United States
Environmental Protection
Agency
Office of December 1989
Pesticides and Toxic Substances
Washington, DC 20460
Pesticides
v>EPA EBDC
SPECIAL REVIEW
TECHNICAL SUPPORT
DOCUMENT
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EBDC
TECHNICAL SUPPORT DOCUMENT
POSITION DOCUMENT 2/3
THE ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDES AND TOXIC SUBSTANCES
OFFICE OF PESTICIDE PROGRAMS
SPECIAL REVIEW AND REREGISTRATION DIVISION
SPECIAL REVIEW BRANCH
401 M STREET, S.W.
WASHINGTON, D.C. 20460
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EXECUTIVE SUMMARY
On July 17, 1987, (52 FR 27172) EPA initiated a Special
Review of the ethylene bisdithiocarbamate (EBDC) pesticides.
There are five EBDC active ingredients currently registered:
mancozeb, maneb, metiram, nabam, and zineb. All registrations of
a sixth EBDC, amobani, have been cancelled. The initiation of the
Special Review was based on the Agency's determination that
exposure to ethylenethiourea (ETU), a common contaminant,
metabolite, and degradation product of these pesticides, may pose
carcinogenic risks to humans from dietary exposure and risk of
cancer, developmental and thyroid effects to mixers, loaders, and
applicators (including homeowners). The Agency determined that
the risk criteria, as described in 40 CFR 154.7(a)(2) and
154.7{a)(6), were met or exceeded by use of EBDC pesticides. The
Agency at the same time solicited information to support its
assessment of the benefits of the EBDCs.
Maneb, mancozeb, metiram and zineb are registered for use to
prevent damage by fungi to a wide variety of food and ornamental
crops as well as being used as seed and seed piece treatments, as
soil treatments, and for home gardens. Approximately 12 to 18
million pounds of all EBDCs are used in the U.S. each year,
primarily on potatoes, apples, cucurbits, tomatoes, onions, sweet
corn and small grains.
In 1986, the zineb technical registrants cancelled their
registrations, but one end use femulator agreed to support a
number of uses. All uses of zineb were suspended by the Agency
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in July 1988 when that formulator failed to submit data required
under FIFRA section 3(c)(2)(B). In July 1989 that formulator
notified the Agency that he wanted to voluntarily cancel his
registrations and the Agency issued a second notice to the
remaining formulators in October 1989. At the time the Position
Document was issued, no formulators had yet agreed to support
zineb registrations.
All nabam agricultural food and feed use registrations have
been suspended since 1985. On March 13, 1989, the registrant of
the suspended food uses (Rohm and Haas Company) requested that
the Agency cancel all the suspended food uses of nabam. The
Agency's acceptance of this request is imminent. Nabam is
currently registered as a fungicide on ornamental plants and as a
biocide in industrial cooling tower water systems, oil well
drilling fluids and pulp and paper mills. Registrants holding
nabam registrations on industrial sites requested voluntary
cancellation of sugar beet and sugarcane transport and flume
water nabam uses in 1987, but have retained the use of nabam in
sugar mill grinding, crusher or diffuser systems.
As part of the Special Review process, the Agency evaluates
the risks and benefits associated with the uses of a pesticide
and then proposes any regulatory actions necessary to ensure that
use of the pesticide does not result in unreasonable adverse
effects. In determining which uses to cancel, the Agency
considered the aggregate risks posed by the EBDCs, the extent to
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which registered uses are being supported by registrants and,
where appropriate, the risks and benefits of individual uses.
ETU has been classified by the Agency as a Group B2
carcinogen (probable human carcinogen) based on evidence that it
induced an increased incidence of thyroid follicular cell
adenomas and adenocarcinomas in rats and thyroid and liver tumors
in three strains of mice. The classification as a Group B2
carcinogen is also supported by structure-activity relationships,
since several other thyroid inhibitors which are structurally
related to ETU (e.g., thiouracil and thiourea) have also been
found to induce hepatomas and/or thyroid tumors in rodents.
Available studies also show ETU demonstrated the ability to cause
developmental effects (hydrocephalus) in rats and thyroid effects
(hyperplasia) in rats, mice, and monkeys.
The Agency's assessment of ETU's potential carcinogenic,
developmental, and thyroid risks in the PD I was based on a
limited exposure data base. Estimates of carcinogenic risks were
based on mancozeb (and ETU) residue and exposure data. Develop-
mental and thyroid risk estimates were based on mancozeb (and
ETU) and surrogate exposure studies and an assumption of 100
percent dermal absorption.
Since issuance of the Notice of Initiation of a Special
Review, the Agency has received additional toxicity and exposure
data on the individual EBDCs and an ETU. These data have been
used to refine the risk estimates presented in this document.
Due to the fact that all nabam agricultural food and feed uses
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are suspended and are in the process of being voluntarily
cancelled, the Agency has not required any additional crop
residue data on nabam.
From an assessment of all available data, the Agency
estimates a 95 percent upper-bound ETU carcinogenic dietary risk
of 4 x 10"4 to the general public from exposure to ETU from
consumption of food crops treated with maneb, mancozeb and
roetiram. This risk estimate would increase if the uses of zineb
also were allowed to continue. This estimated carcinogenic
dietary risk is based on field residue studies for maneb,
mancozeb, and metiram where the parent compound (EBDC) and ETU
were measured, and took into consideration percent of crop
treated estimates. Due to the fact that analytical methods are
unable to determine the source of the ETU contribution from
individual EBDC chemicals (more than one EBDC is registered for
use on some crops) and that currently available analytical
methods cannot distinguish among the various EBDC fungicides
unless the identity of the pesticide used is known, carcinogenic
dietary risk is considered in this document as the total ETU
contribution to individual crops. ETU risk estimates for
individual crops treated with EBDCs range from 10"10 (crenshaw
melons) to 10"4 (apples). See Table 11-17.
Developmental dietary margins-of-safety/margins-of-exposure
(MOSs/MOEs) were calculated for each EBDC parent compound. All
developmental dietary MOSs/MOEs were over 600. See Table 11-18.
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Carcinogenic mixer/loader/applicator (M/L/A) risks range
from 10"3 to 10"7. For commercial agriculture and industrial
workers with the incorporation of protective clothing (coveralls
over shirts and pants, chemical resistant gloves, shoes, socks,
and goggles or a face shield), only one estimate of carcinogenic
M/L/A risks remains at 10"3: commercial applicators using maneb
on ornamentals. For some homeowner uses (i.e., maneb on
homeowner vegetables, ornamentals, fruit trees, and turf sites
and mancozeb on homeowner fruit trees and turf sites), no
practical additional protective clothing requirements reduce
estimated risks to reasonable levels (estimated risks exceeding
10"6 and low benefits). Consequently, these homeowner uses are
proposed for cancellation.
Developmental (acute exposure) and thyroid effects (chronic
exposure) MOSs/MOEs were estimated for agricultural workers,
commercial applicators, homeowners, and industrial workers who
may be exposed to ETU from the application of all EBDC pesticide
products. With incorporation of protective clothing, several
MOSs/MOEs still remained below 100 for developmental toxicity
(maneb on homeowner turf) and thyroid effects (maneb on grapes
and commercial ornamentals and nabam in sugar and paper mills).
See Table 11-20. Due to the fact that the Agency has M/L/A
exposure data that enable it to estimate ETU M/L/A exposure
contribution from individual EBDC parent compounds, M/L/A risks
are given for each EBDC pesticide.
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The benefits of the EBDCs were assessed in terms of the
economic impacts which would result if the chemicals were fully
withdrawn from the market for the particular uses and users were
forced to substitute alternatives. Benefits in this document are
calculated in terms of producer impacts and efficiency impacts.
Producer impacts are increased costs for growers. Efficiency
impacts are defined as society costs, or the loss to society of
the dollar value of goods and services no longer available as a
result of the action. Efficiency impacts include costs to
growers, as well as to consumers and others. Producer impacts
are provided for crops where it is assumed growers will not be
able to pass on the increased costs of production. Efficiency
impacts are provided where it is assumed that impacts would occur
at more than one level of the production/distribution chain. For
some of these crops, such as tomatoes, higher production costs
could be offset by higher yields gained through use of
alternative pesticides. Other factors considered were the
efficacy, phytotoxicity, potential for fungal resistance and cost
of each alternative. Crops for which there are no viable
registered alternatives are: asparagus, corn (field and sweet),
cranberries, endive, lettuce, and spinach. Two of these crops
have estimated individual ETU carcinogenic risks of greater than
10"7 (lettuce and spinach). The estimated annual benefit from
all dietary uses is $46 to $75 million in producer impacts and
$90 to $305 million in efficiency impacts if use on all 55 crops
was cancelled. Estimated annual benefit from non-food
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agricultural and industrial uses is $5 to $15 million in producer
impacts.
The Agency examined a range of options to reduce the
unreasonable carcinogenic, developmental and thyroid effects of
the EBDCs to the general public from consumption of foods treated
with these pesticides and/or to applicators, mixers, and loaders
who use these pesticides. For dietary exposure, these included
extending preharvest intervals and modifying application
practices such as reducing application rates. However, the
available information (including information submitted in
response to the PD 1) is insufficient to assess the feasibility
of these measures. The Agency urges interested parties to
provide data or other analyses to demonstrate the impact of such
measures as reductions in application rates or frequencies or
increases in preharvest intervals, as ways of reducing exposure
from particular crops. EPA will consider this information when
the Agency develops its final decision concerning the EBDCs. EPA
urges interested parties to seek technical guidance from the
Agency early on so that the most useful, valid data are
developed.
For mixers, loaders, and applicators of EBDCs, the Agency
considered requiring additional protective clothing to that
specified in the Registration Standards for maneb, mancozeb,
metiram and nabam (coveralls for mixer/loaders and coveralls and
gloves for applicators) for agricultural workers and commercial
applicators. Based on surrogate data, these additional measures
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are estimated to reduce exposure in excess of 40 percent,
depending on the protective measures utilized. The Agency did
not consider it practical to require the above-mentioned
additional protective clothing for homeowners.
Based on its analysis of the risks and benefits, the
Agency proposes the following regulatory actions:
A. Food Crop Uses
In determining the appropriate regulatory action, the Agency
considered (1) the risks posed by the EBDCs from lifetime dietary
exposure, (2) the estimated excess lifetime cancer risks
resulting from exposure during the time it will take to complete
the Special Review process, (3) the extent to which registered
uses are supported by registrants, (4) the risks and benefits of
individual uses, where appropriate, (5) the risks associated with
alternative fungicides that likely would be used if EBDC
registrations are cancelled, and (6) the likelihood that
additional data and information might result in a different final
decision.
Based on its analysis, EPA has determined that dietary risks
from a lifetime of exposure are unreasonable, and therefore, the
Agency proposes to cancel many of the food uses of the EBDCs. At
the same time, EPA is convinced that risks from exposure during
the time needed to complete the Special Review process are
negligible since registrants have acted to sharply restrict
pesticide usage beginning in 1990. (See Chapter V.) Thus, more
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severe action is not necessary to protect the American public in
the short-run.
To ensure that risks from short-term exposure are
negligible, the Agency will proceed with certain actions to
reduce exposure. These actions involve deleting uses from
certain registrant labels pursuant to requests by those
registrants and tolerance revocations to reduce exposure on both
domestic and imported crops. In addition, EPA should be
receiving monitoring data from registrants which will provide
data on actual residue levels; the Agency will take further
action if estimated risks during the pendency of its deliberation
are unacceptable.
The Agency proposes the cancellation of 45 food uses of
maneb, mancozeb and metirara and all uses of zineb. Forty-two
uses of maneb, mancozeb and metiram and all the uses of zineb are
being cancelled due to unacceptably high risk of ETU and the
present lack of support for these uses by registrants. The
remaining three uses of maneb, mancozeb and metiram are being
proposed for cancellation because the risks of the individual
uses outweigh the benefits.
All zineb uses are currently suspended and the only
technical registrant has requested voluntary cancellation of its
registrations. In addition, on September 6, 1989, the four major
registrants of maneb, mancozeb and metiram requested EPA to
delete 42 of 55 uses from their registrations. They planned to
retain 13 uses. Their action would decrease risk from 4 x 10"
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to 2 x 10'5. The 13 uses proposed to be retained by these
registrants are almonds, asparagus, bananas, cranberries, figs,
grapes, onions, peanuts, potatoes, sugar beets, sweet corn,
tomatoes and wheat. By the registrants' action, maneb would be
registered for use on almonds, bananas, potatoes, sugar beets and
sweet corn; mancozeb would be registered for use on asparagus,
bananas, cranberries, figs, grapes, onions, peanuts, potatoes,
sugar beets, sweet corn, tomatoes and wheat; and metiram would be
registered for use on potatoes. The estimated cumulative benefit
from these 13 crops is $14 to $27 million in producer impacts.
This voluntary action by registrants was taken in an effort
to reduce possible dietary risks associated with consumption of
EBDC-treated commodities. Once the registrants' action becomes
final, the deleted uses cannot be reinstated until such time as
the registrants apply to reinstate these uses and the Agency
determines the risks associated with these uses are found to be
acceptable.
The four technical registrants of maneb, mancozeb and
metiram control a significant share of the EBDC market but not
all of it. However, EPA believes that the action of these
registrants has altered the market sufficiently that it is
appropriate to consider that only the use of maneb, mancozeb and
metiram on 13 crops are likely to remain.
EPA considered the registrants' action and concluded that,
while it constituted a major step to reduce dietary risk, it did
not go far enough to reduce risks to acceptable levels.
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Therefore, EPA proposes to retain the use of maneb, mancozeb and
metiram on ten of the 13 crops (almonds, asparagus, cranberries,
figs, grapes, onions, peanuts, sugar beets, sweet corn and wheat)
and proposes to cancel use on three crops three (potatoes,
tomatoes and bananas). The estimated risks resulting from the
ten retained crops would be 3 x 10"6 and estimated benefits would
be $13 to $26 million in producer impacts.
B. Tolerances
Within 90 days of the issuance of this document, the Agency
intends to propose tolerance revocations for the 45 food uses of
maneb, mancozeb and metiram and all (58) food uses of zineb
proposed for cancellation in this Preliminary Determination. The
Agency presently intends to finalize the tolerance actions,
reflecting consideration of public comments, when all products
for particular uses are voluntarily cancelled, or the Agency
issues the Final Determination, whichever occurs earlier. In
issuing final rules to revoke tolerances, the Agency will set
tolerance expiration dates which take into consideration any
crops which were treated legally before the effective date of the
cancellation. Tolerances for retained uses will be reevaluated
once the Agency receives metabolism and residue data required
under the EBDC Comprehensive Data Call-Ins and Registration
Standards. Any necessary adjustments to raise or lower existing
tolerances will be proposed at that time.
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C. Non-Industrial Uses
The Agency proposes a label language requirement that
commercial agricultural workers (M/L/A) applying EBDC pesticides
wear coveralls over long-sleeved shirt and long pants, chemical-
resistant gloves, shoes, socks, and goggles or a face shield.
Additionally, during mixing and loading, a chemical-resistant
apron must be worn. With incorporation of the above-mentioned
protective clothing requirements, MOSs/MOEs for workers using
EBDC products on agricultural sites would all increase above 100
except for maneb uses on grapes and ornamentals which are
proposed for cancellation because EPA has determined that risks
exceed benefits.
The Agency estimates that the cost of the above protective
clothing would range from $0.75 to $1.5 million if every
commercial agricultural user of EBDC pesticides needed to buy the
protective equipment. However, the Agency believes the costs of
this requirement would actually be much lower because most
growers already own such equipment as it is required for use when
applying a number of other agricultural chemicals.
The Agency proposes a label language requirement
establishing an interim reentry interval of 24 hours for all EBDC
products used on agricultural sites. This interim reentry
interval will remain in effect until dislodgeable foliar residue
data (showing EBDC and ETU exposure to agricultural workers
reentering treated fields for the purposes of hand harvesting,
pruning, weeding, etc.) required in the EBDC Registration
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Standards and as required in the March 1989 EBDC Data Call-in
Notice are submitted and evaluated. These data are due to be
submitted in July 1990. The Agency believes that there would be
little if any economic impact from this requirement.
The Agency did not consider that additional protective
clothing requirements for homeowners would be a viable means of
reducing risks because the Agency believes that homeowners will
not go to the expense of purchasing or wearing protective
clothing. Therefore, EPA proposes to cancel the use of maneb on
turf by homeowners where MOSs/MOEs are under 100, and risks
outweigh benefits.
In addition, because millions of households have gardens and
many more have lawns which could be treated, the Agency is
concerned about estimated cancer risks which exceed 10"6 for
homeowners applying EBDCs. EPA believes such risks exceed the
benefits of use. Homeowner sites which have estimated risks
exceeding 10"6 are: (1) mancozeb on fruit trees and turf and (2)
maneb on vegetables, ornamentals, fruit trees and turf. See
Table 11-19. Little or no economic impact is expected because
home gardeners can switch from maneb to mancozeb for vegetables
and ornamentals and can use captan on fruit trees instead of
EBDCs. The Agency estimates that less than one percent of
residential lawns are treated with EBDCs and any impact would be
negligible. Therefore, EPA proposes to cancel homeowner use of
mancozeb on fruit trees and turf, and homeowner use of maneb on
vegetables, ornamentals, fruit trees and turf.
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D. Industrial Uses
The Agency proposes a label language requirement that all
industrial workers (M/L/A) applying EBDC pesticides wear
coveralls over long-sleeved shirt and long pants, chemical-
resistant gloves, shoes, socks, and goggles or a face shield.
Additionally, during mixing and loading, a chemical-resistant
apron must be worn. Similar label language already appears on
most nabam labels and OSHA requires protective clothing when
applying hazardous chemicals under 29 CFR §1910.132; therefore,
the Agency believes there would be minimal costs resulting from
this requirement.
The Agency proposes cancellation of nabam use in paper mills
and sugar mills based on thyroid MOSs/MOEs below 100 due to
occupational exposure after incorporation of protective clothing
requirements listed above. EPA has determined that risks
outweigh benefits in these cases. If nabam's use were cancelled,
the cost to the paper industry would increase by $700,000. There
are three alternatives for nabam's use in sugar mills. The most
viable alternative (Busan) possibly would increase production
costs between $400,000 to 500,000 if it replaced nabam.
E. Schedule for PD-4
Due to the assumptions surrounding dietary and
mixer/loader/applicator risks, the Agency has required additional
data through FIFRA section 3(c)(2)(B) to further refine risk
estimates. The Agency plans to issue the PD 4 in the spring of
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1991 to allow review and consideration of additional data, which
the Agency currently believes could result in a more refined
risk/benefit assessment of the EBDCs and ETU. However, if new
data or information demonstrate a need to take more immediate
action, the Agency will do so.
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ACKNOWLE DGEMENTS
EBDC Project Team
Office of Pesticide Programs Team Members
Valerie M. Bael
Janet Andersen
Karis L. North
Gary L. Ballard
Christen R. Bashor
Leung Chang
Kenneth W. Clark
Henry Craven
Kerry Dearfield
Richard P. Dumas
Michael P. Firestone
Judith W. Hauswirth
Patrick Holden
Susan V. Hummel
Albin Kocialski
Richard N. Lee
Richard Levy
Susan T. Lewis
Curt Lunchick
Irving Mauer
E. Neil Pelletier
Franklin D. Rubis
Esther C. Saito
William Sette
J. Robert Tomerlin
Linda L. Taylor
Douglas J. Urban
Edward Zager
Senior Review Manager, SRB
Section Chief, SRB
Review Manager, SRB
Supervisory Economist, BEAD
Occupational Safety
Specialist, OSB
Chemist, HED
Agronomist, EEB
Biologist, EEB
Geneticist, HED
Economist, BEAD
Chemist, NDEB
Supervisory Chemist, HED
Chemist, SACB
Chemist, DEB
Pharmacologist, HED
Entomologist, EEB
Senior Statistician, HED
Environmental Protection
Specialist, RD
Chemist, HED
Geneticist, HED
Plant Pathologist, BEAD
Environmental Protection
Specialist, RD
Chemist, HED
Toxicologist, HED
Plant Pathologist, HED
Toxicologist, HED
Supervisory Biologist, EEB
Supervisory Chemist, DEB
External Office Team Members
Michael Branagan
Barbara Britton
Philip J. Ross
John Fleucheus
Daniel Helfgott
Analyst, OPPE
Analyst, ORD
Attorney, OGC
Attorney, OGC
Environmental Protection
Specialist,OCM
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TABLE OF CONTENTS
Executive Summary i
Acknowledgements xvi
Listing of Tables xxi
Glossary xxiii
1. INTRODUCTION
A. REGULATORY BACKGROUND
1. The Special Review Process 1-1
2. Special Review Actions 1-2
B. Organization of this Position Document 1-7
C. CHEMICAL BACKGROUND
1. Chemical and Physical Characteristics 1-8
2. Registered Uses and Production 1-12
3. Tolerances 1-19
II. ASSESSMENT OF RISKS AND ANALYSIS OF REBUTTAL COMMENTS
A. EFFECTS OF CONCERN
1. Carcinogenicity II-l
a. Hazard Identification II-2
b. Mutagenicity 11-14
c. Non-Genotoxic Tumor Formation 11-19
d. Summary of ETU Metabolic and
Pharmacokinetic Properties 11-21
e. Structure-Activity-Relationship 11-24
f. Human Studies 11-24
g. Weight-of-Evidence for Carcinogenicity . 11-24
h. Dose Response 11-27
i. Determination of Carcinogen Potency
Factor (Q-|*) for Risk Calculations 11-28
2. Developmental Effects 11-29
3. Thyroid Effects 11-31
4. Aquatic Effects 11-32
5. Avian Toxicity 11-33
6. Ground Water 11-34
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B. EXPOSURE ANALYSIS
l. Dietary Exposure 11-35
a. Background 11-35
b. Carcinogenicity and Thyroid Effects .... 11-39
c. Developmental Effects 11-60
2. Worker Exposure 11-71
a. Methodology II-71
b. Agricultural Uses 11-73
c. Commercial ornamentals 11-79
d. Homeowner Lawns and Gardens 11-80
e. Industrial 11-86
C. RISK CHARACTERIZATION
1. Dietary 11-90
a. Carcinogenic 11-91
b. Developmental Toxicity 11-94
c. Thyroid Effects 11-99
d. Conclusions 11-100
2. Mixer/loader/applicator 11-102
a. Carcinogenic 11-102
b. Developmental and Thyroid Effects 11-107
c. Conclusions 11-108
D. REBUTTAL ANALYSIS
1. Carcinogenicity 11-120
2. Mutagenicity 11-124
3. Developmental Effects 11-126
4. Thyroid Effects 11-127
5. Exposure 11-130
6. Other 11-139
III. ASSESSMENT OF BENEFITS AND ANALYSIS OF REBUTTAL COMMENTS
A. ASSESSMENT OF BENEFITS
1. Method of Analysis III-l
2. Introduction III-3
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3. Food crops 111-13
a. Root/tuber crops 111-13
b. Onions 111-20
c. Leafy vegetables 111-22
d. Cole crops 111-30
e. Peanuts 111-33
f. Peppers 111-35
g. Tomatoes 111-36
h. Curcurbits 111-39
i. Apples 111-41
j. Peaches and Nectarines 111-45
k. Cranberries 111-46
1. Grapes 111-47
m. Bananas 111-49
n. Sweet corn 111-51
o. Small grains 111-53
p. Other crops 111-56
4. Seed Treatments 111-57
5. Non-food crops 111-57
a. Ornamental plants 111-57
b. Turfgrass 111-59
6. Industrial sites 111-61
a. Paper mills 111-61
b. Water cooling systems 111-62
c. Sugar mills 111-63
d. Oil Well Drilling Fluids 111-64
e. Metal Working Coolants 111-65
B. ANALYSIS OF REBUTTAL COMMENTS 111-66
IV. RISK/BENEFIT ANALYSIS AND REGULATORY OPTIONS
A. INTRODUCTION IV-1
B. RISK CONCLUSIONS IV-1
1. Carcinogenicity IV-2
2. Developmental Toxicity IV-3
3. Thyroid Effects IV-3
4. Risks from Alternatives IV-3
C. BENEFITS CONCLUSIONS IV-7
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D. DEVELOPMENT OF REGULATORY OPTIONS IV-8
1. Measures to Reduce Dietary Exposure .... IV-10
a. Preharvest interval IV-10
b. Modify Application Practices IV-10
2. Measures to Reduce Exposure to Applicators,
Mixer/Loaders and Fieldworkers IV-11
a. Protective Clothing IV-12
b. Reentry Intervals IV-13
3. Measures to Reduce Industrial Worker
Exposure IV-14
E. RISK/BENEFIT ANALYSIS OF REGULATORY OPTIONS .. IV-14
1. Option 1: Continuation of Registration
Without Changes IV-14
2. Option 2: Continuation of Registrations
with Modifications to the Terms and
Conditions of Registration IV-15
3. Option 3: Partial Cancellation IV-18
4. Option 4: Cancellation IV-30
V. PROPOSED REGULATORY OPTIONS V-l
A. FOOD CROP USES V-2
B. TOLERANCES V-8
C. NON-INDUSTRIAL USES V-9
D. INDUSTRIAL USES V-ll
VI. REFERENCES VI-1
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Table
Table
Table
Table
Table
Table
Table
Table
1-1:
1-2:
1-3:
II-l:
II-2:
II-3:
II-4:
II-5:
II-6:
II-8:
II-9:
Table II-10a:
Table II-10b:
Table II-10c:
Table 11-11:
Table 11-12:
Table 11-13:
Table 11-14:
Table 11-15:
Table 11-16:
Table 11-17:
Table 11-18:
Table 11-19:
Table 11-20:
Table III-l:
Table III-2:
Table III-3:
Table III-4:
Table III-5:
Table III-6:
Table IV-1:
Table IV-2:
xxi
List of Tables
EBDC Nomenclature
Chemical and Physical Properties of EBDCs
EBDC Registered Sites
Liver Tumors in ETU-Treated Mice
Tumor Induction in Rats by ETU
Histopathology Data from Graham et al. (1975)
Mutagenicity of ETU
Mutagenicity of the EBDCs
Structural Activity
Summary of Average Residue Estimates for Maneb
Summary of Average Residue Estimates for Mancozeb
Summary of Average Residue Estimates for Metiram
Summary of EBDC and ETU Processing Data
FDA Monitoring Data and State Data for EBDCs and
ETU 1985-1989
Anticipated Residues for Maneb and Maneb-Derived
ETU for Acute Exposure
Anticipated Residues for Mancozeb and Mancozeb-
Derived ETU for Acute Exposure
Anticipated Residues for Metiram and Metiram-
Derived ETU for Acute Exposure
Mixer/Loader/Applicator ETU Exposure Estimates for
Sweet Corn, Grapes and Apples
Use Practices Information: EBDCs on Sweet Corn
Use Practices Information: EBDCs on Grapes
Commercial Nursery Ornamental EBDC Exposure
Estimates
Homeowner EBDC Exposure Estimates
ETU Dietary Carcinogenic Risks
EBDC Individual Crop Risks (ETU Dietary
Carcinogenic)
Developmental Dietary Risks
Mixer/Loader/Applicator Carcinogenic Risk
Estimates (incorporating protective clothing)
Mixer/Loader/Applicator Developmental and Thyroid
MOSs/MOEs
Percent of Crop Treated with EBDC Fungicides
Summary of Usage and Benefits of EBDCs for
Selected sites
Alternative Fungicides Registered for Use Against
Various Potato Diseases
Fungicides Registered for Control of Tomato
Diseases
Fungicides Registered for Control of Certain Apple
Diseases
Summary of EBDC Fungicides Registered to Control
Diseases of Grapes
Toxicity and Status of Alternatives to the EBDCs
Estimated Risks and Benefits of Crops Which Would
Be Proposed for Cancellation and Retention
-------
XXI1
Table IV-3:
Table IV-4:
Table IV-5:
Table IV-6:
Cost-Effectiveness Estimates for EBDC Cancellation
Estimated Risks and Benefits of EBDC Crops Which
Would Be Proposed for Cancellation Under the 55
Crop Approach
Estimated Risks and Benefits of EBDC Crops Which
Would Be Proposed for Retention Under the 55 Crop
Approach
Summary of M/L/A MOSs/MOEs for Developmental and
Thyroid Effects and/or Carcinogenic Risks and
Benefits for Sites Proposed for Cancellation
-------
xxiii
GLOSSARY
ADI: Acceptable Daily Intake: See definition of Reference
Dose.
ai: Active Ingredient.
Agricultural uses:
Includes food and non-food (i.el, commercial
ornamental and turf) EBDC product uses.
Data Call-in Notice:
[FIFRA Section 3(c)(2)(B)] The Agency's
authority to require additional data to support
existing registrations.
Efficiency Impacts:
The loss to the overall economy of the dollar value of
the goods and services no longer available as a result
of the cancellation action. This measure reflects the
gains and losses to growers, distributers, retailers
and consumers. Embedded in the efficiency measure is
the producer impact; therefore, producer and efficiency
impacts are not additive.
EPA: The U.S. Environmental Protection Agency; also "the
Agency."
FIFRA: The Federal Insecticide, Fungicide, and Rodenticide
Act (as amended 1988).
Industrial uses:
Limited to EBDC products used in industrial
settings.
Invalid: Studies which have been found to be deficient in some
vital parameter or those studies which have been judged
not to be scientifically sound or those studies whose
reliability is seriously questioned.
LC50: Median Lethal Concentration: a statistically derived
concentration of a substance that causes death in 50
percent of test animals, expressed as weight or volume
of test substance per volume of air (e.g., mg/L or
ppm) .
LD5Q: Median Lethal Dose: a statistically derived dose
that causes death in 50 percent of animals when
-------
XXIV
LEL:
administered by the route indicated, expressed as
weight of substance per unit weight of test animal
(e.g., mg/kg).
Lowest Effect Level:
MOS/MOE: Margin-of-Safety/Margin-of-Exposure:
The calculation of a margin of safety or margin of
exposure involves division of an appropriate NOEL by a
worker's estimated exposure. The result is a
unitless figure which gives an indication of how close
a worker's exposure dose is in relation to the NOEL for
laboratory animals.
MPI: Maximum Permissible Intake (MPI): A term relative to
human dietary exposure. The MPI is expressed im mg/kg
and is calculated by multiplying the RfD by the body
weight of a human.
MRID: Master Record Indentification (number): EPA's system
of tracking studies used in support of registrations.
NO(A)EL: No Observable (Adverse) Effect Level: A maximum dose
used in a test which produces no observed (adverse)
effects.
OPP: The Office of Pesticide Programs of the U.S. EPA.
ppm: Parts per million.
PADI: Provisional Acceptable Daily Intake: An acceptable
daily intake of pesticide residue based on a limited
toxicological data base.
PAI: Pure active ingredient.
Producer Impacts:
Affects to growers or users due to increased costs from
using more expensive alternatives and losses due to
possibly reduced yields.
Reference Dose: The Reference Dose (RfD) is an
estimate (with uncertainty up to an order of magnitude)
of a daily exposure to the human population (including
sensitive subgroups) that is likely to be without an
appreciable risk of deleterious effects during a
lifetime. The RfD is a benchmark dose from which to
gauge the potential effects of the chemical at other
doses. Usually, doses less than the RfD are not likely
RfD:
-------
XXV
to be associated with adverse health risks, and are
therefore less likely to be of regulatory concern.
Technical: Active ingredient as manufactured.
Technical Registrant: Registrant of the technical material.
TMRC: Theoretical Maximum Residue Contribution: An
estimate of dietary exposure obtained by multiplying
residue tolerance levels for a given pesticide by the
average daily per capita food consumption figure, then
adding the exposure figures for each crop. TMRC is
usually expressed in terms of mg ai/kg bodyweight/day.
-------
I. INTRODUCTION
The Environmental Protection Agency is examining the
ethylene bisdithiocarbamates (maneb, mancozeb, metiram, nabam and
zineb) because of carcinogenic, developmental and thyroid effects
caused by ethylenethiourea (ETU), a common contaminant,
metabolite and degradation product of these pesticides as
outlined in the Position Document 1 (PD 1), published in 1987 (52
FR 27172). In 1986, all registrants of amobam (another EBDC
pesticide) voluntarily cancelled their registrations in response
to a Data Call-in Notice requiring the submission of additional
data to support their product registrations.
Data available at this time has led the Agency to conclude
that the continued registration of EBDC products for use on
certain food crops, commercial ornamentals and home garden sites
and in some industrial uses would result in unreasonable adverse
effects to humans.
In determining which uses to cancel, the Agency considered
the aggregate risks posed by the EBDCs and ETU, the extent to
which registered uses are being supported by registrants and,
where appropriate, the risks and benefits of individual uses.
A. REGULATORY BACKGROUND
1. The Special Review Process
The term "Special Review" is the name now used for the
process previously called the Rebuttable Presumption Against
Registration (40 CFR Part 154).
The Special Review process provides a mechanism through
which the Agency gathers risk and benefit information about
-------
1-2
pesticides that appear to pose risks of adverse effects to human
health or the environment that may be unreasonable. Through
issuance of various notices and Technical Support Documents, the
Agency publicly sets forth its position and invites participation
in the Agency's review of suspect pesticides by pesticide
registrants, the U.S. Department of Interior, the U.S. Department
of Agriculture, user groups, environmental groups, and other
interested persons.
Risk information submitted to and/or gathered by the Agency
must be evaluated and considered in light of benefit information.
If the Agency determines that the risks appear to outweigh the
benefits, the Agency can initiate action under FIFRA to cancel,
suspend, and/or require modification of the terms and conditions
of registration.
2. Special Review Actions
The Federal Insecticide, Fungicide, and Rodenticide Act, as
amended, (FIFRA) and its regulations require the Agency to review
the risks and benefits of the uses of pesticides.
The regulatory history of the EBDCs includes a full Special
Review. In 1977, The Agency initiated a Rebuttable Presumption
Against Registration or RPAR (now known as a Special Review)
based on the assumption that the EBDCs and ETU posed three
potential risks to humans and/or the environment:
carcinogenicity, developmental toxicity and acute toxicity to
aquatic organisms. Three additional areas of concern were
identified as thyroid toxicity, mutagenicity and skin
-------
1-3
sensitization. In 1982, the Agency concluded this Special Review
by issuing a Final Determination PD 4 which adopted risk
reduction measures to preclude unreasonable adverse effects
pending development of additional data needed to arrive at a more
refined assessment of the risks. The Agency concluded that the
potential risk of acute toxicity to aquatic organisms could be
reduced through the addition of a label statement warning users
of a hazard to fish. Potential risks to applicators from
developmental and thyroid effects could be adequately reduced by
requiring protective clothing. Potential dietary exposure
resulting from consumption of EBDC-treated home grown produce was
addressed by a label statement highlighting preharvest intervals
on labels of home use products. The Agency also concluded that
there were insufficient exposure data to reach any regulatory
conclusions regarding the potential risk of carcinogenic effects
to humans. Additional data were required to be submitted to
address mutagenic effects. The skin sensitization effect was
determined not to meet the criteria for an RPAR.
On July 17, 1987, the Agency issued a second Notice of
Initiation of Special Review of the ethylene bisdithiocarbamate
(EBDC) pesticides (maneb, mancozeb, metiram, nabam and zineb)
because of carcinogenic, developmental and thyroid effects caused
by ethylenethiourea (ETU), a common contaminant, metabolite and
degradation product of these pesticides. This document, also
referred to as a Position Document 1 or PD 1, detailed the bases
for the Agency's decision to initiate the Special Review (52 FR
-------
1-4
27172). The Agency had determined that registrations containing
the EBDC pesticides met or exceeded the 40 CFR risk criteria
relating to carcinogenicity to humans from dietary exposure and a
risk to applicators and mixer/loaders for thyroid and
developmental effects. Subsequently, the risk criteria in 40 CFR
162.11 were superseded by new criteria set forth in 40 CFR 154.7
(a) (2) and (a)(6) relating to carcinogenicity to humans from
dietary exposure and a risk to applicators and mixer/loaders for
thyroid and developmental effects. Data available at that time
led the Agency to conclude that the continued registration of
EBDC products for use on certain food crops, on commercial
ornamentals, on home garden sites and in some industrial uses
might result in unreasonable adverse effects to humans. The
Notice invited comments from the registrants as well as from the
public. The comment period lasted 45 days and all rebuttal
comments received during the comment period were evaluated.
In March 1989, Rohm and Haas (the sole registrant holding
nabam agricultural uses) requested that all nabam food uses be
voluntarily cancelled. The Agency's acceptance of this request is
imminent. Registrants holding nabam registrations on industrial
sites requested voluntary cancellation of sugar beet and
sugarcane transport and flume water nabam uses in 1987, but have
retained the use of nabam in sugar mill grinding, crusher or
diffuser systems.
In 1986, the zineb technical registrants cancelled their
registrations. At that time, the Agency notified end use
-------
1-5
suppliers of their lack of a registered supplier. After the
first notification in 1986, one end use formulator agreed to
support a number of uses. In July, 1989 that formulator notified
the Agency that he wanted to voluntarily cancel his registrations
and the Agency issued a second notice to the remaining
formulators in October 1989. At this time no formulator had yet
agreed to support zineb registrations.
On September 6, 1989, the four technical product registrants
of maneb, mancozeb and metiram (Rohm and Haas, duPont de Nemours,
Pennwalt, and BASF) applied to the Agency to amend their
registrations and end use labels to remove 42 of 55 food uses and
to restrict formulation of their technical products only into
products labeled for uses which have been retained. Only
thirteen crops were proposed for retention by the registrants.
These registrants will label all their EBDC technical and end use
materials manufactured after September 6, 1989; and all existing
EBDC technical stocks and end use products remaining after
January 2, 1990, to specify for use on only the food commodities
as follows: maneb (almonds, bananas, potatoes, sugar beets and
sweet corn), mancozeb (asparagus, bananas, cranberries, figs,
grapes, onions, peanuts, potatoes, sugar beets, sweet corn,
tomatoes and wheat), and metiram (potatoes). The affect of
relabeling the technical product is that it now will become
unlawful for downstream formulators to use these sources of
technical in end use products labeled for use on these 42 deleted
commodities. The manufacturers have also petitioned the Agency
-------
1-6
to reduce tolerances for the remaining 13 food uses. They also
notified the Agency that they would not object if the Agency
proposed to revoke tolerances for the 42 food uses being deleted.
This voluntary action by registrants was taken in an effort to
reduce possible dietary risks associated with consumption of
EBDC-treated commodities. Once the registrants' action becomes
final, the deleted uses cannot be reinstated until such time as
the registrants apply to reinstate these uses and the Agency
determines risks associated with these uses are acceptable.
Once the zineb registrations are formally cancelled and the
42 food uses are formally removed from the technical registrants'
maneb, mancozeb and metiram labels, the Agency will notify the
respective formulators that there is no longer a registered
source of supply for these uses. No use of zineb is likely to be
supported. If the maneb, mancozeb and metiram formulators want
to retain any or all of the 42 uses, they must both locate an
alternate source for the technical product and fulfill all data
requirements for that technical product and the particular end
uses retained, including those which are presently the subject of
FIFRA section 3(c)(2)(B). Failure to take these steps will
result in suspension under FIFRA section 3(c)(2)(B).
Until the Agency contacts the formulators, determines
whether any of them will continue to support any or all of the 42
maneb, mancozeb and metiram uses which the technical registrants
are dropping, and takes any suspension or cancellation actions
that may be necessary, all 55 uses are still legally registered
-------
1-7
and must be considered in this Preliminary Determination.
However, recognizing that all currently registered technical
producers have deleted the 42 uses from their labels, and have
placed language on their technical products which prohibits
formulation for use on any of the removed uses, the Agency
acknowledges that these 42 uses may in the near future no longer
by supported by any registrant. Thus, while 55 tnaneb, mancozeb
and metiram food crop sites are registered now, in the near term
it is possible that only 13 may remain.
B. Organization of this Position Document.
This Position Document 2/3 (PD 2/3) addresses the risks and
benefits of the uses of the EBDC pesticides, regulatory options,
and the proposed decision. This document contains five parts.
Chapter 1 is the Introduction. Chapter II discusses the
potential risks of EBDC pesticide use. It includes descriptions
and evaluations of the risk information, exposure data, rebuttal
submissions and analyses, and the Agency's risk conclusions.
Chapter III discusses the benefits of different EBDC pesticide
uses, discusses the assumptions and limitations of these
estimates, describes rebuttal submissions on the benefits of
EBDCs and the Agency's response to these submissions. Chapter IV
describes the possible regulatory options to reduce the risks and
evaluates the risks and benefits of these regulatory options.
Chapter V summarizes the regulatory actions which the Agency
proposes to take. Chapter VI gives the references cited in this
document.
-------
1-8
C. CHEMICAL BACKGROUND
1. Chemical and Physical Characteristics
The Ethylene Bisdithiocarbamates (EBDCs) are the group of
fungicides consisting of five registered pesticide active
ingredients: mancozeb, maneb, metiram, nabam and zineb. Table
1-1 gives the common and chemical names accepted for use in the
ingredient statement on pesticide products as required by FIFRA,
as well as trade names and the Chemical Abstract Service (CAS)
name. Table 1-2 presents the chemical structure, molecular
formula and weight, solubility and other physical and chemical
properties associated with each EBDC.
The chemistry of the EBDCs is complicated by their
instability and their propensity to form polymers, especially in
the presence of certain ubiquitous metallic ions. They begin to
degrade with production and continue to degrade with storage and
application. Important factors influencing chemical degradation
are presence of oxygen, humidity, temperature and pH. A number
of common degradation products have been reported. While all of
these can result from the degradation of any EBDC, the relative
proportions of the degradates appear to be different for the
individual EBDCs. Ethylenethiourea (ETU) appears to be the
dominant degradation product of all EBDCs and the one of greatest
toxicological concern.
-------
1-9
Table 1-1
EBDC Nomenclature
Common Name Label Name
Trade Name(s)
CAS Name
1. Mancozeb
2. Maneb
3. Metiram
4. Nabam
5. Zineb
Manganese EBDC
Disodium EBDC
Dithane M-45
Manzate 200
Zinc EBDC
Manzate
Dithane M-22
Polyram
Parzate
Dithane D-14
Chem Bam
Nabasan
Dithane Z-78
[[1,2-ethanediylbis[carbamo-
dithioato]](2-)[manganese
mixture with [[1,2-ethane-
diylbis[carbamatethioato],
(2-)] zinc
[[1,2-ethanediylbis[carbamo-
dithioato]](2-)] manganese
Metiram
Disodium 1,2-ethanediylbis
[carbamodithioate]
[[1,2-ethanediylbis[carbamo-
dithioate] ](2-)]zinc
1 Zinc ion and manganese ethylene bisdithiocarbamate 80 percent, a
coordination product of manganese 16 percent, zinc 2 percent and ethylene
bisdithiocarbamate 62 percent.
2 Mixture of 5.2 parts by weight (83.9 percent) of ammoniates of [ethylene
bisdithiocarbamato]zinc with 1 part by weight (16.1 percent)
ethylenebis[dithiocarbamic acid], bimolecular and trimolecular cyclic
anhydrosulfides and disulfides.
-------
Table 1-2
Chemical and Physical Properties of EBDCs
Chemical Structure Empirical Formula Formula Wt Physical Properties Solubility
Mancozeb: V 271 2/ Grayish yellow powder
r s -^
II
CH2NHC-S-
CH2NHC-S-Mn-
S
which decomposes before
melting; flash point
138' C.
(Zn)y
X
Maneb:
(a) monomer C4H4N2S4Mn 265.3 Yellow crystalline solid
which decomposes before
HN-CH2-CH2-NH melting and on exposure
£ S | to moisture or to acids.
VVC
(b) polymer (C4H4MnN2S4)x 3/ Light-colored solid
-* C ^
5
u
CH2NHC-S-
* i
melting and on exposure
to moisture or acids.
X
Hetiram:
"~P S S "I (CifiHssNiiSigZ^Jjj Light-yellow solid which
|| " l| decomposes at 140 C;
CH2NHC-S- CH2NHC-S- 1088.6 2/ unstable under strongly
| | acid or alkaline
CH5NHC-S-Zn(NH3)- CH2NHC-S- conditions or a comblna-
II l| tion of heat and
L S 4.3 S Jx moisture.
Practically insoluble
in water and other
organic solvents.
Slightly soluble in
water and insoluble '
in most organic I
solvents.
Similar to monomer.
become
Jb^S»fc\Jfc^S
Practically insoluble
in water and in most
organic solvents;
soluble with de-
composition in
pyridine.
-------
Table 1-2
Chemical and Physical Properties of EBDCs (continued)
Chemical Structure Molecular Formula Molecular Wgt Physical Properties
Solubility
Nabam:
S
CH2NHCSNa
1 - +
O12NHCSNa
M
C4H6N2Na2G4 256 Colorless crystals of
limited solubility;
generally marketed in
solution.
Soluble in water
(20 pet) to form
yellow solution.
Zineb:
(a) Monomer
HN-CH2-CH2-NH
C4H6N2S4Zn
275.8
(b) Polymer
S
II
CH2NHC-S-
CH2NHC-S-Zn-
S
EIU:
O^-NHs*
(C4H6N2S4Zn)x
102.2
Off-white solid which
decomposes before
melting; negligible
vapor pressure at 25 *C;
somewhat unstable to
light, neat and moisture.
Light-colored powder
powder produced when
from concentrated
aqueous solutions of
nabara with zinc sulfate.
Practically insoluble
in water (lOp/m at
25'C) but soluble in
pyridine, chloroform
and carbon disulfide.
Similar to
White crystals melting
at 203* to 204'C
Soluble in water;
insoluble in acetone,
ether, chloroform and.
benzene
Variable
Formula weights for mancozeb and metiram are estimated for the mononer
Indefinite
-------
1-12
2. Registered Uses and Production
Approximately 225 1 pesticide products containing EBDCs as
active ingredients are federally registered. The technical
materials are produced by Pennwalt Corporation (maneb); BASF
(metiram); Rohm and Haas Company and E.I. duPont de Nemours
(mancozeb); and Alco Chemical Corporation, Vinings Chemical
Corporation and Rohm and Haas Company (nabam).
The first use of this class of chemicals as fungicides was
in 1935, when nabam was used for the control of fungal diseases
on tomatoes. In 1943, zinc sulfate was added to nabam
suspensions to improve the fungicidal activity, and then the
reaction product (zineb) became widely used to control fungal
diseases on plants. The manganese salt (maneb) was developed in
1950. Since 1950, the zinc manganese complex of ethylene
bisdithiocarbamates (mancozeb), the diammonium salt (amobam) and
zinc ammoniates (metiram) have been developed as fungicides. In
1986, all amobam registrants voluntarily cancelled their
registrations in response to receiving a requirement to submit
additional data to support their product registrations.
These pesticides are intended for use as protectants against
fungal pathogens and are used on a wide variety of commercial and
home garden fruit, vegetable and ornamental crops and turf, as
seed piece treatment, as a soil treatment and industrially as a
antimicrobial in water cooling systems (towers and airwashers),
1 This does not include amobam, zineb, or nabam agricultural
food use registrations which are all suspended and/or cancelled.
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1-13
oil well drilling rigs and in pulp, paper and sugar mills. Maneb 2
is primarily used for control of early and late blight diseases
of potatoes and tomatoes and for control of scab and other fungal
diseases of apples. Mancozeb 2 is registered on 28 food crops,
the major ones being apples, grapes, potatoes, sweet corn,
tomatoes and onions. Metiram 2, primarily used on potatoes for
control of early and late blight, is registered for use on 12
food crops and three non-food crops. Nabam registrations for use
on agricultural non-food crops (ornamentals) are currently
suspended; the registrations for use on agricultural food uses
have been requested to be voluntarily cancelled. Active nabam
registrations are for use as biocides at industrial sites. Table
1-3 lists all registered uses of the EBDCs.
