[Federal Register Volume 59, Number 114 (Wednesday, June 15, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-14422]
[[Page Unknown]]
[Federal Register: June 15, 1994]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 2E4070/P581; FRL-4780-5]
RIN 2070-AC18
Pesticide Tolerances for Benomyl
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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SUMMARY: EPA proposes to recodify tolerances for combined residues of
the fungicide benomyl and its metabolites in or on the raw agricultural
commodities avocado, dandelion, and papaya. This amendment, which was
requested in a petition submitted by the Interregional Research Project
No. 4 (IR-4), would establish tolerances for regionally restricted
registration of the pesticide on these commodities.
DATES: Comments, identified by the document control number [PP 2E4070/
P581], must be received on or before July 15, 1994.
ADDRESSES: By mail, submit written comments to: Public Response and
Program Resources Branch, Field Operations Division (7506C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. In person, bring comments to: Rm. 1132, CM #2,
1921 Jefferson Davis Hwy., Arlington, VA 22202.
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'' (CBI). Information so marked will
not be disclosed except in accordance with procedures set forth in 40
CFR part 2. 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 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: Hoyt L. Jamerson,
Registration Division (7505W), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St. SW., Washington, DC 20460.
Office location and telephone number: Sixth Floor, Crystal Station #1,
2800 Jefferson Davis Highway, Arlington, VA 22202, (703)-308-8783.
SUPPLEMENTARY INFORMATION: The Interregional Research Project No. 4
(IR-4), New Jersey Agricultural Experiment Station, P.O. Box 231,
Rutgers University, New Brunswick, NJ 08903, has submitted pesticide
petition (PP) 2E4070 to EPA on behalf of the Agricultural Experiment
Stations of Florida and Puerto Rico. This petition requests that EPA
recodify tolerances established pursuant to section 408(e) of the
Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(e), for
combined residues of the fungicide benomyl, methyl 1-(butylcarbamoyl)-
2-benzimidazolecarbamate, and its metabolites containing the
benzimidazole moiety (calculated as benomyl) in or on the raw
agricultural commodities avocado and papaya at 3 parts per million
(ppm) and dandelion at 10 ppm. Specifically, IR-4 proposes that EPA
remove the tolerances for avocado, dandelion, and papaya from 40 CFR
180.294(a) and insert these tolerances under 40 CFR 180.294(b), which
lists tolerances established in support of regional registration. This
amendment would regionally restrict registration for use of benomyl on
dandelion and papaya to Florida and use on avocado to Florida and
Puerto Rico.
IR-4's request is in response to EPA's reregistration review of
benomyl, which determined that the available residue data are adequate
to support continued registration for use of benomyl on dandelion and
papaya in Florida and avocado in Florida and Puerto Rico. Additional
residue data will be required to expand the area of usage. Persons
seeking geographically broader registration should contact the Agency's
Registration Division at the address provided above.
The scientific data submitted in the petition and other relevant
material have been evaluated. The toxicological data considered in
support of the proposed action include:
1. Metabolism studies in mice indicate that benomyl is primarily
metabolized to methyl 2-benzimidazole carbamate (MBC), which is
converted to 2-aminobenzamidole and 5-OH-MBC. Elimination of
metabolites occurs rapidly in urine and feces, with no unusual
localization of benomyl or its metabolites in animal tissues.
2. A 2-year feeding study in dogs with a no-observed-effect level
(NOEL) of 500 ppm (equivalent to 12.5 milligrams (mg)/kilogram (kg)/
day. Biochemical changes, hepatic cirrhosis, decreased weight gain and
lower food consumption were observed at a feeding level of 2,500 ppm
(equivalent to 125 mg/kg/day).
3. A three-generation reproduction study with rats fed diets
containing 0, 100, 500, or 2,500 ppm (equivalent to 0, 5, 25, or 125
mg/kg/day) with a NOEL of 100 ppm based on decreased pup weanling
weights at the 500 ppm and 2,500 ppm feeding levels.
4. Benomyl and MBC have been shown to cause developmental toxicity
in rats. The most common abnormality in studies with rats was
microphthalmia. With benomyl, anomalies observed in mice included short
and/or kinky tail, fused vertebrae, fused ribs, and cleft palate.
NOEL's for developmental toxicity are established at 30 mg/kg/day for
rats and 50 mg/kg/day for mice for benomyl. For MBC the NOEL for
developmental toxicity in rats is established at 10 mg/kg/day.
5. Mutagenicity studies indicate that benomyl and MBC have weak
mutagenic activity that is primarily attributable to adverse effects on
the cellular spindle apparatus. Both compounds produced positive
effects in tests to assess structural chromosome aberrations, which is
consistent with a cellular spindle effect. Equivocal results were
obtained in studies performed to assess gene mutation, while tests for
other genotoxic effects were negative.
6. A 2-year feeding/carcinogenicity study with rats fed diets
containing 0, 100, 500, or 2,500 ppm of benomyl with a NOEL of 2,500
ppm (equivalent to 125 mg/kg/day). There were no carcinogenic or
systemic effects observed under the conditions of the study.
