[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) *  *  *  

------------------------------------------------------------------------
                                                              Parts per 
                         Commodity                             million  
------------------------------------------------------------------------
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