The pesticide products containing EBDCs are most commonly
formulated as wettable powders, dusts and concentrates (solution
and suspension). There are also other formulations available as
water dispersible granules.
Approximately 12 to 18 million pounds of EBDCs have been
used in the United States annually. The largest agricultural
crop uses in pounds of active ingredient per year (Ibs a.i./yr)
are: potatoes (approximately 3.5 million Ibs a.i./year), apples
(approximately 3.5 million Ibs a.i./year), cucurbits
(approximately 2.0 million Ibs a.i./year), tomatoes
(approximately 1.4 million Ibs a.i./year), onions (approximately
2 See earlier discussion of request to amend labels for
registered EBDC technical materials.
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1-14
Table 1-3
EBDC Registered Sites
SITE
EBDC FUNGICIDE "
MANCOZEB MANEB METIRAM
NABAM
Almond R
Apple R R R
Apricot R
Asparagus R R R
Banana R R
Barley R
Beans (green & dried) R
Broccoli R
Brussels Sprouts R
Cabbage R
Cantaloupe R R R
Carrot R R
Casaba melon R R
Cauliflower R
Celery R R R
Chinese Cabbage R
Collards R
Corn, Field R
Corn, Pop R
Corn, Sweet R R R
Crabapple/Quince R
Cranberry R R
Crenshaw melon R R
Cucumber R R R
Eggplant R
Endive R
Fennel R
Fig R
Grapes R R
Honeydew melon R R
Kale R
Kohlrabi R
Lettuce R
Lima beans R
a = All agricultural nabam uses have been suspended for several years and the
registrant has requested voluntary cancellation of all agricultural food uses,
The registrant for the technical zineb material has requested voluntary
cancellation of all uses.
R = Registered use
S = Suspended use
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1-15
Table 1-3
EBDC Registered Sites (continued)
SITE MANCOZEB MANEB METIRAM NABAM
Food Crops
Mustard Greens R
Nectarine
Oats R
Onion R R
Papaya R R
Peach R
Peanuts R R
Pear R
Pecan R
Peppers R
Pineapple propagation stock R
Potatoes R R R
Potatoes {seed piece) R R R
Pumpkin R
Rhubarb R
Rye R
Spinach R
Squash * R R
Sugar Beets R R R
Tomato R R R
Turnips R
Watermelon R R
Wheat R
Non-Food Crops
African Violets R
Anthurium R
Arborvitae R
Arizona Cypress R
Asters R R
Azalea R R S
Begonia R
Buckeye R
Buffaloberry R R
Camellia R R S
Caprifig R
Carnation R R S
Chrysanthemum R R S
Cordyline R
Cotton R R
* Mancozeb is registered only for use on summer squash
-------
1-16
SITE
Non-Food Crops
Table 1-3
EBDC Registered Sites (continued)
MANCOZEB MANEB METIRAM
NABAM
Cyclamen
Dahlias
Delphinium
Dieffenbachia
Douglas-Fir
Dracaena
Eastern Redcedar
Elm
Epcot Display Crops
Euonymous
Fatsia
Ficus
Firethorn
Flowering Crabapple
Flowering Dogwood
Fuchsia
Geranium
Gladiolus
Hawthorn
Holly
Hollyhock
Honeysuckle
Horsechestnut
Hydrangea
Iris
Japanese Aralia
Japanese Aucuba
Juniper
Ligustrum
Lilies
Magnolia
Maple
Marigold
Mountain ash
Mountain-laurel
Narcissus
Oak
Orchids (Dendrobium spp.)
Ornamental Conifers
Ornamental Ferns
Ornamental Flowering Plants
Ornamental Herbaceous Plants
Ornamental Plants
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
-------
1-17
SITE
Non-Food Crops
Table 1-3
EBDC Registered Sites (continued)
MANCOZEB MANEB METIRAM
Ornamental and/or Shade Trees
Ornamental Turf
Ornamental Woody Shrubs/Vines
Pachysandra
Pansies
Peonies
Peperomia
Philodendron
Photinia
Pleomele
Poinsettia
Pyracantha
Rhododendron
Rose
Schefflera
Skunkbush Sumac
Snapdragon
Statice
Syngonium
Tobacco
Tulips
Venus Fly Trap
Viburnum
Walnut
White Ash
Zinnia
Seed Treatment
Barley
Beans
Corn (field)
Cotton
Flax
Oats
Peanuts
Peas
Rice
Rye
Safflower
Sorghum
Soybeans
Sugar beets
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
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1-18
Table 1-3
EBDC Registered Sites (continued)
SITE MANCOZEB MANEB METIRAM NABAM
Seed Treatments
Sunflower R
Tomato R
Wheat R R
Industrial Sites
Air Washer Water System R
Brewery Pasteurizers R
Commercial and Industrial R
Water Cooling Towers
Fuel Oil (No. 2 oil, R
Intermediate fuel oil,
and No. 6 oil),
Lubricating Oil, and
Hydraulic Fluid (storage)
Leather R
Leather Processing Liquors R
Metalworking Cutting Fluids R
Oil Recovery Drilling Fluids R
Oil Recovery Water R
Preservation in Pulp and Paper R
Mills
Preservation of Adhesives and R
Animal Glues, Inks, Latex,
Mineral Slurries, Paints and
Coatings and Paper Coatings
Pulp and Paper Mill Systems R
Seawater Heat Exchangers R
Sugar Beet Flume Water R
Transporting and Washing
Systems
Sugar Beet Processing Water R
Sugarcane Processing R
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1-19
810,000 Ibs a.i./year), sweet corn (approximately 700,00 Ibs
a.i./year) and small grains (approximately 650,000 Ibs
a.i./year).
3. Tolerances
The Agency has established tolerances for maneb, mancozeb,
metiram and zineb. EPA has not established any tolerances for
nabam residues. However, FDA has established a food additive
regulation for nabam residue in beet and cane sugar and sugar
molasses. These nabam residues result from the use of nabam as
an industrial biocide in sugar mills. The tolerances for each of
the EBDCs are expressed as zineb because available analytical
methodology cannot distinguish among the various EBDCs. The
tolerance levels range from 0.1 ppm to 65 ppm with most
tolerances being 4-7 ppm. The tolerances for each are listed
below.
The tolerances for MANEB (40 CFR 180.110) in or on these raw
agricultural commodities for preharvest uses or for a combination
of preharvest and postharvest uses are as follows:
(1) 45 ppm - sugar beet tops;
(2) 10 ppm - apricots, beans (succulent forms), broccoli,
Brussels sprouts, cabbage, cauliflower, Chinese cabbage,
collards, endive (escarole), kale, kohlrabi, lettuce, mustard
greens, nectarines, papayas, peaches, rhubarb, spinach, turnip
tops ;
(3) 7 ppm - apples, beans (dry form), carrots, cranberries,
eggplants, figs, grapes, onions, peppers, pumpkins, turnip roots;
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1-20
(4) 5 ppm - celery, sweet corn;
(5) 4 ppm - bananas, cucumbers, melons, summer squash,
tomatoes, winter squash;
(6) 2 ppm - apples;
(7) 0.1 ppm - almonds, potatoes.
The tolerances for METIRAM (40 CFR 180.217) are as follows:
(1) 5 ppm - celery;
(2) 4 ppm - cantaloupes, cucumbers, tomatoes;
(3) 2 ppm - apples;
(4) 0.5 ppm - pecans, potatoes.
The tolerances for MANCOZEB (40 CFR 180.176) are as follows:
(1) 65 ppm - peanut vine hay, sugar beet tops;
(2) 25 ppm - the straws of barley, oats, rye and wheat;
(3) 10 ppm - crabapples, fennel, pears, quinces, papayas;
(4) 7 ppm - apples, cranberries, grapes;
(5) 5 ppm - celery, corn fodder and forage, the grains of
barley, oats, rye and wheat;
(6) 4 ppm - bananas, cucumbers, melons, summer squash,
tomatoes;
(7) 2 ppm - carrots, sugar beets
(8) 0.5 ppm - popcorn grain, fresh corn, cottonseed,
kidney, liver, onions, peanuts;
(9) 0.1 ppm - asparagus, corn grain;
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1-21
Food and feed additive tolerances have been established for
mancozeb under Section 409 of FIFRA. These tolerances are as
follows:
Food Additive (40 CFR 186.6300, formerly 21 CFR 193.460)
28 ppra - raisins
20 ppm - bran of wheat, barley, oats and rye
1 ppm - flour of wheat, barley, oats and rye
Feed Additive (40 CFR 186.6300 formerly 21 CFR 561.410.
20 ppm - milled feeds of wheat, barley, oats and rye.
The tolerances for ZINEB (40 CFR 180.115} are as follows:
(1) 60 ppm - hops;
(2) 25 ppm - beet tops, Chinese cabbage, collards, romaine,
Swiss chard;
(3) 10 ppm - endive, kale, lettuce, mustard greens, spinach;
(4) 7 ppm - apricots, beans, beets (garden roots only),
blackberries, boysenberries, broccoli, Brussels sprouts, cabbage,
carrots, cauliflower, cherries, citrus fruits, cranberries,
currants, dewberries, eggplants, gooseberries, grapes, guavas,
kohlrabi, loganberries, mushrooms, nectarines, onions, parsley,
peaches, peanuts, pears, peas, peppers, plums (fresh prunes),
pumpkins, quinces, radishes (with or without tops) or radish
tops, raspberries, rutabagas (with or without tops) or rutabaga
tops, salsify, strawberries, summer squash, turnips (with or
without tops) or turnip greens, youngberries;
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1-22
(5) 5 ppm - celery, sweet corn;
(6) 4 ppm - cucumbers, melons, squash, tomatoes;
(7) 2 ppm - apples;
(8) 1 ppm - wheat;
(9) 0.1 ppm - corn grain.
The tolerances for nabam (21 CFR 173.320) established by FDA are
as follows:
3 ppm - sugar beets or sugar cane from the use of nabam in
sugar mill grinding, crusher or diffuser systems (secondary
direct food additive).
No food additive regulation was established for the sugar
beet transport and flume water use because the Agency believes
that residues resulting from this use would be adequately covered
by the tolerance of 3 ppm in 21 CFR 173.320. FDA also
established an indirect food additive regulation covering the use
of nabam as a slimicide added to the process water for the
production of paper and paperboard which will contact food (21
CFR 176.300).
-------
II. ASSESSMENT OF RISKS AND ANALYSIS OF REBUTTAL COMMENTS
A. EFFECTS OF CONCERN
1. Carcinogenicity
The carcinogenicity risk assessment process consists of four
steps. In the first step, hazard identification, all relevant
toxicity information is presented and a qualitative weight-of-
the-evidence judgment is reached on the likelihood that the
pesticide is a human carcinogen. In the second step, dose-
response assessment, experimental data are used in conjunction
with certain assumptions and a mathematical model to extrapolate
the likely upper-bound of excess human cancer risk to the low
dose range. The third step is exposure assessment in which human
exposures via various routes and sources are estimated. Finally,
in the fourth step, risk characterization, the results of the
exposure and dose-response assessments are coupled to project the
plausible upper-bound of the excess cancer risk under different
conditions of exposures. This step also includes a summary of
the strength of the qualitative evidence, plus a treatment of the
uncertainties in the final assessment. In this chapter, the
carcinogenic hazard identification and dose-response assessment
will first be discussed. Then will follow a discussion of the
developmental toxicity and thyroid effect concerns. After a
discussion of dietary and non-dietary exposure, risk estimates
for all three effects will be presented, followed by a rebuttal
analysis.
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II-2
a. Hazard Identification
Despite its comprehensive data base on ETU, the Agency
currently does not have adequate carcinogenicity studies for any
of the EBDC parent compounds. Earlier this year, the Agency
received preliminary results of a rat carcinogenicity study on
mancozeb which is due in June, 1991. The registrants conducting
the mancozeb studies have indicated that the final results should
be available well before this deadline, probably in time to be
included in the PD 4. Depending on the results of this study,
adjustments to the potency factor (Q*) may be necessary.
Carcinogenicity studies with both the rat and mouse have been
required under FIFRA section 3(c)(2)(B) for each of the EBDC
chemicals through either Registration Standards or Data call-in
Notices. Data from these studies may not be available for the
scheduled PD 4. If any of these studies indicate there are
additional unacceptable risks, the Agency will take further
regulatory action.
The Agency does have an extensive data base on the
carcinogenicity of ETU. Most recently, ETU was tested for
carcinogenicity in rats and mice by the National Testing Program
(NTP) using both an in utero protocol and the standard NTP
protocol. The NTP pathology peer review group met in late
August, 1988. The data tables from the review of these studies
were received by the Agency in March, 1989; the final report is
expected to be issued in late 1989 or early 1990. The data from
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II-3
the portion of the studies conducted in accordance with the
standard protocol for a carcinogenicity study have been used in
the current risk assessment to determine the new preliminary Q,*.
The remaining data (namely those also encompassing in utero
exposures) will be reviewed over the next several months, and
included in the final risk assessment, as appropriate. In any
case, the ETU Q* is not likely to change significantly from that
derived originally (less than an order of magnitude).
In the first EBDC PD 1 (1977) the original presumption of
carcinogenicity was based on five studies that reported positive
carcinogenic responses when either maneb, zineb or ETU was tested
on laboratory animals. Metiram was tested for carcinogenicity in
rats (Hunter et al., 1981) and mice (Hunter et al.( 1979);
however, results of these studies are considered inconclusive due
to faulty study design. Carcinogenicity studies are not yet
available on mancozeb and nabam although a preliminary report on
mancozeb has been submitted to the Agency under FIFRA
section 6(a)(2).
The five positive carcinogenic studies on maneb, zineb and
ETU are summarized as follows. Balin (1970) observed increased
numbers of lung adenomas in mice fed weekly doses of maneb (500
mg/kg/body weight) by stomach tube for 6 weeks. Likewise,
Chernov et. al. (1969) observed increased occurrence of lung
adenomas in mice fed weekly doses of zineb (3500 mg/kg/body
weight) by stomach tube for 6 weeks. When weekly doses of zineb
-------
II-4
were reduced to 1750 mq/kg/body weight but continued for 11
weeks, lung adenomas were again observed in treated animals but
not in control groups. Innes et. al. (1969) observed marked
increases in liver tumors in mice fed single daily doses of ETU
(646 ppm) for over 80 weeks. Ulland et. al. (1972) fed two
different doses of ETU (350 or 175 ppm) daily to rats for 18
months. Thyroid carcinomas developed in test animals at both
dose levels but did not develop in controls. Graham et. al.
(1975) fed ETU to rats at doses of 500, 250, 25 or 5 ppm for
nearly 2 years. A dose-related increase in thyroid follicular
cell carcinomas and adenocarcinomas was observed at 500 and 250
ppm; thyroid follicular cell adenomas at 250 ppm; and thyroid
follicular cell hyperplasia at 250, 125, 25 and 5 ppm.
Although in 1982 the Agency concluded that qualitatively the
EBDCs may have the potential to cause carcinogenic effects in
humans, it agreed with rebutters that several deficiencies in the
Balin and Chernov et. al. studies made them unreliable for use in
a quantitative risk assessment. At that time, the Agency decided
that there were insufficient data to reach any regulatory
conclusions concerning potential carcinogenic effects to humans.
However, the uncertainties did not pertain to whether ETU induced
tumors in animals. In relation to the ETU studies (Innes et.
al., Ulland et. al., and Graham et. al.), the Agency believed
then and continues to believe that results of these studies
constituted sufficient evidence to show that ETU is carcinogenic.
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II-5
In 1982 the Agency relied on the Innes chronic mouse study on ETU
to conduct a quantitative risk assessment and stated in its 1982
EBDC Decision Document (PD 4) that ETU is a strong animal
carcinogen and has the potential to cause cancer in humans.
The same three ETU studies, along with portions of the new
NTP studies were used by the Agency in its current carcinogenic
risk assessment. A more detailed discussion of each follows:
1) Innes et. al. (19691
In this study, two hybrid strains of mice were used,
(C57BL/6 x C3H/Anf)Fl and (C57BL/6 x AKR)F1. Eighteen mice per
sex per group were used in the treatment group. Only one dose
was tested which was stated to be the maximum tolerated dose.
When the mice were seven days old, 215 mg/kg ETU was given by
gavage. At 28 days of age, the mice were started on diets
containing 646 ppm (96.9 mg/kg/day) of ETU. After a total of 83
weeks of treatment, the mice were sacrificed. Histopathology
consisted of examination of all major organs and of all grossly
visible lesions. Thyroid glands were not examined. The
incidence of liver tumors seen which were not classified as
adenomas or carcinomas but only as hepatomas is outlined in the
following table which was taken from EPA's Cancer Assessment
Group (CAG) risk assessment document on ethylene
bisdithiocarbamates (CAG, June 7, 1979). The Agency concluded
that, although information on the type and incidence of hepatomas
would have been helpful in their deliberations, the high
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II-6
incidence (56-100%) in the ETU-treated animals compared to the
controls (0-21%) was certainly indicative of an carcinogenic
response to the chemical. See Hauswirth, June 16, 1988.
Table II-l
Liver Tumors in ETU-Treated Mice
STRAIN DOSE fppm) MALES FEMALES
(C57BL/6 X C3H/Anf)Fl 0 3/14 (21%) 0/18 (0%)
(C57BL/6 X C3H/Anf)Fl 646* 14/16 (88%) 18/18 (100%)
(C57BL/6 X AKR)F1 0 1/18 (6%) 0/18 (0%)
(C57BL/6 X AKRJF1 646* 18/18 (100%) 9/16 (56%)
after 28 days
2) Ulland et. al. (1972)
In a study reported by Ulland, groups of 26 Charles River
rats per sex were administered 175 or 350 ppm (8.75 and 17.5
mg/kg/day respectively) of ETU in the diet for 18 months. The
control group consisted of 32 male and 32 female rats. After 18
months of treatment, 5 rats/sex were sacrificed and the remaining
rats were placed on-control diets until termination of the study
at 24 months. No thyroid lesions were seen in the control group.
The number of animals examined was not given. All five male rats
in the high dose group sacrificed at 18 months had hyperplastic
goiter; 3 had thyroid follicular cell cancer. The authors did
state that "possibly additional carcinomas could have been
discovered if serial sections had been done in the goitrous
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II-7
gland." The following table (Table II-2) was taken from the
published report and lists the incidence of thyroid lesions in
ETU-treated rats.
Table II-2
Tumor Induction in Rats by ETU
Dose and No. Affected
Lesion
Thyroid carcinoma**
(follicular)
Thyroid solid cell
adenoma
Hyperplastic goiter
Simple goiter
Liver hyperplastic nodule
350
males
17
0
17
2
1
ppm
females
8
1
13
4
0
175ppm
males females
3
0
9
4
2
3
2
6
2
1
** Two with lung metastases
3) Graham et. al. (19751
In this study, five groups of 5 week old male and female
Charles River rats were placed on diets containing 0, 5, 25, 125,
250 or 500 ppra ( 0, 0.05, 0.25, 6.25, 12.5, 25 mg/kg/day) ETU.
The duration of the study was 2 years. At 18 and 24 months, 5
rats per sex from each group were given 5 uCi 1 1 I (microcuries
of radioactive iodine) by i.p. injection, fasted for 24 hours and
sacrificed. At the end of 66 weeks, 3 rats/sex/group were placed
on the control diet for the remainder of the study to determine
the reversibility of thyroid toxicity due to ETU. Only rats with
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II-8
enlarged thyroids were placed in these groups. Ten
animals/sex/group were also sacrificed at 2, 6 and 12 months.
Data on these animals were not included in this report.
Body weight gain was statistically significantly reduced
(p<0.01) at the highest dose tested at 18 and 24 months for both
males and females as compared to controls: males (-18 percent)
and females (-15 percent) at 18 months; males (-26 percent) and
females (-27 percent) at 24 months. Increased 131i uptake was
statistically significantly increased in male rats at 18 months
in the 25 and 125 ppm groups and decreased at 500 ppm. At 24
months in male rats, I uptake was significantly increased in
the 5 ppm group and decreased in the 500 ppm group. Because of
131I uptake variability, there were no statistically significant
differences in 131i uptake in female rats.
Histopathology incidence data were combined for males and
females. An increase in the number of rats with cataracts/
keratitis and with thyroid follicular adenocarcinoma/carcinoma
was observed in the groups fed 250 and 500 ppm (12.5, 25
mg/kg/day) ETU; with thyroid adenomas in the 250 ppm (12.5
mg/kg/day) group; and with thyroid hyperplasia in the 5, 25, 125
and 250 ppm (0.25, mg/kg/day) groups'. The LEL is 5 ppm (0.25
nig/kg/day) for the effects of ETU on the thyroid in this study.
Relevant data are summarized in Table II-3.
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II-9
Table II-3
Histopathology Data from Graham et al. (1975)
TUMOR INCIDENCE DATA FOR
RATS GIVEN ETU fPPml
PARAMETER 0 5 25 125 250 500
Pathological lesions
Cataracts/keratitis 210 2 6 12
Thyroid carcinoma/
adfenocarcinoma
(follicular)
Thyroid adenomas
Thyroid hyperplasia
Parathyroid hyperplasia
2
2
4
6
2
-
20
11
1
5
41
8
2
1
44
2
16
21
27
3
62
3
3
0
Statistics were not reported for the histopathological data.
Historical control data were not available. An attempt was made
to obtain more detailed information (i.e. incidence data for
males and females, separately) on this study from FDA; however,
the final report of this study has not yet been located in their
files.
In August 1986, the Toxicology Branch Peer Review Committee
(composed of scientists within the Office of Pesticide Programs
as well as other Agency programs) met to evaluate and to discuss
the adequacy of the above-mentioned three ETU carcinogenicity
studies. Other ancillary information was also considered in the
determination of ETU's carcinogenicity (i.e., mutagenicity data,
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11-10
structure activity relationships, etc.)- The Committee agreed
that each of the three studies, when considered separately, did
not meet current test standards for the evaluation of
carcinogenicity. However, the Committee believed that,
collectively, along with the other information considered, they
were adequate to conclude that ETU is carcinogenic in rats and
mice. Subsequent to the Peer Review (1987), the slides from the
Innes mouse study (referred to above as the third study) were
reread by Anver of ICF-Clement using the NTP diagnosis criteria.
In rereading the slides of the B6C3F1 strain, Anver classified 72
percent of the original hepatomas as carcinomas in both males and
females. In 1969 when the study was conducted, the general term
"hepatomas" was used to collectively describe both benign and
malignant liver tumors. Additionally, 83 percent of the
hepatomas in the males (15/18) of the second strain tested were
classified as carcinomas while 13 percent of the hepatomas in the
females were classified as carcinomas. The incidence of liver
tumors in both sexes of both strains in control groups was either
non-existent or greatly diminished compared to the magnitude of
the response in the treated groups.
4) National Toxicology Program fNTPl f19891
The National Toxicology Program (NTP) recently made data
available on ETU in studies conducted in rats and mice. These
studies were of an unusually complex design when compared with
the usual NTP carcinogenicity bioassay. Besides including
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11-11
treatment groups which received the traditional pattern of
exposure (beginning at about eight weeks of age and continuing
until the end of the experiment at two years), there also were
treatment groups in which animals were exposed in utero
essentially from the moment of conception, continuing throughout
their lifetimes. While preliminary evaluation of data from these
additional exposure scenarios indicate tumor responses somewhat
different from those seen in the standard treatment groups, only
data from the standard treatment group have been used in this
current risk assessment since the remaining data are still under
review. It is anticipated that all of the data from this complex
exposure paradigm will be evaluated thoroughly in the next few
months. This evaluation will be incorporated into the final risk
assessment which will accompany the final regulatory decision on
the EBDCs.
As mentioned above, data from the studies of traditional
design (standard treatment group) were used in this current risk
assessment. Before conducting the long term mouse study, a 90-
day feeding study was conducted to determine appropriate dose
levels. Ten mice per sex per dose received either 0, 125, 250,
500, 1000 or 2000 ppm of ETU. The most important effects
observed were the histopathologic changes in the thyroid and
liver. Follicular cell hyperplasia of the thyroid follicles was
present in most of the male and female mice receiving 1000 and
2000 ppm ETU. Altered strain affinity of hepatocytes in the
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11-12
centrilobular areas in the liver (central portion of the liver
lobe) was primarily present in male and female mice in the higher
dose groups. This lesion was however, more severe in male mice.
Cellular atypia and/or alteration of hepatocytes in the
centrilobular areas in the liver was also observed in ten of ten
male mice at 2000 ppm. No females had this lesion in the 2000
ppm group. However, one of ten females in each of the 250 and
1000 ppm dose groups showed this lesion.
Based on the results of the 90-day mouse feeding study,
animals were fed doses of 0, 333 or 1000 ppm ETU in the diet for
up to two years. The results were as follows: In the female
mice, treated at the low dose, 30% of the animals exhibited liver
adenomas only while an additional 58% showed liver carcinomas for
a combined total of 88%. At the high dose, only 2% exhibited
adenomas while 96% were diagnosed with carcinomas. This
contrasts sharply with a total of only 8% of the females in the
control group exhibiting either adenomas (4%) or carcinomas (4%).
Males also showed dose-related effects in the liver. Although
the incidences of liver adenomas (16%) and carcinomas (30%)
(total of 47% of animals with tumors) was obviously higher in
male than female controls, the treated males showed significantly
higher tumor rates when compared against their concurrent
controls. Virtually all males exhibited tumors at the high dose
(2% with adenomas, 98% of them with carcinomas) while a total of
68% of the males at the low dose had tumors (adenomas = 28%;
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11-13
carcinomas = 40%). Centrilobular cytomegaly (scattered giant
cells in the area of the central portion of the liver lobe which
are generally recognized as potential precursors to
carcinogenicity) was evident in both treated groups of both sexes
but not observed in the controls. Cellular necrosis was not
observed in any group. The thyroid gland in female mice showed
dose related increases in follicular cell hyperplasia when
compared to controls (4%, 26%, 94%). Male mice showed follicular
cell hyperplasia only at the high dose tested (0%, 0%, 88%).
Female mice showed statistically significant increases in
follicular cell multiple adenomas and carcinomas at the high dose
only. No thyroid carcinomas or adenomas were observed in
controls. In males, follicular cell adenomas and carcinomas
appeared to a greater extent in the high dose group total (62%)
than in controls (2%) or the low dose group (2%).
Before conducting the long term rat studies, a 90-day
feeding study was conducted to determine appropriate dose levels.
Ten rats per sex per dose received 0, 60, 125, 250, 500 and 750
ppm ETU. Based upon the parameters examined, it was concluded
that the most important effects observed were those
histopathologic changes in the thyroid. Follicular hyperplasia
and thyroid adenomas were seen in both male and female rats
primarily in the 250 ppm and higher dose groups. These lesions
were more severe and involved a larger number of males in all
dose groups.
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11-14
In the new NTP study conducted on rats, the thyroid gland
was the principal target organ for ETU. Based on the 90-day rat
feeding study, animals were fed ETU in their diet at levels of 0,
83 or 250 ppm for up to two years. Hyperplasia ranged between 0-
9% for control groups, whereas hyperplasia in all treated groups
was between 18 and 64%. Follicular cell adenocarcinomas occurred
in 58% of the high dose group of males compared to 2% in
controls. In females, it was 16% for adenocarcinomas at the high
dose compared with 4% for controls. (Rinde, August 10, 1989,
Preliminary Peer Review of Ethylene Thiourea).
b. Mutagenicity
ETU and the EBDCs have been tested for mutagenicity in
several assay systems. Results of the available studies were
both positive and negative. However, the body of evidence for
ETU and the individual EBDCs suggest that they are capable of
inducing a variety of genotoxic effects (Dearfield, September 25,
1989 and July 22, 1988). These include responses in gene
mutation assays, structural chromosomal assays, and other
genotoxic effects. The assay systems and results are summarized
in Tables II-4 and Table II-5 below.
A major consideration that should be taken into account when
examining the genotoxicity of ETU is the magnitude of these
positive responses. While ETU induces a variety of genotoxic
endpoints, it does not appear to be a potent genotoxic agent.
Since ETU does not appear to be very potent, and is not extremely
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11-15
Table II-4
Mutagenicity of ETU
ASSAY SYSTEM
RESULT
Transformation in C3H 10T 1/2 cells Negative
Transformation for promotion in C3H 10T 1/2 cells Negative
Drosophila, sex-linked recessive lethal Negative
E. Coli WP2 Reversion Negative
Chromosomal aberrations in Chinese Hamster DON cells Negative
Mouse dominant lethal Negative
Chromosomal aberrations in bone marrow - mice Positive
UDS - HeLa cells Positive
UDS - human fibroblasts Negative
Micronucleus test - mice Negative
B. Subtilis Rec assay Positive
Transformation in BHK 21 cells Positive
Sister chromatid exchange in bone marrow
and liver cells (in vivo) Negative
Sister chromatid exchange in CHO cells (in vitro) Negative
Chromosomal aberrations in CHO cells Negative
Gene mutation - mouse lymphoma cells Negative
Gene mutation - CHO-HGPRT assay Negative
S. cerevisiae - mitotic recombinants Positive
Ames Assay
his G-46, TA 98,
100, 1535,1537,1538
Positive, negative
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11-16
Table II-5
Mutagenicity of the EBDCs
(Acceptable Studies Submitted to the Agency)
TEST SYSTEM
Ames Salmonella
Sister chromatid
exchange-CHO cells
Host mediated
assay - mice
Cytogenetics - rats
bone marrow
Unscheduled DNA
synthesis - rat
Gene mutation -
CHO cells
Transformation C3H
10T 1/2
Transformation pro-
motion assay
C3H 10T 11/2
Saccharomyces
cerevisiae D3
mitotic recombin.
METIRAM
NT
positive
negative
negative
negative
positive
negative
equivocal
positive
MANEB
negative
negative
negative
negative
negative
negative
negative
NT
positive
MANCOZEB
negative
positive
negative
negative
negative
negative
negative
negative
positive
NABAM
NT
positive
equivocal
negative
positive
positive
negative
NT
NT
NT = not tested
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11-17
toxic to test cells and organisms, it is not surprising to find
reviewed that ETU does not induce effects in many of the assays.
Therefore, in many instances, positive and negative results in
the same assay are reported from different investigators, but
these results may be dependent upon the test conditions in each
individual laboratory. Usually there are problems with many of
the negative assays in protocol or reporting and in many studies
the concentration levels are not high enough for an adeguate
test.
An additional concern for ETU may be the aspect of
nitrosation of ETU. There are suggestions that ureas (such as
ethylenethioureas) can be nitrosated with sodium nitrite at
appropriate acidities. Many ethylene bisdithiocarbamate-treated
products are cooked and eaten. With ETU as a metabolite along
with a contaminant as a nitrosating source, humans could be
exposed to conditions where nitrosation in the stomach may occur.
Nitrosated ETU and ETU in combination with sodium nitrite have
been demonstrated to induce potent genotoxic effects in gene
mutation assays and in in vivo micronucleus and chromosomal
aberration assays. Therefore, this aspect of ETU genotoxicity
should be a concern if humans are exposed to ETU above certain
amounts.
In many instances, the induced genotoxic effects by the
EBDCs are not particularly striking, for example, in the SCE
assays. However, in some instances, the response is
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11-18
significantly large, e.g. the response to mancozeb in the in
vitro cytogenetic assays. Also, there is no single assay where
all the EBDCs provide consistently elevated and substantial
positive responses. This demonstrates that these compounds
apparently are not consistent in their genetic activity with many
negative results found in addition to the positive results. An
in depth examination is necessary to ascertain their potential
genotoxicity. Of the five EBDCs tested, mancozeb induced a
larger number of positive effects (Deerfield, 1989), including
positive cytogenetic results from exposed humans (Jablonicka et
al, 1989) that would provide the most evidence among the EBDCs
for a mutagenicity concern. (It should be noted that mancozeb
had more test results available than the other EBDCs.) Overall,
therefore, it appears that the EBDCs do present a genotoxicity
concern with each of the individual compounds inducing enough of
a variety of genetic effects to elicit such a concern. This
evidence provides some support in a weight-of-evidence
consideration for potential carcinogenicity of these compounds.
It is well recognized that a correlation exists between
genotoxic agents and carcinogenicity in that many, but not all,
mutagenic agents contribute to or induce tumor formation.
Experimental evidence has shown that ETU is capable of altering
DNA in a variety of test systems. ETU has been shown to produce
thyroid tumors in the rat and liver and thyroid tumors in the
mouse. It can, therefore, be said that the positive mutagenicity
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findings provide general support for the carcinogenic
observations of ETU in both rats and mice. However, if it can be
shown that the positive results in these mutagenicity studies
have no direct relevance to the initiation of thyroid tumors in
the rat, one might argue that the thyroid tumors in the rat may
be the result of a positive physiological feedback mechanism
resulting from the inhibition of thyroid hormone production. If
only thyroid tumors were observed following exposure to these
substances, valid evidence supporting a hormonally based
mechanism of activity might lead the Agency to modify the way it
views the carcinogenic potential of ethylenethiourea and
introduce the concept of threshold into the quantification of
carcinogenic risk. However, these chemicals also induce liver
tumors and no supportable or adequate scientific argument has
been put forth to persuade the Agency to alter its current policy
for the quantitative assessment of this endpoint.
c. Non-Genotoxic Tumor Formation (Threshold Concept)
The physiological relationship between the pituitary gland
and thyroid gland is well known. Decreased levels of thyroid
hormones which threaten homeostasis results in the enhanced
secretion of thyroid stimulating hormone (TSH) from the anterior
pituitary with a subsequent rise in thyroid hormone levels. The
return of thyroid hormone levels to acceptable levels results in
a negative feedback mechanism with decreased levels of thyroid
stimulating hormone being secreted by the anterior pituitary and
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a subsequent decrease in the production of thyroid hormone. An
imbalance in this relationship where decreased thyroid hormone
levels cannot be compensated for results in the chronic
stimulation of the thyroid with attendant changes in thyroid
gland morphology (follicular cell neoplasia). This positive
feed-back mechanism is well documented and can be induced
experimentally by a variety of proven means. Thyroid gland
follicular cell neoplasia has been experimentally induced by low
iodine diets, subtotal thyroidectomy, intrasplenic transplants of
thyroid tissue and transplantation of anterior pituitary tumors
producing thyroid stimulating hormone. Ethylene thiourea (ETU)
has been demonstrated to inhibit iodide peroxidase in vitro and
may have the same effect on the thyroid gland in vivo. Iodide
peroxidase catalyzes the iodination of tyrosine and the coupling
of the resultant iodotyrosyl residues to produce the active
thyroid hormones. Thus, ETU interferes with the biosynthesis of
thyroid hormones by inhibiting iodide peroxidase with the
resultant effect of positive feedback to the pituitary for as
long as is sufficient to maintain decreased thyroid hormone
levels. In animal experiments, ETU induces thyroid tumors under
test conditions of chronic administration and adequate dosing.
The argument can therefore be advanced that at dose levels of ETU
that do not interfere with iodide peroxidase or interfere with it
at some non-critical level, ETU should not cause thyroid tumors
since the dose of ETU will be at a level below which an
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exacerbated positive feedback would not occur. This argument has
been presented to the Agency's FIFRA Scientific Advisory Panel
and the Science Advisory Board. Each has given its cautious
approval to this approach. Although the approach has been
sanctioned, the threshold concept itself is still being
considered by the Agency and will be presented to the FIFRA
Scientific Advisory Panel in 1990.
d. Summary of ETU Metabolic and Pharmacokinetic
Properties
Animal metabolism of the EBDCs is rapid and ETU and ethylene
isdiisothiocyanate sulfide (EBIS) are major metabolites. Carbon
disulfide and dimethylamine are formed in rats treated orally
with mancozeb, maneb and zineb (Lyman 1971; Seidler et al. 1970;
Vonk 1974; Truhaut 1973). Formation of these metabolites is
expected following ingestion of EBDCs due to the acid environment
of the stomach. Truhaut et al. (1973) identified EBIS, ETU, EU
(ethyleneurea) and EDA (ethylenediamine) in the feces and urine
of rats treated with mancozeb. After a single oral dose of 14C
mancozeb in rats, about 15 percent of the total radioactivity was
found in the urine and about 71 percent (47 percent as unchanged
mancozeb) appeared in the feces (Lyman, 1971). Before
elimination, radioactivity localized in the thyroid gland.
Measurements indicated that roughly 18 mole percent of the EBDCs
were converted to ETU. Within 5 days after a single oral dose of
radiolabeled maneb was administered to rats, about 55 percent of
the total radioactivity was found in the urine and feces (Seidler
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et al. 1970). Metabolites of zineb were identified as EDA, ETU,
and EBIS. ETU and EBIS were the major metabolites found in urine
of rats treated with zineb (Truhaut, 1973).
Jordan and Neal (1979) studied the metabolism of KC maneb
and zineb administered orally (0.25 m. mole/kg) in mice. After
48 hours, 91 percent of the maneb and 65 percent of the zineb
were recovered. Of total recovered radioactivity, less than 10
percent was found in the urine after administration of each
chemical. Of metabolites recovered in the urine, about 15
percent was ETU with most of the balance as unidentified polar
products. No EBIS was found. In the same experiment, ETU and
EBIS were fed separately to mice. One hundred percent of the
administered radioactivity from the ETU (0.25 m. mole/kg) was
recovered rapidly with almost 50 percent found in the urine. Of
that, 52 percent was unchanged ETU, 12 percent was EU with 37
percent polar products. After 48 hours, only 54 percent of the
administered radioactivity from KC -EBIS (0.25 m. mole/kg) was
recovered. Of this, 74 percent was in the urine, mostly as polar
products, but with some conversion to ETU. The authors concluded
that a small percentage of orally administered maneb and zineb is
converted to ETU in mice. The ETU is further metabolized in
part, followed by excretion in the urine and, perhaps, the feces.
In a comparative study, Iverson et al. (1980) examined the
metabolism of ETU in rats and cats. In rats, urinary excretion
of radioactivity after 24 hours was 82 percent of the total dose
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administered. Besides, ETU (62.6 percent of recovered
radioactivity), imidazoline, inidazoline, EU and other
metabolites were found. In contrast, in cats, S-methyl ETU
represented 64.3 percent of urinary radioactivity, with the
balance as ETU, EU and other metabolites.
Studies of the metabolism of ETU administered to pregnant
animals have revealed that mice and rats differ in the
disposition of the chemical, and that mice are able to metabolize
ETU more completely and more rapidly than rats (Battelle, 1982).
The calculated half-life of ETU and its metabolites in maternal
blood was 5.5 + 0.4 and 9.4 ± 0.6 hours for mice and rats,
respectively (Ruddick et al., 1977). Except for the thyroid,
there is virtually no accumulation of ETU in treated rats, since
over 80 percent of the absorbed dose is eliminated in the urine
24 hours after dosing (Kato et al., 1976). This is in contrast
to an accumulation in mouse liver and a 40 percent urinary
excretion over the same time span (Battelle, 1982).
In summary, although the above studies indicate general
metabolic pathways for the EBDCs and ETU in laboratory animals,
recovery of radioactivity was generally incomplete and the
balance of metabolites present was not adequately identified.
The studies show that ETU may be formed by diverse pathways from
the parent compounds and may be further metabolized giving rise
to several byproducts, not all of which are characterized.
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e. Structure-Activity-Relationship
The common EBDC degradate and metabolite ETU is structurally
related to the EBDCs and several thyroid inhibitors. EBDC and
ETU structures are shown in Table II-6.
Chronic studies on thiourea have shown that it induces
hepatomas and thyroid enlargement in rats. Thyroid neoplasia was
not observed. In another study in rats, thiourea was reported to
induce malignant tumors of the face. Thiourea was negative for
mutagenicity in the Ames Salmonella assay for tester strains
TA1530 and 1538 but positive in TA100, negative for sex-linked
recessive lethals in Drosophila and for unscheduled DNA synthesis
in rat hepatocytes, positive for mutag'enicity in S. cerevisiae
D6, and positive for transformation in Syrian hamster embryo
cells and Rauscher MLV/RE cells.
Methimazole, propylthiouracil and thiouracil all induce
thyroid tumors in rats. Propylthiouracil also induces thyroid
tumors in hamsters and guinea pigs and pituitary adenomas in
mice. Thiouracil induces hepatomas and thyroid tumors in mice.
f. Human Studies
The Agency is not aware of any valid human epidemiology
studies which evaluated exposure to ETU or any of the EBDCs.
g. Weight-of-Evidence for Carcinogenicity
The Agency considers the following facts regarding the
toxicology data on ETU to be important in the weight-of-evidence
determination of the carcinogenic potential of ETU.
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Table II-6
Structural Activity
ETU Thyroid Inhibitors
H Propylthiouracil
I
Thiourea
Methimazole
H Thiouracil
Maneb Mancozeb
CH, - N,
I
CH2 - N
= S
Metiram
H S
I II
CH2 - N - C - S -
CH2 - N - C - S - Mn
I II
H S
x > 1
H
I
CH, - N - C - S -
I 2
CH, - N - C - S - Zn(NHo) ~
- I II
H S
Nabam
H S
i ri
CH2 - N - C - S -
CH, -N-C-S-Mn
2 I II
H S
X > 1
H S
I H
- N - C - S -
- N - C - S -
I H
H S
Zineb
Zn,
CH2 -
H
1
N -
r
H
S
II
C - S
C - S
II
S
- Na
- Na
H
1
CH2 - N -
CH5 - N -
1
H
S
II
C - S
C - S
II
S
—
~
- Zn
—
X > 1
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»• ETU has been shown to induce thyroid adenomas and carcinomas
(mostly follicular) in F344 and Charles River CD rats. ETU has
been shown to induce hepatomas in (C57BL/6 x C3H/Anf) Fl and
(C56BL/6 x AKR)F1 mice after 83 weeks of treatment (Innes, 1969)
and adenomas/carcinomas in the livers of B6C3F, mice, along with
thyroid and pituitary adenomas and thyroid carcinomas (NTP,
1982) .
* ETU has been shown to induce liver tumors (single and
multiple adenomas and carcinomas) in mice and thyroid effects
(hyperplasia and follicular cell adenomas and carcinomas) in mice
and rats. Pituitary adenomas were also increased in female mice.
•• ETU has shown both positive and negative results in a variety
of mutagenicity studies. There was enough of a mutagenicity
concern to provide supportive evidence of the carcinogenic
effect. Nabam, metiram and mancozeb have been shown to be
positive for sister chromatid exchanges in CHO cells and nabam
and mancozeb for unscheduled DNA synthesis in rat hepatocytes;
maneb, mancozeb and nabam are negative in the Ames Salmonella
assay; and metiram and nabam are positive for gene mutation in
CHO cells.
•• ETU is structurally related to, and a degradate and metabolite
of, the EBDCs. Qualitatively, maneb and zineb have been shown to
cause carcinogenic effects (lung adenomas) in mice (Balin, 1970
and Chernov et al., 1969). However, the results of these studies
were considered inconclusive due to faulty study design and
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considered unreliable for use in a quantitative risk assessment.
The Agency now has preliminary information (in addition to the
NTP/ETU study) submitted under FIFRA section 6(a)(2) on mancozeb.
Evaluation of thyroid tissues from Sprague-Dawley rats indicates
that, at the high dose tested, (0, 20, 60, 125 or 750 ppm) there
is a statistically significant increase in follicular cell
adenomas and carcinomas in male rats and a statistically
significant increase in females when follicular cell adenomas and
carcinomas are combined. The incidence of follicular cell
lesions in all other groups appear comparable to control values.
»• ETU is also structurally similar to thiourea, methimazole,
propylthiouracil and thiouracil. Thiourea and thiouracil induce
hepatomas in rats and mice, respectively. Methimazole,
propylthiouracil and thiouracil all induce thyroid tumors in
rats. Propylthiouracil also induces pituitary adenomas in mice.
» ETU is rapidly metabolized in both the rat and the Rhesus
monkey. Excretion is primarily in the urine.
h. Dose Response
The Agency concludes, based upon the available evidence,
that ETU meets the criteria of a Group B2 Carcinogen (probable
human carcinogen) according to its Guidelines for Carcinogen Risk
Assessment. This classification is based on the following:
•• ETU induced an increased incidence of thyroid follicular cell
adenomas and adenocarcinomas in F344 and Charles River CD rats
(three separate studies) and of liver tumors in three strains of
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mice [(C57BL/6 x C3H/Anf) Fl, (C57BL/6 x AKRJF1, and B6C3F,].
ETU induced thyroid tumors in rats after one year or less of
treatment. It also induced a high incidence of both thyroid
tumors in rats and hepatomas in mice to an unusual degree in a
single experiment.
This classification is also supported by positive structure-
activity data since several other thyroid inhibitors (i.e.,
thiouracil and thiourea) have been found to induce hepatomas
and/or thyroid tumors in rodents. The Agency also notes that in
the rat studies, evidence of progression of the neoplastic
process in the thyroid was present. Results of the available
mutagenicity studies were both positive and negative. There was
enough of a mutagenicity concern to provide supportive evidence
of the carcinogenic effect.
While the Agency agrees that, while not all of the
carcinogenicity studies considered were carried out in strict
accordance with current Guideline for Carcinogen Risk Assessment
studies, it considers the studies adequate to conclude that ETU
is carcinogenic to rats and mice due to the nature and magnitude
of the dose-response seen.
i. Determination of Carcinogen Potency Factor (Q^*) for
Risk Calculations
The original Q^ for ETU was derived by the Agency's Cancer
Assessment Group (CAG) from the Innes mouse study. It was
calculated to be 0.14 (rag/kg/day) '\ At that time, it was chosen
over other possible outcomes because it gave the highest Q,*.
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The new preliminary Q,* [0.6 (mg/kg/day)"'] which is being used in
this document to calculate risks is based on data on female mouse
liver tumors observed in a new NTP study on ETU. Although NTP
data on the rat thyroid were made available to the Agency to
calculate a new Q^*, the mouse data were chosen because it
provided a slightly higher potency factor.
As stated earlier, the new NTP studies included a number of
unique exposure scenarios. Data associated with the in utero
exposure will be reviewed to determine if these data would
provide a more valid basis from which to derive a quantitative
estimate of hazard/risk. In that case, the preliminary Q,* used
in this current risk assessment could change in either direction
depending upon the dose rate to the fetus determined during the
in utero phase of the animal's lifetime exposure.
2. Developmental Effects
The no-observable-adverse-effect level (NOAEL) for
developmental toxicity resulting from exposure to ETU is <5.0
mg/kg. ETU was shown to be developmentally toxic at dose levels
lower than those that produced no apparent maternal toxicity or
fetal lethality. At 5.0 mg/kg/day, which was the lowest dose
tested, developmental toxicity was observed in the form of
delayed ossification of the parietal bone (in the skull).