7. A 2-year carcinogenicity study with rats fed diets containing 0,
100, 500, 2,500/10,000 or 5,000 ppm of MBC (equivalent to 0, 5, 25,
125/500 or 250 mg/kg/day). There were no carcinogenic effects observed
under the conditions of the study.
8. Carcinogenicity studies for benomyl and MBC were conducted with
CD-1 mice fed diets containing 0, 500, 1,500 or 7,500/5,000 ppm benomyl
or 0, 500, 1,500, 7,500 (females) or 7,500/3,750 (males) ppm MBC. The
high dose for benomyl was reduced to 5,000 ppm at 37 weeks in males and
females due to weight loss, and the high dose for MBC was reduced to
3,750 at 66 weeks in males due to increased mortality; all males were
sacrificed at 73 weeks. Both studies resulted in an increased incidence
of benign or combined malignant and benign tumors of the liver. The
tumorigenic responses were found to be compound related, e.g., they
occurred with significant positive trends, and the elevated incidences
exceeded historical rates for these tumor responses. The responses were
also associated with foci of cellular alterations that are considered
preneoplastic and imply that there is a progression of hepatic lesions.
9. Carcinogenicity studies for MBC were also conducted with Swiss
SPF mice and HOE NMRKf mice. Liver tumors were observed in studies
using Swiss SPF mice, but there were no carcinogenic effects observed
with HOE NMRKf mice.
The Agency has classified benomyl and MBC as Group C carcinogens
(possible human carcinogens). This classification is based on the
Agency's ``Guidelines for Carcinogen Risk Assessment,'' published in
the Federal Register of September 24, 1986 (51 FR 33992). The decision
supporting classification of benomyl and MBC as possible carcinogens
(Group C) rather than probable carcinogens (Group B) is based primarily
on the following:
1. The 2-year carcinogenicity study with rats was negative for
carcinogenic effects.
2. The carcinogenic responses observed with benomyl and its
metabolite MBC were confined to the mouse liver.
3. The liver tumors produced by benomyl and MBC were observed in
two genetically related strains of mice (CD-1 and SPF Swiss), which are
known to have high background incidence rates of liver tumors; there
was no increased incidence of liver tumors observed in HOE NMRKf mice.
4. Benomyl produced weak mutagenic effects consistent with cellular
spindle poison activity rather than gene mutation. This pattern of
mutagenic activity correlates with the observed developmental toxicity
of benomyl.
EPA announced in the Federal Register of December 6, 1977 (42 FR
61788), that a Special Review for benomyl had been initiated based on
information indicating that benomyl posed risks of mutagenicity (point
mutation and chromosomal aberrations), spermatogenic depression and
teratogenic effects, acute toxicity to aquatic organisms, and
significant population reduction in nontarget organisms.
In the Federal Register of August 30, 1979 (44 FR 51166), the
Agency issued a Preliminary Notice of determination, which concluded
that benomyl continued to pose the risks noted above with the exception
of point mutations and significant population reductions in nontarget
organisms. In the Notice and the accompanying Position Document 2/3,
the Agency weighed the risks and benefits of use together and
determined that certain modifications to the terms and conditions of
use were necessary to reduce the risks to applicators.
Prior to the publication of the final benomyl regulatory decision,
the Agency received new studies (the mice carcinogenicity studies
discussed above), indicating that benomyl and its major metabolite MBC
are carcinogenic. The Agency's position concerning the Special Review
for benomyl was published in the Federal Register of October 20, 1982
(47 FR 46747). In the Notice of Determination Concluding the Special
Review for benomyl, the Agency determined that the benefits exceed the
risk from use of benomyl products if a dust mask is used when mixing
and loading for aerial application. Registrants were required to amend
their product labels to require use of a dust mask for persons who mix
and load benomyl for aerial application.
More recently, dietary risk assessments have been conducted for
benomyl in association with the requested recodification of tolerances
for avocado, dandelion, and papaya. These risk assessments were
conducted for MBC since benomyl readily hydrolyzes to MBC. Dietary risk
assessments were conducted based on percent of the Reference Dose (RfD)
utilized, carcinogenicity, and developmental toxicity. The results of
these risk assessments are as follows:
Percent RfD utilized
An RfD for MBC was calculated at 0.033 mg/kg bwt/day by dividing
the benomyl RfD of 0.05 mg/kg body weight (bwt)/day by 1.53, the ratio
of the molecular weight of benomyl to the molecular weight of MBC. The
benomyl RfD is based on a NOEL of 5 mg/kg bwt/day from the three-
generation rat reproduction study and an uncertainty factor of 100.
