significance compared to controls. There was over a 
doubling of the concurrent control incidence and a positive trend for 
carcinomas. The male carcinoma incidence was also outside the 
historical control data provided by the submitting company. It was 
noted that about 50% of the significantly positive combined incidence 
was contributed by carcinomas. Also, there appears to be a progression 
towards malignancy across the dose groups.
    Female mice had significant dose-related increasing trends in 
hepatocellular adenomas and combined adenomas and/or carcinomas. There 
were no significant differences in the pair-wise comparisons of the 
dosed groups with the controls.
    Nonneoplastic changes in the liver were also observed in male mice 
at all dose levels. At the 200-ppm level, males had a significant 
increase in the incidence of focal cellular changes, large vacuoles, 
and swollen sinusoidal cells in the liver. At the highest dose tested, 
males also had a significantly increased incidence of pigmentation in 
the sinusoidal cells of the liver and focal cellular changes in the 
pancreas, increased absolute and relative liver weight, and decreased 
body weight and body weight gain. Female mice did not exhibit any 
cellular changes in the liver, although there was some effect on body 
weight at the 600-ppm dose and slight increases in liver weights at the 
highest dose tested as well.
    There is extensive structure-activity relationship (SAR) support 
for the [[Page 3611]] tumor response associated with imazalil. Closely 
related compounds with the chlorinated benzene moiety, e.g., 
etaconazole, cyproconazole, tebuconazole, induced hepatocellular 
adenomas, and malignant carcinomas in both sexes of several strains of 
mice. The mutagenicity data for imazalil did not indicate genotoxic 
activity; however, a data gap was identified and additional testing is 
required.

B. Proposed Food Additive Revocations

    Acephate. EPA is proposing to revoke the food additive regulation 
of 0.02 ppm for the combined residues of acephate (O,S-dimethyl 
acetylphosphoramidothioate) and its cholinesterase-inhibiting 
metabolite, methamidophos, set to cover use of the pesticide in food-
handling establishments. This food additive regulation is codified at 
40 CFR185.100. EPA is proposing to revoke this food additive regulation 
because the Agency has determined that acephate induces cancer in 
animals. Thus, the regulation violates the Delaney clause in section 
409 of the FFDCA.
    Triadimefon. EPA is proposing to revoke the food additive 
regulations for triadimefon (1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-
1,2,4-triazol-1-yl)-2-butanone) and its metabolite beta-(4-
chlorophenoxy)-alpha-(1,1-dimethylethyl)-1H-1,2,4triazole-1-ethanol set 
to cover residues in or on milled fractions of barley (except flour) 
and milled fractions of wheat (except flour). The food additive 
regulations, which are codified at 40 CFR 185.800, are set at 4 ppm. 
EPA is proposing to revoke these food additive regulations because the 
Agency has determined that triadimefon induces cancer in animals. Thus, 
the regulations violate the Delaney clause in section 409 of the FFDCA.
    Iprodione. EPA is proposing to revoke the food additive regulations 
for iprodione [3-(3,5-dichlorophenyl)-N-(1-methylethyl)-2,4-dioxo-1-
imidazolidinecarboxamide], its isomer [3-(1-methyl-ethyl)-N-(3,5-
dichlorophenyl)-2,4-dioxo-1-imidazolidinecarboxamide], and its 
metabolite [3-(3,5-dichlorophenyl)-2,4-dioxo-1-
imidazolidinecarboxamide] set to cover residues in dried ginseng at 4 
ppm and raisins at 300 ppm. The food additive regulations for iprodione 
are codified at 40 CFR 185.3750. EPA is proposing to revoke these food 
additive regulations because the Agency has determined that iprodione 
induces cancer in animals. Thus, the regulation violates the Delaney 
clause in section 409 of the FFDCA.
    Imazalil. EPA is proposing to revoke the food additive regulation 
for imazalil set to cover residues of the fungicide imazalil 1-[2-(2,4-
dichlorophenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole and its metabolite 
1-(2,4-dichlorophenyl)-2-(1H-imidazole-1-yl)-1-ethanol in citrus oil at 
a level of 25 ppm. This food additive regulation is codified at 40 CFR 
185.3650. EPA is proposing to revoke this food additive regulation 
because the Agency has determined that imazalil induces cancer in 
animals, and thus violates the Delaney clause in section 409 of the 
FFDCA.

III. Consideration of Comments

    Any interested person may submit comments on this proposed action 
on or before April 18, 1995 at the address given in the section above 
entitled ``ADDRESSES.'' Before issuing final actions, EPA will consider 
all relevant comments. Comments should be limited only to the 
pesticides and food additive regulations subject to this proposed 
notice. After consideration of comments, EPA will issue a final order 
determining whether revocation of the regulations is appropriate and 
making a final finding on whether these pesticides induce cancer within 
the meaning of the Delaney clause. Such order will be subject to 
objections pursuant to section 409(f) (21 U.S.C. 348(f)). Failure to 
file an objection within the appointed period will constitute waiver of 
the right to raise issues resolved in the order in future proceedings.

IV. Executive Order 12866

    Since this proposed action is being taken under the Delaney clause, 
which requires the Agency to act without considering the costs or 
benefits of the action, the Agency has not completed an evaluation of 
the economic impacts of this particular action. Nevertheless, pursuant 
to an agreement between EPA and OMB, this action was submitted to OMB 
for an informal 10-day review. As required by the Executive Order, any 
comments or changes made in response to OMB suggestions or 
recommendations have been documented in the public record. In addition, 
the Agency welcomes any comments and information regarding the impacts 
of this proposed action. These could contribute to an analysis of the 
impacts of similar future actions.

V. 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.

VI. 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, 
Recording and recordkeeping requirements.

    Dated: January 10, 1995.

Lynn R. Goldman,
Assistant Administrator for Prevention, Pesticides and Toxic 
Substances.

    Therefore, it is proposed that 40 CFR part 185 be amended as 
follows:

PART 185--[AMENDED]

    1. The authority citation for part 185 continues to read as 
follows:

    Authority: 2l U.S.C. 346a and 348.

Sec. 185.100   [Removed]

    2. By removing Sec. 185.100.


Sec. 185.800   [Removed]

    3. By removing Sec. 185.800.


Sec. 185.3650   [Removed]

    4. By removing Sec. 185.3650.


Sec. 185.3750   [Removed]

    5. By removing Sec. 185.3750

[FR Doc. 95-1062 Filed 1-17-95; 8:45 am]
BILLING CODE 6560-50-F