Although the author (Khera, 1973) indicated that this observation
was limited to a few large sized litters and involved small
areas, the effect was observed in offspring of dams treated prior
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to pregnancy through day 15 of gestation as well as in dams
treated only during days 6-15 of gestation in a separate
experiment. In both experiments, delayed ossification was
clearly dose related and at higher rates than in controls and
appears to be a sensitive indicator of exposure to ETU. It would
appear, therefore, that there is no no-observable-effect level in
this study. It was also stated in the publication by Khera, that
in personal communication with W.H. Newsome, the ETU was detected
in term fetuses at concentrations comparable to those found in
maternal tissues following oral treatment with 20 or 40 mg/kg of
ETU from days 7 to 20 of pregnancy and it could, therefore, not
be determined whether the malformations arose as a result of
direct action on the fetus or indirectly by altering maternal
thyroid or other functions. In the previously-mentioned new NTP
study conducted on rats and mice, results indicated that ETU
affected thyroid function as manifested by thyroid hyperplasia in
both species. However, a mouse study conducted by Teramoto
showed no developmental toxicity at doses as high as 800
mg/kg/day by gavage (0, 200, 400, 800 ppm). Administration of
T3/T4 with ETU to pregnant rats appears to reduce the incidence
of some of these effects. ETU has also been shown to cause a
wide variety of anomalies in rats (Ruddick et. al., 1975). It
would appear that simple inhibition of the thyroid gland may not
necessarily be the mechanism by which developmental effects are
manifested in rats. Although a no-observable-effect level (NOEL)
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was not established in the Khera rat study, the Agency believes
the NOAEL is close to the NOEL and could be used for the purposes
of calculating Margins-of-Safety/Margins-of-Exposure.
A rabbit study conducted with nabam has recently been
submitted to the Agency. The available data show nabam to be a
developmental toxicant eliciting major malformations and other
manifestations of developmental toxicity in a dose related manner
and at all tested dose levels. The findings include hydrocephaly
(confirmed after visceral examination with soft spot and/or domed
cranium observed externally), frontals and parietals incompletely
ossified, increased incidence of resorptions and an overall
increased incidence of malformed fetuses per litter. In
addition, the data did not uncover any apparent maternal toxicity
at the lowest dose, 3 mg/kg/day nabam. An increased incidence of
abortions and other effects were apparent at the high dose level,
60 mg/kg/day nabam. (NOTE: Animals were dosed with Aquatreat
DN-30 which is 30 percent nabam. Therefore, tested dose levels
were actually 0, 3, 30, and 60 mg/kg/day nabam). It was the
opinion of the reviewer that, even though the study did contain
some deficiencies, the rabbit study is a valid study and the
results support the conclusion that nabam is a developmental
toxicant in the rabbit.
3. Thyroid Effects
Two subchronic ETU toxicity studies can be found in the open
literature. The purpose of both studies was to examine in some
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detail the subchronic effects of ETU on the thyroid. In the
Graham study (1972), levels of 50, 100, 500 or 750 ppm were fed
in the diets to male Osborne-Mendel rats for 30, 60, 90 and 120
days. A NOEL was not determined in this study due to significant
effects of ETU seen on thyroid weights at all dosage levels at
120 days. In the Freudenthal (1977) rat study, a NOEL of 5 ppm
was determined for the effects of ETU on the thyroid of Charles
River Sprague-Dawley rats. Thyroid toxicity seen at levels above
5 ppm consisted of thyroid hyperplasia, decreased uptake of 125 I
(radioactive iodine) by the thyroid and decreased serum levels of
T3 and T4. The LEL (Lowest Effect Level) was 25 ppm. Similar
effects were observed in the mouse and rat subchronic studies
done prior to the new NTP bioassays in these studies.
In a study done by Battelle Columbus Laboratories (1982) in
Sprague-Dawley rats, it was shown that serum T3 and T4 levels
returned to normal within 2-4 weeks after discontinuing ETU in
the diet. Administration of T3/T4 along with ETU did not
completely reverse the effects of ETU on T3/T4 levels.
4. Aquatic organisms
Although not a subject of this Special Review, existing data
indicate that maneb may pose acute risks to aguatic organisms.
Data received by the Agency (in response to April 1987
Comprehensive Data Call-in Notices) show the following acute 96
hour LC50 s for rainbow trout: maneb (0.20 ppm), mancozeb (0.46
ppm), and metiram (between 46-100 ppm). Based on available
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cold water fish toxicity data, maneb and mancozeb are highly
toxic; and metiram is slightly toxic. Maneb was similarly
demonstrated to be highly toxic to warm water fish and
invertebrates. The LC50 values for bluegill sunfish and Daphnia
were 0.27 ppm and 0.31 ppm, respectively.
Additional chronic aquatic organism and environmental fate
data are needed to further examine the risk of maneb to aquatic
organisms. EPA has required a complete set of environmental fate
data through the maneb, mancozeb, metiram and nabam Registration
Standards. Once these data are received and reviewed, the Agency
will make a determination concerning these potential risks.
5. Avian toxicity
Although not a subject of this Special Review, a letter from
the registrants summarizing data from studies done in response to
the April 1987 Mancozeb Registration Standard indicates that
mancozeb may cause reproductive effects in birds. Although the
Agency has not yet reviewed the studies themselves, the
preliminary summary suggests adverse effects on mallard
reproduction at dietary concentrations of 250 ppm and higher, and
on bobwhite reproduction at 500 and 1000 ppm. The final
evaluation is expected to support a NOEL of at least 250 ppm in
the bobwhite. An estimate of the NOEL in the mallard based on
plotting data for the most sensitive parameter (number of eggs
laid vs. log of the dose) is 50 ppm. In order to confirm this
NOEL, a second reproduction study is being conducted. When
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results of these studies are received and reviewed, the Agency
will make a determination concerning these potential risks.
6. Ground water
Although not a subject of this Special Review, the Agency
has requested small scale retrospective ground water monitoring
data for each of the EBDC parent compounds through Data Call-In
Notices dated October, 1988. These Data Call-in Notices were
issued in response to environmental fate data (submitted by EBDC
registrants in response to the July 20, 1984 Data Call-in
Notices) which indicated that EBDC parent compounds have the
potential to leach into ground water. Data have been submitted
to the Agency documenting the occurrence of ETU in ground water
in Maine in areas where maneb and mancozeb are the most widely
used pesticides. No other incidents of EBDCs or their degradates
in ground water are know (EPA/OPP, 1988). The Agency has decided
that additional data are needed to define further the extent of
any ground water problem. These data are due to the Agency in
February 1992.
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B. EXPOSURE ANALYSIS
Because of the EBDCs' broad spectrum of use on food crops,
the entire U. S. population may be exposed to EBDC and ETU
residues through the diet. Also, mixers/loaders/applicators may
be exposed to the EBDCs and ETU primarily from dermal contact
and, to a lesser degree, from inhalation of the substance applied
on crop and non-crop sites, including nabam's use in cooling
towers, oil rigs, and sugar and pulp and paper mills.
1. Dietary Exposure
Dietary exposure is both chronic and acute. When EBDC
fungicides are used on food crops, the Agency is concerned about
chronic exposure to ETU because of the carcinogenicity and
thyroid effects of ETU, and acute exposure to ETU because of the
developmental toxicity of ETU. Both chronic and acute exposure
to ETU may occur by direct exposure by eating EBDC-treated food
with ETU residues and by in vivo conversion of EBDC residues to
ETU.
a. Background
In the PD 1, the Agency expressed concern regarding the
chronic dietary exposure to consumers of food treated with EBDC
pesticides. This concern was based on a assessment of dietary
exposure and risk from ETU derived from mancozeb due to
carcinogenic risk of ETU. This analysis was discussed in the
Mancozeb Registration Standard (Guidance for the Reregistration
of Pesticide Products containing Mancozeb as the Active
Ingredient, EPA, April, 1987). The Agency was concerned about
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consumers exposed to ETU due to ETU residues in or on EBDC-
treated crops as well as through in vivo conversion of the EBDC
residues to ETU. At that time, the Agency estimated dietary
exposure to only mancozeb and ETU from commodities treated with
mancozeb, as it only had acceptable residue data on this EBDC
fungicide at that time. The exposure estimates were based on
average residues of mancozeb and ETU from residue data on crops
treated with mancozeb. These data were adequately supported by
storage stability data. The average residues of mancozeb and ETU
were adjusted to take into account percent of crop treated. At
the time of the PD 1, percent of crop treated data were available
for EBDCs as a group, but not for each individual EBDC fungicide.
Consequently, the percent of crop treated for the EBDCs as a
group was used to estimate risk in the PD 1.
Although not discussed in the EBDC PD I, the Agency also
conducted dietary exposure assessments for the developmental and
thyroid effects of ETU. These exposure analyses were discussed
in the Mancozeb Registration Standard.
Prior to the publication of the PD 1, the Agency had crop
residue data for maneb and metiram from the 1985 and part of the
1986 growing seasons. These data were not considered in the PD 1
because they were not supported by storage stability studies
conducted concurrently with the residue studies. Storage
stability studies conducted after the 1985 growing season
suggested there may be significant degradation of both EBDC and
ETU residues during frozen storage. The amount of data available
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on nabam and ETU residues derived from nabam also were too
limited to use in the PD 1.
Since the PD 1, the Agency has received crop residue,
processing and storage stability data for maneb and metiram (and
ETU derived from maneb and metiram) as a response to the Special
Review Storage Stability Data Call-in Notice of 3/31/87, and
additional data received as a response to earlier Data Call-in
Notices. After the comment period for the PD 1 closed,
additional crop residue and processing data were received from
Rohm and Haas in response to the Mancozeb Registration Standard,
from Pennwalt in response to the Maneb Registration Standard, and
from BASF in response to the Metiram Registration Standard.
Additional processing studies on leafy greens were received from
the National Food Processors Association (NFPA) and other
interested groups. The Agency also has obtained updated percent
of crop treated information, listed by individual EBDC chemical.
(See Chapter III, Table III-l.) These data and information have
been incorporated into the Agency's current Dietary Exposure
Assessment. One registrant (Rohm and Haas) submitted existing
market basket type monitoring data for EBDCs and ETU conducted in
the late 1970s. Additional monitoring data for EBDCs and ETU
also have been received from FDA and the States. These data are
discussed in the Agency's Response to Comments.
The results of the limited FDA, State and registrant-
submitted monitoring studies available suggest that residues of
EBDC's and ETU may substantially degrade between harvest and
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consumption. Due to the limited number of samples tested, these
data were considered too limited to use for a quantitative
dietary exposure estimate in this document. Therefore, for use
in further refining dietary exposure estimates, EPA has required
EBDC registrants to conduct and submit a residue monitoring
study. Data have been required for one major crop in each crop
group for which EBDCs are registered, for major processed
commodities and for meat and milk. Extrapolations will be made
by crop groupings to other commodities. All data are due to EPA
in September 1990. Issuance of the Agency's Final Determination
PD 4 is anticipated in Spring 1991. The Agency will consider any
such data received by this date. If the market basket survey is
not received or produces invalid results, the Agency will make
its final determination dietary risk assessment on the best
available data it has at that time.
For the EBDC PD 2/3, exposure to the EBDC parent compounds
and ETU have been considered. Both chronic and acute exposure
analyses were performed for maneb, mancozeb, metiram, nabam and
for ETU derived from each EBDC compound (See Hummel, 1988, 1989;
Kovacs, 1986; and Tomerlin, 1988, 1989 analyses).
The approach to estimating the anticipated residues for
chronic or acute exposure is governed by the type of data
available for a given pesticide/crop combination. For the EBDCs,
field trial, processing, washing and cooking data were available
for maneb, mancozeb and metiram. Limited monitoring data for
EBDCs and ETU were also available but the number of samples per
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commodity and the number of commodities analyzed were too limited
to use for dietary exposure assessment. (Note that due to
analytical limitations, monitoring data cannot distinguish among
the various EBDCs, nor can it determine the source of any ETU
present.) There are no raw agricultural commodity tolerances
established for nabam. Regulations have been established by the
Food and Drug Administration under 21 CFR 173.320 (b)(3) for
nabam residues following application to sugar mill grinding,
crusher and/or diffuser systems (secondary direct food additive);
and under 21 CFR 176.300 for the use of nabam as a slimicide
added to the process water for the production of paper and
paperboard which will contact food (indirect food additive).
These two uses are under FDA's jurisdiction.
b. Carcinogenicity and Thyroid Effects
For chronic exposure, the Agency attempts to estimate the
average residue in food at the time of consumption (Anticipated
Residue). The anticipated residue is then multiplied by an
average lifetime food consumption estimate (based on the overall
average consumption of infants to adults from the 1977-1978 USDA
Nationwide Food Consumption Survey for the U. S. population and
the estimated percent of crop treated) to yield the Anticipated
Residue Contribution (ARC). The ARC is then multiplied by the
carcinogen potency factor (Q,*) for each parent compound to
estimate the potential carcinogenic effect. The ARC is also
compared to the Reference Dose (RFD) to estimate potential for
non-carcinogenic effects (in this case, on the thyroid). Chronic
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11-40
analyses also were performed for carcinogenicity of ETU from the
use of each EBDC parent compound. Tables II-7 A, B and C present
residue estimates used in the chronic exposure analysis for
maneb, mancozeb, metiram and nabam, respectively.
Carcinogenic risk was estimated as a combination of several
factors: 1) ETU exposure both from direct exposure (in or on
EBDC-treated food commodities) and from indirect exposure
(resulting from metabolic conversion of EBDC residues to ETU in
the body after consumption of EBDC-treated food commodities), 2}
a time factor, and 3) a body surface correction factor.
Assessing carcinogenic risk in this manner provides an upper
bound estimate of average individual risk which applies to 240
million people.
Since food commodities treated with EBDC pesticides contain
both EBDC residues and ETU residues, two exposure estimates are
necessary to calculate total ETU dietary exposure. A direct ETU
exposure estimate is calculated from ETU residues found in or on
estimate is calculated from EBDC residue estimates on food
commodities that metabolically convert to ETU in the body (also
referred to as in vivo conversion). To estimate indirect ETU
estimated exposure, EBDC exposure is multiplied by a metabolic
conversion factor of 0.075 (7.5 percent). Total ETU exposure is
the sum of estimated exposure from these two sources.
-------
11-41
Table II-7a
Summary of Average Residue Estimates for Maneb
Average Residues fppml
Commoditv Maneb ETU
Carrots
washed
cooked
Potatoes
washed
baked flesh
baked skins
whole, cooked
Sugar Beets
White Sugar
Molasses
Dried Pulp
Sugar Beet Tops
Turnips
washed
cooked
Turnip Tops
washed
cooked
Onions, Green
washed
Onions, bulb
washed
cooked
Celery
washed
cooked
Lettuce, Leaf; Endive
washed
Lettuce, Head
washed
Spinach , Collards
washed
cooked
Mustard Greens
washed
cooked
Broccol i , Kohlrabi ,
Brussels Sprouts
washed
cooked
Cabbage, untrimmed
Cauliflower,
Chinese Cabbage
10
7.5
6.0
0.013
0.009
0.009
0.009
0.009
0.35
0.13
0.13
0.46
42
14
10
8.2
48
14
0.48
6.1
4.6
5.9
4.4
3.5
65
19
0.65
17
5.0
0.28
0.084
23.
7.0
0.23
51.
15
0.51
20.
6.0
0.20
3.0
0.023
0.023
1.3
0.002
0.002
0.002
0.004
0.002
0.004
0.004
0.004
0.004
0.50
0.29
0.29
2.0
0.29
0.12
2.2
0.27
0.27
0.16
0.16
0.90
0.35
0.15
3.0
0.18
0.076
0.007
0.003
0.34
0.14
1.3
0.15
0.063
2.2
0.092
0.039
0.9
0.040
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11-42
Table II-7a (Cont.)
Summary of Average Residue Estimates for Maneb
Average Residues (ppml
Maneb ETU_
Cabbage, trimmed
washed
cooked
Kale
washed
cooked
Beans, Succulent
Cooked/canned
Cooked/ frozen
Cooked/pureed
Cannery waste
Beans , Dry
washed
cooked
Succulent Bean Vines
Dry Bean Vines
Peppers
washed
cooked
Tomatoes, Eggplant
washed
cooked
Wet pomace
Dry pomace
Canned whole
Catsup
Paste
Juice from past
Cucumber
washed
Squash
washed
cooked
Melons, Pumpkin
washed
washed, peeled
peeled, cooked
Apples
washed
cooked
fresh Juice
Cooked Juice
Wet Pomace
Dry Pomace
Apple Sauce
Apple Baby Food
1.0
0.30
0.010
22.
6.6
0.22
3.1
0.031
0.22
0.031
4.0
2.5
0.18
0.025
640
220
6.4
2.5
0.32
2.6
1.0
0.13
1.6
0.86
0.86
0.86
0.86
0.86
0.90
0.35
0.230
0.137
0.018
0.28
0.11
0.056
0.007
7.2
4.3
0.65
0.36
0.36
33
93
0.65
0.36
0.003
0.003
0.044
0.11
0.046
1.0
0.075
0.31
0.18
0.23
0.14
0.045
0.045
0.24
1.7
6.2
0.03
0.03
0.032
0.002
0.002
0.11
0.002
0.52
0.002
0.002
0.52
0.52
0.075
0.075
0.003
0.003
0.046
0.004
0.004
0.002
0.014
0.043
0.043
0.075
0.11
0.075
0.53
3.2
0.075
0.075
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11-43
Table II-7a (Cont.)
Summary of Average Residue Estimates for Maneb
Average Residues fppm)
Commodity
Maneb
ETU
Apricots
washed
cooked
Peaches
washed
cooked
Nectarines
washed
cooked
Grapes
washed
cooked
Dry Pomace
Wet Pomace
Thick juice
Raisins
Raisin Waste
Almonds
Almond Hulls
Sweet Corn (K+CWHR)
washed, cooked kernel
Corn Fodder
Corn Cannery Waste
Bananas, whole
Banana, edible portion
Figs
Cranberries
Papayas
pulp
Rhubarb-see celery
34
21
3.1
69
41
6.2
21
12
1.9
4.0
2.4
0.36
2.6
2.4
0.25
1.1
6.5
0.44
120
0.088
0.013
33
3.8
0.070
0.035
0.95
0.40
2.8
1.4
Averacie
Commodity
Milk Local Milkshed
Milk National Basis
Beef Liver
Beef Kidney
Beef Muscle
Beef Fat
Eggs
Poultry Liver
Poultry Kidney
Poultry Muscle
Poultry Fat
Maneb
0.050
0
0
0
0
0
0
0
0
0
0
2.5
2.5
2.6
1.4
1.4
1.7
0.41
0.41
0.50
0.014
0.014
0.032
0.20
0.07
1.9
0.24
0.50
0.010
0.020
0.003
0.003
0.088
0.048
0.016
0.008
0.015
0.012
0.002
0.002
Residues (DDHI)
ETU
0.018
0
0
0
0
0
0
0
0
0
0
food commodities. An indirect ETU exposure
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11-44
Table II-7b
Summary of Average Residue Estimates for Mancozeb
Residue fppm)
Commodity
Carrots
washed
cooked
Potatoes
washed
cooked
Wet Peel
Dry Peel
Potato Chips
Potato Granules
Sugar Beets
White Sugar
Molasses
Dried Pulp
Sugar Beet Tops
onions, dry bulb
washed
cooked
Celery, untrimmed
trimmed
washed
cooked
Tomatoes
washed
cooked
Juice
Wet Pomace
Dry Pomace
Puree, sauce, ketchup
Paste
Cucumbers
washed
cooked
Melons
peeled
washed
cooked
Squash
washed
cooked
Mancozeb
0.090
0.068
0.054
0.013
0.009
0.009
0.013
0.013
0.013
0.013
0.21
0.040
0.040
0.40
39
0.060
0.045
0.036
1.7
1.1
0.34
0.011
2.5
0.98
0.13
0.12
0.088
0.35
0.28
0.83
0.55
0.22
0.028
2.8
1.4
0.54
0.069
0.53
0.21
0.027
ETU
0.002
0.002
0.011
0.002
0.002
0.003
0.003
0.003
0.003
0.003
0.002
0.002
0.002
0.002
0.35
0.002
0.002
0.008
0.010
0.004
0.004
0.050
0.017
0.017
0.098
0.052
0.040
0.12
0.098
0.18
0.010
0.010
0.028
0.020
0.010
0.010
0.054
0.002
0.002
0.017
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11-45
Table II-7b (Cont.)
Summary of Average Residue Estimates for Mancozeb
Average Residue fppml
Commodity
Apples
washed
cooked
Wet pomace
Dry pomace
Juice, canned
Canned apples
(sauce, slices)
Pears
washed
cooked
Grapes
washed
cooked
Dry Pomace
Wet Pomace
Juice
Raisins
Raisin Waste
Corn, Sweet
cooked
Corn Fodder
Corn, Field
grain & proc. comm.
Field Corn Fodder
Wheat grain
bran
shorts
flour
bread
Wheat Straw
Oats, Rye - see wheat
Barley
kernel
bran
flour
husk
rough
shorts
Barley straw
Asparagus
washed
cooked
Bananas, whole
peeled
cooked
Mancozeb
8.3
5.0
0.25
12.
57
1.6
0.25
7.1
4.3
0.21
0.83
0.50
0.025
0.50
0.25
0.003
0.30
1.8
0.16
0.16
30.
0.020
5.2
0.13
0.28
0.15
0.15
0.08
9.2
0.72
1.40
0.04
0.04
5.2
4.9
0.04
30
0.040
0.003
0.0004
0.66
0.33
0.010
ETU
0.29
0.29
0.33
0.33
0.29
0.29
0.29
0.020
0.020
0.052
0.010
0.010
0.014
0.027
0.010
0.024
0.010
0.012
0.003
0.003
0.14
0.002
0.002
0.002
0.002
0.002
0.002
0.002
0.020
0.002
0.012
0.018
0.002
0.089
0.013
0.018
0.20
0.002
0.002
0.003
0.002
0.001
0.005
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11-46
Table II-7b (Cont.)
Summary of Average Residue Estimates for Mancozeb
Average Residue fppm)
Commodity
Caprifigs - no data
Cottonseed
(all commodities)
Cranberries
washed
cooked
Papayas
peeled
washed
cooked
Peanuts
(all commodities)
hulls
hay
Pineapple - no data
Mancozeb
0.29
2.1
1.3
0.063
5.8
2.9
1.7
0.087
0.020
0.13
7.4
ETU
0.030
0.020
0.020
0.029
0.13
0.065
0.065
0.078
0.002
0.002
0.010
Averaae Residues foom)
Commodity
Milk Local Milkshed
Milk National Basis
Beef Liver
Beef Kidney
Beef Muscle
Beef Fat
Eggs
Poultry Liver
Poultry Kidney
Poultry Muscle
Mancozeb
0.020
0.01
0.04
0.02
0.02
0.002
0.001
0.001
0.001
0.001
ETU
0.008
0.004
0.007
0.005
0.004
0.002
0.0004
0.001
0.002
0.002
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11-47
Table II-7c
Summary of Average Residue Estimates for Metiram
Averacre Residue (x>pm)
Commodity
Potatoes
washed
baked flesh
baked skins
Wet Peel
Dry Peel
Potato Chips
Potato Granules
baked whole
Sugar Beets
White Sugar
Molasses
Dried Pulp
Celery *
washed
cooked
Tomatoes
washed
cooked
Wet pomace
Dry pomace
Canned whole
Catsup
Paste
Juice from paste
Puree
Cantaloupe *
washed and peeled
peeled and cooked
Apples
washed
cooked
Fresh Juice
Cooked Juice
Wet Pomace
Dry Pomace
Apple Sauce
Apple Baby Food
Sweet Corn (K+CWHR)*
washed, cooked
Pecans
Peanuts
Meal
Oil
Peanut Hulls
Peanut Vines
Metiram
0.020
0.015
0.015
0.015
0.020
0.020
0.020
0.020
0.015
0.003
0.001
0.002
0.039
65
19
0.65
0.53
0.21
0.027
0.064
0.12
0.027
0.032
0.042
0.027
0.037
0.28
0.056
0.007
3.3
2.0
0.30
0.17
0.17
15
43
0.30
0.16
0.088
0.013
0.020
0.020
0.020
0.020
0.020
28
ETU
0.021
0.021
0.021
0.022
0.021
0.021
0.021
0.021
0.021
0.050
0.050
0.11
0.051
0.35
0.15
3.0
0.030
0.030
0.054
0.037
0.035
0.043
0.090
0.11
0.046
0.081
0.004
0.002
0.014
0.47
0.47
0.48
0.50
0.48
0.69
1.9
0.48
0.48
0.003
0.003
0.002
0.010
0.010
0.010
0.070
0.80
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11-48
Table II-7c (Cont.)
Summary of Average Residue Estimates for Metiram
Average Residue (ppm)
Commodity Metiram ETU
Milk - Local Milkshed 0.030 0.020
Milk - National Basis 0 0
Beef Liver 0 0
Beef Kidney 0 0
Beef Muscle 0 0
Beef Fat 0 0
Eggs 0 0
Poultry Liver 0 0
Poultry Kidney 0 0
Poultry Muscle 0 0
Poultry Fat 0 0
*Data are translated from maneb, since no
recent residue data were submitted for metiram
residues on celery, cantaloupe, or sweet corn.
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11-49
Time is another factor to be considered when estimating
carcinogenic risk. Estimates of upper-bound lifetime
carcinogenic risks for adults are based on assumed exposure over
a 70-year lifespan. For the overall U.S. population, exposure is
assumed to continue over an entire lifetime. When estimating
carcinogenic risks for children and infants, adjustments are made
to estimate exposure for the time period they remain in a
specific age subgroup (e.g., infants who are 0 to 1 year olds and
younger children who are 1 to 6 year olds). Consideration is
also taken into account for the specific types of foods typically
consumed by each age subgroup.
Currently, the Agency also incorporates body surface
correction factors when calculating carcinogenic risks. The
carcinogen potency factor (C^*) for ETU is based upon studies in
which animals are dosed over virtually their entire lives.
Usually, EPA makes a correction of the dose comparing the ratio
of body weight to surface area of the adult animal tested versus
the ratio of body weight to surface area of adult humans.
However, the ratios of body surface areas to body weights for
children and infants are not the same as is this ratio for adults
and thus an additional correction factor is included to more
accurately estimate the risk to these two subgroups. The Q,* of
0.6 (mg/kg/day)"1 used to calculate dietary risk for the overall
population was further adjusted to account for infants by 0.51
percent and for children aged 1 to 6 by 0.64 percent, based upon
information described in Diem and Lentner, 1975. This additional
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11-50
body weight to surface area adjustment to the "adult" C^* to
estimate carcinogenic risk to children and infants has not been
done previously by the Agency for other pesticides. The Agency
invites comment on this approach.
There are two basic approaches to estimating anticipated
residues. The first uses field or "farm gate" data provided to
the Agency as a requirement in the tolerance setting process.
(See Residue Chemistry Guidelines, Subdivision O, Pesticide
Assessment Guidelines.) For chronic exposure, the average
residue from field trial data may be multiplied by processing and
degradation factors to yield the anticipated residue estimate.
Processing factors may include factors to account for commercial
processing, washing,cooking or other food preparation methods.
The second approach would be to base the estimate on monitoring
data for raw and processed commodities. Monitoring data have the
potential to reflect the effect of different application rates,
PHIs, storage times and conditions and percent of crop treated.
The estimate from monitoring data could be adjusted for the
effect of washing, cooking or other food preparation methods.
Commercial processing may increase or decrease residue
levels. For the EBDCs, processing may convert parent EBDC
residues to ETU. Currently, EPA requires processing studies only
if there is a possibility that the processing may concentrate
residues such that total residues in the processed commodity will
exceed total residue levels in the raw agricultural commodity.
Processing studies where residues are expected to be reduced are
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11-51
optional. These include studies on washing, trimming, peeling,
freezing, canning and cooking (boiling, baking and frying).
Without these data, the Agency estimated dietary exposure based
on field trial data.
Many of the basic food commodities (e.g., grains, potatoes
and apples) are stored either under cold or ambient storage
conditions for extensive periods of time. Decline of residues in
stored commodities can be factored into the anticipated residue
estimate, provided information on the commercial distribution of
stored vs. unstored commodities is available.
Finally, whichever process for estimating residues is used,
jji vivo conversion of EBDCs to ETU must be taken into account.
Since final carcinogenicity studies for the specific EBDC's are
unavailable, the Agency's exposure and risk assessment for each
EBDC chemical includes the ability of the EBDC chemicals to be
converted metabolically to ETU. EBDC data available to the
Agency indicate that the ETU metabolic conversion rate i
for all parent EBDC compounds is approximately 7.5 percent of the
amount of EBDC consumed. The Agency has multiplied the exposure
estimates for each EBDC parent compound by 7.5 percent to account
for the ability of EBDCs to metabolically convert to ETU in vivo
on a weight for weight basis.
To estimate "farm gate" residues for maneb, metiram and
mancozeb, the Agency used the average EBDC residues from residue
field trial data from studies conducted close to the maximum
rate, minimum PHI, and at least the typical number of
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11-52
applications that are allowable on the label. If residues from a
lower application rate than the maximum application rate were
used, then the residue estimate was increased proportionally to
the maximum application rate to determine the maximum residues
which might occur. For ETU residue estimates, the Agency used
the average ETU residue from field trial data, corrected for the
degradation of ETU in frozen sample storage when that degradation
in storage in that commodity or a similar commodity exceeded 20
percent. To correct for degradation in frozen storage, the
Agency divided the ETU level as determined in field studies by
the fraction of ETU remaining as determined in controlled frozen
storage stability studies.
Farm gate residue estimates were further refined to take
into account some of the effects of treatment of the commodity
after harvest, such as commercial processing, washing, peeling,
trimming, and cooking. Rohm and Haas submitted a study conducted
by Chilton Research Services (MRID #403819-17) in 1977 which
indicated that an estimated 99 percent of restaurants, households
and food processors use some type of preparation procedure for
foods (washing, soaking, rinsing, peeling, trimming) except that
an estimated 93 percent of restaurants use a processing procedure
on apples. EBDC residue estimates were reduced by up to 93
percent when the effects of washing were taken into account. ETU
residue estimates were increased by up to 12.5 percent of the
EBDC residue estimate to account for the effects of cooking.
Peeling and trimming factors were determined for a few
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11-53
commodities. The effects of cold or ambient storage used in
normal channels of trade could not be factored into the analysis
since no data were available for these effects.
For EBDC anticipated residue estimates in commercial
processed commodities of apples, sugar beets, tomatoes, snap
beans, grapes, corn, peanuts, barley and wheat the Agency
multiplied the anticipated residue estimate for the raw
agricultural commodity by a concentration/reduction factor
determined in processing studies required to support tolerances.
For potatoes, no concentration of mancozeb or metiram was
observed and no conversion of EBDC to ETU was observed, since all
samples had non-detectable residues. Residue estimates for
potatoes and potato products were made based on limits of
detection.
For ETU anticipated residue estimates in processed
commodities of apples, sugar beets, tomatoes, snap beans, grapes,
barley and wheat the Agency multiplied the EBDC anticipated
residue estimate for the raw agricultural commodity by the
percent conversion (parent EBDC to ETU) determined in processing
studies, and added the ETU residue estimate from the raw
agricultural commodity.
No data on the effects of ambient or cold storage used in
normal channels of trade are available for any crops treated with
EBDC fungicides. However, based on available data, it is known
that residues of EBDCs and ETU decline during frozen storage
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11-54
(Kovacs, 1987) and, therefore, would also be expected to decline
in ambient and/or cold storage.
For EBDCs, washing and cooking studies (Hummel, 1988a;
Hummel, 1989) have been conducted on tomatoes, spinach, potatoes
and carrots. Some additional washing data were found in
processing studies. Washing reduces residues of EBDC parent
compound, but has little effect on ETU residue levels. Cooking
converts EBDC residues to ETU residues. Washing factors for
reduction of EBDC residues on washing and cooking and factors for
the percent conversion of EBDC to ETU on cooking were determined
from these studies. Peeling factors were available for bananas
and papayas. Trimming factors were available for celery from
mancozeb residue studies (Hummel, 1988c). The processing factors
are summarized below in Table II-8.
Table II-8
Summary of EBDC and ETU Processing Factors
Commodity
Apples (Fruit)
Tomatoes (Fruiting Veg.)
Leafy Vegetables
Beans
Carrots (Root Crops)
Ave. EBDC Ave. EBDC
Washing Cooking
Factor Factor
0.
0.
0.
0.
0.
60
39
30
07
75
X
X
X
X
X
0.03 - 0.09 X
0.05 X
<0.01 X
0.01 X
0.60 X
Peeling
EBDC
EBDC to ETU
Percent
Conversion
0.45%
1.7 - 4.6%
4.1%
7.6%
12.5%
Factors
ETU
Bananas, Papayas 0.5 X 0.5 x
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11-55
Apple EBDC residues and EBDC residues in other fruits were
multiplied by a factor of 0.6 to account for the effect of
washing and by a factor of 0.03 - 0.09 to account for the effect
of cooking. ETU residues on apples and other fruits were
adjusted by a 0.45 percent conversion factor of EBDC to ETU on
cooking. This factor is the EBDC to ETU conversion factor from
the metiram processing study for applesauce (Hummel, 1988b;
1989). Residues in other commodities were estimated in a similar
manner. The washing and cooking factors and percent conversion
from EBDC to ETU upon cooking are determined using the EBDC
residue in the raw agricultural commodity, since the conversion
factors were determined from cooking and processing studies using
unwashed raw agricultural commodities. Residues in baked whole
potatoes have been estimated by assuming that baked whole
potatoes contain 10 percent baked skins and 90 percent baked
flesh.
The FDA and several states (CA, FL and NY) monitor for EBDCs
and/or ETU. No USDA monitoring data are available for EBDCs or
ETU. The FDA, as part of their enforcement program for
pesticides, collects four types of monitoring data: domestic
surveillance, domestic compliance, import surveillance and import
compliance. FDA, in their surveillance monitoring program,
monitors a wide variety of agricultural and processed commodities
for numerous contaminants, including pesticides, using
multiresidue methods of analysis which are capable of determining
a variety of contaminants from a single sample analysis. In
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11-56
their surveillance monitoring program, FDA also conducts
selective surveys to acquire information on specific pesticides,
commodities or pesticide/commodity/country combination.
Monitoring data for EBDCs and ETU are from selective surveys,
since EBDCs and ETU are not analyzed by FDA's multiresidue
methods.
In addition, FDA conducts the Total Diet Study (also called
the Market Basket Survey) in which pesticide residues are
determined in food prepared for consumption. The Total Diet
Study is designed to estimate dietary intake of selected
pesticides by various U.S. age-sex groups. Foods are collected
four times per year in retail markets at 12 locations throughout
the U.S. and are prepared as table-ready (cooked) before
analysis. Each market basket consists of 234 foods that
represent at least 90 percent of the items in the American diet.
Thirteen of the 234 foods are now being analyzed for ETU,
however, no results of ETU analyses are available at this time
(E. Gunderson, FDA, personal communication, 10/10/89).
The United States Department of Agriculture, Food Safety and
Inspection Service (USDA-FSIS) monitors for pesticide and drug
residues in meat and poultry as part of their National Residue
Program. However, no samples have been analyzed for EBDCs or
ETU.
A number of States have pesticide monitoring programs.
These programs generally supplement the FDA and USDA monitoring
programs. Eight states are now supplying their monitoring data
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11-57
to FDA in the FOODCONTAM data base. Three (CA, FL and NY) of the
eight states have been monitoring for EBDCs and/or ETU. The
Agency receives regular reports from FOODCONTAM. Monitoring data
available at the time the Comments to the EBDC PD 1 were reviewed
are described in an Agency memo (Hummel, 7/13/88). Recently the
EPA has received additional monitoring data from FDA and the
States. Most of the new data are from samples analyzed for EBDC.
Very few samples were analyzed for ETU. The recently received
monitoring data include the following:
FDA Monitoring for 1988 and 1989
FOODCONTAM Data base (State data from CA, NY and FL)
California Special Survey for EBDC residues
USDA provided summaries of State data, including State Monitoring
data from the FDA's FOODCONTAM data base and the California
Special Survey for EBDCs. The EPA already had received FDA
monitoring data for 1978-1988 and some of the FOODCONTAM data.
All available domestic U.S. monitoring data from FDA and the
States from 1985-1989 are summarized in Table II-9. About 1300
domestic U.S. samples were analyzed for EBDCs, but very few
samples were analyzed for ETU.
FDA and State monitoring data (1985-1989) were not used for
estimating dietary exposure because of the insufficient number of
samples that were collected and analyzed for EBDCs and/or ETU.
Since EBDCs and ETU are not detected by FDA's PAM I multi-residue
analytical methodology, far fewer samples were analyzed by FDA
for EBDCs and/or ETU than for other pesticide chemicals, such as
-------
11-58
Table II-9
FDA Monitoring Data and State Data
for EBDCs and ETU 1985-1989 to date (7/6/89)
EBDC Residues
Crop Total # Ave. Res. #ND
Samples (Don) (0.02Dpm)
Root Crops
Carrots
Potatoes
Radishes
Beets
Beet Tops
Turnips
Turnips w/ tops
Ginger root
Onions
Garlic
Sugar Beet pulp
Leafy Vegetables
Broccol i
Cabbage
Cauliflower
Brussels Sprout
Celery
Chinese Cabbage
Bok Choy
Col lards
Escarole
Kale
Lettuce
Endive
Mustard Greens
Spinach
Kale
Swiss Chard
Turnip greens
Kohlrabi
Legumes & Grains
Green Beans
Beans
Peas
Peas, Chinese
Corn on Cob
30
52
2
5
2
7
3
7
5
2
1
37
61
11
7
30
i,
3
19
1
11
126
5
10
54
6
3
10
3
13
1
11
5
23
0.053
0.020
0.020
0.020
0.020
0.186
0.020
0.020
0.020
0.020
0.020
0.201
0.032
0.064
0.045
0.115
0.215
1.247
0.139
0.020
0.074
0.152
0.020
6.413
1.586
0.283
0.020
1.347
0.020
0.242
0.020
0.020
0.616
0.020
29
51
2
5
2
5
3
7
5
2
1
26
59
10
6
24
3
2
15
1
10
117
5
4
34
5
3
3
3
12
1
11
4
23
*
Pos.
1
1
0
0
0
2
0
0
0
0
0
11
2
1
1
6
1
1
4
0
1
9
0
6
20
1
0
7
0
1
0
0
1
0
Max.
Res.
1.0
0.04
0.8
3.1
0.55
0.5
0.19
2.0
0.8
3.7
0.76
0.61
6.0
54.5
41.3
1.6
5.7
2.9
3.0
ETU Residues
Total 0 Ave. Res. #ND it Max.
Samples (ppm) Pos. Res.
2 0.002 2 NO
12 3.552 3 9 9.22
1 0.22 0 1 0.22
24 0.048 10 24 0.21
66 0.020
66
NO
-------
11-59
Table 11-9. continued
FDA Monitoring Data and State Data
for EBDCs and ETU 1985-1989 to date (7/6/89)
EBDC Residues
Crop Total * Ave. Res. #ND
Samples (open) (0.02Dom)
Pome Fruits
Apples
Apple Juice Con
Pears
Stone Fruits
Apricots
Peaches
Nectarines
Plums
Cherries
Cucurbits
Cantaloupes
Melons
Cucumbers
Squash
35
2
12
9
5
2
4
5
27
20
58
64
0.071
0.020
0.043
0.020
0.020
0.020
0.020
0.020
0.057
0.178
0.044
0.020
32
2
11
9
5
2
4
5
26
18
57
64
# Max.
Pos. Res.
3 0.73
0
1 0.3
0
0
0
0
0
1 1.03
2 2.5
1 1.4
0
ETU Residues
Total # Ave. Res. #ND # Max.
Samples (own) Pos. Res.
10 0.029 3 7 0.12
Other Fruiting Vegetables
Tomatoes
Tomatoes (canned)
Peppers
Eggplant
136
20
81
7
0.054
0.089
0.032
0.020
126
19
80
7
10 1.4
1 1.4
1 1.0
0
13 0.015 10 3 0.07
1 0.012 0 1 0.012
Small Fruits & Berries
Strawberries
Raspberries
Grapes
Other
Mushrooms
Bananas (import
Almonds
Artichokes
Asparagus
Avocados
Mangoes
Kiwi
Papayas
Pineapple
29
0
9
16
126
1
1
15
1
2
3
1
4
0.065
0.473
0.089
0.036
0.020
0.020
0.020
0.020
0.020
0.020
0.020
0.020
27
0
8
13
121
1
1
15
1
2
3
1
4
2 1.0
0
1 4.1
3 0.68
5 1.6
0
0
0
0
0
0
0
0
8 7 1 0.06
7 0.101 2 5 0.188
Total tt samples 1331 1223
Averages include non-detectable residues as 0.02 ppm
82 41
Averages include NO as 0.002 ppm
-------
11-60
captan, which are detected by FDA's PAM I multiresidue
methodology. Although a total of about 1300 samples of various
foods were analyzed for EBDCs and/or ETU by FDA and the States,
no more than 15 samples per commodity were analyzed for both EBDC
parent compounds and ETU derived from these compounds. The
registrant's monitoring data were not used because those data
were determined to be invalid for several reasons such as the
limited number of samples tested and the lack of valid storage
stability studies. However, the average residues found in the
limited data available from FDA and State monitoring studies
(including the California Survey for EBDCs) are generally 1 to 2
orders of magnitude lower than the Agency's current exposure
estimates. For these reasons, the Agency believes that current
residue estimates are likely to overestimate cumulative dietary
risk and individual risk on many crops. Once the Market Basket
survey data required under the authority of FIFRA section
3(c)(2)(B) are received (September 1990) and reviewed, the Agency
will make any necessary adjustments to its dietary risk
estimates.
c. Developmental Effects
For acute exposure, the Agency attempts to estimate the
maximum likely residue distribution of single day exposures for
certain population subgroups. Anticipated Residues for acute
exposure were based on the maximum residues or 95th percentile
residues from residue field trials, along with processing factors
for washing, cooking and commercial processing, as described
-------
11-61
above for chronic exposure analysis. Adjustment for percent of
crop treated is not appropriate for an acute analysis and is not
done, because an acute effect may result from exposure to a
residue in a single serving. Acute analyses were performed for
developmental effects of ETU from the use of each parent EBDC
compound. Tables 11-10 A, B and C present residue estimates used
in acute exposure analyses for maneb, mancozeb, metiram and
nabam, respectively.
-------
11-62
Table II-10a
Anticipated Residues for Maneb and Maneb
Derived ETU for Acute Exposure
Residue (ppm)
Commodity
Carrots
washed
cooked
Potatoes
washed
baked flesh
baked skins
baked whole
Wet Peel
Dry Peel
Potato Chips
Potato Granules
Sugar Beets
White Sugar
Molasses
Dried Pulp
Sugar Beet Tops
Turnips
washed
cooked
Turnip Tops
washed
cooked
Onions, Green
washed
cooked
Onions, bulb
washed
cooked
Celery
washed
cooked
Lettuce, Leaf
washed
Lettuce, Head
washed
cooked
Spinach
washed
cooked
Collards
washed
cooked
Maneb
18.
9.0
9.0
0.099
0.049
0.049
0.049
0.049
0.099
0.099
0.099
0.099
2.7
1.0
1.0
3.5
179
19
9.5
9.5
122
61
61
22
11
11
12
6.1
6.1
180
108
108
119
18
11
11
92
55
55
92
55
55
ETU
0.080
0.080
2.4
0.003
0.003
0.17
0.69
0.22
0.003
0.003
0.003
0.003
0.004
0.004
0.004
0.004
1.7
0.043
0.043
2.5
0.68
0.68
15
0.040
0.040
2.7
0.16
0.16
1.7
1.3
1.3
23
1.7
1.7
0.29
0.29
2.4
0.47
0.47
12
0.47
0.47
12
-------
11-63
Table II-10a
Anticipated Residues for Maneb and Maneb
Derived ETU for Acute Exposure (continued)
Commodity
Mustard Greens
washed
cooked
Broccoli, unwashed
washed
cooked
Kohlrabi
washed
cooked
Brussels Sprouts
washed
cooked
Cabbage, untrimmed
Cabbage, trimmed
washed
cooked
Chinese Cabbage
washed
cooked
Cauliflower
washed
cooked
Kale
washed
cooked
Beans, Succulent
Cooked/ canned
Cooked/ frozen
Cooked/pureed
Cannery waste
Beans, Dry
washed
cooked
Succulent Bean
Vines
Dry Bean Vines
Peppers
washed
cooked
Tomatoes
washed
Wet pomace
Dry pomace
Canned whole
Catsup
Residue
Maneb
85
51
51
48
29
29
48
29
29
48
29
29
16
2.1
1.3
1.3
2.1
1.3
1.3
2.1
0.020
0.27
57
34
34
11
0.11
0.80
0.11
15
6.3
0.44
0.44
2140
702
24
17
17
12
8.5
7.4
4.0
4.0
4.0
(ppm)
ETU
0.20
0.20
10
0.24
0.24
6.0
0.24
0.24
6.0
0.24
0.24
6.0
0.11
0.020
0.020
0.27
0.020
0.020
0.27
0.020
0.020
0.27
0.32
0.32
7.2
0.24
1.1
0.62
0.80
0.47
0.090
0.090
0.57
9.0
14
0.080
0.080
1.2
0.002
0.002
0.025
2.4
0.025
0.025
-------
11-64
Table II-10a
Anticipated Residues for Maneb and Maneb
Derived ETU for Acute Exposure (continued)
Residue (ppm)
Commodity Maneb ETU
Tomatoes (cont'd)
Paste 4.0 2.4
Juice from paste 4.0 2.4
Eggplant see tomatoes
Cucumber 3.4 0.10
washed 2.4 0.10
cooked 2.4 0.26
Squash 0.95 0.002
washed 0.66 0.002
cooked 0.66 0.044
Melons 2.3 0.015
washed 1.6 0.015
cooked 1.6 0.12
Pumpkin 2.3 0.015
washed 1.6 0.015
cooked 1.6 0.12
Apples 30 0.51
washed 21 0.51
cooked-see applesauce
Fresh Juice 1.5 0.78
Cooked Juice 1.5 0.64
Wet Pomace 139 2.6
Dry Pomace 388 13.9
Apple Sauce 2.7 0.64
Apple Baby Food 1.5 0.64
Apricots 156 3.9
washed 109 3.9
cooked 109 24
Peaches 175 5.5
washed 122 5.5
cooked 122 6.3
Nectarines 75 2.0
washed 52 2.0
cooked 52 2.3
Grapes 15 0.54
washed 8.4 0.54
cooked 8.4 0.60
Dry Pomace 9.6 1.2
Wet Pomace 9.0 0.75
Thick juice 0.55 7.5
Raisins 4.3 1.4
Raisin Waste 24 2.4
Almonds 2.3 0.010
Almond Hulls 368 0.10
-------
11-65
Table II-10a
Anticipated Residues for Maneb and Maneb
Derived ETU for Acute Exposure (continued)
Residue (ppm)
Commodity
Sweet Corn (K+CWHR)
washed
cooked
Corn Fodder
Corn Cannery Waste
Bananas, whole
Banana, edible
portion
Figs
Cranberries
Papayas
Rhubarb
washed
cooked
Beef Commodities
Milk
Liver
Muscle
Kidney
Fat
Poultry Commodities
Whole eggs
Liver
Kidney
Muscle
Fat
Maneb
1.9
0.13
0.13
93
3.8
0.22
0.050
3.2
0.74
5.2
180
108
108
0.21
0.44
0.14
0.19
0.23
0.014
0.11
0.04
0.03
0.30
ETU
0.016
0.016
0.16
0.24
0.048
0.023
0.030
0.066
0.012
0.002
1.3
1.3
23
0.15
0.13
0.058
0.12
0.019
0.010
0.023
0.018
0.011
< 0.0016
-------
11-66
Table II-10b
Anticipated Residues for Mancozeb and Mancozeb
Derived ETU for Acute Exposure
Commodity
Maximum Residue (ppm)
Mancozeb ETU
Apples, Crabapples,
Quinces
Washed
Cooked
Juice
Dry pomace
Wet pomace
Pears
Washed
Cooked
Asparagus
Washed
Cooked
Bananas
Pulp
Peel
Puree can
Slices can
Barley grain
Kernel
11 W/o husk
Husk
Rough
Bran
Shorts/germ
Flour
Sweet corn
Corn grain
Meal
Oil
Flour
Germ
Grits
Hull
Soapstock
Oats, rye,
wheat grain
Bran
Shorts
Flour
Bread
Fines
Overs
17
11.9
0.68
1.8
150
34
31
22
22
0.09
0.0063
0.0063
0.71
0.71
11.91
3.1
10.85
0.93
22.32
20.77
0.48
1.3
1.65
3
2
1.65
0.83
8.25
11.6
0.32
0.32
0.32
0.42
0.06
0.06
0.20
0.006
0.115
0.11
0.11
0.6
0.27
0.06
0.06
0.02
0.004
-------
11-67
Table II-10b
Anticipated Residues for Mancozeb and Mancozeb
Derived ETU for Acute Exposure (continued)
Maximum Residue (ppm)
Commodity Mancozeb ETU
Celery, Fennel 3.8 0.018
Trimmed 2.508 0.007
Washed 2.99 0.007
Cooked 2.99 0.32
Carrots 0.66
Washed 0.33
Cooked 0.33
Potatoes 0.1 0.02
Peels 0.18
Baked flesh 0.022
Baked skin 0.027
Flakes 0.022
Blanched
Whole baked
F. Fries
Peeled
Chips
Granules
Sugarbeets 0.6 0.05
Pulp 1.14 0.02
Molasses 0.02 0.002
Sugar 0.02 0.002
Sugarbeet tops 60
Cottonseed 1.1 0.11
& Processed prod
Cranberry 8.38 0.09
Washed 5.87 0.09
Cooked 5.87 0.128
Grapes 11.4 0.01
Washed 7.98 0.09
Cooked 7.98 0.141
Raisins 21 0.04
Wet pomace 3.65
Dry pomace 4.79
Raisin waste 32.49
Juice
clear 0.21
Thick 0.32
Pasteurized 0.07
Canned 0.1
Cucumbers 1.8 0.08
Washed 1.26 0.08
Cooked 1.26 0.163
-------
11-68
Table II-10b
Anticipated Residues for Mancozeb and Mancozeb
Derived ETU for Acute Exposure (continued)
Maximum Residue (ppm)
Commodity Mancozeb ETU
Melons
Cantaloupes
Watermelons
Washed
Cooked
Squash, summer
Washed
Cooked
Onion, bulb
Washed
Cooked
Papaya
Pulp
Canned
Peanuts
Meal
Oil
Tomatoes
Washed
Juice
Paste
Puree
Catsup
Canned
Animal products
Milk
Beef
Muscle
Liver
Kidney
Fat
Eggs
Chicken
Liver
Breast
Kidney
Thigh
3.49
2.44
2.44
1.44
1.01
1.01
0.48
0.34
0.34
33.64
0.14
0.44
0.31
5.4
0.39
0.39
<0.62
2.3
1.0
0.5
0.2
0.02
0.01
0.01
0.01
0.01
0.05
0.05
0.21
0.02
0.02
0.086
0.003
0.003
0.4
0.005
0.032
0.032
0.030
0.185
0.111
0.077
0.024
0.094
0.10
0.20
0.13
0.06
0.004
0.01
0.02
0.02
0.02
-------
11-69
Table II-10c
Anticipated Residues for Metiram and Metiram
Derived ETU for Acute Exposure
Cron
Residue (ppm)
Maneb ETU
Potatoes
washed
baked flesh
baked skins
Wet Peel
Dry Peel
Potato Chips
Potato Granules
Sugar Beets
White Sugar
Molasses
Dried Pulp
Celery *
washed
cooked
Tomatoes
washed
Wet pomace
Dry pomace
Canned whole
Catsup
Paste
Juice from paste
Cantaloupes - washed *
cooked
Apples
washed
cooked
Fresh Juice
Cooked Juice
Wet Pomace
Dry Pomace
Apple Sauce
Apple Baby Food
Sweet Corn (K+CWHR) *
washed
cooked
Pecans
Peanuts
Meal
Oil
Peanut Hulls
Peanut Vines
0.02
0.01
0.01
0.039
0.02
0.02
0.02
0.02
0.44
0.17
0.17
0.58
180
126
126
1.3
0.91
0.79
0.43
0.43
0.43
0.43
0.43
1.6
1.6
5.4
3.8
3.8
0.27
0.27
25
70
0.49
0.27
1.9
0.13
0.13
0.02
0.02
0.02
0.02
0.02
50
0.17
0.17
0.17
0.17
0.17
0.17
0.17
0.17
0.21
0.05
0.05
0.05
1.3
1.3
21.