Available information on anticipated residues and percent of crop
treated was incorporated into this analysis to estimate the Anticipated
Residue Contribution (ARC). The ARC is generally considered a more
realistic estimate than an estimate based on tolerance-level residues
and 100 percent crop treated. The ARC from existing tolerances
(including avocado, dandelion, and papaya) is estimated at 0.000248 mg/
kg bwt/day and utilizes 0.8 percent of the RfD. The ARC for children
aged 1 through 6 years old (the subgroup most highly exposed) utilizes
1.4 percent of the RfD.
Cancer Risk Assessment
The upper-bound carcinogenic risk from benomyl-derived MBC for the
U.S. population from existing tolerances is estimated at 1 X 10-6.
The carcinogenic risk assessment was based on an upper-bound potency
estimator (Q*) for MBC of 4.2 X 10-3* and assumes a 70-year
lifetime exposure. This estimate is within the range of carcinogenic
risk that EPA generally considers negligible.
Developmental toxicity
The population group of interest for this assessment is females
aged 13 and above, the subgroup that most closely approximates women of
child-bearing age. EPA divided the calculated exposure of the highest
exposed individual in this population subgroup (0.1 mg/kg bwt/day) into
the developmental NOEL for MBC of 10 mg/kg bwt/day to get a Margin of
Exposure of 100. This means that the persons most highly exposed to
benomyl-derived MBC in their diet would receive 1/100 the dose that
represents the NOEL from rat studies for developmental toxicity for
MBC. Less than 1 percent of the population of females 13 or older are
exposed through the diet to MBC at 0.1 mg/kg bwt/day or higher. For
developmental toxicity, the Agency is not generally concerned unless
the Margin of Exposure is below 100.
An adequate analytical method is available for enforcement
purposes. The analytical method for enforcing this tolerance is
available in the Pesticide Analytical Manual, Vol. II (PAM II).
There is no reasonable expectation that secondary residues will
occur in milk, eggs, or meat of livestock and poultry since there are
no livestock feed items associated with this action.
There are currently no actions pending against the continued
registration of this chemical.
Based on the information and data considered, the Agency has
determined that the tolerances established by amending 40 CFR part 180
would protect the public health. Therefore, it is proposed that the
tolerances be established as set forth below.
Any person who has registered or submitted an application for
registration of a pesticide, under the Federal Insecticide, Fungicide,
and Rodenticide Act (FIFRA) as amended, which contains any of the
ingredients listed herein, may request within 30 days after publication
of this notice in the Federal Register that this rulemaking proposal be
referred to an Advisory Committee in accordance with section 408(e) of
the FFDCA.
Interested persons are invited to submit written comments on the
proposed regulation. Comments must bear a notation indicating the
document control number, [PP 2E4070/P581]. All written comments filed
in response to this petition will be available in the Public Response
and Program Resources Branch, at the address given above from 8 a.m. to
4 p.m., Monday through Friday, except legal holidays.
Under Executive Order 12866 (58 FR 51735, Oct. 4, 1993), the Agency
must determine whether the regulatory action is ``significant'' and
therefore subject to all the requirements of the Executive Order (i.e.,
Regulatory Impact Analysis, review by the Office of Management and
Budget (OMB)). Under section 3(f), the order defines ``significant'' as
those actions likely to lead to a rule (1) having an annual effect on
the economy of $100 million or more, or adversely and materially
affecting a sector of the economy, productivity, competition, jobs, the
environment, public health or safety, or State, local, or tribal
governments or communities (also known as ``economically
significant''); (2) creating serious inconsistency or otherwise
interfering with an action taken or planned by another agency; (3)
materially altering the budgetary impacts of entitlement, grants, user
fees, or loan programs; or (4) raising novel legal or policy issues
arising out of legal mandates, the President's priorities, or the
principles set forth in this Executive Order.
Pursuant to the terms of this Executive Order, EPA has determined
that this rule is not ``significant'' and is therefore not subject to
OMB review.
Pursuant to the requirements of the Regulatory Flexibility Act
(Pub. L. 96-354, 94 Stat. 1164, 5 U.S.C. 601-612), the Administrator
has determined that regulations establishing new tolerances or raising
tolerance levels or establishing exemptions from tolerance requirements
do not have a significant economic impact on a substantial number of
small entities. A certification statement to this effect was published
in the Federal Register of May 4, 1981 (46 FR 24950).
List of Subjects in 40 CFR Part 180
Environmental Protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: May 31, 1994.
Stephanie R. Irene,
Acting Director, Registration Division, Office of Pesticide Programs.
Therefore, it is proposed that 40 CFR part 180 be amended as
follows:
1. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 346a and 371.
2. In Sec. 180.294, by amending paragraph (a) in the table therein
by removing the commodities avocado, dandelion, and papaya and by
amending paragraph (b) by adding and alphabetically inserting the same
commodities, to read as follows:
Sec. 180.294 Benomyl; tolerances for residues.
* * * * *
(b) * * *
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Parts per
Commodity million
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Avocado.................................................... 3
Dandelion.................................................. 10
Papaya..................................................... 3
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[FR Doc. 94-14422 Filed 6-14-94; 8:45 am]
BILLING CODE 6560-50-F