0.05
0.05
0.05
0.31
0.05
0.05
0.31
0.31
0.015
0.12
0.73
0.73
0.75
0.78
0.75
1.1
3.1
0.75
0.75
0.016
0.016
0.14
0.002
0.07
0.04
0.04
0.26
1.2
-------
11-70
Table II-10c
Anticipated Residues for Metiram and Metiram
Derived ETU for Acute Exposure (continued)
Residue (ppm)
Crop Maneb ETU
Animal Products
Milk
Beef Liver
Beef Kidney
Beef Muscle
Beef Fat
Eggs
Poultry Liver
Poultry Kidney
Poultry Muscle
Poultry Fat
0.05
0.14
0.12
0.07
0.12
0
0
0
0
0
0.04
0.04
0.12
0.05
0.05
0
0
0
0
0
*Data are translated from maneb, since no recent residue
data were submitted for metiram residues on celery,
cantaloupe, or sweet corn.
-------
11-71
2. Worker Exposure
a. Methodology
Agricultural workers, commercial applicators and homeowners
are potentially exposed to ETU through mixing, loading and
applying EBDC pesticide products to food and non-food crops and
conducting field labor in treated areas. Based on available data,
it appears that exposure results primarily from dermal contact.
Respiratory exposure is 1-2 percent of the total exposure for
non-dust formulations and hence is considered negligible
(Lunchick, June, 22, 1988).
The Agency estimated exposure based on surrogate data bases
for other pesticides with similar application methods and
published literature for dermal and respiratory exposure. For
estimating total daily exposure to ETU, respiratory exposure is
added to dermal exposure after being corrected for individual
EBDC absorption factors. Dermal absorption factors of 9 percent
for nabam and 6 percent for metiram were used based on actual
measurements in studies on those chemicals. The dermal
absorption factor for mancozeb was changed from 1 percent (used
in the PD 1) to an upper-bound of 10 percent because of
limitations in dosages in the currently available study. For
maneb, an upper-bound dermal absorption value of 30 percent
(based on an ETU dermal absorption study) was used in the absence
of adequate data. See Rispin (August 26, 1988). In addition,
the results of metabolism studies for each of the EBDCs were used
to calculate their metabolic conversion to ETU. For this
-------
11-72
assessment, the Agency determined the exposure to ETU and each
EBDC encountered by persons doing discrete tasks in the use of an
individual EBDC fungicide. The discrete tasks are mixing the
spray mixture, loading the pesticide mixture into the spray
equipment, applying the spray mixture and ancillary tasks such as
flagging for aerial application, or planting treated potato seed
pieces. For certain uses when the tasks are performed by a
single person, the exposures are combined. Additional data have
been required through the March 1989 Data Call-in Notice
pertaining to fieldworker exposure.
Available data indicate that the concentration of ETU as a
contaminant can vary among products containing the same EBDC and
among products containing different EBDCs. Rohm and Haas
submitted spray stability data as part of its rebuttal to the
PD 1 (March, 1988). These data were evaluated and incorporated
into the current exposure assessment. For estimating direct ETU
exposure to mixers and loaders from preparing and loading the
EBDC spray mixture, the Agency used 0.1 percent of the EBDC
exposure estimates for mancozeb and maneb based on the above
mentioned study. For estimating direct ETU exposure to
applicators, the Agency took into consideration the additional
exposure to ETU formed while spraying. Available data indicate
that ETU residues increase in the spraying mixtures to 0.2
percent and 6 percent of the amount of mancozeb and of maneb
present, respectively. No data for ETU contamination are
-------
11-73
available for metiram and nabam. For those two EBDCs, the Agency
used 0.5 percent for mixer/loaders and 0.6 percent for
applicators, as was done in the PD 1. These percentages
reflected the percentage of ETU exposure to
mixers/loaders/applicators compared to mancozeb that was observed
in a mancozeb exposure study. Available data also indicate that
the EBDCs and ETU are unstable in tank mix formulations,
degrading after being mixed with diluent. Based on these limited
data, the Agency assumes that mixer/loader/applicator exposure to
ETU is dependent on the percent of ETU present which has been
expressed as a percentage of the parent EBDC. In order to more
precisely predict mixer/loader/applicator exposure for the ETU
breakdown product for each EBDC and respective formulation types,
the Agency has required EBDC registrants to submit tank mix
stability data for representative end-use products of all
formulation types through FIFRA section 3(c)(2)(B). These data
are due to EPA in December, 1989.
b. Agricultural Uses
The EBDCs are applied to fruit and vegetable crops to
prevent damage by fungi and to protect harvested crops from
deterioration. The majority of these uses are pre-harvest and
are discussed in more detail in Section III of this document.
The EBDCs are also used as a seed treatment for potatoes.
Application methods include ground boom, airblast and pressure
sprayers.
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11-74
In the PD 1, the Agency evaluated non-dietary exposure to
applicators of mancozeb to apples by airblast and aerial sprays,
to onions by ground boom and aerial spray, to potatoes by ground
boom, chemigation, aerial and seed treatment and to tomatoes by
air, ground boom and hand-sprayers (home gardens). The exposure
to mixers/loaders wearing long-sleeved shirts, long pants and
chemical-resistant gloves was estimated to be 0.28 mg/lb ai by
the dermal route and 4.3 ug/lb ai by the inhalation route of
exposure when handling wettable powders (Everhart et al., 1985
and Zogorski and Lafferty, 1985) .
Since publication of the PD 1, the Agency has received
additional use information and has revised its exposure estimates
for workers who apply EBDC products. Based on this information,
the assumptions used by the Agency in the PD 1 that ETU exposure
to the mixer/loader is 0.5 percent of exposure to the parent
compound and for the applicator is 0.6 percent of the parent
compound has been changed as discussed in Section II.B.2.a above.
Because of the many different crops for which EBDC products can
be applied, and certain similarities among them, the Agency
selected four crops which it believes represent exposures
associated with all other crops and types of application. They
are sweet corn, grapes, apples and potato seed pieces. Sweet
corn represents row crops and ground boom application, grapes
represent airblast application with trellised crops, apples
represent airblast application in orchards and potato seed pieces
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11-75
represents preplant treatment of seeds. Exposure estimates
assume the use of long-sleeved shirts and long pants during
mixing/loading and application and the use of chemical-resistant
gloves during mixing and loading. The exposure estimates were
based on surrogate data bases and published literature and
adjusted for dermal absorption (as previously discussed) when
estimating risks. See Lunchick (July 5, 1988). The Agency's
dermal and inhalation exposure estimates for sweet corn, apples
and grapes are presented in Table 11-11.
During ground boom application, the dermal and inhalation
exposures to the applicator were estimated to be 4.6 mg/hr and 84
ug/hr, respectively (Lunchick, 1988). These estimates were
adjusted to a 1.0 Ib ai/A application rate and assume the use of
long pants and long-sleeved shirts. Airblast applicator exposure
was estimated to be 0.66 mg/lb ai by the dermal route and 1.0
ug/lb ai by inhalation (Zogorski and Lafferty, 1985).
-------
Table 11-11
Mixer/Loader/Applicator EBDC and ETU Exposure Estimates
for Sweet Corn, Grapes and Apples
DERMAL EXPOSURE (mg/kg/)
Daily Annual
INHALATION EXPOSURE
Daily Annual
Sweet Corn
Grapes
Apples
The direct
CROP
Sweet Corn
Grapes
Apples
Maneb
Mancozeb
Maneb
Mancozeb
Maneb
Mancozeb
ETU exposures
EBDC
Maneb
Mancozeb
Maneb
Mancozeb
Maneb
Mancozeb
0.50
0.38
0.81
0.74
3.1
3.1
from ETU in
ETU DERMAL
Daily
18
0.61
34
1.2
130
5.3
2.0
1.5
13
11
22
22
the dry formulation
EXPOSURE (jug/kg)
Annual
72
2.4
540
18
910
37
8.6
6.5
4.6
4.2
17.0
17.0
and spray mix
ETU INHALATION
Daily
340
11
56
4.0
210
21
34
26
74
63
120
120
are as follows:
EXPOSURE (ng/kg)
Annual
1400
44
900
60
1500
150
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11-77
(1) Sweet corn
Maneb and mancozeb are applied to sweet corn by ground boom
application. The following table presents use information:
Table 11-12
Use Practices Information: EBDCs on Sweet Corn
Application Acres Treated Actual Spray Application
EBDC (Rate Ib ai/Al Daily Time fhrl Per Year
Maneb 1.6 31 2.9 4
Mancozeb 1.2 31 2.9 4
(2) Grapes
Maneb and mancozeb are also applied to grapes by over-the-
vine high pressure sprayers. The high pressure foliage-
penetrating spray produces an exposure pattern more analogous to
airblast application. The number of applications per year is
based on the Agency's estimate of an average vineyard of 100
acres which are treated four times a year. The following is use
information:
Table 11-13
Use Practices Information: EBDCs on Grapes
Application Acres Treated Actual Spray Application
EBDC (Rate Ib ai/Al Daily Time fhrl Per Year
Maneb 2.4 25 2.9 16
Mancozeb 2.0 27.5 3.2 15
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11-78
(3) Apples
Mancozeb and maneb are applied to apples at an average
application rate of 6.5 Ib a.i. per acre by airblast sprayers to
36 acres per day. The exposure estimates given in Table 11-11
are based on seven applications in an average year.
(4) Potato Seed Treatment
Maneb and mancozeb are used as seed treatments for potato
seed pieces. The Agency's exposure assessment is based on a
study done using captan, mancozeb and maneb applied to seed
pieces at 0.8 Ib ai/100 Ibs of cut potatoes (cwt). (See Stevens
•
et al., 1980.) Exposure during seed treatment includes filling
the duster and cutting and sorting potatoes. Workers were
monitored for dermal and inhalation exposure using traditional
passive dosimetry techniques. They wore long pants, long-sleeved
shirts and jackets. Dusting machine workers wore leather gloves.
During the first operation the potato cutting machine was located
indoors; during the second operation the cutting machine was
located outdoors.
Dermal exposure to workers filling the duster outdoors was
7.5 mg/hr.; inhalation exposure was 0.61 mg/hr. The exposure for
workers filling the duster indoors was 1.2 mg/hr for dermal and
0.15 mg/hr for inhalation exposure. The overall weighted means
of 10 replicates were 3.1 mg/hr dermal and 0.29 mg/hr inhalation
exposure.
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11-79
There appeared to be no difference in exposure to workers
involved with cutting and sorting seed potatoes whether the
duster was located indoors or outdoors. The mean dermal exposure
to 30 workers was 0.52 mg/hr. This estimate incorporates the
study author's assumption of no exposure to the hands because
workers cutting and sorting were wearing gloves (i.e., hand
exposure from putting on and taking off gloves was not measured).
The mean respiratory exposure was 0.039 mg/hr. The exposure
values for drivers of tractors pulling the planting rig was 0.37
mg/hr and 0.037 mg/hr for dermal and inhalation exposure,
respectively. The observers riding on the rear of the planter
had a mean dermal exposure of 0.33 mg/hr and a mean respiratory
exposure of 0.027 mg/hr.
Based on data used in the Captan Position Document PD 4
(February, 1989), the entire seed potato treating and planting
operation in Maine occurs over five consecutive days. For a two
person operation, the Agency estimated that one individual would
spend 0.44 hrs/day filling and 8.8 hrs/day cutting.
c. Commercial ornamentals
Maneb and mancozeb are applied to commercial ornamental
trees, plants and shrubs by tractor-mounted power hand-held spray
guns. The Agency estimates that these pesticides are applied 10
times a year to approximately 6 acres of nursery stock in those
nurseries that apply EBDC pesticide products. Two acres are
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11-80
sprayed daily requiring 3 days to treat the nursery once and 30
days to treat it 10 times.
The Agency relied on three surrogate studies (Maddy and Fong,
1983, Abbott et al., 1987, and Copplestone et al., 1976) to
estimate worker exposure through the use of EBDCs on nursery
stock because no actual exposure data were available. The
applicator exposure was estimated to be 43 mg/lb. a.i. by the
dermal route and 33 ug/lb. a.i. by the inhalation route. The
mixing/loading exposure during commercial ornamental spray
operations is expected to be similar to mixer/loader exposure
during agricultural uses in that the EBDCs are being added to
spray tanks. The Agency evaluated mixer/loader exposure for EBDC
use on apples, tomatoes, onions and potatoes. Exposure was
estimated to be 0.28 mg/lb ai by the dermal route and 4.3 ug/lb
ai by the inhalation route (assuming mixer/loaders wearing long
pants, long-sleeve shirts and chemical-resistant gloves).
Exposure estimates are presented in Table 11-14.
d. Homeowner Lawns and Gardens
Homeowners apply maneb, mancozeb and metiram to vegetables,
strawberries, ornamentals, fruit trees and turf by either a
compressed air hand-held sprayer or a hose-end sprayer.
Two surrogate studies were used to estimate exposure to
homeowners:
1) Kurtz and Bode (Application Exposure to the Home
Gardener, American Chemical Society Symposium Series #273, 1985)
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11-81
measured exposure to gardeners applying carbaryl to vegetables by
compressed air sprayers. The mean dermal exposure to individuals
adding wettable powders to a compressed air sprayer and applying
the spray while wearing long-sleeved shirt and long pants is 120
mg/lb ai. Inhalation exposure was not measured.
2) Chevron Chemical Company, 1988 (in support of the
reregistration of acephate). Chevron conducted a study with
acephate showing dermal exposure to homeowners using hose-end
sprayers while wearing long pants and long-sleeve shirts of 450
mg/lb ai. The inhalation exposure was below detectable levels
(0.15 mg/lb ai).
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11-82
Table 11-14
Commercial Nursery Ornamental
EBDC Exposure Estimates
Maneb/Mancozeb to Commercially Grown Ornamentals
Dermal
Mixer/Loader:
Applicator:
Combined Daily:
Combined Annual:
Respiratory
Mixer/Loader:
Applicator:
Combined Daily:
Combined Annual:
0.28 mg/lb ai x 2.4 Ib ai/acre x 2.0 acres/day
x 170 kg = 0.019 mg/kg/day
43 mg/lb ai x 2.4 Ib ai/acre x 2.0 acres/day x
1/70 kg = 2.9 mg/kg/day
0.019 mg/kg/day +2.9 mg/kg/day =2.9 mg/kg/day
2.9 mg/kg/day x 30 days/yr = 87 mg/kg/yr
4.3 ug/lb ai x 2.4 Ib ai/acre x 2.0 acres/day x
1/70 kg = 0.29 ug/kg/day
33 ug/lb ai x 2.4 Ib ai/acre x 2.0 acres/day x
1/70 kg = 2.3 ug/kg/day
0.29 ug/kg/day +2.3 ug/kg/day =2.6 ug/kg/day
2.6 ug/kg/day x 30 days/yr = 78 ug/kg/yr
Direct Exposure to ETU in Maneb/Commercially Grown Ornamentals
Dermal
Mixer/Loader:
Applicator:
Combined Daily:
Combined Annual:
0.019 mg/kg/day x 0.1% = 0.019 ug/kg/day
2.9 mg/kg/day x 6% = 170 ug/kg/day
= 170 ug/kg/day
170 ug/kg/day x 30 days/yr = 5100 ug/kg/yr
Direct Exposure to ETU in Maneb/Commercially Grown Ornamentals
Respiratory
Mixer/Loader:
Applicator:
Combined Daily:
Combined Annual:
0.29 ug/kg/day x 0.1% = 0.29 ng/kg/day
2.3 ug/kg/day x 6% = 140 ng/kg/day
= 140 ng/kg/day
140 ng/kg/day x 30 days/yr = 4200 ng/kg/yr
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11-83
Table 11-14
Commercial Nursery Ornamental
EBDC Exposure Estimates (continued)
Direct Exposure to ETU in Mancozeb/Commercially Grown Ornamentals
Dermal
Mixer/Loader: 0.019 mg/kg/day x 0.1% = 0.19 ug/kg/day
Applicator: 2.9 mg/kg/day x 0.2% = 5.8 ug/kg/day
Combined Daily: =5.8 ug/kg/day
Combined Annual: 5.8 ug/kg/day x 30 days/yr = 170 ug/kg/yr
Respiratory
Mixer/Loader: 0.29 ug/kg/day x 0.1% = 0.29 ng/kg/day
Applicator: 2.3 ug/kg/day x 0.2% = 4.6 ng/kg/day
Combined Daily: 0.29 ng/kg/day +4.6 ng/kg/day =4.9 ng/kg/day
Combined Annual: 4.9 ng/kg/day x 30 days/yr = 150 ng/kg/yr
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11-84
Table 11-15
Homeowner EBDC Exposure Estimates
Maneb or Mancozeb/Homeowner
Dermal
Daily Vegetables: 120 mg/lb ai x 2.6 Ib ai/acre x 0.02
acres/day x 1/70 kg = 0.089 mg/kg/day
Annual Vegetables: 0.089 mg/kg/day x 6 days/yr =0.53 mg/kg/yr
Daily Ornamentals: 120 mg/lb ai x 2.6 Ib ai/acre x 0.014
acres/days x 1/70 kg = 0.062 mg/kg/day
Annual Ornamentals: 0.062 mg/kg/day x 5 days/yr =0.31 mg/kg/yr
Daily Turf: 450 mg/lb ai x 7.6 Ib ai/acre x 0.1 acres/day
x 1/70 kg = 4.9 mg/kg/day
Annual Turf: 4.9 mg/kg/day x 2 days/yr =9.8 mg/kg/yr
Daily Fruit Trees: 450 mg/lb ai x 0.12 Ib ai/day x 1/70 kg =
0.77 mg/kg/day
Annual Fruit Trees: 0.77 mg/kg/day x 6 days/yr =4.6 mg/kg/yr
Direct Exposure to ETU in Maneb/Homeowner
Dermal
Daily Vegetables: 0.089 mg/kg/day x 6% = 5.3 ug/kg/day
Annual Vegetables: 5.3 ug/kg/day x 6 days/yr = 32 ug/kg/yr
Daily Ornamentals: 0.062 mg/kg/day x 6% = 3.7 ug/kg/day
Annual Ornamentals: 3.7 ug/kg/day x 5 days/yr = 19 ug/kg/yr
Daily Turf: 4.9 mg/kg/day x 6% = 290 ug/kg/day
Annual Turf: 290 ug/kg/day x 2 days/yr = 580 ug/kg/yr
Daily Fruit Trees: 0.77 mg/kg/day x 6% = 46 ug/kg/day
Annual Fruit Trees: 46 ug/kg/day x 6 days/yr = 280 ug/kg/yr
Direct Exposure to ETU in Mancozeb/Homeowner
Dermal
Daily Vegetables: 0.089 mg/kg/day x 0.2% = 0.18 ug/kg/day
Annual Vegetables: 0.18 ug/kg/day x 6 days/yr =1.1 ug/kg/yr
Daily Ornamentals: 0.062 mg/kg/day x 0.2% = 0.12 ug/kg/day
Annual Ornamentals: 0.12 ug/kg/day x 5 days/yr =0.60 ug/kg/yr
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11-85
Table 11-15
Homeowner EBDC Exposure Estimates (continued)
Direct Exposure to ETU in Mancozeb/Homeowner
Dermal
Daily Turf: 4.9 mg/kg/day x 0.2% = 9.8 ug/kg/day
Annual Turf: 9.8 ug/kg/day x 2 days/yr = 20 ug/kg/yr
Daily Fruit Trees: 0.77 mg/kg/day x 0.2% = 1.5 ug/kg/day
Annual Fruit Trees: 1.5 ug/kg/day x 6 days/yr =9.0 ug/kg/yr
Metiram/Homeowners Roses
Dermal
Daily: 120 mg/lb ai x 0.003 Ib ai/day x 1/70 kg =
0.0053 mg/kg/day
Annual: 0.053 mg/kg/day x 10 days/yr = 0.053
mg/kg/yr
Direct Exposure to ETU in Metiram/Homeowners Roses
Dermal
Daily: 0.0053 mg/kg/day x 0.6% = 0.032 ug/kg/day
Annual: 0.032 mg/kg/day x 10 days = 0.032 ug/kg/yr
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11-86
e. Industrial
The Agency has limited use information on nabam's industrial
uses. Two types of loading systems are used: open pour-loading
and closed-loading. Of the industrial uses of nabam, only the
water cooling systems (tower) and oil well drilling fluids use an
open pour-loading system in addition to closed loading systems.
The Agency has no exposure data on nabam used in industrial
settings. To estimate exposure, the Agency used information from
a submission from Alco Chemical Company and Vinings Chemical
Company (May 5, 1988, MRID number 014503) that includes the
Agency's surrogate data for mixer/loaders open-pouring liquid
formulation agricultural pesticides and using closed-loading
systems (Lunchick, May 9, 1988).
The contribution of inhalation exposure to total exposure was
estimated using data obtained by Maitlen (1982). Maitlen studied
various liquid formulations of pesticides which were open poured.
The dermal exposure to the mixer/loaders wearing gloves was 2.2
mg/hr when normalized to the 1.0 Ib ai/A application rate and the
inhalation exposure was estimated to be 45 ug/hr when the
material is applied at 1.0 Ib ai/A. In comparing inhalation and
dermal exposure data during open pouring with protective gloves
of liquid formulations in agricultural settings, the Agency
estimated based on the Maitlen data that the inhalation exposure
was 2 percent of the dermal exposure (Lunchick, June 22, 1988).
Dermal exposure during open pour loading was estimated to be:
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11-87
Cooling Towers: 0.049 mg nabam/kg/day
0.0016 mg ETU kg/day
Drilling Fluids: 0.12 rag nabam/kg/day
0.0039 mg ETU/kg/day
Based on 2 percent of the above dermal exposure estimates, the
inhalation exposure to nabam containing microbiocides is as
follows:
Cooling Towers: 0.98 ug nabam/kg/day
0.032 ug ETU/kg/day
Drilling Fluids: 2.4 ug nabam/kg/day
0.078 ug ETU/kg/day
(1) Paper mills
According to information received by the Agency (Shema,
1978, McGrew, 1978 and Dowler, 1978), 10 to 50 percent of the
total 690 U.S. paper mills use nabam products. Nabam is added as
ready-to-use liguids to pulp and paper mill water systems by
means of automated pumps. Assuming that the number of paper
mills and range of nabam use continues to reflect those figures
and one operator at each of the paper plants using nabam is
involved in servicing the water system, 70 to 345 operators are
potentially exposed. Potential exposure occurs when opening
drums, attaching and detaching metering devices and disposing of
empty drums. Estimates of the time expended for opening a drum
and attaching and detaching metering devices is one to two
minutes. Disposal of empty drums requires approximately 15
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11-88
minutes. Depending on work loads, an operator might handle from
one drum every 14 days to two drums per day. Product labels
state that operators must wear long pants, long-sleeved shirts,
boots, a face shield and rubber gloves when handling the product.
Due to the fact that this is a closed system operation, it is
assumed there would be minimal exposure occurring during coupling
and uncoupling when protective clothing is used. (See Pelletier
July 18, 1988.)
(2) Water Cooling Systems
Nabam products are fed into water systems by means of a
measuring device attached to product containers (Syssman, 1978
and McGrew, 1978) at a concentration of from three to six ppm.
Both open-pour loading and closed loading systems are used.
Systems are treated every three to seven days at utility and
industrial sites by one operator and at institutional sites by
contract service operators who handle from 5 to 20 systems daily.
The Agency has no estimates of the number of operators exposed or
the number of facilities using nabam products. Exposure occurs
when opening drums, detaching and reattaching metering devices,
disposing of empty drums and cleaning the system. Time expended
for opening a drum and attaching and detaching the metering
devices is from one to two minutes. Disposal of empty drums is
about 15 minutes and cleaning tasks account for approximately 10
minutes. Product labels state operators must wear long pants,
long-sleeved shirts, boots, a face shield and rubber gloves.
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11-89
Exposure is minimal due to OSHA regulations described earlier,
concerning protective clothing requirements for persons applying
nabam.
(3) Sugar Mills
Nabam products are added to sugar-cane grinding, crusher and
diffuser systems as a metered continuous drip feed to a
concentration of 10 to 20 ppm of cane. Approximately 50 percent
of the 20 cane mills and 30 beet mills in the United States use
nabam. Assuming one operator handles the nabam products, a total
of 25 workers are exposed. Exposure occurs when opening drums,
attaching and detaching metering devices and disposing of empty
drums. Estimated exposure time is 2 minutes for opening the drum
and attaching and detaching metering devices and 15 minutes for
disposing of empty drums (McGrew, 1978). Product labels state
that workers must wear long pants, long-sleeved shirts, boots, a
face shield and rubber gloves when handling the product. As this
is a closed loading system, exposure is expected to be minimal
when correctly using protective clothing. (See DPRA, 1988d.)
(4)1 Oil well Drilling Fluids
Little information is available on nabam use practices or
exposure potential for this site. The Agency is aware, however,
that nabam is added to drilling fluids in open-pour and closed
loading systems. Open-pour loading systems provide higher
potential exposure to workers than in closed loading systems. It
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11-90
is estimated that five percent or less of the sites use nabam.
(See DPRA, 1988d.)
(5) Metal Working Coolant
Although registered for this use, according to two sources
(Dowler, 1978 and McGrew, 1978), nabam is not used as an additive
for metal working coolants. An alternative chemical, methylene
bisthiocyanate, is being used.
C. Risk Characterization
1. Dietary
To estimate dietary exposure and then compare that estimate
to a previously determined Reference Dose (RfD), or to estimate
potential carcinogenic effect by multiplying by the carcinogen
potency factor (C^*), the Agency has developed the Dietary Risk
Evaluation System, ORES, formerly known as the Tolerance
Assessment System (TAS). This computer-based tool is based on
consumption patterns derived from a survey conducted by the U.S.
Department of Agriculture (1977-78) which involved 3-day dietary
records for 30,770 individuals and 3734 food items. The ORES can
estimate dietary exposure and risk for the U.S. population and 22
subgroups of the U.S. population. DRES is capable of using
"anticipated residues" combined with consumption data as a means
of generating a realistic risk assessment. Anticipated residues
and percent of crop treated estimates were used in the DRES to
estimate dietary risks from residues of EBDCs and ETU in foods.
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11-91
a. Carcinogenic
Carcinogenic risk due to ETU from dietary exposure is the
combination of risk from direct ETU residues plus the risk from
ETU formed by in vivo metabolic conversion of the parent EBDC
residue. Risks from each of these exposures were estimated for
ETU derived from each EBDC parent compound.
In the PD 1, the dietary risk from ETU derived from mancozeb
only was estimated because no adequate data were available for
other EBDCs. The potential direct dietary risk (not including
effects of in vivo conversion) from exposure to ETU based on
mancozeb field residue data was estimated to be 5 x 10"6. This
was obtained by multiplying the daily estimated exposure to ETU
[3.6 x 10"5 mg/kg/day], based on consumption estimates from the
food factor system and using the percent of crop treated
estimates from all EBDCs] by the cancer potency factor for ETU
designated as the Q,* [0.14 (mg/kg/day)"1] based on the Innes
study. In addition, the Agency also estimated dietary risk of
1.7 x 10"5 from exposure to ETU from conversion of mancozeb, in
vivo, after eating food containing mancozeb residues. Metabolism
studies in rats showed that 50 percent of mancozeb residues were
absorbed through the gastrointestinal tract and that 24 mole
percent are then metabolically converted to ETU (DiDonato et al.,
1985). The in vivo risk estimate in the PD 1 was obtained by
multiplying the dietary exposure to mancozeb of 9.7 x 10"*
mg/kg/day by 12 percent (50 percent x 24 percent) to yield a
dietary exposure to ETU of 1.2 x 10"4 mg/kg/day. Multiplying
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11-92
this by the Q,* yielded a risk estimate of 1.7 x 10"5. The total
potential dietary risk from exposure to ETU from the use of
mancozeb on food crops was estimated in the PD 1 to be 2.2 x
10~5, which was obtained by adding 5 x 10"6 and 1.7 x 10"5.
Based on the exposure assumptions described in section II.B,
EPA has estimated dietary risks for ETU exposure for the maneb
and metiram in this PD 2/3 and reestimated dietary risk to ETU
from the use of mancozeb. These risk estimates differ from those
presented in the PD 1 in that: 1) they are based on crop residue
data from maneb and metiram also, and additional crop residue
data for mancozeb, 2) the in vivo conversion rate used is 7.5
percent calculated on a weight-to- weight basis (as compared to
12 percent calculated on a mole basis used in the PD 1) based on
a recently submitted rat metabolism study and using a molecular
weight conversion factor, 3) adjustment corrections were made for
washing, trimming and cooking, (4) the new preliminary Q,* of 0.6
(mg/kg/day)"1 was employed and (5) zineb risk estimates are not
included (See Hummel memos June 30, 1988 and July 12, 1988.) The
combined ETU dietary risk based on direct exposure to ETU
residues (not including in vivo conversion) in foods from all
EBDC fungicides with registered food uses is now estimated to be
1.1 x 10"A to the general population. To better approximate
actual ETU dietary risk from consumption of foods treated with
the EBDCs, the dietary risk estimates from in vivo conversion of
EBDCs to ETU were added to the dietary risk estimates for direct
dietary exposures to ETU, which results in a combined total risk
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11-93
estimate of 4.0 x 10~4 to the general population. Table 11-16
presents ETU risk estimates from direct exposure, in vivo
conversion and total risk estimates (direct exposure plus in vivo
conversion) from the use of EBDCs:
TABLE 11-16
ETU Dietary Carcinogenic Risks
Parent In vivo In vivo Direct Direct Total
Chemical Exp ETU Exp Risk ETU Exp Risk Risk
Mancozeb .00165 .00091 5.9E-05 .00089 4.0E-05 9.9E-05
Maneb .00365 .00034 2.0E-04 .00132 6.0E-05 2.6E-04
Metiram .00038 .00044 2.7E-05 .00017 7.7E-06 3.5E-05
TOTALS2.9E-041.1E-044.OE-04
Exp = exposure estimates in mg/kg body weight/day
Although there are currently no food tolerances established
for nabam under 40 CFR Section 180, FDA established a secondary
direct food additive regulation (21 CFR 173.320) which permits
nabam residues of 3 ppm on raw sugar beets or sugar cane from the
use of nabam in sugar mill grinding, crusher or diffuser systems.
The registrant of nabam has requested voluntary cancellation of
all agricultural food and feed uses and sugar beet and sugarcane
transport and flume water use.
Because the source of the ETU contribution from individual
EBDC chemicals cannot be determined unless the EBDC pesticide
used is known, and currently available analytical methods cannot
distinguish among the various EBDC fungicides and the EBDC
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March 7, 1990
NOTE TO : Janet Andersen
Special Review Branch
FROM: Rita Briggs
DRES
SUBJECT: Amendment to TABLE 11-16 in EPA's EBDC SPECIAL REVIEW
TECHNICAL SUPPORT DOCUMENT
This is a follow-up to the meeting Bob Tomerlin and I had
with you yesterday regarding the errors found in Table 11-16 in
the EBDC Technical Support Document. Having checked the ORES
estimates for EBDC and ETU exposure which should have been used
(see Tomerlin's memo, 9/21/89), we concluded that the Table
should be revised as follows:
TABLE 11-16
ETU Dietary Carcinogenic Risks
Chemical
Mancozeb
Maneb
Metiram
Parent In Vivo In Vivo Direct Direct Total
Exp. ETU Exp Risk ETU Exp Risk Risk
.00089 .000067 4.0E-05 .000091
.00132 .000099 6.0E-05 .00034
.00017 .000013 7.7E-06 .000044
5.5E-05 9.5E-05
2.0E-04 2.6E-04
2.7E-05 3.5E-05
You may want to consider adding an errata sheet to the PD2/3
to reflect these changes before the SAP meeting.
cc: DRES, Kocialski (SACB), Quest (SACB), Zager (DEB), Fenner-
Crisp
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11-94
fungicides are often substitutes for one another, dietary risk is
considered by the Agency in this risk assessment to be the total
estimated risk from ETU (from direct exposure and in vivo
conversion) from the use of all EBDCs on the individual crops.
See Table 11-17 for a listing of estimated ETU dietary
carcinogenic risks by individual crop for direct exposure to ETU
plus in vivo conversion.
b. Developmental Toxicity
In the PD 1, developmental risk from dietary exposure was
not discussed. However, a developmental toxicity risk assessment
for this effect was conducted for the Mancozeb Registration
Standard (Guidance for the Reregistration of Pesticide Products
containing Mancozeb as the Active Ingredient, EPA, April, 1987).
Both direct exposure to ETU residues on the crops and in vivo
conversion of mancozeb to ETU were considered. To estimate
maximum exposure on a given day, maximum residues of mancozeb and
ETU were estimated. It was assumed that 100 percent of the crop
was treated using all available residue data (not necessarily at
the maximum rate). Label PHIs were factored into the analysis.
All dietary margins of exposure were found to be above 100 (based
on a NOAEL for ETU of < 5mg/kg) for developmental effects for the
U.S. population of pregnant women from exposure to ETU from the
use of mancozeb on crops.
-------
11-95
Table 11-17
EBDC Dietary Carcinogenic Risk Estimates
from the Use of EBDCs Listed by Individual Crop
CROP CARCINOGENIC ETU RISK 1
FIGS 2 0
PINEAPPLE <10 "10
CRENSHAWS <10 "10
PECANS 4.0 X 10 "10
FENNEL 9.6 X 10 "10
ASPARAGUS 2.4 X 10 "9
RYE 3.5 X 10 "9
ALMONDS 7.3 X 10 "9
PUMPKIN 1.1 X 10 "8
KOHLRABI 1.3 X 10 "8
PEANUTS 3 1.6 X 10 "8
EGGPLANT 2.5 X 10 "8
ENDIVE 3.2 X 10 "8
CASABA 5.7 X 10 '8
OATS 5.8 X 10 "8
COTTON 6.4 X 10 "8
FIELD CORN 7.2 X 10 "8
WHEAT 1.1 X 10 "7
HONEYDEW 1.4 X 10 "7
PAPAYAS 1.8 X 10 "7
CAULIFLOWER 2.7 X 10 "7
SWEET CORN * 2.7 X 10 "7
BARLEY 3.3 X 10 "7
CANTALOUPE 3.4 X 10 "7
1 Estimates of ETU from use of nabam and zineb on
agricultural crops have not been included. For nabam, all
agricultural uses have been suspended for several years, there is
no known use and registrants have requested voluntary cancellation
of all agricultural uses. For zineb, all uses have been suspended
since July 1988 and the company holding the technical registration
has requested voluntary cancellation of all uses.
2 Registrant request of September 6, 1989 will eliminate food
use on figs, retaining only non-food use. Estimated risk before
registrant action was 1.5 x 10"
3 Estimate assumes that all labels are modified in accordance
with the registrant action of September 6, 1989. Previously,
estimated risk was 1.3 X 10
4 Estimate assumes that all labels are modified in accordance
with the registrant action of September 6, 1989. Previously,
estimated risk was 3.3 X 10"7 .
-------
11-96
Table 11-17
EBDC Dietary Carcinogenic Risk Estimates (Continued)
from the Use of EBDCs Listed by Individual Crop
CROP CARCINOGENIC ETU RISK
SQUASH 3.4 X 10 '7
SUGAR BEETS 5 3.7 X 10 "J
BRUSSELS SPROUTS 3.8 X 10
ONIONS 6 4.7 X 10 ;
CRANBERRIES 5.2 X 10 'T
CRABAPPLES 6.1 X 10 ''
RHUBARB 6.5 X 10 ~7
KALE 7.1 X 10
GRAPES 7 9.0 X 10 'J
CUCUMBERS 9.2 X 10
NECTARINES 1.0 X 10
BANANA 1.2 X 10 "6
CABBAGE 1.2 X 10
PEARS 1.5 X 10 '6
POTATOES 1.7 X 10
WATERMELON 1.9 X 10 "*
LIMA BEANS 2.4 X 10
LETTUCE 3.0 X 10 "6
PEPPERS 3.4.X 10 "6
APRICOTS 6.7 X 10
BROCCOLI 1.3 X 10 "*
COLLARDS 1.3 X 10 ~*
SPINACH 1.5 X 10 '*
TOMATOES 8 1.6 X 10 "^
MUSTARD GREENS 1.7 X 10 '*
TURNIPS 1.7 X 10 "*
CELERY 1.8 X 10
5 Estimate assumes that all labels are modified in accordance
with the registrant action of September 6, 1989. Previously,
estimated risk was 1.4 X 10"6 .
6 Estimate assumes that all labels are modified in accordance
with the registrant action of September 6, 1989. Previously,
estimated risk was 7.1 X 10"6 .
7 Estimate assumes that all labels are modified in accordance
with the registrant action of September 6, 1989. Previously,
estimated risk was 4.0 X 10"5 .
8 Estimate assumes that all labels are modified in accordance
with the registrant action of September 6, 1989. Previously,
estimated risk was 2.5 X 10"5 .
-------
11-97
Table 11-17
EBDC Dietary Carcinogenic Risk Estimates (Continued)
from the Use of EBDCs Listed by Individual Crop
COMMODITY CARCINOGENIC ETU RISK
CARROTS 1.9 X 10 "5
BEANS 2.5 X 10 "5
PEACHES 4.2 X 10 "5
APPLES 1.0 X 10 "4
TOTAL ESTIMATED RISK FROM CROPS 4.0 X 10 "
MEAT 9 1.8 X 10 "7
MILK (NATIONAL) 10 5.6 X 10 "7
MILK (LOCAL MILK SHED) 11 1.8 X 10 '6
TOTAL ESTIMATED DIETARY RISK 4.0 X 10 "4
Estimate assumes that all labels are modified in accordance
with the registrant action of September 6, 1989. Previously,
estimated risk was 1.8 X 10"6 .
10 Estimate assumes that all labels are modified in accordance
with the registrant action of September 6, 1989. Previously,
estimated risk was 5.6 X 10"6 .
11 Local milk shed dietary risk estimates are a worse case
estimate representing small regions where dairy cows may be
consuming a diet composed of only EBDC-treated food such as apple
pomace from EBDC-treated apples, sugar beet wastes from EBDC-
treated sugar beets and other processed food wastes from crops
treated with EBDCs.
-------
11-98
In the PD 2/3, developmental risk from dietary exposure to
ETU from consumption of food treated with EBDC pesticides was
estimated by comparing the maximum exposure estimates of each
EBDC chemical (mg/kg body wt./day) to the NOAEL from ETU (<5
mg/kg/day) from a rat teratology study (Khera, 1973). A maximum
exposure estimate represents the maximum amount of ETU ingested
by a consumer on any given day. The comparison between exposure
and the NOAEL is expressed as a Margin-of-Safety (MOS) or Margin-
of-Exposure (MOE). An acute dietary exposure analysis using
anticipated ETU residues from each EBDC chemical was used to
estimate the distribution of single-day exposure for the
appropriate population subgroup, which in this case are females
of child-bearing age. The analysis assumes that ETU levels occur
uniformly within each food commodity at the anticipated residue
levels. The following table (11-18) presents estimated average
margins-of-safety/margins-of-exposure for consumers of foods
treated with EBDCS and presumed to contain ETU residues although
metabolic conversion of EBDC to ETU has not been included. For
more information see Tomerlin (1988 reviews).
-------
11-99
Table 11-18
Developmental Toxicity Dietary Risks1
Maneb
Mancozeb
Metiram
Estimated
Average
Exposure
fmg/kg/day)
0.006458
0.001003
0.001141
Estimated
Average
MOS/MOE
770
4985
4300
1 All agricultural nabam uses were suspended several years ago
and registrants have requested voluntary cancellation of all
agricultural uses.
c. Thyroid Effects
In the PD 2/3, the toxicology endpoint used in calculating
the oral (dietary) reference dose (RfD) for ETU derived from the
parent EBDCs was based on thyroid hyperplasia at a Lowest Effect
Level (LEL) of 0.25 mg/kg/body weight/day from a 2-year rat
feeding study (Graham et al, 1975). A 3000-fold uncertainty
factor was used in deriving the RfD of 0.00008 mg/kg/body
weight/day. Exposure estimates (ARC) from direct ETU exposure
and conversion of EBDC to ETU were calculated from the
anticipated residue estimates and corrected for percent of crop
treated. Total estimated ETU exposure from each EBDC parent was
compared to the RfD for thyroid hyperplasia. The estimate of
total ETU exposure for all 55 mancozeb, maneb and metiram food
crops was equivalent to 825 percent of the RfD for the general
U.S. population, 3313 percent for infants and 1837 percent for
-------
11-100
children. The estimate of total ETU exposure for the 13
registrant retained food crops is 35 percent for the general U.S.
population, 40 percent for infants and 71 percent for children.
d. Conclusions
Although the current estimates of dietary risk are based on
the best available data, the Agency believes that the currently
available residue data are likely to overestimate dietary
exposure and risk for two possible reasons: (1) the residue
estimates are likely to be higher than those on the "dinner
plate", and (2) the percent of crop treated is not precisely
known for sites with low usage. The exposure estimates are based
on residue data submitted to support tolerances with some
corrections for the effects of commercial processing, washing and
cooking.
Field trial data at the maximum registered rate and the
minimum PHI, required to support tolerances represent "farm gate"
exposure. However, foods are not always treated at the maximum
rate nor are they always harvested at the minimum PHI; in many
cases, crops are treated at less than the maximum rate, or are
harvested several days before the minimum PHI. Additionally, the
limited amount of FDA monitoring data available to the Agency
suggest in some cases the possibility of lower levels of residues
than those found in the field studies even after taking into
consideration expected reductions due to commercial processing,
washing, cooking and percent of crop treated. The Agency expects
that a well-designed and well conducted residue monitoring study
-------
11-101
could in some cases more accurately estimate ETU residues "at the
dinner plate" and could conceivably support different risk
estimates which may be one to two orders of magnitude lower than
our current risk estimates. The March 1989 EBDC DCI required
registrants to design and conduct a market basket study to gather
this data and submit the information by September 1990.
EBDC and ETU residues have both been shown to degrade in
frozen storage. Frozen storage stability data and limited data
on commodities harvested at different PHIs show a decline in EBDC
and ETU residues with time in frozen storage and in the field.
Ambient and cold storage degradation data for EBDCs and ETU in
normal channels of trade could enable the Agency to model
degradation rates.
In cases where the percent of crop treated was believed to
be less than 10 percent, the Agency used a constant percent of
crop treated estimate of 10 percent because of the lack of
refined use data. This was true in all cases except for wheat
where the Agency had sufficient data to believe the percent of
crop treated was in the 1 percent range. Where actual percent of
crop treated may be less than 1 percent, the estimated risk for
that commodity could be possibly inflated by as much as one order
of magnitude. The industry market basket survey could more
closely reflect actual usage patterns and may help to further
define percent of crop treated in some cases. These data will be
considered in the Agency's Final Determination along with any
other residue data which the Agency currently has or obtains in
-------
11-102
response to this or other documents.
2. Mixer/loader/applicator risks
a. Carcinogenic Risks
ETU carcinogenic risk estimates for persons mixing, loading
and applying EBDC pesticides range from 10"3 to 10~7. These risk
estimates are based on current label requirements for
mixer/loaders (long pants, long-sleeved shirts, gloves, hat and
boots). The addition of protective clothing (coveralls over
long-sleeved shirt and long pants, chemical-resistant gloves,
shoes, socks and goggles or a face shield and a chemical-
resistant apron) may reduce risks to mixers/loaders in excess of
40 percent and applicators in excess of 65 percent. When such
protective clothing requirements as specified in the maneb,
mancozeb, metiram and nabam Registration Standards and as
proposed in this document for maneb, mancozeb, metiram and nabam
are factored into these risk estimates, only one carcinogenic
risk estimate remains at above ID'S commercial ornamental
applicators using maneb. See Table 11-19.
-------
11-103
Site
Apples
Onions
Potatoes
Table 11-19
Mixer/Loader/Applicator Carcinogenic Risk Estimates
(incorporating protective clothing*)
MANEB
Tomatoes
Sweet corn
Grapes
Commercial
Ornamentals
Homeowner
Application
Method
Aerial
Airblast
Aerial
Groundboom
Aerial
Groundboom
Chemigation
Seed treatment
Fill/cut/plant
Aerial
Groundboom
Groundboom
Groundboom
Handsprayer
Vegetable
Ornamental
Fruit trees
Turf
No. Days
Exposed
1
7
6
6
4
7
2
5
5
3
7
4
15
30
6
5
2
6
Estimated Excess
Carcinocrenic Risk
M/L
1
1
4
2
1
2
5
2
1
5
E-6
E-4
E-5
E-5
E-4
E-5
E-5
E-5
E-5
E-5
A
1
2
4
4
1
4
4
4
2
1
E-7
E-4
E-6
E-5
E-5
E-5
E-6
E-5
E-5
E-4
c
N/A
3 E-4
N/A
6 E-5
N/A
5 E-5
4 E-5
1 E-5
4 E-6
N/A
6 E-5
3 E-5
1 E-4
1 E-5
1 E-3
1 E-3
2 E-5
1 E-5
4 E-4
2 E-4
* Protective clothing consists of coveralls for mixer/loaders and coveralls and
chemical-resistant gloves for applicators. Protective clothing is not factored
into homeowner risk estimates.
M/L = mixer/loader
A = applicator
C = combined (mixer/loader/applicator is same person)
N/A = not applicable
-------
11-104
Site
Apples
Onions
Potato
Table 11-19
Mixer/Loader/Applicator Carcinogenic Risk Estimates
(incorporating protective clothing*)
MANCOZEB
Tomatoes
Sweet corn
Grapes
Commercial
Ornamentals
Homeowner
Application
Method
Aerial
Airblast
Aerial
Groundboom
Aerial
Groundboom
Chemigation
Seed treatment
Fill/cut/plant
Aerial
Groundboom
Groundboom
Groundboom
Handsprayer
Vegetables
Ornamentals
Turf
Fruit trees
No. Days
Exposed
1
7
6
6
4
7
2
5
5
3
7
4
15
30
6
5
2
6
Estimated Excess
Carcinogenic risks
M/L A C
1
4
2
7
4
8
2
8
4
2
E-6
E-5
E-5
E-6
E-5
E-6
E-5
E-6
E-6
E-5
8
4
8
1
2
8
9
1
3
2
E-8
E-5
E-7
E-5
E-6
E-6
E-7
E-5
E-6
E-5
N/A
8 E-5
N/A
2 E-5
N/A
2 E-5
2 E-5
2 E-5
2 E-6
N/A
2 E-5
7 E-6
4 E-5
3 E-6
2 E-4
2 E-4
4 E-6
2 E-6
8 E-5
4 E-5
* Protective clothing consists of coveralls for mixer/loaders and coveralls and
chemical-resistant gloves for applicators. Protective clothing is not factored
into homeowner risk estimates.
M/L = mixer/loader
A = applicator
C = combined (mixer/loader/applicator is same person)
NA = not applicable
-------
11-105
Table 11-19
Mixer/Loader/Applicator Carcinogenic Risk Estimates
(incorporating protective clothing*)
METIRAM
Estimated Excess
Carcinogenic risk
Application No. Days
Site Method Exposed M/L A C
Apples Aerial 1 9 E-7 4 E-6 N/A
Airblast 7 2 E-5 1 E-4 1 E-4
Potatoes Aerial 4 3 E-5 4 E-6 N/A
Groundboom 7 6 E-6 2 E-5 2 E-5
Homeowner Handsprayer
Roses 10 3 E-7
*Protective clothing consists of coveralls for mixer/loaders and coveralls an
chemical-resistant gloves for applicators. Protective clothing is not factored
into homeowner risk estimates.
M/L = mixer/loader
A = applicator
C = combined
+PC = plus protective clothing (coveralls and gloves)
-------
11-106
Table 11-19
Mixer/Loader/Applicator Carcinogenic Risk Estimates
NABAM
Estimated Excess
Carcinogenic risk*
Application
Site Method
Cooling Towers Open-pour
Close-pour
Secondary
Oil Recovery Close-pour
Oil Well Drilling
Fluids Open-pour
Fracturing
Fluids Close-pour
Sugar/Paper
Mills Close-pour
No . Days
Exposed
48
48
48
48
26
26
M/L/A
4 E-5
5 E-5
4 E-5
1 E-4
6 E-6
8 E-5
* Risk estimates assumed only protective clothing as specified on the nabam
product labels.
M/L/A = mixer/loader/applicator
-------
11-107
b. Developmental and Thyroid Effects
Margins-of-safety/margins-of-exposure were calculated for
agricultural workers, commercial applicators, industrial workers
and homeowners who may be exposed to EBDC pesticide products.
Developmental and thyroid MOSs/MOEs were calculated using daily
exposure estimates. For mancozeb and metiram where information
was available on the parent compound, the developmental NOEL for
the parent and the NOEL for ETU were used to calculate the
MOS/MOE resulting from exposure to either mancozeb or metiram and
to the ETU derived from those parent compounds. For maneb and
nabam, the Agency used the developmental study NOEL for ETU (< 5
mg/kg/day) and used in vivo conversion of the parent to ETU plus
direct ETU exposure to calculate the MOSs/MOEs. Thyroid
MOSs/MOEs also were calculated using seasonal exposure estimates
for those sites which the Agency considers as having high
consecutive exposure scenarios (i.e., grapes, apples and
commercial ornamentals). For mancozeb, maneb and metiram,
information was available on the parent compound and, therefore
MOSs/MOEs were calculated based on exposure to the parent plus
direct exposure to ETU (0.25 mg/kg/day). For nabam where there
was no information available on the parent, MOSs/MOEs were
calculated based on direct exposure to ETU and an in vivo
conversion. The Agency believes that although thyroid MOSs/MOEs
based on repeated daily exposures represent "worst case", it is
prudent to calculate them in this manner due to the fact that
these workers may not have time to recover from thyroid effects
-------
11-108
before their next exposure. The Agency's current data base does
not provide a definitive basis for determining a likely recovery
period for thyroid effects.
Several MOSs/MOEs were below 100. With incorporation of
additional protective clothing requirements as specified in the
mancozeb, maneb, metiram and nabam Registration Standards and as
proposed as requirements in this document for mancozeb, maneb,
metiram and nabam (coveralls over long-sleeved shirts and long
pants, chemical-resistant gloves, shoes, socks and goggles or a
face shield and a chemical-resistant apron), most MOSs/MOEs
increased to 100 or higher. See Table 11-20.
c. Conclusions
Assumptions surrounding mixer/loader/applicator
developmental and thyroid risk estimates are:
1) Due to the lack of dermal absorption data on the parent
compound, an upper-bound estimate of 30 percent absorption factor
was used for maneb based on an ETU dermal absorption study. This
may overestimate exposure by 3-fold because dermal absorption for
maneb is expected to be closer to mancozeb and metiram (between
6-10 percent) as they are structurally similar chemicals. This
would increase most MOSs/MOEs (with additional protective
clothing) to over 100 except for thyroid effects from maneb used
on grapes and commercial ornamentals. See Table 11-20. Dermal
absorption data have been required for maneb and its ETU
degradate through FIFRA section 3(c)(2)(B). These data are due
-------
TABLE 11-20
Mixer/Loader/Applicator Developmental and Thyroid MOSs/MOEs
(With full proposed protective clothing)
Site
Apples
Onions
Potatoes
Application
Method
Aerial
M/L
A
Airblast
M/L
A
C
Aerial
M/L
A
Groundboom
M/L
A
C
Aerial
M/L
A
Flagger
No. Days
Exposed
1
1
7
7
7
6
6
6
6
6
4
4
4
Groundboom
M/L
A
C
Chemigation
C
7
7
7
MANEB
Developmental
1500
14000
360
160
110
670
8000
1600
640
460
180
2900
830
1500
1000
620
200
Margin-of-Safety/Margin-of-Exposure
Thyroid
Daily Seasonal
750000
150000
21000
230
220
42000
13000
100000
1100
1100
17000
7400
1200
82000
1500
1500
67000
o
SO
Seed treatment 5
2100
150000
-------
TABLE 11-20
Mixer/Loader/Applicator Developmental and Thyroid MOSs/MOEs
(With full proposed protective clothing)
Site
Tomatoes
Sweet corn
Grapes
Application
Method
Aerial
M/L
A
C
Groundboom
M/L
A
C
Groundboom
M/L
A
C
Groundboom
M/L
A
C
Commercial
Ornamentals
M/L
A
C
No. Days
Exposed
3
3
3
7
7
7
4
4
4
15
15
15
30
30
30
MANEB
Developmental
300
3700
620
1700
750
520
1690
1000
630
1400
600
400
16000
120
120
Margin-of-Safety/Margin-of-Exposure
Thyroid
Seasonal
32000
13000
2100
110000
1100
1100
188000
2500
2500
20
36000
410
400
88000
170
170
i
H-
^-
o
-------
TABLE 11-20
Mixer/Loader/Applicator Developmental and Thyroid MOSs/MOEs
(With full proposed protective clothing)
MANEB
Margin-of-Safety/Margin-of-Exposure
Application No. Days Thyroid
Site Method Exposed Deve1opmenta1 Daily Seasonal
Homeowner*
Vegetable
Ornamental
Fruit trees
Turf
Handsprayer
C
C
C
C
6
5
2
6
3100
4500
360
60
2400
4100
270
130
M/L = mixers and loaders
A = applicators
C = one person mixing, loading and applying the pesticide
D = daily exposure
S = seasonal exposure
* = additional protective clothing requirements were not factored into homeowner risk estimates.
-------
TABLE 11-20
Mixer/Loader/Applicator Developmental and Thyroid MOSs/MOEs
(With full proposed protective clothing)
Site
Apples
Onions
Potatoes
Application No. Days
Method Exposed
Aerial
M/L
A
Airblast
M/L
A
C
Aerial
M/L
A
C
Groundboom
M/L
A
C
Aerial
M/L
A
Flagger
Groundboom
M/L
A
C
1
1
7
7
7
6
6
6
6
6
6
4
4
4
7
7
7
MANCOZEB
Deve1opmenta1
170000
1000000
33000
11000
8000
56000
560000
100000
170000
56000
42000
15000
220000
40000
170000
83000
56000
Margin-of-Safety/Margin-of-Exposure
Thyroid
Daily Seasonal
750000
4700000
21000
7100
5400
42000
420000
78000
125000
42000
31000
17000
270000
45000
110000
54000
36000
i
^-
H-
M
-------
TABLE 11-20
Mixer/Loader/Applicator Developmental and Thyroid MOSs/MOEs
(With full proposed protective clothing)
Application
Method
No. Days
Exposed
Tomatoes
Sweet corn
Grapes
Chemigation
C 2
Seed treatment
C 5
Aerial
M/L
A
Groundboom
M/L
A
C
Groundboom
M/L
A
C
Groundboom
M/L
A
C
3
3
7
7
7
4
4
4
15
15
15
MANCOZEB
Developmental
17000
200000
24000
280000
170000
56000
42000
170000
83000
56000
167000
42000
33000
Margin-of-Safety/Margin-of-Exposure
Thyroid
Daily Seasonal
8300
2100
1700
38000
180000
36000
420000
107000
36000
27000
188000
94000
63000
50000
12500
10000
-------
TABLE 11-20
Mixer/Loader/Applicator Developmental and Thyroid MOSs/MOEs
(With full proposed protective clothing)
MANCOZEB
Margin-of-Safety/Margin-of-Exposure
Application No. Days
Site Method Exposed
Commercial
Ornamentals
Homeowner *
Vegetables
Ornamentals
Turf
Fruit trees
M/L
A
C
Handsprayer
C
C
C
C
30
30
30
6
5
2
6
Developmental
880000
8300
8300
83000
140000
1700
11000
Thyroid
Daily Seasonal
44000 130000
420 1200
420 1200
62000
120000
3800
8300
M/L = mixers and loaders
A = applicators
C = one person mixing, loading and applying the pesticide
D = daily exposure
S = seasonal exposure
* = additional protective clothing requirements were not factored into homeowner risk estimates,
-------
TABLE 11-20
Mixer/Loader/Applicator Developmental and Thyroid MOSs/MOEs
(With full proposed protective clothing)
Application
Site Method
No. Days
Exposed
METIRAM
Margin-of-Safety/Margin-of-Exposure
Thyroid
Deve1opmenta1
Daily
Seasonal
Apples
Potatoes
Aerial
M/L 1
A 1
Airblast
M/L 7
A 7
C 7
Aerial
M/L 4
A 4
Flagger 4
Groundboom
M/L 7
A 7
C 7
5500
1200
1300
300
240
590
5300
870
5700
1900
1400
750000
5400
14700
230
230
4800
8200
1200
110000
1800
1800
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TABLE 11-20
Mixer/Loader/Applicator Developmental and Thyroid MOSs/MOEs
(With full proposed protective clothing)
METIRAM
Margin-of-Safety/Margin-of-Exposure
Application No. Days Thyroid
Site Method Exposed Developmental Daily Seasonal
Homeowner* Handsprayer
Roses
C 10 150000 - 240000
- - ._ - __-___--___
M/L = mixers and loaders
A = applicators
C = one person mixing, loading and applying the pesticide
D = daily exposure
S = seasonal exposure
* = additional protective clothing requirements were not factored into homeowner risk estimates
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TABLE 11-20
Mixer/Loader/Applicator Developmental and Thyroid MOSs/MOEs
(With full proposed protective clothing)
Secondary Oil
Recovery closed
Sugar/Paper
Mills
closed
48
26
NABAM
Application
Site Method
Cooling
Towers open
closed
Oil Well
Drilling
open
closed
No . Days
Exposed
48
48
48
26
Devel
5700
4800
2300
21000
5900
1500
Margin-of-Safety/Margin-of-Exposure
Thyroid
Daily
280
240
120
1100
290
75
Seasonal
2200
1800
880
15000
2200
1100
M/L = mixers and loaders
A = applicators
C = one person mixing, loading and applying the pesticide
D = daily exposure
S = seasonal exposure
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to the Agency in May 1990 and will be used to further refine
M/L/A developmental and thyroid estimates.
2) Daily exposure estimates used to calculate thyroid
MOSs/MOEs may present "worst case" risks because they assume a
high level of exposure over a short period of time. This is
compared to seasonal MOSs/MOEs which assume a lower level of
exposure over a longer period of time.
3) Exposure to ETU was assumed to be linearly proportional
to that of the parent EBDC. Based on limited data, the amount of
ETU, expressed as a percent of the parent EBDC after 4 hours in a
tank mix, varied from 0.1 percent to 0.2 percent for mancozeb to
6 percent for maneb wettable powder formulations. Given the
similar pattern of use for the various EBDCs on a given
commodity, the difference could, in some cases, result in a
difference of up to 60-fold in M/L/A exposure and risk, depending
on which EBDC product was used for a particular use. See
Firestone (October 14, 1988). Tank mix stability data required
by the Agency's March 1989 Data Call-in will be helpful to refine
estimates of the ETU breakdown in EBDC products and more
accurately define risk estimates. These data are due to EPA in
December 1989.
4) Due to the lack of nabam exposure data on industrial use
exposure, exposure estimates for nabam's industrial uses were
based on agricultural closed and open-pour systems. The open-
pour method of transferring agricultural pesticides into spray
tanks produces significant dermal exposure even with the use of
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protective clothing. The less sophisticated and more variable
equipment used in agricultural settings makes its applicability
for estimating exposure to industrial sites limited. Data on the
use of antimicrobials in industrial settings (oil field uses,
pulp and paper mill systems, cooling water systems and
metalworking fluids) indicate that worker exposure is minimal.
See (Lunchick - Review of Chemical Manufacturers
Association Antimicrobial DCI Rebuttal, October 15, 1987). The
Agency believes that risk estimates derived from agricultural
exposure data may possibly overestimate exposure for nabam's
industrial uses. The March 1989 DCI required dermal exposure
data on oil well drilling (open-pour systems) and sugar/paper
mills (closed systems). These data are due to EPA in March 1990.
The Agency will refine worker exposure risk estimates upon
evaluation of the required exposure studies.
D. REBUTTAL ANALYSIS
The Agency received comments relating to risks in response
to the PD 1. The rebuttal comments and the Agency's responses to
the rebuttal comments are contained in the following sections:
carcinogenicity, mutagenicity, developmental effects, thyroid
effects and exposure. Rebuttal comments are on file in the EBDC
Public Docket. All comments received during the public comment
period are addressed in this document.
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1. Carcinogenicity
Rebuttal Comment;
ETU should not be classified as a Group B2 carcinogen since
the effect only occurs above an exposure threshold.
Agency Response:
Since ETU induces an increased incidence of thyroid
follicular cell adenomas and adenocarcinomas in rats and
hepatomas in mice, it has been placed in Group B2 (probable human
carcinogen) for carcinogenicity as defined in criterion "a" of
the Agency's Cancer Risk Assessment Guidelines. This
classification is also supported by positive structure-activity
data since several other thyroid inhibitors (i.e. thiouracil and
thiourea) have been found to induce hepatomas and/or thyroid
tumors in rodents. If the Agency develops a policy on the
classification of "threshold" carcinogens and if the registrant
is able to show that the induction of thyroid and liver tumors is
a threshold phenomenon, the Agency would re-evaluate the weight-
of-evidence and the appropriateness of the currently employed
method for quantitative risk assessment would occur.
Rebuttal Comment:
The Agency is relying on the same carcinogenicity studies of
ETU that it relied upon in the original 1977 Rebuttable
Presumption Against Registration which were determined to have
several deficiencies.
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Agency Response;
The Agency agrees that there are deficiencies in these
studies, but due to the nature of these deficiencies (relating to
study design), the Agency feels that they do not invalidate the
tumor responses seen in the rat (thyroid) and mice (liver)
studies. In addition, the new NTP studies provide very strong
validation of the observation of tumors in the earlier studies.
The NTP studies were conducted more in line with current FIFRA
test guidelines. In light of these tumor responses, the weight-
of-evidence is sufficient to place ETU in Group B2 (probable
human carcinogen).
Rebuttal Comment;
The Innes mouse study does not meet current standards for a
carcinogenicity study.
Agency Response;
The Agency agrees that the Innes (1969) mouse study does not
meet current standards for a carcinogenicity study in the mouse
and in that sense has certain deficiencies (e.g., insufficient
numbers of animals, only one dose tested, no individual animal
data and thyroid glands not examined). However, the study
provides evidence of a dramatic response (100 percent) in the
liver tumor rates in males of one strain of mice and females in
the other strain of mice. The registrant for mancozeb has had
the slides from this study reread in light of current criteria
for classifying liver tumors. Since the incidence of liver
tumors in the treated B6AKF male mice is still 100 percent and
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the incidence of liver tumors in females of this strain and males
and females of the B6C3F,, strain are similar to the original
incidence of hepatomas as diagnosed by Bionetics, this
reevaluation of the liver slides from the Innes study largely
reconfirms the original magnitude of response and should have no
significant impact on the quantification of risk as already
performed by the Agency. A comparison of the results of three
evaluations (Bionetics 1968, Willigan 1979, and ICF-Clement 1987)
is summarized in Hauswirth (June 16, 1988).
Rebuttal Comment:
Since mouse data were used for calculating the QT*, the
conversion rate of mancozeb to ETU in the mouse, not the rat,
should be used in determining the risk of exposure by various
routes to ETU.
Agency Response:
The Agency used the conversion factor for mancozeb to ETU
derived from a rat metabolism study for the purposes of risk
assessment. This was the only available metabolism study on
mancozeb. For the purposes of risk assessment for humans, the
conversion factor that should be used is the one that would best
approximate the conversion factor applicable to man. The Agency
believes it is more appropriate to use the available rat
metabolism data rather than to estimate the conversion factor for
the mouse.
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Rebuttal Comment;
A surface area correction should not be done when
determining the Q^* for ETU.
Agency Response;
The Agency's current Cancer Risk Assessment Guidelines
support using surface area correction when determining a C^* for
any substance, including ETU. The Cancer Risk Assessment
Guidelines state "in the absence of comparative toxicological,
physiological, metabolic, and pharmacokinetic data for a given
suspect carcinogen, the Agency takes the position that the
extrapolation on the basis of surface area is considered to be
appropriate because certain pharmacological effects commonly
scale according to the surface area" (Dedrick, 1973; Freireich et
al., 1966; Pinkel, 1958). The interspecies extrapolation for
carcinogenic effects is accounted for by expressing the dose as
ing/squared meter body surface area/day. To modify the rodents'
experimental dose to human equivalent dose by surface area
assumes that different sized animals are not equally sensitive to
equal concentrations. This is based on the observation that
smaller animals are more efficient eliminators of the parent
compound and/or its metabolites than larger animals. This
difference in elimination ability is accounted for by the
difference between the species surface area to volume ratio.
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2. Mutagenicity
Rebuttal Comment:
ETU is not mutagenic. In 1986, a battery of mutagenicity
assays on ETU were submitted to the EPA Toxicology Branch Peer
Review Committee for consideration. In addition, results of
mutagenicity assays with maneb, metiram, mancozeb and nabam were
summarized by the Committee to further evaluate the mutagenic
risks associated with ETU exposure. The committee determined
that results of available mutagenicity data could not be used as
supportive information regarding the carcinogenic potential of
ETU.
Agency Response;
The Agency has performed a more recent evaluation of
available information on ETU for genetic activity (see Dearfield,
July 22, 1988). It was concluded that the body of evidence for
ETU suggests that ETU is capable of inducing a variety of
genotoxic endpoints. These include responses in gene mutation
assays (e,.g., Salmonella and mouse lymphoma assays), structural
chromosomal assays (e.g., aberrations in cultured mammalian cells
as well as a dominant lethal assay) and other genotoxic effects
(e.g., bacterial rec assay and yeast conversion assay). It must
be noted that while ETU does induce a variety of genotoxic
endpoints which serves as support for mutagenicity concern, ETU
does not appear to be a relatively potent genotoxic agent. For
example, there are instances where positive and negative results
in the same type of mutagenicity assay are reported from
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different investigators; however, these results may be dependent
upon the test conditions in each individual laboratory (e.g.,
problems in protocol, reporting or use of low concentration
levels). Overall, it appears that ETU produces a spectrum of
genotoxic effects and provides a basis for a mutagenicity concern
for ETU. The mutagenicity concern would provide support in the
weight of evidence determination of ETU's carcinogenic potential.
The Agency therefore disagrees with the commenter that ETU is not
mutagenic.
Rebuttal Comment:
ETU does not pose a genotoxic hazard to mammalian species.
Agency Response;
The Agency disagrees with the commenter'that ETU does not
pose a genotoxic hazard to mammalian species. See the Agency
response to the previous rebuttal comment for discussion
concerning the mutagenicity concern for ETU and evidence for a
genotoxic hazard to mammalian species. In addition, there are
suggestions that urea from ETU may be nitrosated with sodium
nitrite at appropriate pH's. As many EBDC-treated products are
cooked and consumed, humans may be exposed to ETU as a metabolite
and contaminant under conditions where nitrosation in the stomach
could occur. Nitrosated ETU and ETU in combination with sodium
nitrite have been demonstrated to induce potent genotoxic effects
in gene mutation assay and in vivo micronucleus and aberration
assays. Therefore, this aspect of ETU genotoxicity may provide
an increased concern to humans.
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3. Developmental Effects
Rebuttal Comment;
The differences in developmental toxicity potential of ETU
in various species can be explained by different rates or extent
of metabolism in these species.
Agency Response;
The Agency agrees that differences in the response of
various species to the developmental effects of ETU could be due
to different rates or extent of metabolism of ETU in these
species. If the mouse metabolizes ETU at a faster rate than the
rat, one would expect that ETU would be shown to be
developmentally toxic in the rat but not in the mouse. The
commenter also states that the half-life for elimination of ETU
in the cat is 3.5 hours and that the cat possesses a metabolic
pathway for ETU not present in the rat. ETU is not
developmentally toxic to the cat. The Agency is not certain of
the point of the registrant's discussion. If the registrant is
suggesting that human metabolism may be more like the cat than
the rat, and that differences in metabolism explain the different
developmental responses in various species, the Agency does not
believe there is sufficient information available to conclude
either point. The Agency, as noted, used a metabolic conversion
rate which best approximated that factor as applicable to humans.
As explained earlier, it believes rat metabolism to be
appropriate in this case.
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4. Thyroid Effects
Rebuttal Comment;
A threshold exists for the effects of ETU in the thyroid of
rats and in the liver of mice.
Agency Response:
The Agency agrees that a threshold may exist for the non-
carcinogenic effects of ETU on the thyroid and that a threshold
mechanism may exist for the formation of thyroid adenomas and
carcinomas in the rat. However, the Agency does not believe that
a NOEL for the non-carcinogenic chronic effects of ETU on the
thyroid of rats has been demonstrated. Although the Agency
agrees that a NOEL for the non-carcinogenic effects of ETU on the
mouse liver has been established, it does not agree that a
threshold mechanism by which ETU causes liver tumors has been
demonstrated. Definitive evidence has not been presented on the
mechanism by which ETU causes mouse liver tumors. In the absence
of such evidence, the Agency believes it is prudent to assume
that mouse liver tumors observed following exposure to ETU lack a
threshold for this phenomenon.
Rebuttal Comment:
Rohm and Haas commented that the Agency used the wrong
toxicological endpoint for determining the ratio of NOELs for the
liver effects of ETU versus mancozeb. "EPA calculated the
potential carcinogenic risk for mancozeb based on mouse liver
tumor induction by ETU. However, it established metabolic
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conversion of mancozeb to ETU based on data from another species,
the rat."
Agency Response;
The registrant is correct in that the Agency used different
endpoints for determining the ratio of NOELs of ETU to mancozeb
in the mouse. Nevertheless, the ratio of NOELs for the liver
effects of ETU versus mancozeb calculated by the Agency are
identical to those reported by Rohm and Haas from the CD-I mice
study (O'Hara and DiDonato, 1985). The ratios for thyroid
hyperplasia were stated as ETUcmancozeb at 10 ppm:100 ppm and the
ratios for increased liver weights as ETU:mancozeb at 100 ppm:
1000 ppm.
Using these same NOELs determined for the effects of each of
these chemicals on the thyroid, the Agency has estimated the same
ratios for thyroid and liver effects of ETU and mancozeb.
Rebuttal Comment;
The Agency is not correct in its determination of a NOEL for
the effects of ETU on the thyroid in the subchronic ETU rat study
conducted by Freudenthal (1977). The commenter states that the
NOEL for thyroid effects due to ETU reported in the Freudenthal
subchronic study was 25 ppm.
Agency Response;
The Agency disagrees with the commenter. The Agency review
dated March 7, 1986 set the NOEL for thyroid effects at 5 ppm
based upon an increase in the incidence of thyroid hyperplasia,
scored as moderate, seen at the 25 ppm dose level at 60 days but
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not at 90 days. The Agency believed that the effect at 25 ppm
was treatment related due to the scoring of the lesion as
moderate and since the effect was not seen in the control group
nor in the animals sacrificed at 90 days.
Rebuttal Comment;
ETU does not elicit the same magnitude of an effect in man
on thyroid function that it does in the rat. The maneb
registrant states that man has a reservoir of T4 that "is always
available to counteract stimulation of the thyroid, while in
rodents, inhibition of T4 synthesis and/or release causes
immediate stimulation of the thyroid."
Agency Response;
While the Agency agrees that thyroid function may be
controlled somewhat differently in humans than in the rat, a
United Kingdom factory worker study concluded that T4 levels in
workers were lowered due to ETU exposure (Smith, 1984). Since
the effect of ETU on thyroid function in the human (including its
impact on T4 recovery) is not known definitively, the Agency is
relying on the results of rodent studies to extrapolate to the
human.
Rebuttal Comment;
Results of health surveys indicate that workers can be
exposed for long periods of time to ETU with no adverse effects
on thyroid function. The mancozeb registrant has cited two
health surveys to support this point: 1) Gorden, C.F., de Fonso,
L.R., and Smith, J.M., "A Study of the Thyroid Function (T3, T4,
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TSH) of Workers Involved in the Manufacture and Packaging of
Dithane Fungicide Products" (1975) and 2) Braverman, L.E.,
Lipworth, L. and Charkes, D., "A Health Survey of Workers
Involved in the Manufacture and Packaging of Dithane Fungicide
with Special Reference to Thyroid Function" (1978). Both studies
had been previously submitted by the registrant on August 25,
1978 (Volumes 2 and 5) in response to the 1977 EBDC RPAR.
Agency Response:
Although the Agency agrees in general with the conclusion
reached by the registrant on both of these particular studies, a
major criticism of these studies is that the level of Dithane or
of ETU to which these workers were exposed is not known and,
therefore, it is difficult to relate the results of these studies
with other exposure scenarios resulting from the use of mancozeb.
5. Exposure
Rebuttal Comment;
The Agency did not correctly calculate the conversion rate
of mancozeb to ETU.
Agency Response;
The Agency agrees with the commenter that the conversion
from mancozeb to ETU was not calculated correctly. The Agency
has applied a molecular weight adjustment of 38% (the molecular
weight of ETU is 38% of the molecular weight of the parent EBDC)
to its previous calculation of a 20% conversion of EBDC parent to
ETU. Therefore, the in vivo exposure to ETU from any
administered dose of parent EBDC is approximately 7.5% of the
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administered dose, or for every 100 mg EBDC administered, 7.5 mg
ETU are generated.
Rebuttal Comment;
Due to the distinctions among the different EBDCs (chemical
structure and use pattern), dietary exposure data regarding one
of the EBDC's cannot always be generally extended to the other
EBDCs.
Agency Response;
The Agency agrees that there are differences among the
different EBDCs both in terms of the chemical structure and
sometimes the use pattern. As a result of the Storage Stability
Data Call-in Notices of 3/31/87, the Agency now has crop residue
data for maneb and metiram and for ETU derived from these two
pesticides. These data have been used to assess dietary exposure
to these chemicals. Based on the residue data received, some
differences in levels of EBDC parent and ETU in foods are noted.
Maneb and maneb-derived ETU residues were generally significantly
higher than mancozeb or metiram ETU residue levels. Metiram and
metiram-derived ETU residues were generally higher than mancozeb
or mancozeb-derived ETU residue levels. Differences in residue
levels were generally within one order of magnitude.
There are also similarities among the different EBDCs both
in terms of chemical structure and use pattern. The EBDCs all
degrade to ETU and can be determined by analytical methods based
on carbon disulfide evolution. The formula weights for the
monomers of all EBDCs are similar.
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Although it perhaps would be preferable to base dietary
exposure estimates on residue data from the individual EBDC
chemical, when residue data were unavailable for one EBDC, data
from other EBDCs were used because the differences in residue
levels among the various EBDCs were generally less than one order
of magnitude. In this document, this type of extrapolation was
done for metiram and metiram-derived ETU on several crops.
Rebuttal Comment;
One registrant (Rohm and Haas) made its own estimates of
dietary exposure to mancozeb and ETU using field trial data and
the Dietary Risk Evaluation System (ORES). Rohm and Haas states
that EPA combined data from all of the EBDC's. The dietary
exposure estimates by Rohm and Haas are based on data for only
mancozeb. Rohm and Haas then reduced the mancozeb residue
estimates to account for the effect of washing, and reduced the
ETU residue estimates to account for a one percent conversion of
EBDC to ETU during the analysis.
To support the need for correction for the effects of
washing, Rohm and Haas submitted (MRID 3403819-17) a 1977 survey
of homemakers, restaurants and food processors on food processing
(washing, trimming and peeling). The study showed that an
estimated 99 percent of restaurants, households, and food
processors use some type of preparation procedure (washing
(soaking), rinsing, peeling, trimming), except that an estimated
93 percent of restaurants use a preparation procedure for apples.
Washing (soaking) and/or rinsing is reportedly done by an
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estimated 97 percent of food processors. According to the study,
households wash or rinse >80 percent of each commodity studied
except onions. Restaurants wash >85 percent of all commodities
studied except onions and corn. Onions and corn are generally
peeled and husked, respectively. No data were submitted to
support the one percent conversion of EBDC to ETU upon analysis
of food crops. Several references to applicator exposure studies
were cited.
Agency Comment;
Rohm and Haas appears to have used the same mancozeb and ETU
residue field trial data as EPA used in the PD 1, although the
EPA accession numbers and/or MRID numbers of the data used by
Rohm and Haas were not given as part of their comments. The Rohm
and Haas residue estimates, before correcting for washing,
trimming and conversion to ETU on analysis are very similar to
those of EPA as presented in the PD 1. However, since
publication of the PD 1, the Agency has revised its mancozeb and
mancozeb-derived ETU residue exposure estimates for mancozeb-
treated crops from those residue field trial studies because
additional residue data for mancozeb and ETU derived from
mancozeb have been submitted. Some adjustments were made for
differences in the application rate between the data and
registered label rates. EBDCs are generally used at rates close
to the maximum registered rate close to harvest. Based on the
Agency's experience with data on non-systemic pesticides where
multiple applications were used, the application rate used
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closest to harvest generally has the greatest effect on the
residue at harvest.
In the PD 1, the percent of crop treated for EBDCs as a
group were the only data available for EPA: data were not
available for each individual EBDC pesticide. For the PD 2/3,
the percent of crop treated has been broken down for each
individual EBDC chemical.
EPA agrees with Rohm and Haas that many crops typically are
washed before consumption. In the PD 2/3, EPA has corrected the
residue estimates for the effects of washing, based on
conservative washing factors (the minimum reduction shown in
washing studies rather than the average or maximum reduction).
EPA disagrees with Rohm and Haas that the ETU residue
estimates should be adjusted for a one percent conversion during
analysis. No data were submitted to support the one percent
conversion of EBDC to ETU. The references cited by Rohm and Haas
that support such a reduction are for applicator exposure studies
rather than for residue studies. The Agency agrees that there
may have been a problem with conversion to ETU during analysis in
the past, but it believes the problem is largely corrected based
on data recently received on other EBDC chemicals that show no
significant conversion problems during analysis. Any recently
submitted residue studies are not expected to suffer from the
problem of conversion of EBDC to ETU during analysis because of
improvement in the analytical methods for ETU, including a better
understanding of causes of degradation during analysis. In fact,
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studies submitted by the other registrants (BASF and Pennwalt) do
not show any significant conversion of EBDC to ETU during
analysis or storage, with the possible exception of tomato
commodities. EPA notes that Rohm and Haas residue data on
tomatoes from the early 70's showed high residues of ETU, but
that Rohm and Haas residue data on tomatoes from the mid 80's
reported much lower residues of ETU.
Rebuttal Comment:
The Agency's dietary estimates, except for bananas, should
be considered worst case, since the estimates are based on
residue data where the crops were not washed, trimmed or peeled
before analysis and data for the shortest preharvest interval
(PHI) were used. Rohm and Haas points out that levels of both
mancozeb and ETU decline rapidly in the field, and that most
commodities are stored weeks or months before consumption.
Additionally, both mancozeb and ETU are unstable in processed
foods and decline rapidly with time.
To support their contention that the exposure estimates are
worst case, Rohm and Haas submitted market basket studies and
table top studies, including analysis of 1000 samples, showing
low residues of both EBDC and ETU. The studies report as an
EBDC, any residue responding to the carbon disulfide evolution
methods of analysis. See Hummel (July 13, 1988) for a list of
the studies, along with their MRID numbers.
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Agency Comment:
The same registrant's market basket studies and table top
studies were previously submitted to EPA by the EBDC registrants
as dietary exposure studies submitted in rebuttal to the 1977
RPAR. The studies were discussed in the EBDC Decision Document
of October 14, 1982. At that time, the studies were found to be
inconsistent and deficient in design and of questionable value in
determining representative exposure to populations potentially
exposed to EBDC and ETU residues. The Agency maintains this
position regarding the utility of these data. Although the
analysis of 1000 samples sounds considerable, very few samples of
each commodity were analyzed. Only 2 to 30 samples of each
commodity were analyzed, generally 10 to 18 samples per
commodity. This was an insufficient number of samples on which
to base a dietary exposure analysis. Additionally, only
summaries of data were provided and there were no data on sample
history for any of the samples. This latter deficiency is
particularly significant given the propensity of EBDC and ETU
residues to degrade in frozen storage.
FDA and the States have also done monitoring for EBDCs and
ETU. These data were discussed in Section II.B.l.b of this
document. Approximately 1300 samples were analyzed for EBDC
and/or ETU by FDA and the States from 1985 to 1989. FDA analyzed
about 100 samples for EBDC and/or ETU from 1978 to 1985. As in
the registrant's market basket studies described above, FDA and
the States analyzed very few samples of each commodity. No more
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than 15 samples of any commodity were analyzed for both EBDC and
ETU from 1985 to 1989. Very few processed commodities were
analyzed. No USDA data are available for EBDCs or ETU. USDA
does not monitor for EBDCs or ETU as part of their National
Residue Program.
FDA and State monitoring data from 1978 to 1989 for EBDC's
and ETU residues were summarized by the Agency. A copy of this
summary is included in Hummel (July, 1988; November, 1989).
To obtain additional dietary exposure data, the Agency
required registrants of EBDC pesticides to generate and submit
residue monitoring data from a market basket survey, through its
Data Call-in authority under FIFRA section 3(c)(2)(B). These
data are required to be collected in a manner which should
preclude the problems of the previous studies. These data are
due to be submitted to the Agency by September, 1990.
Rebuttal Comment
A mancozeb registrant submitted two applicator exposure
studies and a study of the stability of mancozeb formulations.
The studies are:
1. Hickey, K., et al. "Dermal and Respiratory Exposure of
Orchard Airblast Sprayer Operators to Mancozeb During Mixing,
Loading, and Spraying Operations" (1986).
2. Muma, R. and K. Hickey. "A Comparative Study of the
Exposure of Orchard Workers During the Application of Different
Formulations of Mancozeb" (1985).
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3. Haines, L.D. "Stability of WP EBDC Spray Slurries and
Rate of Ethylenethiourea Formation" (1985).
Agency Response;
The Agency has reviewed these studies and incorporated
pertinent data into its revised exposure assessment presented in
section II.B (3)(b) of this document.
Rebuttal Comment;
A mancozeb registrant states that the level of direct ETU
exposure derived from their products is less than that used in
the Agency's PD 1 document (0.6 percent of the exposure to
mancozeb for applicators, 0.5 percent for mixer/loaders). The
commenter states that an applicator will be exposed to ETU equal
to 0.1 percent of EBDC exposure and a mixer/loader will be
exposed to 0.2 percent.
Agency Response:
The Agency reviewed the registrant's data and found
agreement between the analysis of the mancozeb formulation for
ETU, expressed as a percent of mancozeb, and the ETU exposure to
individuals handling mancozeb expressed as a percent of mancozeb
exposure. A revised exposure assessment has been conducted which
incorporates a direct ETU exposure to mixer/loaders of 0.1
percent of the mancozeb exposure and a direct ETU exposure to
applicators of 0.2 percent of the mancozeb exposure. The
registrant's data also indicated that applicators handling the
maneb wettable powder will receive an exposure of 6.0 percent of
the maneb exposure. The 6.0 percent figure has also been used in
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11-139
the revised exposure assessment. The data indicate that
mixer/loaders handling the maneb wettable powder received a
direct ETU exposure of 0.1 percent of the maneb exposure. This
information was incorporated into the revised exposure
assessment.
6. Other
Rebuttal Comment:
The Natural Resources Defense Council (NRDC) supports the
initiation of the Special Review for the EBDC fungicides and
urges the Agency to complete it as soon as possible.
NRDC agrees that the Agency was correct in utilizing mancozeb
residue data to initiate the Special Review of all EBDC
chemicals.
Agency Response;
Whenever possible, the Agency will use actual field residue
or monitoring residue data. For the PD 1, the Agency estimated
EBDC dietary risks based on mancozeb field residue data because
it did not have acceptable data on the other EBDC chemicals. For
the PD 2/3, the Agency has used actual field residue data for
maneb, mancozeb and metiram.
Rebuttal Comment:
NRDC suggests that if residue chemistry data submitted by
EBDC registrants in response to Data Call-ins are inadequate, the
Agency should suspend the use of those registrations.
-------
11-140
Agency Response;
It is the Agency's general policy to suspend product
registrations for failure to take appropriate steps in response
to a Data Call-in Notice, including but not limited to failure to
submit adequate data in response to FIFRA section 3(c)(2)(B)
requirements. In examining issues relating to whether a
registrant has taken appropriate steps to meet data requirements
or the adequacy of data submissions, EPA considers a number of
factors, including but not limited to the nature and origin of
the problems with the data, the extent to which studies were
conducted according to Agency requirements, and the nature of the
registrants efforts to generate the data, even if the data turn
out to be unacceptable for risk assessment purposes. The Agency
did not issue Notices of Intent to Suspend to some EBDC
registrants for failure to submit data sufficient for risk
assessment purposes based upon its assessment of the registrants'
efforts to generate the data. However, some Notices of Intent to
Suspend were issued in instances where no data at all were
submitted or the effort and/or the conduct of the study was
deemed not to be adequate.
Rebuttal Comment:
NRDC has stated that EBDC registrants have not met the
burden of proving the safety of existing tolerances. NRDC urges
the revocation of all Section 409 tolerances for the EBDCs.
Agency Response;
Within 90 days of issuance of the PD 2/3, the Agency plans
to propose tolerance revocation actions consistent with the PD
-------
11-141
2/3 proposal. The Agency plans to finalize tolerance
revocations, allowing time for lawfully treated produce to pass
through.
Rebuttal Comment:
NRDC argued that the Federal Government has not protected
consumers from EBDC residues in the diet. The multiresidue
methods used by FDA to identify pesticide residues in food cannot
detect the EBDCs or ETU, and the methods available for
specialized tests are time consuming, of questionable accuracy,
and unsuitable for enforcement purposes. In addition, very few
samples have been tested for the EBDCs using the specialized
methods currently available. GAO indicated that FDA had analyzed
only 154 domestic samples for EBDCs between 1978 and 1987.
Additionally, the Agency has stated in the mancozeb Registration
Standard that the available methods are inadequate for
enforcement purposes because none are specific for mancozeb. EPA
should not allow the widespread continued use of EBDCs in
agriculture when FDA is unable to detect the presence of these
residues in food and enforce EPA's tolerances.
Agency Response;
Methodologies for EBDCs and ETU are available in the Food
and Drug Administration's Pesticide Analytical Manual Volume II
(PAM II). The available methodology for EBDCs analyzes the EBDCs
as a group by degradation to carbon disulfide (Keppel method),
and thus can be considered a multiresidue method. EPA has
received reports of difficulties in using the EBDC and ETU
-------
11-142
methodology from the State of California Department of Food and
Agriculture (CDFA). Although there are some drawbacks to the
Keppel method, the Keppel method is the best method known to the
Agency for tolerance establishment and enforcement purposes.
This method was collaboratively studied (JAOAC 5±:52B, 1971) and
is designated as the official, final action method by AOAC for
certain dithiocarbamate formulations (AOAC 14th Edition 6.537).
The method is listed as method III in PAM II; and is used by FDA
for enforcement purposes. The Agency believes that the Keppel
method provides satisfactory results and good reproducible
recoveries when used by analysts experienced with the method.
For ETU, the Agency recommends the Onley method (AOAC 14th
Edition 29.119:554). The Onley method for ETU has been studied
collaboratively, is the official, final action method for
potatoes, spinach, applesauce and milk, and provides acceptable
results when properly validated with recovery and control data.
The Agency agrees that the FDA multiresidue methods
available in the Pesticide Analytical Manual Volume I (PAM I) do
not detect EBDCs or ETU, and thus FDA and the States analyzed
fewer samples for EBDCs than for pesticides which were capable of
being detected by the PAM I multiresidue methods. However, EPA
has no current policy of requiring that a pesticide be capable of
being analyzed by a multiresidue method. The registrants have
been required to test the EBDCs and ETU using the FDA PAM II
multiresidue methods. The results of some of these tests are now
-------
11-143
available. Mancozeb, maneb, metiram and ETU were not detected by
the PAM I methods.
Regarding the suitability of analytical methods for
enforcement purposes, the Agency has required, from the
registrants, methodology which is specific for each EBDC
pesticide. These data have been required through the
Registration Standards and/or Comprehensive Data Call-in Notices
for each of the EBDCs. The registrants have reported
difficulties in developing specific analytical methodology. In
the absence of such specific methodology, the Agency recommends
the use of the Keppel method for enforcement purposes.
Additionally, the Agency is conducting a Special Review of all
EBDC pesticides as a group, partially because of the difficulties
of distinguishing among the various EBDCs and because ETU is a
common metabolite and degradate of all of the EBDCs and is of
significant toxicological concern.
Existence of specific enforcement methodology and ease of
use of analytical methodology are not the only criteria used by
the Agency in determining registration status or initiation of
Special Reviews. If specific analytical methods are developed
and replace the Keppel method as the official enforcement method
for the EBDCs, FDA will need to use five different methods
instead of the one analytical method currently used.
Rebuttal Comment;
A nabam registrant requested that the Agency terminate the
Special Review process for nabam. They contended that nabam is
-------
11-144
used exclusively as an industrial microbiocide and that margins-
of-safety associated with these uses are acceptable. They
submitted two reports: "Exposure and Risk Assessment for
Applicators of Nabam Containing Microbiocides" and "Benefits of
Nabam Containing Microbiocides."
Agency Response:
The Agency disagrees with the registrant that EPA should
terminate the Special Review of nabam. Nabam has registered
industrial uses. The Agency has reviewed the registrant's
applicator exposure study and noted that a NOEL of 0.25 mg/kg/day
was used in their risk assessment for thyroid toxicity. The
Agency disagrees with margins-of-safety/margins-of-exposure
calculated using a NOEL of 0.25 mg/kg/day and points out that, in
its opinion, a NOEL for the effects of ETU on the thyroid has not
been determined (Graham et al., 1975). In this study, an LEL
(Lowest Effect Level) was established at 5 ppm (0.25 mg/kg/day).
Information submitted on the benefits of nabam were
incorporated into the Agency's risk/benefit analysis of nabam.
-------
III. ASSESSMENT OF BENEFITS AND ANALYSIS OF REBUTTAL COMMENTS
A. ASSESSMENT OF BENEFITS
1. Method of Analysis
The information used to evaluate the benefits of the EBDCs was
derived from several sources. These sources include: public
comments in response to the PD 1, the registrants, USDA/State
Extension Service and research personnel, published State pest
control recommendations, scientific literature including the
American Phytopathological Society's Fungicide and Nematicide
Test Results for the years 1955 to 1987, National Pesticide
Information Retrieval System (NPIRS), the USDA/State/EPA 1978
Assessment of EBDC Fungicide Uses in Agriculture, analyses
prepared by the Agency staff, a Cooperative Agreement between the
Agency and the University of Georgia, and an Agency contractor
(Development Planning and Research Associates).
The general approach of this analysis was to evaluate, on the
basis of available information, the possible economic impacts of
a range of regulatory options including the cancellation of some
or all registered uses for EBDC fungicides, or modifications to
current methods of use of EBDC fungicides. Cancellation options
included an analysis of alternative pest control technologies
including non-chemical methods. Chemical alternatives were
determined from a listing of registered pesticides. The most
probable alternatives to EBDCs were chosen on the basis of cost,
efficacy, market availability and the suggested uses by State
experts and the Cooperative Extension Service. Future Agency
actions or market or marketing decisions by registrants or users
-------
III-2
could change the availability and use of certain alternatives.
Analyses were conducted on major sites/commodities. Analyses on
individual sites/commodities were conducted which considered
scenarios involving cancellation of combinations of fungicides.
These quantitative analyses provide the basis for the benefits
assessment presented here and are available from the EBDC public
docket.
Benefits in this document are calculated in terms of producer
impacts and efficiency impacts. Producer impacts were based on
projected changes in production costs, crop yield reductions and
quality reductions. Efficiency impacts were calculated for three
crops where there are potentially substantial impacts beyond the
grower level. Efficiency impacts are defined as society
(growers, distributors, consumers and others) costs, or the loss
to society of the dollar value of goods and services no longer
available as a result of the action. The limits of this
analysis include assumptions which were made based on the limited
usage information available, limited comparative data on yield
and quality factors associated with the use of alternative
fungicides and non-chemical control measures, and the limited
information on minor use crops. In addition, the Agency assumed
that only registered alternatives would be available as chemical
replacements for the EBDCs if their registrations were cancelled.
This is a conservative approach because new fungicides are being
developed and tested on many
-------
III-3
crops for which EBDCs are registered. For some minor crops such
as fennel and many ornamental crops, the Agency has no
information on use or on comparative performance. However, the
Agency recognizes the potential importance of EBDC use on such
minor crops and encourages factual data in support of EBDC
benefits or information on other control methods (chemical or
otherwise) to be submitted in response to this document.
2. Introduction
Four EBDCs, mancozeb, maneb, metiram, and nabam, have
registered fungicidal uses in the U.S. As discussed earlier, all
zineb uses have been suspended, the registrant for the technical
product has requested voluntary cancellation of all zineb uses
and no other registrants have accepted the responsibility to
support the registrations. Therefore, EPA concluded that the
benefits from zineb use are low and no further quantitative
assessment of benefits is presented.
The EBDCs are registered to prevent crop damage caused by
fungal pathogens to certain fruit, nut, vegetable, field and
ornamental (including turfgrass) crops. They are also registered
for use as seed treatments for selected field and vegetable
crops, as pre-plant treatments for potato seed pieces, as soil
treatments and for home gardens. The sole registrant still
holding registrations for use of nabam on agricultural sites has
recently requested voluntary cancellation of nabam on all
agricultural food sites; these registrations have been suspended
for several years and there is no known use of nabam on any
-------
III-4
agricultural crops. Nabam is registered for use as an
antimicrobial pesticide in recirculating water systems, sugar
mills, pulp and paper mills, oil recovery systems, adhesives,
glues, coatings and paints.
EBDCs are registered for use on over 150 sites. Their broad
spectrum of activity and relatively low cost appear to have made
them relatively important and widely used fungicides. EBDCs also
have a multi-site mode of action (affecting two or more enzyme
systems) and are used in some cases in combination with
fungicides which have single or limited-site modes of action.
This practice is carried out to slow or prevent the development
of fungal resistance which has been demonstrated to occur when
limited mode of action fungicides are used exclusively. Total
usage of the EBDCs in the U.S. has been estimated at 12-18
million pounds active ingredient (ai) per year. The largest crop
uses by volume of EBDC applied are apples, cucurbits, onions,
potatoes, small grains, sweet corn and tomatoes. The largest
crop uses in terms of proportion of the crop treated are apples,
cucurbits, lettuce, onions, peppers, potatoes, spinach, as well
as some other leafy greens (Table III-l).
Cancellation of all currently registered uses is projected to
result in first year foregone benefits to producers of
approximately $46 to $75 million from changes in the costs of
disease control and in short term losses due to possibly reduced
yields. In addition to these losses, efficiency losses are
estimated at $90 to $305 million per year. Although these may be
-------
III-5
Table III-l
Percent of Crop Treated with EBDC Fungicides a
Crop Maneb Mancozeb Met i ram
Fruits and Nuts
Almond
Apple
Apricot
Banana
Crabapple/ quince
Cranberry
Fig/Caprif ig
Grape
Papaya
Peach/nectarine
Pecan
Pear
Pineapple
propagation stock
Vegetables
Asparagus
Bean (green&dry)
Broccoli
Brussels sprouts
Cabbage
Cantaloupe
Carrot
Casaba melon
Cauliflower
Celery
Collard
Corn (sweet)
Crenshaw melon
Cucumber
Eggplant
* = No estimate is
NA = Not applicable
NR = Not registered
9
10
4
10
NR
10
*
4
*
4
NR
NR
NR
*
38
15
10
16
2
12
2
20
16
90
12
2
6
<1
available
; not appl
NR
35
NR
34
*
5
NA
19
*
NR
NR
11
NA
3
NR
NR
NR
NR
6
12
6
NR
10
NR
6
6
70
NR
for this site
ied to growing
a = Nabam not included because all agricult
NR
10
NR
NR
NR
NR
NR
NR
NR
NR
1
NR
NR
*
NR
NR
NR
NR
1
NR
NR
NR
10
NR
1
NR
*
NR
crop
:ural uses he
suspended for several years and there is no known use;
registrants have requested voluntary cancellation of all
agricultural uses
-------
III-6
Table III-l
Percent of Crop Treated with EBDC Fungicides (continued)
Crop
Vegetables
Endive
Fennel
Honeydew
Kale
Kohlrabi
Lettuce
Lima beans
Mustard green
Onion
Peppers
Potato b
Pumpkin
Rhubarb
Spinach
Squash
Tomato
Turnip Greens
Watermelon
Field Crops
Barley
Oats/ rye
Wheat
Sugarbeets
Peanuts
Corn, field
* = No
Maneb Mancozeb
<1
NR
2
90
*
60
38
90
3
56
7
30
*
48
2
8
90
2
NR
NR
NR
2
NR
NR
estimate is
NA = Not applicable
NR = Not registered.
b = Excluding seed
NR
*
6
NR
NR
NR
NR
NR
72
NR
32
*
NR
NR
6
20
NR
6
<1
<1
<1
2
4
<1
available for this
piece treatment
Met i ram
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
4
NR
NR
NR
NR
1
NR
NR
NR
NR
NR
*
0
NR
site.
-------
III-7
sizable impacts in the aggregate, they represent a small amount
relative to per capita food expenditure, even if costs are borne
by consumers. However, losses are often borne unequally, and
some severe localized losses may be incurred by current users of
EBDC fungicides and by some processors of these growers' output.
Because of the uncertain impact on yield and quality, these
estimated losses in production are somewhat more difficult to
predict than the projected increased costs of disease control
resulting in a larger range in numerical values. The estimated
impacts due to yield and quality losses possibly represent an
overestimation because in the long term the grower sector may
increase acreage to compensate for expected yield losses, such
grower losses may be partially offset by increased commodity
prices and use of alternative fungicides which may be registered.
In calculating these impacts, it is assumed that only currently
registered alternatives or currently accepted non-chemical
technology would be available at the time of cancellation. It is
expected that for all uses, the burden would be largely borne by
the user and/or consumer.
A site-by-site summary of EBDC usage and impacts of
cancellation on certain food crops is presented in Table III-2.
Therein, information is presented on the major use sites and on
the sites with a high percentage of the crop treated with EBDCs.
Presented below is a narrative discussion of the results
summarized in Table III-2, organized by food crop groupings which
currently account for the most usage.
-------
Table III-2
Surmary of Usage and Benefits of FHT-s for Selected Sites
Ai/Year Percent
1000 lb(%) of Site
Use Treated
Significance
Carrots 25 20-25
Potatoes 3.544 43
Onions 810 75
Key Pests
Altemaria
leaf spot
Cercospora
leaf spot
Early blight
Late blight
Botrytis leaf
blight
Downy mildew
Purple blotch
Availability
of Economic
Alternatives
chlorothalonl 1
triphenyltin
hydroxide
copper fungicides
chlorothalonl l
TPIH
anilazine
coppers
chlorothaloni 1
chlorothaloni 1+meta-
laxyl
Iprodicre
Type
Cost of treatment
Production
Consumer
Cost of treatment
Production
Consumer
Cost of treatment
pnrjufiMr inj^rf qf Cancellatica
Extent
Approximately $125,000
Negligible
Negligible
$4.4 million increase
1-2% increase valued at about
$4 million
No net effect
$6.5 million total increase
or $70/A. on affected acres.
75% of acreage impacted
Production costs increase <5%.
\
Minor
Cost increase
offset by slightly
improved production
Minor M
I-H
M
00
-------
Table III-2
Stannary of usage ana Benefits of FHTs for Selected Sites (continued)
Qctfrtt_flf. Usape
AI/Year Percent
1000 lb(%) of Site
Use Treated Key Pests
Celery 175 27-35 Early blight
Late blight
Availability
Alternatives Type
chlorothalonil Producers
benomyl
anilazine
coppers
tniopnanate-methyl
GonsuBQers
Bcmnnroifi TiiBMt-'^ Qf Gflnc.piiivt"|flrn
Extent
Possible yield loss up to 14% on
affected acres; aggregate costs
up to $310,000.
Price increase up to 8 - 13%.
Longer term impacts will be less
significant.
Significance
Significant
advantages for
nonusers. Users
would about break
even in snort run
In long run.non-
users would
dominate production
Minor impact in
food butaet
Welfare Loss
$1.3 to $3.4 million in short
run.
Mrvtorai-o
Lettuce
540
60
Downy mildew
captan
coppers
metalaxyl
Cost of treatment Slight reduction on 130,000 acres Minor impacts
Production
Producer price
Consumer
Welfare Loss
Up to 11% reduction on current
acreage & up to 24% reduction on
affected acres when resistent
occurs.
Potential 80% increase in price
from S12.50/CWT to $17 to $22/CHT
or $220 - $430 mil. revenue loss
after first year.
Potential increase in retail
price in short run from about
$0.90 to $1.40 - $1.60. Over
long run, effects would be
reduced.
$40 - $204 million
Major impacts in
second year
Major disruption to
market.
Major impacts in
the second year.
Estimated impacts
could be mitigated
through regional
production shifts
and imparts
changes.
-------
Table III-2
Sumaiy of usage and Benefits of EBDCs for Selected sites (continued)
AI/Year Percent
1000 lb(%) of Site
Use Treated
Spinach 80 42
Cole crops 270 10
(cabbage.
broccoli,
cauliflow-
er, Bru-
ssel spro-
uts)
Leafy 150 90+
Greens (if available)
Peanuts 260 4
Peppers 550 56
•fcmatoes 1.350 25-30
Kay Pests
Downy mildew
Downy mildew
Altemaria
downy mildew
powdery mildew
Altemaria
diseases
Leaf spot
Rust
Anthracnose
Fruit rot
rorg eye spot
Early blight
Late blight
Availability
of Economic
Alternatives
none
chlorothalonil
none identified
benonyl
chlorothalonil
copper hydroxide
tniophanate-methyl
TPTH
ziram
chlorothalonil
amlazine
coppers
ziram
Type Extent
User Possible shift out of production
to alternative crops in affected
regions.
•L^UI IKI**!.* T.uiwu^i>.ml - 1 i»u4 I*uwui*.iiju1
ten— user increaseu price ana increased
production In other regions would
reduce price Increase over time.
Producer Estimated impact of $19 million.
No inpacts
anticipated
Production Potential yield loss en affected
acres of 50% -100%.
User $2.4 million in Increased costs
potential negligible yield
effects.
Production Up to 40% yield reduction leading
to $23 - $40 mil. reduction in
farm gate revenue.
Cost of treatment $3.2 million increase
Production 5-14% increase on 10-20% of
acreage, valued at $3.1 million
n
Significance
Severe local
inpacts on affected
acreage.
unknown
Major
Major
Minor
Major
i~-i
M
M
t— •
o
Cost Increase
generally offset
by inproved
production
Consumer
No net effect to consumers
-------
Table III-2
Stannary of Usage and Benefits of EEDCs for Selected Sites (continued)
Extent of Usage
Al/Year Percent
1000 lb(%) of Site
Use Treated
cucurbits 2,000 45-55
Apples 3,500 48
Cranberry 15 15
Grapes 300 20-25
Banana 53 (HI) 44
9,000-11,000
(Latin An. )
Key Pests
Downy mildew
Gunny Stan
blight
Altemaria
Anthracnose
Cercospora leaf
spot
Rust
Fly speck
Powdery mildew
Scab
Sunner diseases
Fruit rot
Twig rot
Rnnopsis
Downy mildew
Black rot
SigatoXa
disease
Availability
of Economic
Alternatives
chloroUialonil
benonyl
coppers
metalaxyl-fchloro-
tnalonil
triadimefon
captan
benonyl
femarimol
trlforlne
triadinefon
chlortnalonil
bencnyl
triadimefon
ferbam
coppers
iprodione
captan
propiconazole
tridanorpn
petroleum oil
coppers
Type
Cost of treatment
Production
Consumer
Cost of treatment
Production
Consumer
Cost of treatment
Cost of treatment
Production
Consumer
cost of treatment
Rnrairiii^c, IflKftct. of Cancellatia
Extent
$8.5-10.5 million increase in
aggregate or about $48 per
affected acre
No impact
No Impact
$15.25/acre reduction or $4.7
million saying
Maxloun of 9% loss on affected
acres 0.5-1.6% loss overall
valued at $5-17 million
less than 1% change in price
About $100,000 per yaer.
-$0.36 to +$10.95 per acre
change
2-5% reduction East & Midwest
<1% of tot. U.S. production
$1-3 million reduction in value
of output
Hone
Cost increase of $300 to $400 per
acre or $300,000 to $400,000 In
aggregate to domestic U.S.
\
Significance
Minor
Minor
Moderate on
affected acres
Minor overall
Minor
Minor S
M
Minor "-
Minor for total
U.S.
Moderate for
localized areas
None
Minor for domestic
U.S.
-------
Table III-2
Stannary of Usage and Benefits of ranrs for Selected Sites (continued)
BttfflL
of Usaae
AI/Year Percent
1000 lb(%) of Site
Use Treated Key Pests
Sweet Com 700
19 Blight
ftist
Availability
of Economic
Alternatives
chlorothalonil for
fresh market corn.
No registered
alternatives for
sweet com grown for
processing.
EV^fimTHlic TlHTWt Of ^'nvH}llflt'iC
Type Extent
Cost of treatment $0.75 per acre treatment cost
increase for sweet corn grown In
Florida. Total cost increase of
$405,000.
Production Yield losses in Midwest
XI
Significance
Minor
Minor
Small
grains
650
0.4
Leaf spot
Leaf rust
Stem rust
Tan spot
Glume blotch
triadimefon
propiconazole
consumer
User
Nonuser
(principally Minnesota and
Wisconsin). Severe effects of
30% yield loss on 50,000 or more
acres 1 year out of 5. 10% yield
loss 2 or 3 years out of 5.
$1.7-$2.1 million yield loss.
Probable rise in price of canned Minor
and frozen sweet com (less than
10% price increase) in years with
yield losses.
$2.0-$14.3 million Increased cost Minor
and passible yield losses; 0.2%
of crop value; loss of positive
returns on affected acres near
upper end of loss estimate.
Possible increased prices of 1 to Minor
3 cents per bushel (less than 1%
price increase).
i
^-
ro
-------
111-13
3. Food Crops
a. Root/tuber crops
1. Carrots
California, Texas, Florida, Michigan, Wisconsin and
Washington are the major carr.ot producing states. Maneb and
mancozeb are registered for control of two major foliar diseases
of carrots (Alternaria and Cercospora leaf spots). Alternaria
occurs in all carrot growing areas while Cercospora problems are
scattered, affecting Texas and Michigan but not California and
Florida. EBDCs are recommended and used in all carrot producing
areas with an estimated 20 to 25 percent of U.S. carrot acreage
or about 21,000 acres treated with EBDC fungicides (USEPA,
1988c). The number of seasonal applications varies with disease
pressure in the regions where the crop is grown. State
recommendations indicate that three applications usually are made
in the Northwest; in California two to three applications may be
made; in Florida 10 to 14 applications may be made; and in the
Midwest up to 12 applications may be required. A typical
mancozeb product would be applied at rates ranging from 1.2 to
1.6 Ib ai per acre and maneb at 0.8 to 2.4 Ib ai per acre.
Alternative fungicides registered for the control of these two
foliar diseases include various copper compounds, chlorothalonil
and triphenyltin hydroxide. Cultural practices for mitigating
disease incidence include: (1) crop rotation, (2) destruction of
crop debris, and (3) manipulation of fertilization practices.
-------
111-14
The limited data 1 from comparative performance field trials
of the EBDCs and alternatives for the control of the diseases of
concern indicate that the EBDCs and chlorothalonil, a major
alternative, are about equal in disease control and should
provide essentially equivalent yields. Severe disease conditions
were reported for five of the nine trials; EBDCs gave
significantly better disease control and/or yield than no
treatment in three out of the five trials, and EBDCs were not
tested in one of the five trials and in the other trial the EBDC
fungicide was applied at a 14-day interval instead of a 7- to 10-
day interval. There was no statistically significant difference
between chlorothalonil and the EBDCs in any of the tests. Copper
fungicides were included in four of the tests and showed
increased disease control over no treatment in three cases and
increased yields in one case. Of the major carrot growing
states, only Texas lists copper fungicides in its
recommendations. One trial included triphenyltin hydroxide
(TPTH); mancozeb provided significant disease control over TPTH.
If EBDC fungicides were not available, carrot growers would
most likely utilize registered fungicides in conjunction with
cultural practices to accomplish disease control. Use of
chlorothalonil would increase user costs by an estimated $5.33
per acre where users substitute for maneb and $6.45 per acre
where users substitute for mancozeb, due to the current
1 Only nine studies were found in the American
Phytopathological Society's Fungicide and Nematicide Test Results
from 1955 to 1987.
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differences in cost of the pesticides (USEPA, 1988c). These cost
increases are nominal, representing less than two percent of per
acre cash expenses and far less than one percent of gross revenue
per acre. In the first year following cancellation, EPA
estimates that disease control for all carrot growers could
increase by about $125,000 if chlorothalonil is used to replace
EBDC fungicides. These cost increases are not considered by the
Agency to be a serious threat to the viability of carrot
production.
Consumers of carrots and carrot products should not be
seriously affected if EBDC fungicides are not available for
disease control. The volume and quality of production of carrots
is not expected to change as the result of EBDC unavailability.
Because the production cost increase is small, growers will most
likely absorb the cost increase and consumer expenditures for
carrots should be unaffected as the result of a change in the
chemicals used for carrot disease control (Table III-2).
2. Potatoes
Three EBDC fungicides (maneb, mancozeb, and metiram) are
registered for control of two major foliar diseases of potatoes
(early blight and late blight) as well as for control of various
fungi which cause decay of planted seed pieces.
For control of the foliar diseases, the fungicides are
applied as sprays by means of ground equipment, by aerial
equipment and in some instances through various sprinkler
irrigation systems. Applications typically commence when disease
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symptoms are first observed and, depending on disease pressure,
continue at five to 14-day intervals. The number of seasonal
applications for the eastern United States averages seven. For
the north central region, the average number of applications is
nine and for northwestern States and California, the average
number of applications is four. A typical mancozeb product would
be applied at rates ranging from 0.7 to 2.0 pounds ai per acre.
It is estimated that about 3.5 million pounds ai of EBDC
fungicides are applied four times per year to 550,000 thousand
acres of potatoes throughout all major potato growing regions
(USEPA, 1988n).
Seed piece treatment operations are carried out by
individual growers or farm cooperatives. Seed pieces are treated
by means of one of several technigues: a dust hopper over a seed
piece conveyor belt, a metering device mounted on a mechanical
tuber cutter, a revolving drum treater, and a hand-held sifting
device. Usually, eight percent dust formulations are applied at
the rate of one pound per 100 pounds of seed pieces (USEPA,
1988n).
Cultural practices for mitigating foliar disease incidence
include: (1) maintenance of adequate fertilization and soil
moisture to support plant vigor, (2) management of irrigation
practices so that foliage dries as rapidly as possible and (3)
crop rotation excluding disease susceptible solanaceous crops and
their weed relatives. In regard to resistant varieties,
resistance is usually specific to certain fungal strains; also
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varieties resistant to one disease are usually susceptible to one
or more other diseases. In areas where computerized disease
forecasting services are available, the application of treatments
according to predictions of disease outbreaks can reduce the
frequency and rates of application compared to programs of
scheduled applications at regular intervals.
Table III-3 presents a use matrix for alternative registered
pesticides for the control of the two foliar diseases and as seed
piece treatments.
Table III-3
Alternative Fungicides Registered
for Use Against Various Potato Diseases
Fungicide
anilazine
Bordeaux mixture
chlorothalonil
cooper sulf. basic
copper ammon. carb.
copper resinate
copper oxide
copper hydroxide
copper oxychloride
copper oxych. sulf ate
Foliar Diseases Seed Piece
Early Late Treatment
bliaht bliaht
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
formaldehyde x
metalaxyl + chloroth. x x
streptomycin x
thiophanate-methyl x
thiabendazole x
triphenyltin hydroxide x x
Source: NPIRS search, Registration Division label files, and
EPA Compendium of Acceptable Uses.
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The Agency reviewed one hundred and twenty foliar potato
disease field trials which compared the disease incidence and/or
yield differences between EBDCs, alternative fungicides and
untreated controls. The analysis of field trials did not include
data from tests demonstrating non-statistically significant
differences because (1) no disease incidence occurred to
challenge the treatments, (2) disease incidence occurred too late
in the season to have an impact on yield or (3) large variation
among treatment replicates due to situations such as inundation
of some plot replicates. In addition, the simultaneous
occurrence of more than one disease limited the depth of analysis
which could be conducted on the available field trial data.
However, taking these factors into consideration, evaluation of
the available data were made. In 17 trials in which late blight
occurred, chlorothalonil provided significant yield increases
compared with untreated controls and in 72 trials in which late
blight occurred, EBDCs provided significant yield increases
compared with untreated controls. There were no significant
yield differences between the EBDCs and chlorothalonil in
nineteen trials in which late blight occurred. Copper
fungicides, TPTH and anilazine, while significantly better than
no treatment; however, the resulting yields were lower than those
obtained from the use of chlorothalonil or the EBDCs.
In the 32 field trials reviewed in which early blight
occurred, chlorothalonil and the EBDCs produced statistically
significant data yield increases over no treatment.
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Chlorothalonil provided higher yields than EBDCs and either
chlorothalonil or EBDCs provided higher yields than copper
fungicides, TPTH and anilazine. However, the highest yields were
provided by a combination of metalaxyl and chlorothalonil with
slightly lower yields by a combination of metalaxyl and mancozeb.
Overall, the following conclusions can be made for potato early
and late blight disease control: (1) the EBDCs and chlorothalonil
are more efficacious than their alternatives; (2) chlorothalonil
combined with metalaxyl is somewhat more effective than the
EBDCs; and (3) the various copper fungicides are the least viable
alternatives. The copper fungicides and TPTH are often reported
to be phytotoxic and damaged foliage may result in lower yields.
For control of potato seed piece decay, approximately 30
field trials were evaluated by the Agency. The data reviewed
indicated that when there is sufficient disease pressure, all the
registered chemicals provide increased yield over the non-
treatment although the compounds that are tested do not always
rank consistently in the degree of control. Therefore, no
impacts on yields are expected if use of EBDCs on potato seed
piece treatments is cancelled.
The major alternative to EBDCs for foliar disease control is
chlorothalonil. If all acres currently treated with EBDCs are
treated with chlorothalonil, both treatment cost and yield would
be expected to increase. Cost would increase by about $2 per
treatment acre or $8 per acre, based on the current cost of
chlorothalonil. This represents an annual increase in production
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cost of $4.4 million. Depending on the region, yield could
increase by one to two percent valued at more than $4 million per
year. In net, the overall impact to users would be minimal
because increased treatment costs would be offset by increased
revenue from higher yields (Table III-2).
b. Onions
Mancozeb and maneb are registered for disease control of
onions. It is estimated that about 810,000 pounds ai of EBDCs
are applied to 90,000 to 95,000 acres or 75 percent of onion
acreage in all onion growing regions.^ Mancozeb is used on about
70 percent of onion acreage while maneb is used on about five
percent of the acreage (USEPA, 1988k). Mancozeb is registered
for control of Botrytis leaf blight, downy mildew, neck rot and
purple blotch diseases of onions. Maneb is not used as
extensively on onions and is registered for control of Botrytis
leaf blight, downy mildew, and purple blotch.
There is a paucity of performance data available to compare
EBDCs to other fungicides. One trial against downy mildew showed
that there was no significant difference between mancozeb and
copper hydroxide in onion yields, but both were significantly
better than no treatment. A study of purple blotch control
indicated that mancozeb and chlorothalonil provide statistically
similar yields, but that iprodione was significantly better than
either of the other two fungicides. EBDC fungicides reportedly
2 Major onion producing areas are California, the
Northeast, North Central States and the Pacific Northwest.
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failed to control Botrytis leaf blight in New York in an area
where onion monoculture prevails, but in a Florida trial, EBDC
provided better disease control (32 percent yield increase over
no treatment) compared with chlorothalonil (16 percent yield
increase over no treatment) and copper hydroxide (16 percent
yield increase over no treatment). Benomyl provided similar
yields to that of mancozeb. Two reports indicating consecutive
applications of chlorothalonil can suppress onion yields were
noted, it was concluded that if used judiciously with other
fungicides it can be useful in a disease management program
(USEPA, 1988k).
In the absence of EBDCs, chlorothalonil or a chlorothalonil/
metalaxyl combination are likely efficacious alternative chemical
controls for the diseases of concern. Other EBDC substitutes
include copper hydroxide and iprodione which will control purple
blotch, Botrytis leaf blight, and probably neck rot, a disease
caused by another Botrytis species.
EPA has estimated that without EBDCs, based on current
chemical costs, disease control will cost an average of an
additional $70 per affected acre. This estimate is based on an
average of 4.5 applications which would cost an average of $15
per acre per application. In aggregate, for onion growers
production costs would increase by $6.5 million per year. This
represents less than a five percent increase in production costs
or about one percent of the value of production. A grower
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cost increase of this magnitude most likely would cause a minor
increase in the price of onions to consumers.
c. Leafy vegetables
1. Celery
Mancozeb, maneb, and metiram are registered to control the
two major foliar diseases of celery (early blight and late
blight). It is estimated that about 175,000 pounds ai of EBDCs
are used on about 10,000 to 13,000 acres or 27 to 35 percent of
domestic celery acreage. Chlorothalonil is also widely used with
about 25 percent (or less than 10,000 acres) being treated
annually (USEPA, 1988d). Some growers may alternate using
Chlorothalonil and an EBDC fungicide. The fungicides may be
applied by means of ground or aerial equipment or by means of
sprinkler irrigation systems at three to 14-day intervals
depending on disease pressure. In Florida, the fungicides may be
applied as often as twice weekly for 20 to 30 times per season.
Typically EBDC products are applied at 1.6 pounds ai per acre.
Benomyl, Chlorothalonil, anilazine, various copper
fungicides, dichlone, ferbam, sulfur, thiophanate-methyl, thiram,
and ziram are registered for these uses and are EBDC
alternatives.
Certain cultural practices (crop rotation, planting of
resistant varieties) can mitigate disease occurrence, but these
practices cannot control the diseases below the economic
threshold where chemical pesticides are considered necessary to
insure that a grower can produce a marketable crop.
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The Agency reviewed available field studies conducted
between 1955 and 1986. Five studies provided yield information
on control of late blight by EBDCs and alternatives. A Least
Significant Difference was calculated from the estimated variance
between yields reported in the five tests. There was no
statistically significant difference in yield between EBDCs and
the other fungicides tested: benomyl, chlorothalonil, anilazine,
thiophanate-methyl, thiabendazole and basic copper sulfate.
On the other hand, the four studies on early blight did
indicate statistical significance between fungicide treatments.
Mancozeb provided significantly higher yields than benomyl,
thiophanate-methyl, chlorothalonil, anilazine and basic copper
sulfate. In addition, benomyl and thiophanate-methyl are subject
to having fungi develop resistance to their effects. On the
approximately 10,000 acres affected by early blight, yield losses
from substituting chlorothalonil (the next best alternative) for
the EBDCs could result in an estimated 9 to 14 percent yield
reduction compared to the yield expected with EBDC use {USEPA,
1988d). No economically significant yield losses are anticipated
from late blight.
The Agency estimates if EBDC fungicides were no longer
available, growers would spend about $310,000 or over $30 per
acre for alternatives fungicides. In addition to the increase in
treatment cost, total U.S. production is estimated to decline by
2.2 to 3.4 percent because the alternative fungicides provide
less effective control for early blight. This could cause the
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farm gate price of celery to increase by 9 to 14 percent or
$0.97 to $1.36 per cwt. (hundred weight). For growers who
currently use EBDC fungicides to control early blight, revenue is
estimated to fall by as much as $7 million or over $70 per acre
due to increased production costs and reduced yields. However,
total revenue for celery growers in aggregate could increase by
$16.4 to almost $22 million due to higher price received for the
commodity. At the consumer level, the price of celery could
increase by 8 to 13 percent. It is estimated that the efficiency
loss or net loss to society would be between $1.3 to $3.4 million
per year if EBDC fungicides were no longer available to domestic
celery growers (Table III-2).
2. Lettuce
Maneb is registered for foliar use on lettuce for control of
downy mildew. Fungicide applications are made at seven to 14-day
intervals using ground equipment and less often applications are
made by aerial means. It is estimated that 540,000 pounds ai of
maneb are applied to 130,000 acres of lettuce (USEPA, 1988i).
This represents about 60 percent of the lettuce acreage.
Approximately 90 percent of EBDC usage is in California. Arizona
and Florida are the next two largest states in terms of EBDC
usage, each with less than four percent.
Cultural practices such as crop rotation and weed control
practices to eliminate those weed species which serve as disease
hosts are recommended to reduce disease incidence. Commercial
varieties resistant but not immune to downy mildew are available.
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Mildew resistant varieties in some instances become susceptible
due to development of new strains of the causal fungus.
Alternative registered fungicides for control of downy mildew are
captan and various copper compounds.
Limited comparative performance data for downy mildew
control which was available from the open literature, indicate
that maneb, captan and copper sulfate generally, but not in all
cases, reduce the incidence of disease. When the trial results
were statistically analyzed, maneb provided significantly better
disease control to that given by captan and copper compounds. In
trials with metalaxyl, all showed significantly superior disease
control to any of the other alternatives including the EBDCs.
However, the Agency is aware of fungicidal resistance problems
with metalaxyl through California's request for an Emergency
Exemption (section 18 of FIFRA) to apply fosetyl-al because
resistance to metalaxyl has already occurred in some California
lettuce fields. Although metalaxyl provides control for downy
mildew, the Agency believes that fungal resistance is likely to
develop in fields using metalaxyl within the first year after
cancellation of the EBDCs and is likely to become widespread in
one to five years if not used in combination with fungicides
having a multi-site mode of action.
The USDA/Stat'es/EPA Assessment (1978) noted that comparative
performance testing showed copper fungicides caused phytotoxicity
(yellowing of wrapper leaves and necrotic leaf spots) which would
reduce the marketability of treated lettuce. The exact loss
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would depend upon the quality of other lettuce available at the
time of harvest. After consultation with a plant pathologist
from the California Cooperative Extension Service working with
lettuce, EPA estimated that yield losses along the California
coast where downy mildew may be severe, could range up to 25 to
30 percent if EBDC fungicides are not available (USEPA, 1988i).
The economic losses associated with cancellation of EBDC
registrations are separated into impacts the first and subsequent
years. Based on available data, EPA has estimated that in the
first year after cancellation current users of EBDCs would be
able to substitute alternative fungicides, such as metalaxyl and
copper with possibly some quality losses and no quantity losses.
Based on past fluctuation in price due to quality, the reduction
in quality due to cancellation of EBDC registrations is assumed
by the Agency to bring about an overall five percent price
decrease for lettuce which could reduce net revenue (total sales
of lettuce minus costs of production) from $263/acre to $95/acre.
The relatively better quality lettuce from growers who do not
need to control downy mildew is likely to increase in price which
may in aggregate offset the losses incurred by current EBDC users
who may not be able to control downy mildew without EBDCs. The
Agency has made a very conservative assumption, which may prove
not to be true, that no additional alternatives will become
available in subsequent years. Based on this assumption, EPA has
projected that yield could decline by as much as 24 percent for
current users as more growers are unable to use metalaxyl due to
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fungal resistance. However, the downy mildew fungus also may
become resistant to fosetyl-al if it becomes registered for use
on lettuce. If the downy mildew fungus becomes resistant to
metalaxyl and no other effective alternatives are available, the
Agency estimates an overall reduction in yield of 5 to 11
percent. As a result of this yield reduction and the highly
inelastic demand for lettuce, the farm gate price of lettuce is
estimated to increase by 37 to 80 percent and the retail price of
lettuce could increase by 34 to 72 percent.
Depending on how well acreage adjusts, the loss to society
is estimated at $40 to $204 million per year when resistance to
alternative fungicides sets in (Table III-2). The upper bound of
impacts is based on no adjustment in the number of acre grown.
The lower bound is based on acreage adjustments without changing
the proportion of affected and unaffected acres. If acreage
grown could shift to unaffected regions, the overall impact could
be further reduced. It is difficult to estimate the extent of
regional shifts in production because some of the most affected
regions, such as the central coast of California, are the primary
producing regions of lettuce during certain time periods each
year.
3. Spinach
Maneb, the only EBDC fungicide for spinach, is registered
for the control of two foliar diseases of spinach (downy mildew
and white rust). It is applied as foliar sprays or dusts by
ground equipment or by aerial means. Applications begin when the
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disease is first evident and, depending on disease pressure,
continue at seven to fourteen day intervals. An average of 4.5
seasonal applications are made in Texas, Maryland, and Virginia.
One or two applications are made in California. Maneb
formulations are applied at rates ranging from 1.2 to 2.4 pounds
ai per acre. It is estimated that about 80,000 pounds ai of
maneb are applied annually to about 17,000 acres of spinach. The
two largest spinach producing States are California and Texas
each with approximately 25 percent of the acreage. Other major
producing States include New Jersey (7 percent), Oklahoma (6
percent), Colorado (5 percent), and Tennessee (5 percent). It
appears that about 75 percent of spinach is grown for the
processing market.
Non-chemical cultural practices consisting of a three year
crop rotation, using disease free seeds and planting resistant
varieties can mitigate disease incidence, but, in the opinion of
experts contacted by the Agency, none of these controls the
diseases of concern at a level to prevent significant economic
losses from downy mildew and white rust (USEPA, 1988p). Even
resistant varieties suffer yield and quality losses when there is
a heavy disease pressure and environmental conditions favor out-
breaks of disease.
In addition to maneb, various copper compounds are
registered for control of downy mildew; only one of the copper
materials is registered for control of white rust as well as
downy mildew. None of the leading spinach producing states
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recommends copper fungicides for spinach, presumably because
copper fungicides may cause phytotoxicity to spinach as well as
other leafy vegetables. Coppers cause yellowing and necrotic
spotting of leaves and thus their market place acceptance is low.
Only two reports of field evaluations of maneb and
alternatives for the control of downy mildew and white rust could
be found in the Fungicide Nematicide Trial Results between 1955
and 1986. There were no comparisons between maneb and copper
compounds. The reports available indicated that maneb provided
the best control and was preferred over potential alternatives.
A plant pathologist contacted did not know of any trials using
copper fungicides to control downy mildew and/or white rust of
spinach and did not know of any use of copper fungicides to
control these spinach diseases (USEPA, I988p).
According to experts contacted by the EPA, in the absence of
EBDCs, much of the spinach crop grown over winter would not be
marketable because of the yield and quality losses from using no
fungicides or from using copper fungicides. If this acreage has
no other economic use, the loss is estimated to be about $27.5
million per year. Even if all the affected acres are idle, some
production can shift to marginal land where spinach has not
previously been grown over winter. Assuming 30 percent of the
winter crop is grown elsewhere, the economic losses fall to $19
million. In all likelihood, most former users would shift out of
spinach to the next most profitable crop. This could reduce the
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impact further; however, there are insufficient data to estimate
this impact (Table III-2).
d. Cole crops
Cole or crucifer crops include broccoli, Brussels sprouts,
cabbage, cauliflower, Chinese cabbage, collards, kale, kohlrabi
and mustard greens. Cabbage, broccoli, Brussels sprouts, and
cauliflower comprise 80 to 85 percent of the cole crops grown in
the U.S. While California grows the majority of U.S. cole crops,
no one State dominates cabbage production and many States produce
cole crops, especially for local market. Over the last ten
years, annual usage of maneb is approximately 270,000 pounds ai
for the four primary cole crops and, as much as, 150,000 pounds
ai for leafy greens when available.
Maneb is registered to control downy mildew and Alternaria
leaf spot on these crops. Both plant diseases can reduce quality
as well as, directly or indirectly, reduce production. Several
copper fungicides, chlorothalonil, metalaxyl, ziram and ferbam
are registered alternatives to control downy mildew on several of
the crops, in particular, cabbage, broccoli and cauliflower.
Copper fungicides tend to be phytotoxic to the crop and therefore
are not frequently used. Ziram and ferbam are not widely
available and are not recommended by State Extension Service
agents. Metalaxyl is registered only for cabbage, cauliflower
and broccoli. Resistance by the downy mildew fungus to metalaxyl
can develop unless it is used in combination with a multi-site
mode of action fungicide. Therefore, only chlorothalonil or
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chlorothalonil combined with metalaxyl are viable alternatives
for EBDC fungicides to control downy mildew on cole crops.
Alternaria leaf spot is often controlled with the same
fungicide application used to control downy mildew. The major
alternative chemical control is chlorothalonil; cultural controls
include crop rotation, weed management, and irrigating early in
the day to reduce surface moisture.
Comparative fungicide trials reported in Fungicide and
Nematicide Test Results were reviewed for data on both diseases,
25 trials for downy mildew and 7 trials for Alternaria. Only two
studies contained yield data and both showed no significant yield
differences between maneb and chlorothalonil. Maneb,
chlorothalonil and metalaxyl significantly reduced disease
incidence; in only one trial did maneb give significantly better
disease control compared to chlorothalonil. However, metalaxyl
gave significantly better control than maneb or chlorothalonil
alone, but metalaxyl must be combined with either maneb or
chlorothalonil to prevent development of fungal resistance. The
nine trials which included copper fungicides indicated that
copper fungicides provide equal or sometimes better disease
control than maneb although phytotoxicity due to copper was noted
in the studies. Because alternatives will be available for the
primary cole crops, loss of EBDC fungicides should have little or
no impact on downy mildew or Alternaria leaf spot control. For
the remaining cole crops (kale, collards, mustard greens, turnip
greens, and turnips) there are no viable alternative fungicides.
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Consequently, the loss of EBDC fungicides would have a ma]or
impact.
If registrations of EBDC fungicides were cancelled, EPA
estimates that all broccoli, Brussels sprout, cabbage, and
cauliflower acreage currently being treated with maneb would most
likely be treated with chlorothalonil. On a per treatment basis,
chlorothalonil currently is more expensive than maneb, but maneb
is applied more frequently than chlorothalonil (two versus five
applications on average according to experts contacted by the
EPA). When considering total application costs, chlorothalonil
use is less expensive than maneb. Therefore, costs to growers
are expected to decline by less than one percent, causing a
negligible change in net farm income. As a result of the
negligible impact to growers, no market nor consumer impacts are
anticipated (Table III-2).
On leafy greens, EBDC fungicides are the only viable control
for leaf spot causing diseases. EBDC fungicides are currently
available for use in Georgia and Tennessee through Special Local
Need registration and a Emergency Exemption, respectively. There
may be some existing stocks of maneb 3 labelled for these crops
being used in the southeastern U.S. When available, virtually
the entire crop of collards, kale, mustard greens, and turnip
greens would be treated with EBDC fungicides.
3 Use on this crop had previously been deleted from the
registered technical maneb label.
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In states where there is little or no EBDC fungicide
available, such as Texas, an unquantified number of growers have
reportedly lost their second of two cuttings. Consequently,
yields on affected acres have declined by fifty percent. All
acreage is not likely to be affected in any given season;
therefore, the yield impact to the overall crop may be less than
fifty percent. However, the impact to growers and the processors
of leafy greens are expected to be significant.
e. Peanuts
Metiram is registered to control Cercospora leaf spot (early
leaf spot) and mancozeb is registered for rust and Cercospora
leaf spot. It is estimated that 260,000 Ib ai of mancozeb are
used to treat about four percent of the U.S. peanut acreage.
Metiram is rarely, if ever, used on peanuts (University of
Georgia, 1988). Applications are made by means of ground or
aerial equipment or through various sprinkler irrigation systems.
Application commences when disease symptoms first become apparent
and, depending on disease pressure, continues at seven to 14 day
intervals.
Non-chemical cultural practices and the planting of
resistant varieties can mitigate disease incidence; however, none
of the practices directly controls the diseases of concern. Crop
rotation with grass crops, sanitation and early planting can
delay the appearance of the foliar diseases and thus permit a
delay in commencement of fungicide applications. There are no
commercially available varieties which are immune to one or more
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of the diseases. Programs which monitor environmental conditions
favorable for disease development can suggest critical periods of
fungicide applications and possibly reduce the number of
applications.
Alternative fungicides registered for control of Cercospora
leaf spot and rust include chlorothalonil, benomyl, copper
hydroxide and sulfur. Additionally, various copper compounds and
thiophanate-methyl are registered for use against the more
prevalent leaf spot diseases. Where benomyl or thiophanate-
methyl are suggested for use, it is recommended that it be
alternated or tank mixed with a fungicide that is not prone to
the development of fungal resistance.
Fifty-nine field trials comparing disease control and yield
impacts resulting from early and/or late leaf spot were reviewed.
Based on the analysis of the comparative efficacy data of the
chemicals registered for control of early leaf spot, rust, and
complexes of these diseases: (1) chlorothalonil is superior in
control and yield to EBDCs and other fungicides tested; and (2)
among the EBDC fungicides, mancozeb is somewhat superior in
performance to metiram, and maneb is the least effective.
Developing resistance of the leaf spot fungi to benomyl and
thiophanate-methyl is indicated by the progressive loss of
efficacy over the span of years for which efficacy tests were
reported. Among the copper fungicides, copper oxychloride
appeared to be the least effective and copper resinate the most
effective. Sulfur applied as a single active ingredient was the
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least effective fungicide and was reported to cause
phytotoxicity.
The Agency has assumed that EBDC fungicides would be
replaced with chlorothalonil if EBDC registrations were
cancelled. Peanut growers in the Alabama, Florida and Georgia
would be virtually unaffected by loss of EBDCs because of their
limited use of EBDCs and high dependence on chlorothalonil. Late
leaf spot, which is controlled by chlorothalonil, but not EBDCs,
is a problem in these states. However, growers in Virginia,
Oklahoma and Texas where late leaf spot causes less concern,
depend more on EBDC fungicides. It is estimated that growers in
Virginia, Oklahoma and Texas would pay higher prices for disease
control based on current differences in chemical costs. It is
estimated that the impact would be $2.4 million annually (Table
III-2).
f. Peppers
There are approximately 60,000 acres of peppers grown in the
U.S. Florida and California are the two largest pepper producing
states. North Carolina, Georgia, and New Jersey also are major
pepper producing states. There is little EBDC usage in
California whereas in Florida, Georgia, and New Jersey virtually
all of the pepper acreage is treated with EBDC fungicides. In
total, it is estimated that 50 to 60 percent of domestic pepper
acreage is treated with EBDC fungicides.
EBDC fungicides are used to control anthracnose, early
blight, and fruit rot. Currently, there is no economically
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viable alternative fungicide registered for the primary fungal
diseases affecting the pepper crop. Consequently, significant
short term impacts are expected if EBDC fungicides were no longer
available. If additional acreage is not readily available,
production could fall by as much as 40 percent and farm gate
price would increase by about one third from $31 to $42 per cwt.
It is estimated that if acreage could increase, output would fall
by 28 percent and farm gate price would increase by about 24
percent from $31 to $38 per cwt.
If EBDC fungicides are cancelled the loss to all growers
would be between $22.6 to 39.8 million dollars per year.
Consumer expenditure on peppers would increase significantly and
the total loss to society or efficiency loss would be between $49
and $98 million per year (Table III-2).
g. Tomatoes
Tomatoes for both the fresh and processed market are treated
with EBDC fungicides. Approximately 1,350,000 pounds ai of EBDC
fungicides are applied to 100,000 acres of tomatoes. The
Southeast treats almost all of the tomato acreage with EBDCs.
The Midwest region treats up to 60 percent, the Northeast treats
up to 83 percent, and California treats up to 9 percent of its
tomato acreage (USEPA, 1988r).
Mancozeb, maneb and metiram are registered for the control
of up to six foliar and fruit diseases of tomato listed in Table
III-4. The fungicides are applied by means of ground or aerial
equipment or through sprinkler irrigation systems. Applications
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typically commence when disease symptoms are first observed and
are repeated every five to 14 days as long as disease pressure
remains. The average number of seasonal applications ranges from
four in California to 22 in Florida. Alternative fungicides
registered for the control of six tomato diseases are also given
in Table III-4.
Sixty-seven comparative performance evaluations of
fungicides for control of the diseases of concern provided
indications of disease control and the impact on yield. Because
most trials were conducted against varying complexes of tomato
diseases, and there was varying degrees of disease severity among
tests, a statistical analysis of the data was not possible. EPA
estimated the percentage yield lost or gained when chlorothalonil
was substituted for the EBDCs. The average yield changes were
calculated from average treatment yields from field tests
conducted in given regions and reported in the annual
publication, Fungicide and Nematicide Test Results. The EPA
estimated average percentage yield change resulting from a
substitution of chlorothalonil for EBDCs for the Southeast was a
yield increase of 5.5 percent, for the Northwest a 14 percent
increase and for the Midwest an 8 percent increase. Less than
half of the field trials analyzed included captan, ziram, various
copper compounds, and anilazine. These fungicides generally were
less effective and provided lower yields than chlorothalonil and
the EBDC materials.
-------
Table III-4
Fungicides Registered for Control of Tomato Diseases
Fungicides
Disease
Manoozeb
Maneb
Metiram
Zineb
Anilazine
Benomyl
Bordeaux mixture
Captan
Chlorothalonil
Copper oxide
Copper oxychloride
OOCS *
Copper sulfate
Copper airanon. carbonate
Copper resinate
Copper hydroxide
Dichloran
Dichlone
Ferbam
Metalaxyl 2
SEMC 3
Thiram
Ziram
Early
Bliqht
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Late
Bliqht
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Gray
Leaf Soot
X
X
X
X
X
X
X
X
X
Gray
Leaf Mold
X
X
X
X
X
X
X
X
X
X
Septoria
]>af Soot
X
X
X
X
X
X
X
X
X
X
X
Anthracnose
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
I
LO
00
1 Copper oxychloride sulfate
2 In combination with mancozeb
3 Sodium dimethlydithiocarbamate
Sources: NPIRS search, Registration Division label files, EPA Compendium of Accepted
Uses
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111-39
The Agency estimated that cancellation of registration of
EBDC fungicides would result in total replacement of EBDCs by
chlorothalonil. Annual treatment cost per affected acre would be
projected to increase by $4.87 per acre due to the current
differences in chemical costs. The cumulative cost increase in
all regions is estimated to be $3.2 million with the greatest
impact in the Southeast ($1.9 million), followed by the Midwest
($0.6 million), California ($0.4 million) and the Northeast ($0.3
million). However, Agency estimates of percentage yield changes
were determined for EBDC usage shifting to chlorothalonil based
on field tests conducted in several regions of the U.S. Yield
increases for the acreage under high disease pressure where
growers shift to chlorothalonil are expected to range from five
to 14 percent depending on the growing region. The value of
these yield increases for the Southeast is estimated to be $1.9
million and $0.4 million for each of the other three regions.
Therefore, the projected value of the yield increases ($3.1
million) nearly offsets the projected increased price of
substituting chlorothalonil for EBDC fungicides (Table III-2).
h. Cucurbits
Cucurbits are members of the gourd family and include
squash, pumpkins, cucumbers, cantaloupes, watermelons, and other
melons. The Agency review focused on the five cucurbits listed
above; however, most characteristics, such as, primary diseases,
relative usage, and alternative fungicides should apply to the
remaining cucurbits with EBDC registrations. Maneb, mancozeb,
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and metiram are registered to control some or all of the
following: Alternaria leaf blight, angular leaf spot,
anthracnose, Cercospora leaf'spot, downy mildew, gummy stem
blight, Pythium fruit rot, and scab. Angular leaf spot is caused
by a bacterial pathogen; the other diseases are caused by fungal
pathogens. These pathogens may attack the foliage and/or the
fruit and may reduce yields or quality.
The major alternative to the EBDC fungicides is
chlorothalonil, although benomyl, metalaxyl and triadimefon are
used in combination with the EBDCs or chlorothalonil to
supplement control of specific diseases. Copper compounds are
sometimes essential for the control of angular leaf spot. As an
alternative to (or for use in conjunction with) chemical control,
some disease resistant varieties of cucurbits have been
developed. These varieties have greater resistance to specific
diseases and so require lower chemical rates and/or fewer
fungicide applications.
Fungicides are used extensively on cucurbit crops in all
producing States with most acres receiving multiple treatments in
a given year. The estimated annual usage of EBDCs on the five
cucurbits reviewed is 1.2 million to 2.9 million pounds ai per
year with about 40 percent of the acres receiving some form of
EBDC application (DPRA, 1988b). Essentially all fresh cucumbers
are treated with EBDCs.
If the registrations of EBDC fungicides are cancelled, the
cucumber industry would be the most severely affected of the five
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cucurbit market analyzed. As a result of replacing EBDC's with
chlorothalonil, treatment cost would increase by about a $4.5
million per year. Estimated impacts to the five cucurbit markets
due to loss of EBDCs are based on the relatively higher cost of
replacement chemicals which range from $8.5 million to $10.5
million annually (DPRA, 1988b). See Table III-2. No yield
impacts are anticipated.
i. Apples
Metiram, maneb, and mancozeb are registered for use on
apples to control several important diseases (Table III-5). Scab
is considered the most important of these diseases, although
several of the so called "summer diseases" of apples not only can
reduce the value of fresh market apples, but can result in
deterioration of fruit in storage. Fungal diseases of apples can
appear and spread rapidly throughout an orchard and can result in
upwards of 70 percent crop loss if the diseases are untreated.
Diseases of apple are most important in eastern orchards,
moderately important in north central region and least important
in western orchards. Use of EBDC fungicides to control apple
diseases reflects this pattern with treatment of approximately 67
percent, 22 percent and 3 percent of the apple acreage in these
regions, respectively (USEPA, 1988a).
The major alternatives to EBDC fungicides include captan,
benomyl, dodine, copper fungicides, fenarimol, triforine and
triadimefon. Although there are alternatives for each of the
listed diseases for which the EBDCs are registered, no one of
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Table III-5
Fungicides Registered for Control of Certain Apple Diseases
Funcficides
Mancozeb
Maneb
Metirara
Benorayl
Bordeaux Mixture
Calcium
polysul fides
Captan
Copper oxy-
chloride
sulfate
Copper sulfate
Dichlone
Dodine
Fenarimol
Ferbam
Glyodin
Sodium
polysul fides
Sulfur
Thiophanate-
methyl
Thiram
Triadimefon
Triforine
Ziram
Summer Diseases
Frog-eye Botyro- Bulls-
Bitter Leaf spot/ spheria Brooks Brown eye Fly- Sooty
Rot Black Rot Blotch Rot Soot Rot Rot speck Blotch
XX XXX
XX X XXX
XX X X XX
X X
XXX
X X
X X X X X
X
XXX X X X
XXX XX XX
X XX
X
X X X X X XX
X
Other Diseases
Scab
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Cedar
Apple
Rust
X
X
X
X
X
X
X
X
X
X
Quince
Rust
X
X
X
X
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these fungicides is a universal substitute for the EBDC
fungicides (Table III-5). For example, fenarimol and triadimefon
will not control the summer diseases. In addition, resistance to
benzimidazole fungicides (benomyl and thiophanate-methyl) has
developed in some apple orchards, thus eliminating their use in
some orchards and reducing their use in others. Concern has been
expressed that the apple scab fungus and other fungi also may
become resistant to certain systemic fungicides such as
fenarimol, triforine and triadimefon. Due to their multi-site
mode of action, EBDC fungicides are often relied upon to prevent
or slow the development of fungicide resistance to certain other
fungicides.
Many states recommend inclusion of EBDCs into an apple
grower's integrated pest management (IPM) program to control
apple scab. Some growers or various organizations monitor
climatic conditions and amount of fungal spores present to enable
growers to spray orchards only when conditions are conducive to
fungal infection and thus reduce the number of fungicide sprays
applied. Some apple varieties have been produced which are
resistant to apple scab; however, consumer acceptance of new
apple varieties is slow and development of a new apple orchard to
the bearing stage is expensive and requires several years.
Usually, control of both cedar apple rust and quince rust is
accomplished with the same fungicides and in conjunction with
scab controls. Use of EBDCs generally prevents economic loss
from rusts, whereas captan would provide much lower protection
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and benomyl provides none at all. Economic losses would be
expected if captan and/or benomyl were used for rust control on
apples. The systemic fungicides are very effective and would
also prevent economic loss. If EBDCs are not available and if
under the unusual circumstances that the systemic fungicides
could not be applied at the proper time due to weather or fungal
resistance, poor control under heavy disease pressure could
result in yield losses that year and premature defoliation.
Defoliation which would affect the following year's fruit
production. After consulting plant pathologists in apple growing
areas, the Agency estimates that losses would not exceed 10
percent of the crop; losses with current controls generally range
from one to two percent (USEPA, 1988a).
If the EBDCs were no longer available for summer disease
control, combinations and variations of treatments of captan and
benomyl are estimated to provide control of most summer diseases
such that there would be no significant economic impacts. The
exception would be for brown rot where growers would need to rely
on thiram, sulfur or ferbam.
Based on current chemical costs, estimated costs to treat an
apple orchard with captan instead of EBDC fungicides result in an
estimated cost savings of $14.49 to $16.02 per acre or
approximately $4.7 million savings. However, captan is less
effective than EBDCs in controlling apple rust and scab fungi and
estimated losses up to nine percent may occur on acres affected
by apple rust. Agency calculations result in an estimated
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111-45
reduced production of up to nine percent on the affected acres or
for the overall U.S. reduced production of apples by 0.5 to 1.8
percent (approximately a loss of $5 to $17 million). Considering
the savings from using less expensive fungicides and the possible
reduced yields that could result from use of these fungicides,
cancellation of EBDC fungicides could result in net producer
losses of $0.3 million to $10.3 million (Table III-2).
j. Peaches and nectarines
Although maneb is registered for use to control peach leaf
curl, scab, shothole (Coryneum blight) and brown rot or blossom
blight, its use on peaches and nectarines is limited. Brown rot
is one of the most important diseases of peaches and nectarines
as it can attack blossoms, flowers, twigs and fruit. Peach leaf
curl is especially important in California orchards.
There are registered chemical alternatives to treat all four
of the peach and nectarine pathogens for which maneb is
registered. These include captan, chlorothalonil, benomyl,
dichloran, copper fungicides and several sterol inhibiting
fungicides. Comparative efficacy trials reported in the American
Phytopathological Society's Fungicide and Hematicide Test Results
indicate that benomyl and thiophanate-methyl are the most
effective fungicides at controlling brown rot. However, EBDCs
would provide a role as one of the available fungicides which can
slow or inhibit the development of fungal resistance to benomyl
and thiophanate-methyl. EBDC fungicides are infrequently
recommended by State authorities and generally are not considered
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the product of choice by State experts. EBDC fungicides are
applied to less than three percent of the U.S. acreage most of
this usage is for western peach orchards (USEPA, 1988m).
The Agency has estimated that chlorothalonil likely would
replace EBDC fungicides if these registrations were cancelled.
If chlorothalonil totally replaced EBDCs, based on the current
chemical costs, the annual treatment cost per affected acre is
estimated to increase from $10.60 per acre treatment of EBDC to
$13.93 per acre treatment of chlorothalonil which results in a
projected production cost increase of $3.33 per acre. Total cost
increases are estimated to be negligible, less than $14,000, and
no yield effects are expected (Table III-2).
k. Cranberries
In 1987, about 3.3 million barrels of cranberries were
produced in the U.S. with a farm gate value of over $170 million.
Massachusetts and Wisconsin are the two major producing states
accounting for nearly 80 percent of domestic production. In
1988, approximately 15 percent of the cranberry crop was treated
with EBDC fungicides.
EBDC fungicides are used to control fruit rot and twig rot
(primarily in Pacific Northwest). Chlorothalonil is an economic
alternative to EBDC fungicides and is used more widely than
EBDCs. If EBDCs are cancelled, fungicide cost would increase by
about $100,000 per year for the entire industry. This increase
would be negligible.
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1. Grapes
Domestic grape production is highly concentrated in a few
states. Ninety-nine percent of the grapes are produced in
California, Washington, New York, Michigan, and Pennsylvania.
California alone accounts for approximately 90 percent of the
grape production each year. California growers produce several
varieties of grapes that are used to make wine, dried for raisin
production or consumed on a fresh basis. Growers in the other
four major grape-producing states raise few varieties (primarily
Concord grapes) which are crushed for juice, jam and concentrate.
A small quantity of the crush is used for wine production (USEPA,
1988h).
Mancozeb and maneb are registered to control five fungal
diseases of grape. Table III-6 is a matrix of the disease
control claims for each of the registered EBDC fungicides. Black
rot and downy mildew are most important in the eastern U.S.;
Botrytis is important in all grape growing areas; and Phomopsis
cane and leaf spot (or blight) continually has been more
important in California and in the Northeast.
Maneb and mancozeb are widely recommended by State
authorities for control of plant diseases on grapes.
Approximately 300,000 pounds ai of EBDC fungicides are applied
each year to U.S. vineyards representing about 22 percent of the
total grape acreage (USEPA, 1988h).
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Table III-6
Summary of EBDC Fungicides Registered to Control
Diseases of Grapes
Funaal Disease
Black rot
Botrytis bunch rot
Downy mildew
Phomopsis cane blight
Mancozeb
X
X
X
X
Maneb
X
X
Use of resistant varieties can reduce the need for
fungicides. However,°because of the long lived nature of a grape
vineyard and consumer demand for certain wine and raisin
varieties, growers continue to produce the varieties of high
demand.
Alternative fungicides are available for all of these fungal
diseases. Captan, benomyl, iprodione, triadimefon, ferbam,
copper fungicides and dichloran are registered for control of one
or more of the five diseases of concern. Although comparative
product performance data statistically evaluating grape yield
differences between EBDC fungicides and alternatives are not
available, the major benefits from EBDC fungicides appear to be
the multi-site mode of action of these fungicides which helps
reduce the build-up of fungicide resistance and lower production
costs by using the relatively inexpensive EBDCs. It should be
noted that captan and sodium arsenite in California only, are the
only alternatives to mancozeb for Phomopsis cane and leaf spot.
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Production costs may be reduced by $0.36 per acre if growers
switch to captan or increased by as much as $10.95 per acre if
growers switch to benomyl (USEPA, I988h). Experts from grape
producing states indicated that if EBDC registrations are
cancelled most of the economic impacts to grapes would occur in
the East and Midwest due to possible yield losses from black rot
(2 to 5 percent) and downy mildew (0 to 5 percent) (USEPA,
1988h). EPA estimated that overall yield losses would not exceed
five percent. These two diseases are not important in grape
growing areas of the west. In aggregate for the total U.S., the
value of the grape crop is projected to be reduced by an
estimated $1 to $3 million {Table III-2).
m. Bananas
If EBDC registrations in the U.S. were cancelled, all EBDC
food tolerances would be cancelled and food imported into the
U.S. could be seized if contaminated with EBDCs. This analysis
is not intended to consider the economic impacts of the proposed
decision on foreign countries, but does consider any possible
economic impacts the proposed decision would have on U.S.
consumers of bananas, either in reduced availability, reduced
quality or increased price.
Bananas are the single most popular fresh fruit consumed in
the U.S. Commercial banana production in the U.S. is restricted
almost exclusively to Hawaii with virtually all Hawaiian bananas
consumed locally. Essentially all bananas consumed on mainland
U.S. are imported. The major supply countries are: Colombia,
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111-50
Costa Rica, Ecuador, Guatemala, Honduras, and Panama. The U.S.
imported 3,243 thousand tons of bananas in 1986 with an estimated
value at just over $700 million.
Maneb and mancozeb are registered for use on bananas to
control Sigatoka disease and tolerances have been established
that apply to both imported and domestic (Hawaiian) bananas.
Actual quantitative usage of banana fungicides is difficult to
determine. Due to the small amount of acreage in Hawaii
(approximately 1,000 acres), fungicide usage on Hawaiian bananas
is not reported. In addition, there is limited information
available on usage estimates for Latin America. A maximum of
53,000 pounds ai of mancozeb is estimated to be applied to
Hawaiian banana acreage each year. International usage of
mancozeb on bananas is estimated at nine to eleven million pounds
ai annually. Nearly all banana acreage outside the U.S. is
treated with EBDCs because of the importance of Sigatoka disease
to banana production (USEPA, 1988b).
If EBDC registrations were cancelled, banana growers likely
would substitute propiconazole or tridemorph with petroleum oil.
The use of these alternatives could increase annual treatment
cost by $300 to $400 per acre or $300,000 to $400,000 in total.
Minor market and consumer impacts are anticipated.
Banana producing countries are the largest banana consuming
countries. Also, the U.S. consumes about five percent of the
world banana production. The Agency believes it is possible that
any reduced quality bananas or shortages in supply would be
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absorbed by the local economies of the exporting country in order
to maintain a constant supply of high quality product to the
international market. Such a policy would insure market share
and a continued steady supply of needed currency. However, if
exporting counties do not absorb the reduced quality and
shortages in supply, consumer prices in the U.S. may increase.
n. Sweet corn
Sweet corn is widely grown in the U.S. with production for
fresh market sale in the summer occurring in nearly all states.
Production for national sale during the fall, winter and spring
occurs in Florida, Texas and California with only a small
percentage of the production in Texas and California. About a
half dozen northern states grow sweet corn for processing.
Maneb and mancozeb are registered to control northern and
southern corn leaf blight on sweet corn; metiram is registered
for use only in Florida. In addition, mancozeb is registered to
control another foliar fungal disease called common rust.
Northern and southern corn leaf blight tend to be more important
in the southern States and common rust tends to occur more in the
north central States (USEPA, 1988q).
The use of resistant or tolerant varieties is considered by
most State authorities to be the best control measure for these
three diseases. There is general resistance to rust in field
corn hybrids and some sweet corn hybrids, but many commercial
sweet corn hybrids are susceptible to rust, especially the new
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high sugar hybrids preferred for fresh market and by some
processors.
The only registered alternative to the EBDC fungicides for
control of these three diseases is chlorothalonil and according
to the chlorothalonil label, it can only be used on sweet corn
grown for fresh market, not sweet corn grown for processing. In
addition, certain resistant prone fungicides show promise for
control of these pathogens particularly propiconazole for which
registration currently is being pursued. According to experts
contacted by the EPA, use of fungicides is only economical when
disease pressure is moderate to severe and when the fungi invade
young plants (USEPA, 1988q).
Ten field studies on the comparative control of northern and
southern leaf blight were reviewed. No yield data were
available, but a statistical analysis of efficacy data indicated
no significant differences between chlorothalonil and the EBDCs.
Similarly, nine field studies on the comparative control of rust
were reviewed. Mancozeb provided statistically significant
disease reduction over chlorothalonil in only one trail.
Considering the above information, the Agency concluded that if
the EBDC fungicides were no longer available, yields of sweet
corn grown for fresh market sale should not be affected, but
based on current chemical costs, costs for disease control would
rise. The cost per application per acre is projected to increase
by $0.75 if chlorothalonil was substituted for EBDCs resulting in
a yearly cost increase of $405,000 on sweet corn grown in
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111-53
Florida. Because chlorothalonil is not registered for use on
sweet corn that is to be processed, production costs on sweet
corn grown in the Midwest for processing would fall because
growers would not be applying fungicides. However, yields on
affected acres are estimated to decline due to the impacts of the
diseases on cob size, number of ears per plant, and kernel size.
It is estimated that using currently available sweet corn hybrids
(including resistant strains) in two or three years out of five a
10 percent yield loss could occur and in one year out of five a
30 percent yield loss could occur on 50,000 acres or more. The
value of the possible range of crop loss has been estimated at
between $1.7 and 2.1 million (USEPA, 1988q).
Impacts on consumers are estimated to include probable price
increases for canned and frozen sweet corn in years with yield
losses (Table III-2).
o. Small grains
In this country, most of the small grains are grown in drier
regions of the country where fungicide usage is not particularly
beneficial to yield. Currently, in excess of 95 percent of the
domestic wheat, barley, oats and rye acreage is not treated with
fungicides. Average or most likely estimates of annual usage
indicates that 330,000 acres of wheat, 60,000 acres of barley and
15,000 acres of oats and rye are treated with mancozeb (USEPA,
19880). There is no information indicating actual use on rye,
but some use is possible.
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Mancozeb is registered for control of Helminthosporium leaf
spot, leaf rust, Septoria leaf spot, Septoria glume blotch and
tan spot on wheat, barley, oats and rye. Propiconazole is
registered for control of the leaf spots and rust diseases on
wheat, barley and rye (not oats); triadimefon is registered for
control of leaf spots and rust diseases on wheat and barley; and
copper hydroxide is registered for control of leaf spots of wheat
and barley. Fungicides are recommended to be used as part of a
comprehensive disease management program which includes cultural
controls as well as estimating yield loss, crop prices and
production cost before applying any fungicide. Therefore, the
Agency believes that fungicides typically are only used on grain
fields with high yields and that are under irrigation.
Triadimefon and propiconazole are the most likely used
substitutes for EBDC fungicides although they currently are more
expensive than EBDCs. There is not enough information available
to determine the magnitude, if any, of possible yield impacts
from loss of EBDCs on small grains. However, EPA has determined
that overall bounds could range from zero yield loss and cost of
production changes to a value of 30 percent crop loss on the
treated acres if no fungicides were available or if fungal
pathogens became resistant to alternative fungicides. More
likely yield losses are estimated by EPA to be 7.5 to 15 percent
on affected acres.
If EBDC registrations are cancelled, it is estimated that
users of EBDCs could have losses of about $2.0 million attributed
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to projected increased costs of disease control with no yield
loss, about $4.6 million with a 7.5 percent yield loss, $7.2
million with a 15 percent yield loss and about $12.3 million if
yield losses were 30 percent on all treated acres. The four
small grain crops combined have a market value of about $6.6
billion so the worst case loss is estimated to be about 0.2
percent of the combined values of these crops. Under the worst
case, with a 30 percent yield loss, farmers who used EBDCs are
estimated to have a reduction of about 30 percent of gross
revenues per acre, which could result in negative net returns.
Growers with such high yield losses would need to make changes in
practices or crops produced to reduce the magnitude of losses.
In most cases, only farmers with yield losses of under eight
percent would have positive net returns. However, growers with
yield losses in this range still may find it more profitable to
shift out of wheat or barley. Oat producers who used EBDCs
potentially would have more serious problems since this crop
usually is less profitable than wheat or barley and there are no
registered alternatives for oats. Rye is also a less profitable
crop than wheat or barley and, although there are registered
alternatives to EBDCs on rye, growers of rye could have similar
problems as those faced by growers of oats. However, use of
EBDCs on oats and rye is extremely limited and only a few growers
would suffer any impacts.
Loss of EBDCs could result in gains to non-users if the
price per bushel of grain were to rise due to a loss of crop
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yield nationwide, should yield be so impacted. The high estimate
of the increased cost on a per bushel basis would result in
possible gains of up to $90 million which represents up to about
one percent of the crop value. However, it is expected that
price increases would result in relatively small increases in the
price of small grain products.
p. Other crops
Information is not available to enable the Agency to conduct
a quantitative benefits analysis for all crops, especially those
where a small percentage of the crop is believed to be treated. 4
As stated in the introduction to this chapter, the Agency
encourages submission of factual data describing any benefits
that may be gained from the use of EBDC or other fungicides or
other methods of control on any crops, especially usage and
comparative product performance data for minor crops. For crops
marked by an asterisk in Table III-l, the Agency knows of no use
of EBDC's and therefore it assumes there are no benefits on these
sites. Benefits estimates for lima beans and green beans given
in Chapter IV (Table IV-2) were based on an update of the 1978
USDA/States/EPA Assessment of EBDC Fungicides Used in
Agriculture.
4 Crops where the Agency had insufficient data to conduct a
quantitative benefits assessment include: almonds, apricots,
asparagus, casaba melons, crabapples/quince, crenshaw melons,
eggplant, endive, fennel, fig, kohlrabi, papaya, pecans, pears,
peas, pineapples, and rhubarb.
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4. Seed treatments
Mancozeb and maneb are registered for use as a seed
treatment on a variety of crop plants, but the Agency is aware of
use only on small grains (DPRA, 1988c). EBDC seed treatments are
used on small grains in a wide geographic dispersion on eight to
ten percent of the crop. Approximately 830,000 pounds ai of EBDC
are used annually on barley, oats, rye and wheat to help control
smuts, bunt, damping-off, and seedling blights (DPRA, 1988c).
The major alternatives are captan, carboxin, thiram and
triadimenol. Field trial data and the opinion of plant
pathologists lead the Agency to conclude that a combination of
carboxin and thiram generally is more effective than EBDC
fungicides (DPRA, 1988c). EBDC fungicides are often preferred to
captan because the latter does not control the smut and bunt
fungi. Cancellation of EBDC seed treatment uses is estimated to
result in a net aggregate cost increase of $7.4 million because
of the currently higher costs of the carboxin and thiram
combination.
5. Non-food crops
a. Ornamental plants
For this analysis, the term ornamental plants includes shade
trees, landscape woody shrubs and herbaceous perennials,
ornamental conifers, floriculture crops, foliage crops and
bedding plants. Mancozeb and maneb are registered for use on one
or more of these plant groupings which represent over 70 plant
species. The EPA estimates that about 150,000 pounds ai of
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EBDC's are used on ornamental plants. This represents 15 to 20
percent of fungicide usage on ornamentals. Benomyl,
chlorothalonil, dichloran (DCNA), fenarimol, iprodione,
thiophanate-methyl, triadimefon, triforine, vinclozolin and other
fungicides are registered for use on ornamental crop plants.
However, most of these fungicides are not registered for most
ornamental plants. In fact, because the ornamentals share of the
fungicide market is small, there are only a few registered
materials for most plants and there are no registered
alternatives to EBDCs for many diseases of ornamental plants.
EBDC fungicides are recommended by many ornamental plant disease
specialists. Many ornamental plant diseases are not listed on
the pesticide labels, but specialists recommend using EBDC
fungicides to control such diseases if the crop plant is listed
on the label. Labels for benomyl also are quite broad, but
iprodione, fenarimol, triadimefon, triforine and vinclozolin
labels list only a few ornamentals, usually the higher production
crops such as roses, carnations and chrysanthemums. The broad
label increases the value of EBDC fungicides for these crops;
benomyl's usefulness is limited by potential or actual fungal
resistance.
Quality is often equated with yield in the ornamental
industry. The Agency believes that alternatives to EBDCs usually
control a slightly different or, more often, a smaller spectrum
of fungal pathogens than alternative fungicides. Also,
fungicidal resistance, especially to benzimidazole fungicides,
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limits the availability of effective alternatives. EBDCs, with
their broad spectrum of activity, control many types of fungi,
and are valuable to the ornamental industry. Therefore, there
are not fungicides available which are complete replacements for
the EBDCs in the ornamental industry. If growers were to shift
all EBDC usage to chlorothalonil, due to current differences in
chemical costs, treatment costs would increase by approximately
$450,000 per year. Although the Agency does not have
quantitative data to estimate impacts, it believes that some
yield and quality losses would be likely because chlorothalonil
in addition to other alternative fungicides are not perfect
substitutes for EBDCs and are not registered for the wide
spectrum of ornamental plants. Therefore, benefits could be
significantly higher for this commodity group than the projected
increased treatment costs alone.
b. Turfgrass
Mancozeb and maneb also are registered to control fungal
pathogens of turfgrass. For homeowners and also for persons
growing lawns and turfgrass for non-commercial purposes,
judicious management may result in grass-covered areas which may
grow satisfactorily for years without the application of any
fungicides. For the commercial operator, however, such as one
managing a golf course, who requires a "first rate" appearance of
the turfgrass throughout the year, fungicide use may be essential
and necessary, particularly during certain seasons. It is
desirable for such an operator to have a wide range of turfgrass
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fungicides available for use. The use of numerous fungicides
provides the option of continually rotating between several
fungicides which can adequately control the various disease
problems. Such a rotation helps prevent the development of
fungicide resistance, but the Agency does not have the data
necessary to quantify the potential loss if resistance were to
develop following cancellation of EBDC registrations.
Mancozeb is more frequently used and considered a more
valuable fungicide to turfgrass managers than maneb. Mancozeb is
registered to control 11 of the 27 turfgrass pathogens and has
multi-site mode of action. Consequently, it is used in rotation
with or tank-mixed with benzimidazole fungicides and single-site
type fungicides.
EPA has estimated that cancellation of EBDC fungicide
registrations potentially would increase the cost of golf course
maintenance because EBDC fungicides currently are less expensive
than chlorothalonil by approximately $10 per acre or just over
$2,000 per golf course. Because usage of EBDCs is low, the
overall impacts are expected to be minimal, approximately $14,000
on a nationwide basis. However, over 50 percent of the golf
courses surveyed by the EPA reported resistance to benomyl and
the use of multi-site mode of action alternatives such as EBDCs
and chlorothalonil may be needed to control turfgrass problems on
these golf courses in the future (USEPA, 1988s).
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6. Industrial sites
a. Paper mills
The largest industrial user of process water is the paper
industry. The process water needs biocides to prevent the growth
of filamentous fungi, spore and non-spore forming bacteria,
yeasts and other microorganisms which produce slime that can clog
pipes, screens and filters resulting in spots or breaks in the
roll of paper.
Biocides to control slime forming microorganisms are usually
introduced early in the paper making process either on a
continuous-feed basis or by slug feeding. Those paper mills that
use nabam reportedly use a 50:50 combination product of nabam and
dibam; about 250,000 pounds ai of nabam are used annually (DPRA,
1988d). The predominant biocides are MET (methylenebisthio-
cyanate), DMTT (tetrahyro-3,5-dimethyl-2H-l,3,5-thiadiazine-2-
thione) and isothiazolone while nabam/dibam products are used
infrequently along with quaternary ammonium compounds and DBNPA
(2,2-dibromo-3-nitrilopropionamide). About four percent of the
paper produced using biocides in U.S. comes from mills using
nabam/dibam.
The biocide of choice at a particular mill is largely
dependent on factors unique to that mill. These factors include
the pH of the process water, temperature of the system, and type
of paper being produced, among others. Because biocides do not
perform equivalently in any given system, relative cost
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comparisons were made based on average product prices and
treatment rates for the most common conditions.
If nabam uses were cancelled, it is assumed that one-half of
the nabam/dibam treatments would be replaced with MBT and one-
half with isothiazolone. The reason for splitting the nabam
tonnage between the two biocides is to cover the total pH range
at which nabam/dibam is effective. If nabam were cancelled, the
Agency estimates that the cost to the paper industry for biocides
would decline by $700,000 or less than two percent of the
industry costs for biocides. Therefore, the overall production
costs would decrease for those paper mills currently using nabam.
This outcome is based upon the assumption that there is not a
decline in the efficacy of controlling slime-forming
microorganisms through use of alternative control methods.
b. Water cooling systems
The major types of equipment associated with cooling water
systems are cooling towers and air washers, with the former being
by far more prevalent both in terms of numbers and use of
biocides. The function of a cooling tower is to allow the
maximum loss of waste heat from recirculating waters to the
atmosphere. This waste heat can be from industrial or
institutional applications. Microorganisms grow well in the
warm, well oxygenated environment of cooling towers. The slime
produced by the microorganisms can clog the heat transfer system
reducing water flow and cooling ability as well as causing
corrosion and pitting of metal surfaces. Air washer systems
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control humidity and temperature as well as remove airborne
particulates, aerosols and odors. Air washer systems that are
used primarily for climate control require a minimum of biocides,
but those that remove particulates require biocides. Most
cooling water experts agree that there are adequate replacements
for nabam (DPRA, 1988d). Smaller companies servicing water
cooling systems may have fewer alternatives available than will
larger companies because smaller companies may not have the
capital to keep a wide range of products on hand or have the
facilities to store a large number of products. DBNPA, MET and
isothiazolone are the most likely alternatives. Depending on the
alternative chosen, it is estimated that there would be no
increase in costs to an increase of $2.64 per 1000 gallons of
treated water. The high end of this range represents
approximately a 170 percent increase. Water cooling service
companies would probably choose the least expensive alternatives
which would be either DBNPA or MBT and the impacts of nabam
cancellation are estimated to be minimal (DPRA, 1988d).
c. Sugar mills
Both cane and sugar beet mills use biocides, although the
type of mills used in Hawaii do not use nabam (DPRA, 1988d).
Both cane and beet operations use biocides to prevent the growth
of bacteria which interfere with sugar processing. Nabam/dibam,
Busan™ (a combination of disodium cyanodithioimidocarbonate and
potassium n-methyldithiocarbamate), and DBNPA are registered for
use in sugar mills. Other biocide materials include formaldehyde
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and chlorine dioxide which are listed by the FDA in the group of
chemicals that are generally regarded as safe under Title 21,
Chapter 1, Part 182. However, use of formaldehyde and chlorine
dioxide has reduced over the last few years. A few sugar mills
use heat sterilization as an alternative to chemical biocides.
The nabam/dibam combination is the most frequently used biocide
in sugar mills, using approximately 165,000 to 200,000 pounds of
ai a year. Approximately 50 to 60 percent of all mills use
nabam/dibam as a biocide (DPRA, 1988d). Use of DBNPA is limited
because registration labels state that by-products from mills
using DBNPA cannot be used as animal feed.
Nabam/dibam is the lowest cost treatment, followed by Busan
and then formaldehyde (DPRA, I988d). Formaldehyde is considered
the most effective compound and is often used as a rescue
compound if less expensive materials fail. However, as
formaldehyde costs are high, Busan is assumed to be the only
remaining viable choice. Substitution of Busan for nabam/dibam
is estimated to result in an aggregate increased production cost
of $409,200 to $496,900 which would represent less than a 0.02
percent increase relative to the aggregate value of sugar and
sugar processing by-products. The increased costs is due to the
larger amount of ai needed for Busan treatment compared to
nabam/dibam.
d. Oil well drilling fluids
Nabam is registered for use in three oil well fluid
applications: drilling, secondary/tertiary recovery and
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fracturing. The biocides used in oil well fluids are typically
provided by oil well service companies who determine which
chemicals or combination of chemicals are best in each situation.
Alternatives include acrolein, which is only used in
secondary oil recovery systems; DBNPA, which is used in
fracturing; formaldehyde/paraformaldehyde, which was once among
the most widely used, but whose use has declined recently;
glutaraldehyde, used in all three oil well fluid applications;
isothiazolone, whose usage is growing rapidly, but may not work
well in secondary oil recovery systems; quaternary ammonium
compounds, which are used only in secondary oil recovery systems;
and triazine, which is used primarily in fracturing (DPRA,
1988d). Nabam's effectiveness is unclear. Some experts feel it
is very effective, while others feel that it does not perform as
well as alternative biocides and will use nabam only at a
client's request. For oil well fluid use, there is at least one
alternative that costs less to use than nabam/dibam. This fact,
combined with the fact that nabam/dibam has such a small
percentage (less than five percent) of biocide sales in oil well
fluids, implies that aggregate impacts should be minimal.
e. Metal working coolant
Based on available usage estimates, the Agency believes that
nabam is not currently used as an additive for metal working
coolants; therefore, the Agency would assume it has no benefits
at this site. An alternative chemical, methylene bisthiocyanate,
is being used (DPRA, 1988d).
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B. ANALYSIS OF REBUTTAL COMMENTS
Rebuttal comments submitted to the Agency in response to the
Initiation of Special Review (PD l) issued in July, 1987 were
reviewed and the Agency's responses are provided below. Rebuttal
comments are on file in the EBDC Public Docket.
Testimonial Comments
In response to the EBDC PD 1, the Agency received
approximately 100 responses pertaining to the benefits of EBDC
fungicides. Most of these comments were undocumented
testimonials. Generally, these comments claimed the usefulness
of the EBDCs in controlling diseases on a wide variety of
agricultural crops, cost effectiveness of EBDC fungicides as
compared to alternatives and potential for yield and quality
reduction on many crops if the EBDC registrations were cancelled.
These comments also noted that there has been little or no
significant resistance problems with the EBDCs and that they have
been used in conjunction with fungicides to which fungal
resistance has developed or have the potential for resistance
development.
The Agency did not receive any testimonial benefits comments
on non-agricultural uses of the EBDCs.
Rebuttal Comment
Pennwalt Chemical Corporation submitted a two-part response
to the PD 1. The first submission contained estimates of usage,
efficacy, comparative performance and market parameters and used
to develop estimates of changes in benefits under varying
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regulatory scenarios. The second submission was an analysis of
economic welfare impacts of a maneb cancellation.
Aaencv Response
The Agency used the first submission to refine the Agency's
benefit estimates. The Agency agrees with the approach used in
the second Pennwalt submission to assess the economic impact of
cancellation of these EBDC products. However, the analysis was
dependant on the input data and assumptions made about the effect
that maneb and alternative pesticides have on the production of a
given commodity. The specific data that are used to reflect the
market characterization also are crucial (Arnold, 1988; Frohberg,
1988; Malik et al, 1988). The Agency concludes that the
submission relied on comparative efficacy and product performance
assumptions that were not well documented, as well as estimates
of supply and transmission elasticities that do not appear to be
plausible. Therefore, the specific quantitative results cannot
be accepted as correct on their face value.
Rebuttal Comment
Rohm and Haas Company submitted comments which detailed
estimates of pesticide usage patterns for mancozeb and
alternative fungicides on certain crops, cost comparisons on a
per pound/per acre treatment and per season/per acre basis,
comparative yield and quality effects and economic effects.
Aaencv Response
This information has been incorporated into the Agency's own
site-by-site benefit analysis. The submitted information
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111-68
supports Agency conclusions that mancozeb uses have alternatives
for some but not all uses, and that in some cases substitutions
may involve higher costs and/or reduced yields.
Rebuttal Comment
The BASF and FMC Corporations submitted information on
fungicide usage patterns, the properties of metiram and its
alternatives with respect to diseases controlled, descriptions of
major diseases and their effects, crop production statistics,
State recommendation summaries and relative product performance
of metiram and alternative fungicides for apples and potatoes.
Agency Response
This submission generally summarized information already
available to the Agency and has been used in the benefit
assessment.
Rebuttal Comment
Alco Chemical Corporation and Vinings Industries submitted
benefits information on nabam containing microbiocides for
microorganism control in cooling water systems, pulp and paper
mills, cane and beet sugar mills and petroleum recovery
operations. They concluded that for cooling water systems,
pulp/paper mills and cane/sugar beet mills, nabam products are
more cost-effective (dollars per treated volume of protected
material) than were alternative chemicals. For petroleum
recovery operations, they found alternative chemicals to be more
cost-effective on a comparative basis.
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Agency Response
The Agency's analysis found that on all sites analyzed,
alternatives to nabam were more cost-effective. These
differences can be accounted for by different assumptions on
likely treatment rates, probable alternative chemicals used and
the use of wholesale product prices (Alco and vinings) as opposed
to end-user cost estimates.
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IV. RISK/BENEFIT ANALYSIS AND REGULATORY OPTIONS
A. INTRODUCTION
FIFRA requires the Agency to weigh the risks against the
benefits for each use of a pesticide in order to determine
whether continued registration would cause unreasonable adverse
effects on the environment. In Chapters II and III, the Agency
discussed the risks posed by exposure to the EBDCs and the
benefits estimated to be derived from their registered uses. To
determine whether continued registration of the EBDCs is
appropriate, the Agency has identified a number of regulatory
options, and has evaluated each option for its impacts on both
risks and benefits.
In addition, the Agency has identified registered
alternative pesticides for most uses of the EBDCs. The general
risks of the alternative pesticides have been summarized based on
available data (See Table IV-1).
This section identifies the regulatory options available to
the Agency to reduce the risks from the registered uses of the
EBDCs. In conducting its analysis, the Agency considered the
aggregate risks posed by the EBDCs and ETU, the extent to which
registered uses are being supported by registrants and, where
appropriate, the risks and benefits of individual uses.
B. RISK CONCLUSIONS
Exposure to the EBDCs and ETU can occur through application
of the pesticides to food crops and eating foods containing
residues of EBDCs and ETU. Exposure to EBDCs and ETU can also
occur from application to non-food crops and from industrial
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IV-2
application of these pesticides. The entire U.S. population may
be exposed to EBDC and ETU residues from food, non-food and
industrial uses. These exposures and estimated associated risks
are discussed in Sections II.B (2) and (3) of this document.
1. Carcinogenicity
As discussed in the PD 1 and in Section II.A (1) of this
document, the Agency does not have adequate carcinogenicity
studies for any of the individual EBDCs. Long-term animal
studies (rat and mouse) have been required for each of the EBDCs
through Registration Standards and/or Data Call-ins. The Agency
has several positive long-term animal carcinogenicity studies for
the EBDC contaminant, degrac .re and metabolite, ETU. Based upon
the data from these studies, the Agency has concluded that ETU
meets the criteria of a Group B2 carcinogen (probable human
carcinogen). ETU induced an increased incidence of thyroid
follicular cell adenomas and adenocarcinomas in Fisher 344 (NTP,
1989) and Charles River CD rats (Ulland, 1972 and Graham, 1975)
and an increase of hepatomas in three strains of mice (Innes,
1969 and NTP, 1989). Using data from a portion of the NTP mouse
study, the Agency calculated a preliminary new Q,* (potency
factor). This carcinogen potency factor was derived from a
linearized multistage risk model and the estimates of exposure
were then used to estimate the 95th percentile upper bound,
lifetime probability of excess carcinogenic risk to humans. The
EBDCs and ETU have been tested for mutagenicity in several assay
systems. Results of the available studies were both positive and
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IV-3
negative. Evidence of mutagenicity from these studies provided
supportive evidence of the carcinogenic effect. The specific
risk estimates for carcinogenicity were presented in Sections
II.B (3)(a)(1), (b)(1), and (c)(1) of this document and include
both dietary risks and mixer/loader/applicator risks from food,
non-food and industrial uses of the EBDCs.
2. Developmental Toxicity
Section II.A(2) presented the Agency's concerns regarding
developmental/fetotoxic effects of ETU and the EBDCs. Available
data (Khera, 1973) demonstrate ETU's potential to cause these
effects in rats. The NOAEL (No-Observable-Adverse-Effeet Level)
is equal to or less than 5 mg/kg/day. Mancozeb has also been
shown to be developmentally toxic in rats. The NOEL is 128
mg/kg/day. Additionally, rabbits dosed with Aquatreat DN-30 (a
formulated product containing 30% nabam) showed developmental
effects at the low dose tested of 3.0 mg/kg/day.
3. Thyroid Effects
Section II.A (3) presented information on thyroid effects of
ETU and the EBDCs. Studies with ETU and mancozeb have
demonstrated effects in rats and mice (thyroid hyperplasia). The
LEL (Lowest-Observable-Effect Level) from the two year rat study
is less than 5 ppm of ETU.
4. Risks from Alternatives
The chemical alternatives to the EBDCs are listed in Table
IV-l of this chapter along with characterization of the available
information on their carcinogenicity, mutagenicity, and
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FUNGICIDE
IV-4
Table IV-1
Toxicity and Status of Major Alternatives to the EBDCs
TOXICITY/ a
CARCINO
MUTA
REPRO
TERAT
STATUS/1
Anilazine
(Dyrene)
Triadimefon ?
(Bayleton)
Benomyl qC
(Benlate)
Captan B2
Coppers 2
Chlorothalonil B2
Dichloran
Dodine
Ferbam
Iprodione
Metalaxyl E
(Ridomil)
Propiconazole qC/D1
(Tilt)
Sulfur
Thiram
No RS
v-3 ?
RS 12/83
No RS;
SR 82; SRR 87
SR; 2/89
RS 86
SRR 9/88
RS 83
RS 88
SRR 3/88
RS 1/83
RS 7/84
V + = positive finding
- = negative finding
" = no data or additional data required
? = don't know, e.g. dose not high enough, or
regulatory decision made not to ask for more
data
b/ RS = Registration standard
SR = Special Review
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IV-5
SRR = Second Round Review in the Registration Standard Process
B2 = Probable human carcinogen
C = Possible human carcinogen
qC = Possible human carcinogen; risk should be quantified
D = Not classifiable as to human carcinogenicity
E = Evidence of non-carcinogenicity for humans
1 = OPP Peer Review said (q) quantifiable C; the SAP said it was a D.
2 = Data "not available" and required only for HP's used to formulate
products for indoor use only (Ref. RS Copper Sulfate 1986; RS Group II
Copper Compounds 1987).
3 = only one study was (+); " but five were (-).
4 = one or more studies were +; ' there is no additional data being
requested.
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IV-6
reproductive and developmental effects. For several of these
chemicals, the data base is incomplete which makes it difficult
to judge the relative toxicity of the alternatives as compared to
the EBDCs. Missing data will be obtained for these chemicals
through the Agency's reregistration process.
The major alternatives to the EBDCs (excluding nabam) are
captan and chlorothalonil. Benomyl is also used on many of the
same sites. Captan and chlorothalonil are Group B2 carcinogens
and benomyl is a Group C(q) carcinogen (Table IV-1). The Agency
has recently completed a Final Determination PD 4 for captan and
found it not to cause developmental, mutagenic or reproductive
risks of concern at this time. Risks from dietary exposure from
captan are estimated at 10"6. Chlorothalonil was recently
evaluated through EPA's reregistration process. Carcinogenic
dietary risks are estimated to be 10"& from chlorothalonil and
10"6 from its contaminant hexachlorobenzene (HCB), which is also
a B2 carcinogen. It was determined that the risks from
chlorothalonil and HCB did not meet the criteria for initiating a
Special Review at that time. In July, 1987, the Agency issued a
Registration Standard for benomyl. Although it was found to be a
carcinogen, and a developmental and reproductive toxicant, the
Agency at that time determined those risks to be acceptable.
Since that time, the Agency has reconsidered the carcinogenicity
classification of benomyl and has concluded that, in addition to
remaining a possible human (Group C) carcinogen, its carcinogenic
risks should be quantified. The Agency is currently quantifying
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IV-7
those risks. If the risk estimates indicate a potential risk of
concern, the Agency will consider further regulatory action.
As part of the Agency's comparative risk/benefit assessment
of major fungicides, dietary risks for the five EBDC chemicals,
captan and chlorothalonil were compared based on hypothetical
cancellation scenarios. Even though benomyl's risks are now
being quantified, it would not be appropriate to consider benomyl
an alternative to the EBDCs, captan, or chlorothalonil, because
benomyl tends to be used with each of the other three fungicides,
rather than in lieu of them, due to benomyl resistance problems.
(See Fungicide Review Strategy for Captan, Chlorothalonil and the
EBDCs, 1988.) The Agency estimated potential shifts in usage and
dietary risks if one or more of the three fungicides {captan,
chlorothalonil and the EBDCs) were cancelled. No cancellation
scenario caused greater than one-half an order of magnitude risk
increase to any of the three fungicides. It was concluded that
cancellation of one or two of the three fungicides would not
cause a significant difference in the risk/benefit conclusion for
the remaining fungicide(s).
C. BENEFIT CONCLUSIONS
Based on available data, the benefits of the EBDCs were
assessed for all viable regulatory options including the
cancellation of some or all registered uses of EBDC fungicides
and other measures to reduce the risks from EBDCs. As explained
in Section III of this document, if the EBDC registrations on all
food crops were cancelled, estimated direct losses to growers
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IV-8
(producer impacts) would be approximately $46 to $75 million and
projected loss to society, or efficiency impacts, at least in the
short term, would range from approximately $90 to $305 million.
Efficiency impacts are concentrated on three crops: lettuce,
peppers, and celery. A major portion of the projected yield loss
impact would be on apples, onions, wheat, and spinach because of
the lack of viable registered alternatives for these crops. Over
the long term, impacts in yield and consumer prices could be
reduced if more acreage were planted to compensate for the
losses, more effective alternatives were registered, non-chemical
alternatives were developed, etc.
Registered alternatives exist for almost all uses of the
EBDCs, but in most cases the alternatives are more expensive.
However, for some food crops, projected increased production
costs are offset by estimated increases in yields.
The estimated impact of cancellation on non-food uses is $5
to $15 million of producer/user impacts, chiefly for commercial
ornamentals. For certain industrial sites, nabam is more
expensive to use than certain alternatives and costs to
industrial users could decrease with a shift to alternative
biocides.
D. DEVELOPMENT OF REGULATORY OPTIONS
There are four basic options for regulating all pesticides:
Option 1 - Continuation of Registration Without Changes
Option 2 - Continuation of Registration with Modifications
to the Terms and Conditions of Registration
Option 3 - Partial Cancellation
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IV-9
Option 4 - cancellation of All Registrations
Option 1, Continuation of Registration without Change and
Option 4, Cancellation of All Registrations, are at opposite ends
of the risk/benefit spectrum. Adoption of Option 1 would be
appropriate when the Agency has concluded that the level of risk
is acceptable in light of the pesticide's benefits and that
further risk reduction measures are not necessary to assure that
the use of the pesticide meets the standard for continued
registration. Adoption of Options 3 or 4, Partial or Total
Cancellation, would be appropriate when the Agency has concluded
that the risks outweigh the benefits, and that these risks cannot
be mitigated to an acceptable level, in light of the benefits, by
any other measure short of cancellation. Cancellation may affect
all uses of a compound, only specific uses or specific
formulations, or specific application methods. Option 2 is
appropriate when the risks of a pesticide use can be reduced to a
level where the benefits of use outweigh the risks. This risk
reduction is accomplished by modifying the terms and conditions
of the pesticide's registration. These modifications, which are
expressed through the pesticide's labeling, are, for the most
part, changes in the way the pesticide is used or the amount of
the pesticide that may be used. These changes are designed to
reduce exposure to the pesticide and thereby reduce or eliminate
the risk from the pesticide. Risk reduction measures were
considered and evaluated for their potential effectiveness and
feasibility.
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IV-10
1. Measures to Reduce Dietary Exposure
Amounts of pesticide residues on food crops are affected by
such factors as quantity of active ingredient used, the solvents
used for dilution, mode and schedule of application, preharvest
interval, and soil and weather conditions. Several measures were
considered as means by which potential dietary exposure to the
EBDCs and ETU through residues on food crops might be reduced.
a. Preharvest interval
The preharvest interval is the number of days that must
elapse between the final application of a pesticide and actual
harvest of the crop. Lengthening this interval provides more
time for dissipation of residues before crops are harvested and
ultimately consumed. Additionally, lengthening the preharvest
interval can serve as a means of lowering tolerances. The
practicality of extending the preharvest interval for the EBDCs
cannot be evaluated at this time due to lack of efficacy data,
but the Agency believes that extending the preharvest interval
could be equivalent to cancellation on some crops because the
crop could be unprotected from disease during the extended
preharvest interval.
b. Modify Application Practices
Three modified application practices were considered to
reduce EBDC and ETU exposure and risk through reduction in crop
residues: 1) reducing the amount of active ingredient in the
formulations, 2) reducing the amount of formulation applied per
season and 3) reducing the amount of active ingredient applied
-------
IV-11
per acre. Use rates, frequency and the number of applications
per season are based on field evaluations carried out under
various degrees of disease pressure, varying environmental
conditions and in diverse geographic regions. The limited field
trials available comparing application rates of EBDCs were
reviewed by the Agency. These trials indicate that under the
conditions tested, the higher rates tested tend to be more
efficacious and for the very few trials that included a range of
application rates and yield data, the higher rates seemed to
provide higher yields. Fewer applications and lower rates can be
used in some instances where predictive management models are
available which take into account local climatic and disease
conditions. However, such models are currently available for a
small number of crops (Pelletier, 1989). Therefore, based on the
information available, the Agency believes that mandated
modification in application practices could potentially adversely
impact the efficacy of EBDCs as plant control agents and could,
for some crops, be equivalent to cancellation in terms of
potential economic impact.
2. Measures to Reduce Exposure to Applicators,
Mixer/Loaders and Fieldworkers
The potential risks to persons mixing and loading EBDC
formulations, applying the pesticide to crops and working in the
fields treated with the pesticides were estimated and are
summarized in Table 11-19 and 11-20. Specific risk reduction
measures were considered by the Agency:
-------
IV-12
a. Protective Clothing
Dermal and inhalation exposure to the EBDCs and ETU can
occur when mixing, loading, maintaining application equipment,
during application and at the time field workers enter treated
fields to cultivate, apply other pesticides and harvest.
The Agency has evaluated the level of risk reduction gained
and the costs of requiring protective clothing for all
agricultural workers using EBDC fungicides. Protective clothing,
comprised of coveralls worn over a long-sleeved shirt and long
pants, chemical-resistant gloves, shoes, socks, goggles or a face
shield, and a chemical-resistant apron is expected to reduce
dermal exposure to mixer/loaders by 40 percent and to applicators
by 65 percent. The coveralls are not intended to be chemical-
resistant. Since inhalation exposure is estimated to be 1-2
percent of the total exposure, and therefore, considered
negligible, the need for respirators was not considered.
The costs of this protective clothing for workers (mixers,
loaders, and applicators) applying maneb, mancozeb, and metiram
to agricultural crops are estimated to be $25 to $37 per worker
for approximately 30,000 to 40,000 workers or $0.75 to $1.5
million in total (Dumas, 1989). Costs for nabam and zineb are
not included because nabam registrants have requested voluntary
cancellation of all agricultural food uses of nabam and the sole
technical producer of zineb has requested voluntary cancellation.
However, the Agency believes that most persons applying EBDC
fungicides probably use other pesticides which require the use of
-------
IV-13
similar or even more restrictive protective equipment.
Therefore, the Agency believes that the actual cost of requiring
protective clothing of all agricultural workers applying EBDCs
would be considerably lower than $1.5 million.
b. Reentry Intervals
Establishing a reentry interval would allow time for further
breakdown of EBDC residues into ETU and ETU into metabolites or
compounds of less concern. EBDCs meet both the chronic toxicity
and exposure criteria specified in 40 CFR 158.140 for reentry
data. The Agency considered requiring a reentry interval for all
agricultural workers using EBDC fungicides. Presently, the
Registration Standards for maneb, mancozeb, metiram and nabam
specify an interim 24-hour reentry interval be placed on labels
of all maneb, mancozeb, metiram and nabam end-use products
registered for agricultural use. This interim level will remain
in effect until dislodgeable foliar residue data required in the
Registration Standards and in the March 1989 EBDC Data Call In
are submitted, reviewed, and the Agency announces any change in
this reentry interval. These data are due to EPA in July 1990.
Since the Agency does not currently have data on deterioration of
the EBDCs or ETU over time, it has no additional basis on which
to propose a product specific reentry interval other than the
interim reentry interval previously discussed.
The Agency has little data available on the costs imposed on
agriculture from requiring a reentry interval for agriculture
workers. However, the Agency believes that there would be little
-------
IV-14
if any impact from a 24-hour reentry interval because workers
could reenter a treated area within 24-hours if they wore the
protective clothing required for applicators.
3. Measures to Reduce Industrial Worker Exposure
The nabam Registration Standard specified protective
clothing requirements of long sleeved shirts, long pants,
chemical-resistant gloves, shoes, socks and goggles or a face
shield while mixing, loading or applying as well as a chemical-
resistant apron when mixing and loading. Although low MOSs/MOEs
(Margins of Safety/Margins of Exposure) for thyroid effects were
calculated for nabam's use in sugar and paper mills, they were
calculated based on surrogate agricultural data which are
believed to yield higher exposure estimates. Because the
surrogate exposure data may overestimate exposure, the Agency
believes that once nabam-specific exposure data are submitted
(due to be submitted in March, 1990), all thyroid MOSs/MOEs for
nabam may increase above 100.
E. RISK/BENEFIT ANALYSIS OF REGULATORY OPTIONS
OPTION 1 - Continuation of Registration
Without Changes
If the registrations for mancozeb, maneb, metiram and nabam
for use on food crops, non-food crops and industrial sites were
continued without restriction, the estimated total upper-bound
ETU dietary risk would be 10"* with cumulative forgone benefits
of $46 to $75 million in producer impacts and $90 to $305 million
in efficiency impacts. This risk would be higher if uses of
zineb also were allowed to continue. The total risk was
-------
IV-15
estimated by multiplying the estimated exposure by a carcinogenic
potency factor, the C^*. Exposure was estimated using
anticipated residue data, percent of crop treated data, and food
consumption data from the USDA 1977-78 Nationwide Food
Consumption Survey.
Also, there would be low MOS/MOEs (below 100) for thyroid
and developmental effects and/or high cancer risks for
mixer/loaders and applicators using maneb on grapes and
commercial ornamentals, and on homeowner turf, fruit trees,
vegetables and ornamentals? mancozeb on homeowner turf and fruit
trees; and nabam in sugar and paper mills. Benefits are low for
these uses because of the availability of alternatives.
OPTION 2 - Continuation of Registrations with Modifications
to the Terms and Conditions of Registration.
Because of the lack of data, the Agency does not know
whether amending the terms and conditions of registration by
extending pre-harvest intervals or modifying application rates or
practices would reduce the total dietary risk to a significant
extent. The Agency believes that such modifications possibly may
reduce the versatility and efficacy of EBDC products and thereby
reduce their potential benefits. The March 1989 Data Call-in
Notice required use information on the EBDCs which was submitted
in August, 1989. Information on the percent of crop treated was
used along with other available data in conducting the analyses
used for the preliminary determination; most of the submitted
data on comparative efficacy previously were available to the
Agency, but any new information will be included in the final
-------
IV-16
decision. This information and any other available information
will be used to further refine the risk estimates for the
Agency's Final Determination PD 4. Users and other groups are
also encouraged to submit data demonstrating that application
rate, frequency or other exposure variables can be modified to
reduce overall exposure and still retain the efficacy of the
products.
When estimating exposure to mixer/loader/applicators using
EBDCs on agricultural sites, the Agency took into consideration
protective clothing comprised of coveralls worn over a shirt and
pants, chemical-resistant gloves, shoes, socks, goggles or a face
shield for applying plus a chemical-resistant apron when mixing
and/or loading EBDC pesticides. With incorporation of these
additional protective clothing requirements, a few maneb
MOSs/MOEs remained under 100: grapes and commercial ornamentals.
The estimated carcinogenic risk to mixer/loader/ applicators from
the risk of maneb products used on commercial ornamentals is
10"3. No additional protective clothing or equipment appear
practical to reduce these exposures further.
The Agency finds it impractical to enforce a requirement for
protective clothing for homeowner uses as the Agency believes
that homeowners are not likely to go to the added expense of
buying, for example, gloves and goggles or a face shield
considering the small amount of EBDC products used on home
gardens and turf. MOS/MOEs for homeowners applying maneb on turf
are below 100. Estimated carcinogenic risks to homeowners using
-------
IV-17
maneb are greater than Id"6 for all uses; estimated risks to
homeowners using mancozeb are greater than 10"6 for turf and
fruit tree uses.
OSHA regulations, 29 CFR section 1910.132, already require
industrial workers to use protective clothing and protective
clothing requirements specified in the nabam Registration
Standard are on nabam labels. MOS/MOEs for workers using nabam
in sugar and paper mills are estimated to remain below 100 even
when protective clothing is used. However, these estimates are
based on exposure estimates which may need some refinement. The
Agency's March 1989 EBDC Data Call-in Notice will provide nabam
dermal exposure data for oil well drilling fluids and paper and
sugar mills. These data are due to be received in March, 1990.
To the extent that these data are available, they will be used to
further refine the risk estimates for the Agency's Final
Determination PD 4.
The interim 24-hour reentry interval for agricultural
workers which is specified in the Registration Standards for
maneb, mancozeb, metiram and nabam should reduce exposure of
agricultural workers to EBDCs and ETU without imposing
significant costs to the agricultural industry. Workers in
greenhouses or field situations can reenter the treated area if
they wear clothing specified for applicators. EBDC labels for
products used on golf courses state that workers can reenter the
treated area after the spray has dried. The Agency expects to
receive dislodgeable foliar residue data in July 1990 which
-------
IV-18
should allow the Agency to fully evaluate this risk reduction
measure and determine whether any refinements are necessary.
OPTION 3 - Partial Cancellation
This option would propose cancellation of certain food and
non-food uses. The goal of the option would be to reduce
aggregate risks from EBDCs to a level that provides an
appropriate overall balance of risks and benefits. In evaluating
which uses should be cancelled, the Agency initially focussed on
those uses which registrants seem unwilling to support. At this
time, no registrant of zineb has indicated an interest in
supplying the outstanding data for this chemical. All zineb uses
currently are suspended (and have been for some time) and the
only technical registrant has requested that the Agency cancel
its registrations. Given the apparent lack of support for zineb,
which the Agency believes is evidence of a lack of benefits
provided by zineb, zineb uses were deemed least deserving of
retention. Thus, under this option, the Agency would propose to
cancel all zineb uses.
The Agency next turned to an examination of the 55
registered uses of maneb, mancozeb, and metiram. As noted
earlier, the major technical registrants of mancozeb, maneb and
metiram, recently requested that the Agency delete 42 of the 55
uses from their registrations. Maneb would be registered for use
on almonds, bananas, potatoes, sugar beets and sweet corn;
mancozeb would be registered for use on asparagus, bananas,
cranberries, figs (caprifig only), grapes, onions, peanuts,
-------
IV-19
potatoes, sugar beets, sweet corn, tomatoes and wheat; and
metiram would be registered for use on potatoes. The
registrants' action would decrease estimated upper-bound,
carcinogenic risks from 4 x 10~4 to 2 x 10"5. This action
effectively places these 42 uses in a similar situation to the
zineb uses—uses which appear to have been dropped by industry
while technically remaining on the registrations of various
formulators—and thus, under this option, these 42 uses would be
proposed for cancellation.
Therefore, following the registrants' requested deletion of
42 uses, the Agency's analysis focussed on the risks and benefits
of the thirteen crops retained by the registrants. These
thirteen crops have an estimated upper-bound, cumulative excess
lifetime risk of 2 x 10~5 and a cumulative benefit of $14 to $27
million in producer impacts. The Agency considered a risk-
benefit balancing of each crop to determine whether the estimated
dietary risk is reasonable. Using this analysis, EPA identified
three crops (potatoes, tomatoes and bananas) with an unfavorable
risk-benefit balance and accordingly, under this option, EPA
would propose to cancel these three crops. This action would
reduce the estimated lifetime cancer risk to 3 x Id"6 and would
retain the maximum amount of benefits. Table IV-2 summarizes the
crops which would be proposed for cancellation and retention
under an option which assumed only the 13 registrant-retained
crops remain registered.
-------
IV-20
Table IV-2
ESTIMATED RISKS AND BENEFITS OF CROPS WHICH WOULD BE
PROPOSED FOR CANCELLATION AND RETENTION
A. 13 Crops Proposed to be Retained by Major EBDC Registrants
Prooosed for Retention by EPA
Food crop
Almonds
Asparagus
Caprifigs
Corn, sweet
Cranberry
Grapes
Onions
Peanuts
Sugar beet
Wheat
TOTAL
1
Estimated Excess
Carcin. Risk
7 x 10"9
2 x 10
0
Benefits
»-9
3 x 10
-7
5 x 10
9 x 10
5 x 10
2 x 10
1 x 10
-7
-7
-7
-8
-6
1 x 10
-7
3 X 10
-6
Not enough data to quantify;
potential impacts
Not enough data to quantify;
potential impacts
Not enough data to quantify;
potential impacts
$2.1 to $2.5 million producer
impacts
$0.1 million producer impacts
$1 to $3 million producer
impacts
$6.5 million producer impacts
$2.4 million producer impacts
Not enough data to quantify;
potential impacts
$1.6 to $11.7 million producer
impacts
$13 TO $26 million in producer
impacts
Proposed for Cancellation by EPA
Banana 1 x 10"6
Potatoes
Tomato
2 x 10
2 x 10
$0.3 million producer impacts
in U.S.
$0.4 million producer impacts
$0.1 million producer impacts
1 Carcinogenic risk
-------
IV-21
Table IV-2 (Cont.)
ESTIMATED RISKS AND BENEFITS OF CROPS WHICH WOULD BE
PROPOSED FOR CANCELLATION AND RETENTION
B. Crops Proposed to be Deleted from Registrations by Major EBDC
Registrants which also would be cancelled under this option
Food Crop
Apples
Apricot
Barley
Beans
Beans, Lima
Broccoli
Brussels
sprouts
Cabbage
Cantaloupe
Casaba
melons
Crenshaw
melons
Carrot
Cauliflower
Celery
Collards
Corn, field
Cotton
Crabapple
& quince
Cucumbers
Eggplant
Endive
Fennel
Honeydew
melons
Estimated Excess
Carcin. risk
1 x 10"
7 x 10
-6
3 x 10
•7
3 x 10
-5
2 X 10
1 X 10
4 X 10
1 X 10
3 X 10
6 X 10
-6
-5
-7
-6
-7
-9
x 10
-10
2 X 10"
3 X 10
2 X 10"
-7
1 X 10"
7 X 10
-8
6 x 10
-8
6 x 10
-7
9 x 10
-7
3 X 10
-8
3 x 10
1 X 10
-8
-9
1 X 10
-7
Benefits
$0.3-$12.3 million producer
impacts
Not enough data to quantify;
minimal impacts expected
$0.3 to $2.1 million producer
impacts
$1.9 to $ 2.1 million producer
impacts
$0.7 million producer impacts
No impact expected
No impact expected
No impact expected
$0.3 million producer impacts
Not enough data to quantify;
impacts expected
Not enough data to quantify;
impacts expected
$0.13 million producer impacts
No impact expected
$1.3 to 3.4 million efficiency
impacts
Not enough data to quantify;
impacts expected
Not enough data to quantify;
no impact expected
Not enough data to quantify;
no impact expected
Not enough data to quantify;
no impacts expected
$4.0 to $4.9 million producer
impacts
Not enough data to quantify;
potential impacts
Not enough data to quantify;
potential impacts
Not enough data to quantify;
no impacts expected
Not enough data to quantify;
impacts expected
-------
IV-22
Table IV-2 (Cont.)
ESTIMATED RISKS AND BENEFITS OF CROPS WHICH WOULD BE
PROPOSED FOR CANCELLATION AND RETENTION
Food Crop
Lettuce
Kale
Kohlrabi
Mustard
greens
Nectarines
Oats
Papaya
Peaches
Pear
Pecan
Peppers
Pineapple
Pumpkin
Rhubarb
Rye
Spinach
Squash
Turnip
Watermelon
TOTAL
Estimated Excess
Carcin. risk
3 x 10
-6
7 X 10
1 X 10"
-7
2 x 10
1 X 10"
6 X 10"
-5
2 X 10
-7
4 X 10
2 X 10
-5
-6
4 X 10
-10
3 X 10
-6
<1 X 10
1 X 10
-10
7 X 10
4 X 10
2 X 10
3 X 10
2 X 10
2 X 10
3 X 10
-7
-9
-5
-7
-5
•6
Benefits
$40 to $204 million efficiency
impacts
Not enough data to quantify;
impacts expected
Not enough data to quantify;
impacts expected
Not enough data to quantify;
impacts expected
Negligible producer impacts
$0.1 to $0.5 million producer
impacts for oats & rye
Not enough data to quantify;
no impacts expected
<$15,000 producer impacts
Not enough data to quantify;
minimal impacts expected
Not enough data to quantify;
minimal impacts expected
$49 to $98 million in
efficiency impacts
Not enough data to quantify;
potential impacts
$77,000 producer impacts
Not enough data to quantify;
no impacts expected
$0.1 to $0.5 million producer
impact for oats & rye combined
$19 million producer impacts
$3.4 to $4.8 million producer
impacts
Not enough data to quantify;
impacts expected
$0.8 million producer impacts
$32 to $58 million in producer
impacts and $90 to $305
million in efficiency impacts
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IV-23
In summary, under this option the Agency would propose to
cancel all uses of zineb and 45 uses of maneb, mancozeb and
metiram reducing estimated lifetime cancer risk to 3 x 10"6 and
retaining benefits of $13 to $26 million.
If the maneb, mancozeb and metiram registrants had not
deleted 42 of 55 registered uses, the Agency would have pursued
regulatory action based on a risk-benefit analysis of the 55 crop
universe. While EPA believes it is appropriate to consider only
the 13 remaining uses in its proposed action, the Agency is
presenting its 55 crop analysis to (1) provide a full description
of the risks and benefits of the EBDCs and (2) enable all
affected parties to have the best information possible for
purposes of commenting on the Agency's analysis and proposed
action.
In assessing the risks and benefits of the 55 crops, ten
crops yielded an estimated upper-bound, cumulative lifetime risk
of 1 x 10"7 and benefits of $2.4 million. The crops are:
almonds, asparagus, casaba melons, crenshaw melons, eggplant,
endive, figs, peanuts, pineapple and pumpkin. Since these crops
have some benefit and very low risk, they would have been
proposed for retention if the registrants had taken no action.
The remaining crops were then ranked in order of lowest
risk/highest benefit or cost effectiveness ratios (See Table
IV-3). The two crops with the highest benefits, lettuce and
peppers, each have an estimated risk of 3 x 10"6. The benefits
from lettuce are $40 to $204 million in efficiency impacts and
-------
IV-24
Table IV-3
Cost-Effectiveness Estimates for EBDC Cancellation
Site Incidents1
Avoided
Peanuts
Lettuce
Peppers
Onions
Wheat
Sweet corn
Cucumbers
Grapes
Other cucurbits
Spinach
Other small grains
Bananas
Potatoes
Cranberries
Celery
Apples
Beans
Tomatoes
Carrots
Leafy greens
0.1
10.3
11.7
1.6
2.9
0.9
3.2
3.1
9.4
51.4
24.0
4.1
5.8
1.8
61.7
342.9
85.7
54.9
65.1
163.6
Benefit2
Mil
2.4
40.0
49.0
6.5
1.6
1.9
4.0
2.0
4.5
19.0
0.4
0.3
0.4
0.1
1.3
12.0
2.0
0.1
0.1
No
. Dol.
2.4
- 205.0
- 98.0
6.5
- 11.7
1.9
5.0
2.0
5.5
- 19.0
2.6
0.3
0.4
0.1
3.4
- 12.0
2.0
0.1
0.1
estimate
C-E3
$Mil/Incident
43.75 -
3.89 -
4.20 -
4.03 -
0.55 -
2.05 -
1.27 -
0.65 -
0.48 -
0.37 -
0.02 -
0.07 -
0.07 -
0.06 -
0.02 -
0.04 -
0.02 -
0.00 -
0.00 -
43.75
19.93
8.41
4.03
4.01
2.05
1.59
0.65
0.59
0.37
0.11
0.08
0.07
0.06
0.06
0.04
0.02
0.00
0.00
Estimated annual cancer cases from consumption of the
particular crop. Based on estimated dietary risk for U.S.
population using assumptions described in Chapter II.
2 Estimated annual benefits for the particular crop using
assumptions described in Chapter III.
3 Loss in economic benefits per case avoided.
-------
IV-2 5
the estimated benefits from peppers are $49 to $98 million
inefficiency impacts. However, if both crops were retained, the
cumulative dietary risk from the two crops alone is 6 x 10"6. Of
the two, lettuce has the higher estimated benefit. The other two
crops which have a favorable risk/benefit ratio are onions (with
an estimated excess risk of 5 x 10"7 and $6.5 million in producer
impacts) and cucumbers (with an estimated risk of 9 x 10" and $4
to $4.9 million in producer impacts). The cumulative estimated
upper-bound lifetime risk from the ten negligible risk crops as
well as lettuce, onions and cucumbers is 5 x 10"6. The
cumulative estimated benefits are $13 to $14 million in producer
impacts and $40 to $204 in efficiency impacts.
If peppers were included, the total estimated risk would be
8 x 10"6. Total estimated benefits would be $13 to $14 million
in producer impacts and $89 to $302 million in efficiency
impacts. Even though the individual benefits for peppers were
high, the Agency was concerned that the risk contribution of
pepper to the aggregate dietary risk was excessive.
The Agency also considered retaining spinach since the
benefits are high with an estimated 70 percent of the winter
spinach crop potentially affected and economic impacts projected
to be $19 million. However, the Agency decided that although
benefits appeared to be high for this relatively minor crop, the
estimated ETU dietary risk of 10"5 for spinach outweighed the
benefits.
-------
IV-2 6
Forty-two food crops or crop groupings would have been
proposed for cancellation in the absence of the registrants'
action. The following Table IV-4 summarizes the estimated
dietary risks and benefits of the food crops which would be
proposed for cancellation.
For all crops proposed for cancellation and particularly for
peppers and spinach, the Agency requests comments on its
risk/benefit analysis. In addition, EPA seeks information or
whether changes in use practices could reduce risk to an
acceptable level.
-------
IV-27
Table IV-4
ESTIMATED RISKS AND BENEFITS OF EBDC CROPS WHICH WOULD HAVE BEEN
PROPOSED FOR CANCELLATION IN THE ABSENCE OF REGISTRANT ACTION
Food Crop
Apples
Apricot
Banana
Barley
Beans
Beans, Lima
Broccoli
Brussels
sprouts
Cabbage
Cantaloupe
Carrot
Cauliflower
Celery
Collards
Corn, field
Corn, sweet
Cotton
Crabapple
& quince
Cranberry
Fennel
Grapes
Honeydew
melons
Kale
Kohlrabi
Mustard
greens
Nectarines
Estimated excess
Carcin. risk
1 x 10"
7 x 10
1 x 10
-6
-6
3 X 10
-7
3 X 10
2 X 10
1 X 10
4 X 10
1 X 10"
3 X 10"
2 X 10"
3 X 10"
2 X 10
-5
-5
-7
-5
1 X 10
-5
7 X 10
-8
3 X 10
-7
6 X 10
-8
6 x 10
-7
5 X 10
1 X 10
-7
-9
9 X 10
-7
1 X 10
7 X 10"
-7
1 X 10
-8
2 X 10
-5
1 X 10
-6
Benefits
$0.3-$12.3 million producer
impacts
Not enough data to quantify;
minimal impacts expected
$0.3 million producer impacts
in U.S.
$0.3 to $2.1 million producer
impacts
$1.9 to $ 2.1 million producer
impacts
$0.7 million producer impacts
No impact expected
No impact expected
No impact expected
$0.3 million producer impacts
$0.13 million producer impacts
No impact expected
$1.3 to 3.4 million efficiency
impacts
Not enough data to quantify;
impacts expected
Not enough data to quantify;
no impact expected
$2.1 to $2.5 million producer
impacts
Not enough data to quantify;
no impact expected
Not enough data to quantify;
no impacts expected
$0.1 million producer impacts
Not enough data to quantify;
no impacts expected
$1 to $3 million producer
impacts
Not enough data to quantify;
impacts expected
Not enough data to quantify;
impacts expected
Not enough data to quantify;
impacts expected
Not enough data to quantify;
impacts expected
Negligible producer impacts
-------
IV-2 8
Table IV-4 (Cont.)
ESTIMATED RISKS AND BENEFITS OF EBDC CROPS WHICH WOULD HAVE BEEN
PROPOSED FOR CANCELLATION IN THE ABSENCE OF REGISTRANT ACTION
Food Crop
Oats
Papaya
Peaches
Pear
Pecan
Peppers
Potatoes
Rhubarb
Rye
Spinach
Squash
Sugar beet
Tomato
Turnip
Watermelon
Wheat
TOTAL
Estimated Excess
Carcin. risk
6 x 10
-a
2 x 10
-7
4 X 10
2 X 10
-5
-6
4 X 10
-10
3 x 10
-6
2 x 10
7 X 10
-6
-7
4 x 10
-9
2 x 10
3 x 10
-5
-7
1 X 10
-6
2 X 10
2 x 10"
2 x 10"
1 X 10
-5
-7
3 X 10"
Benefits
$0.1 to $0.5 million producer
impacts for oats & rye
Not enough data to quantify;
no impacts expected
<$15,000 producer impacts
Not enough data to quantify;
minimal impacts expected
Not enough data to quantify;
minimal impacts expected
$49 to $98 million in
efficiency impacts
$0.4 million producer impacts
Not enough data to quantify;
no impacts expected
$0.1 to $0.5 million producer
impact for oats & rye combined
$19 million producer impacts
$3.4 to $4.8 million producer
impacts
Not enough data to quantify;
potential impacts
$0.1 million producer impacts
Not enough data to quantify;
impacts expected
$0.8 million producer impacts
$1.6 to $11.7 million
producer impacts
$32 to $58 million in producer
impacts and $90 to $305
million in efficiency impacts
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IV-29
The following Table IV-5 summarizes the estimated dietary
risks and benefits of the food crops which would have been
proposed for retention if the registrants had not taken no
action.
Table IV-5
ESTIMATED RISKS AND BENEFITS OF EBDC CROPS WHICH WOULD HAVE BEEN
PROPOSED FOR RETENTION IN THE ABSENCE OF REGISTRANT ACTION
Estimated Excess
Food crop
Almonds
Asparagus
Caprif igs
Casaba
melons
Crenshaw
melons
Cucumbers
Eggplant
Endive
Lettuce
Onions
Peanuts
Pineapple
Pumpkin
TOTAL
Carcin. Risk
7 x 10~9
2 X 10~9
0 2
6 X 10~9
<1 X 10'10
9 X 10"7
3 X 10"8
3 X 10"8
3 X 10'6
5 x 10"7
2 X 10'8
<1 X 10'10
1 x 10'8
5 x 10"6
Benefits
Not enough data to quantify;
potential impacts
Not enough data to quantify;
potential impacts
Not enough data to quantify;
potential impacts
Not enough data to quantify;
impacts expected
Not enough data to quantify;
impacts expected
$4.0 to $4.9 million producer
impacts
Not enough data to quantify;
potential impacts
Not enough data to quantify;
potential impacts
$40 to $204 million efficiency
impacts
$6.5 million producer impacts
$2.4 million producer impacts
Not enough data to quantify;
potential impacts
$77,000 producer impacts
$13 to $14 million in producer
impacts and $40 to $204
million in efficiency impacts
Carcinogenic risk
2 Registrant has voluntarily cancelled use directly on food crop;
only use remaining is on caprifig which is unlikely to result in
any residue
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IV-30
For risks to mixer/loaders and applicators, the Agency would
also propose cancellation of all sites associated with
unacceptable MOSs/MOEs (those under 100 with low benefits) after
incorporation of additional protective clothing requirements for
workers and without additional protective clothing for homeowners
which EPA considers impractical. In these cases, EPA believes
risks outweigh benefits. In addition, the Agency would propose
cancellation of all sites with estimated upper-bound,
carcinogenic risks to mixer/loader/applicators exceeding 10 for
workers after incorporation of additional protective clothing and
exceeding 10"6 for homeowners without additional protective
clothing. Additional protective clothing requirements are not
considered practical for homeowners. Registrations bearing the
following uses would be affected: (1) maneb on homeowner
vegetables, ornamentals, fruit trees and turf sites and on grapes
and commercial ornamentals; (2) mancozeb on homeowner fruit trees
and turf sites; and (3) nabam in sugar and paper mills. See
Table IV-6. Again, the Agency believes risks outweigh benefits.
OPTION 4 - Cancellation of all registrations
If the registrations of the EBDCs for all food uses were
cancelled, all dietary carcinogenic risks to persons from the
consumption of EBDC-treated foods would be eliminated and all
developmental and thyroid risks to mixer/loader/applicators from
the use of EBDCs on food crops would be eliminated. The
cancellation of the registrations for maneb, mancozeb, metiram,
and nabam would have an estimated $46 to $75 million in producer
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IV-31
Table IV-6
Summary of M/L/A MOSs/MOEs for Developmental and Thyroid
Effects and/or Carcinogenic Risks and Benefits for Sites
Proposed for Cancellation
Maneb
Grapes
Comm. Ornamentals
Homeowner Uses
Fruit trees
Ornamentals
turf
vegetables
Nabam
Sugar Mills
. Paper Mills
Estimated
Risks
20 (TE)
6 (TE)
ID'* (CR)
10"5 (CR)
60 (DE)
ID'* (CR)
10"5 (CR)
75 (TE)
75 (TE)
Benefits
$1 to $3 million
producer impact
Minimal impacts.
Alternatives
available.
Minimal use.
Alternatives
available.
$0.4 - $0.5 million
increase for
alternatives
Alternatives less
expensive.
CR = Carcinogenic Risks
DE = Developmental Effects
TE = Thyroid Effects
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IV-32
impacts and $90 to $305 million in efficiency impacts the first
year following cancellation. Benefits from zineb are assumed to
be minimal based on the lack of support for these uses. With
full cancellation, EPA also would revoke all food tolerances so
that residues in imported as well as domestic crops would be
unlawful. Under this option, uses on many crops with negligible
estimated risks (10"1° to 10"7) would be treated the same as uses
on crops with high estimated risks. In addition, cancellation of
EBDC registrations on many minor crops with no alternatives would
result in some growers experiencing severe impacts.
If registrations of the EBDCs for non-food crops,
commercial, homeowner and industrial uses were cancelled, all
mixer/loader/applicator carcinogenic, thyroid and developmental
risks from EBDCs or ETU exposure would be eliminated.
Cancellation of maneb, mancozeb, metiram, and nabam on these use
sites would have a $5 to $15 million impact in the first year
following cancellation.
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V. PROPOSED REGULATORY OPTIONS
The Agency believes that the estimated aggregate risk from
all of the EBDCs is unacceptably high. The level of estimated
benefits, $46 to $75 million in producer impacts and $90 to $305
million in efficiency impacts in the first year, cannot justify
an estimated dietary risk in the range of 10"4. At the same
time, the Agency does not think that full cancellation is
warranted in light of the estimated benefits of continued maneb,
mancozeb and metiram use on some crops, and the low estimated
carcinogenic, developmental and thyroid risks associated with
certain of the individual crops. Consequently, the Agency
proposes a partial cancellation of EBDC registrations combining
options 2 and 3 - partial cancellation of registrations and
continuation of other registrations with modifications to the
terms and conditions of registration. The goal of this proposal
is to reduce aggregate risks from EBDCs to a level that provides
an appropriate overall balance of risks and benefits. Specific
proposed regulatory actions are outlined below.
EPA tentatively plans not to issue a final decision until
the Agency has had the opportunity to examine market basket data
due to be submitted in September 1990. Dietary risk estimates
presented in this document were based on field residue data which
may well overestimate actual dietary risk. The Agency believes
that a well designed and properly conducted food residue
monitoring study may more accurately estimate ETU residues "at
the dinner plate" and could support risk estimates of as much as
one or two orders of magnitude lower than our current risk
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V-2
estimates for some crops, at which point estimated benefits could
exceed risks for additional food crops than those currently
proposed for retention.
Due to lack of more refined data, developmental and thyroid
MOSs/MOEs for mixer/loaders and applicators were based on upper-
bound exposure estimates. Although many of the resulting
MOSs/MOEs are of concern (<100), and risks are unreasonable
because benefits are low, the Agency believes that actual dermal
exposure and absorption data may increase these MOSs/MOEs.
However, as to both dietary and mixer/loader/applicator risk
issues, in the absence of data sufficient to demonstrate lower
exposure, currently available data will be used to make the Final
Determination risk estimates. In that event, as discussed in
this document, estimated risks outweigh estimated benefits for
many uses.
Due to the assumptions surrounding dietary and
mixer/loader/applicator risks, the Agency has required additional
data through FIFRA section 3(c)(2)(B) to further refine risk
estimates. The Agency plans to issue the PD 4 in the spring of
1991 to allow review and consideration of new exposure data that
should become available which the Agency currently believes could
result in a more refined risk/benefit assessment of the EBDCs and
ETU.
A. Food Crop Uses
In deciding which food uses to retain, the Agency considered
a range of factors. Where the market situation has indicated a
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V-3
lack of support for a particular use, the Agency is proposing to
cancel that use without further detailed analysis. Cancellation
is necessary despite the actions by the technical registrants
because the uses the technical registrants have requested deleted
remain on the registrations of various formulators. For uses
which the technical registrants have retained, the Agency has
examined the risks and benefits of each use, to the extent that
information is available, in evaluating which uses should be
cancelled and which retained.
All zineb uses and the 42 uses dropped by the technical
registrants of mancozeb, maneb, and metiram are proposed for
cancellation on the basis of unacceptable risk and a lack of
support by registrants. It will be difficult for end use
formulators to retain the uses dropped by the technical
registrants. Not only will the formulators need to arrange an
alternate source of supply, but they will also need to generate a
substantial amount of data to support registration of these uses.
The Agency believes the action taken by the technical registrants
has altered the market sufficiently that it is appropriate to
consider that only the 13 crops will remain. Thus, the Agency's
proposed cancellation, in a practical sense, reflects what has,
by and large, already taken place.
Cancelling all zineb uses and the 42 uses of mancozeb, maneb
and metiram dropped by the registrants leaves thirteen food crop
uses: tomatoes, potatoes, bananas, grapes, wheat, cranberries,
onions, sugar beets, sweet corn, peanuts, almonds, asparagus and
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V-4
figs. These crops have an estimated upper-bound, cumulative
lifetime risk of 2 x 10"5 and an estimated cumulative benefit of
$14 to $27 million in producer impacts (see Table IV-2).
The Agency believes the level of estimated upper-bound, risk
associated with these thirteen crops outweighs the associated
benefits. Thus, the Agency finds that action beyond that taken
by the registrants is necessary to reduce risks to acceptable
levels. The Agency considered a risk-benefit balancing of each
crop to determine which crops had estimated benefits which
exceeded the estimated risks and yielded an acceptable cumulative
dietary risk. The Agency determined that ten crops met this
test. These are: grapes, wheat, cranberries, onions, sugar
beets, sweet corn, peanuts, almonds, asparagus and figs. These
ten crops have an estimated upper-bound, cumulative risk of
3 x 10"6 and cumulative benefits of $13 to $26 million in
producer impacts. Therefore, the Agency proposes to cancel three
more crops in addition to the 42 already discussed. These three
crops are tomatoes, potatoes and bananas. Tomatoes have an
estimated risk of 2 x 10"5 and estimated benefits of only $0.1
million. Potatoes and bananas each have estimated risks in the 1
x 10"6 range but less than $0.5 million in estimated benefits.
None of the three crops appears to have sufficient benefits to
exceed these levels of estimated risks, particularly when it is
recognized that these risks need to be added to risks from other
crops to estimate total dietary risk.
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V-5
In determining the appropriate regulatory action, the Agency
considered the interim dietary risk while the Special Review is
being conducted. When estimating excess lifetime cancer risk
over a 70 year lifespan, EPA calculates one risk number for the
general population. This estimate takes into account that a
person moves from infancy through childhood and into being an
adult, and that consumption patterns change with these different
stages. However, when considering a time period of a few years,
EPA calculates risk numbers for both the overall population and
the most sensitive subpopulations. These estimates are estimated
lifetime cancer risks resulting from exposure during the short
time period, and take into account the different types and
amounts of food typically consumed by each subgroup.
EPA calculated the estimated interim dietary risks for three
groups—overall population, non-nursing infants and younger
children 1 to 6 years of age. In estimating the risks, the
Agency used the following assumptions: (1) the time period to
complete the Special Review will be two years (the PD 4 is now
scheduled for the spring of 1991); (2) no zineb use will occur
during this period (all registrants are suspended and the one
technical registrant has requested voluntary cancellation); and
(3) mancozeb, maneb and metiram will be used on only 13 crops
(the four technical registrants control over 90 percent of the
market and all their products will be labeled only for 13 uses
after January 1, 1990.)
-------
V-6
If all 13 crops are available for two more years, EPA
estimates the incremental risk to the general population would be
7 x 10"7. The risk to infants would be 1 x 10~6 and the risk to
children aged one to six would be 1 x 10"6. Given that these
estimates are upper-bound risk numbers (the true risk is just as
likely to be zero as it is to be the upper-bound number), EPA
believes the risks are acceptable.
The interim risks would increase slightly if EPA's final
decision is delayed by a cancellation hearing. At the same time,
EPA's risk numbers are likely to be overestimates because they
are based on field trial data rather than market basket data.
Existing monitoring data, while not sufficient to base regulatory
decisions on, show a clear pattern of being one to two orders of
magnitude less than field trial data. Registrants are now
conducting a market basket survey in an effort to show that
residue levels on fruits and vegetables are lower in the grocery
store than shown in field trials.
If other registrants attempt to support and maintain any of
the 42 food uses which the four technical registrants have
dropped from their label, EPA will consider these uses and
determine whether any additional risk are acceptable. The Agency
plans to closely monitor the marketplace over the next two years
and will take whatever action is necessary to maintain acceptable
interim risks.
As soon as some or all of the 42 crops are cancelled by all
registrants, EPA will finalize tolerance revocations on those
-------
V-7
uses to remove exposure from imported crops as well as domestic
ones. Prior to revocation, the uses of EBDCs on imported food
would slightly increase interim risk.
Additional data from toxicological and exposure studies are
expected to be received by EPA. If any information raises
concerns about interim risk, the Agency is prepared to initiate
prompt, further regulatory action.
In identifying crops for retention of registration, the
Agency considered the feasibility of modifications to reduce
dietary risk, such as lengthening pre-harvest intervals, limiting
application frequencies, or lowering application rates. However,
due to the lack of information, the Agency could not assess the
feasibility of these measures. Without data, it is difficult to
determine if the pesticide would be efficacious under these
varying conditions. The Agency is interested in comments and
data which will help the Agency consider this option more
carefully in the Final Determination. Commenters need to specify
label modifications and provide either data or analysis to show
that the EBDC pesticides could be used efficaciously in
accordance with such rates and practices. Even though the
comment period ends 90 days after publication of this Notice, the
Agency will likely accept residue data through the summer of 1990
when the Market Basket survey is due. Residue data showing
residues resulting from differing application rates or
frequencies or pre-harvest intervals will be needed to show the
risk reduction impact of these measures. To ensure that studies
-------
V-8
provide adequate, valid data, EPA urges that protocols and study
parameters be discussed with the Agency before studies are
initiated.
In conducting the risk-benefit analysis for each crop, the
Agency considered the estimated risks posed by alternatives,
based on currently available data. In preparing the Final
Determination, the Agency will consider not only new data
received on the EBDCs but also new data received on the
significant alternatives and consider the estimated risks and
benefits of EBDC use on each crop in light of the estimated risks
and benefits posed by alternative pesticides. The Agency
specifically requests comment on the benefits for each crop and
on which alternatives are likely to be used.
B. Tolerances
Within 90 days of the issuance of this document, the Agency
intends to propose tolerance revocations for the 45 food uses of
maneb, mancozeb and metiram and all (58) food uses of zineb
proposed for cancellation in this Preliminary Determination. The
Agency presently intends to finalize the tolerance actions,
reflecting consideration of public comments, when all products
for particular uses are voluntarily cancelled, or the Agency
issues the Final Determination, whichever occurs earlier. In
issuing final rules to revoke tolerances, the Agency will set
tolerance expiration dates which take into consideration any
crops which were treated legally before the effective date of the
cancellation. Tolerances for retained uses will be reevaluated
-------
v-g
once the Agency receives metabolism and residue data required
under the EBDC Comprehensive Data Call-ins and Registration
Standards. Any necessary adjustments to raise or lower existing
tolerances will be proposed at that time.
C. Non-Industrial Uses
The Agency proposes a label language requirement that
commercial agricultural workers (M/L/A) applying EBDC pesticides
wear coveralls over long-sleeved shirt and long pants, chemical-
resistant gloves, shoes, socks, and goggles or a face shield.
Additionally, during mixing and loading, a chemical-resistant
apron must be worn. For agricultural workers, where completely
enclosed cabs with positive pressure filtration, or an enclosed
cockpit for aerial application are used, a long-sleeve shirt and
long pants may be worn in place of the protective clothing
described above. Chemical-resistant gloves must be available in
the cab or cockpit and worn upon exiting. During aerial
application, human flaggers are prohibited unless in totally
enclosed vehicles. With incorporation of the above-mentioned
protective clothing requirements, MOSs/MOEs for workers using
EBDC products on agricultural sites would all increase above 100
except for maneb use on grapes and ornamentals which are proposed
for cancellation because EPA has determined that risks exceed
benefits.
The Agency estimates that the cost of the above protective
clothing would range from $0.75 to $1.5 million if every
commercial agricultural user of EBDC pesticides needed to buy the
-------
V-10
protective equipment. However, the Agency believes the costs of
this requirement would actually be much lower because most
growers already own such equipment as it is required for use when
applying a number of other agricultural chemicals.
The Agency proposes a label language requirement
establishing an interim reentry interval of 24 hours for all EBDC
products used on agricultural sites. This interim reentry
interval will remain in effect until dislodgeable foliar residue
data (showing EBDC and ETU exposure to agricultural workers
reentering treated fields for the purposes of hand harvesting,
pruning, weeding, etc.) required in the EBDC Registration
Standards and as required in the March 1989 EBDC Data Call-in
Notice are submitted and evaluated. These data are due to be
submitted in July 1990. The Agency believes that there would be
little if any economic impact from this requirement.
The Agency proposes a label language requirement that
homeowners applying EBDC pesticides wear a long-sleeved shirt and
long pants and rubber gloves. Gloves must be washed thoroughly
with soap and water befor removing; clothes must be changed
immediately after using the EBDC product and laundered separately
from other laundry items before reuse. Homeowners applying EBDCs
must shower immediately after use. The Agency did not consider
that additional protective clothing requirements for homeowners
would be a viable means of reducing risks because the Agency
believes that homeowners will not go to the expense of purchasing
or wearing protective clothing. Therefore, EPA proposes to
-------
V-ll
cancel the use of maneb on turf by homeowners where MOSs/MOEs are
under 100, and risks outweigh benefits.
In addition, because millions of households have gardens and
many more have lawns which could be treated, the Agency is
concerned about estimated cancer risks which exceed 10"6 for
homeowners applying EBDCs. EPA believes such risks exceed the
benefits of use. Homeowner sites which have estimated risks
exceeding 10"6 are: (1) mancozeb on fruit trees and turf and (2)
maneb on vegetables, ornamentals, fruit trees and turf. See
Table 11-19. Little or no economic impact is expected because
home gardeners can switch from maneb to mancozeb for vegetables
and ornamentals and can use captan on fruit trees instead of
EBDCs. The Agency estimates that less than one percent of
residential lawns are treated with EBDCs and any impact would be
negligible. Therefore, EPA proposes to cancel homeowner use of
mancozeb on fruit trees and turf, and homeowner use of maneb on
vegetables, ornamentals, fruit trees and turf.
D. Industrial Uses
The Agency proposes a label language requirement that all
industrial workers (M/L/A) applying EBDC pesticides wear
coveralls over long-sleeved shirt and long pants, chemical-
resistant gloves, shoes, socks, and goggles or a face shield.
Additionally, during mixing and loading, a chemical-resistant
apron must be worn. Similar label language already appears on
nabam labels and OSHA requires protective clothing when applying
hazardous chemicals under 29 CFR §1910.132; therefore, the Agency
-------
V-12
believes there would be minimal costs resulting from this
requirement.
The Agency proposes cancellation of nabam use in paper mills
and sugar mills based on thyroid MOSs/MOEs below 100 due to
occupational exposure after incorporation of protective clothing
requirements listed above. EPA has determined that risks
outweigh benefits in these cases. If nabam's use were cancelled,
the cost to the paper industry would increase by $700,000. There
are three alternatives for nabam's use in sugar mills. The most
viable alternative (Busan) possibly would increase production
costs between $400,000 to 500,000 if it replaced nabam.
-------
VI. REFERENCES
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VI-2
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VI-3
Graham, S.L., W.H. Hansen, K.J. Davis and C.H. Perry (1973).
"Effects of One-Year Administration of Ethylenethiourea upon
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Hauswirth, Judith W. (July 14, 1988). "Maneb-Registrant Response
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2 pp.
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Hummel, Susan V. (August 15, 1989). "Revised Dietary Exposure to
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Hummel, Susan V. (August 17, 1989). "Revised Dietary Exposure to
Metiram and ETU." Hazard Evaluation Division, Office of
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Hummel, Susan V. (August 17, 1989). "Revised Dietary Exposure to
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Hummel, Susan V. (July 13, 1988). " Mancozeb-Registrant Response
to Agency PD-1." Hazard Evaluation Division, Office of
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Hunter, B. et al. (1979). "Metiram tumorigenicity to mice in long
term dietary administration for 13 weeks followed by a 6 week
withdrawal period. (Unpublished study No. BSF/197/77612 by
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00330245.
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VI-4
Hunter, B. et al. (1981). "Metiram toxicity and tumorigenicity in
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VI-7
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VI-9
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