United States
Environmental Protection
Agency
Office of
Pesticides and Toxic Substances
Washington DC 20460
March 1981
v>EPA
Pesticides
Oxyfluorfen (Goal 2E
Position Document No. 1-2-3
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OXYFLUORFEN
POSITION DOCUMENT
Office of -Pesticide Programs
Environmental Protection Agency
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Errata Sheet
Oxyfluorfen PD 1/2/3
The following constitutes a more accurate description of the
EXAMS results than was presented in the PD 1/2/3 (page 43,
Section II .E.I).
"Evidence that oxyfluorfen is toxic to certain aquatic
invertebrates at low levels was also considered (Vilkas,
1978). Although this information raised concerns regarding
all uses of oxyfluorfen, there was a special concern with
respect to soybeans because a portion of the soybean use
pattern area provided habitat for 20 species of endangered
freshwater mussels.
The Agency has conducted a computer simulation of the
expected aquatic environmental concentration of oxyfluorfen.
A small, unstratified lake receiving input from a five acre
watershed was simulated with the Exposure Analysis Modeling
System (EXAMS) developed by the EPA's Athens, Ga., Environmental
Research Laboratory. Using an oxyfluorfen loading value of
0.046 kg/yr, a steady state equilibrium concentration of
30 ppb is attained in the lake hydrosoil. The EXAMS simulation
indicates that oxyfluorfen would be relatively persistent,
with a half-life for system purification of 127.3 days once
the loading ceases."
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- ACKNOWLEDGEMENTS -
EPA OXYFLUORFEN TEAM
Frank Beck, Agronomist, BFSD
Jolene Chinchilli, Project Manager, SPRD
Katherine Devine, Economist, BFSD
William Dykstra, Biochemist, HED
Linda Garczynski, Writer/Editor, SPRD
Timothy Gardner, Section Head, SPRD
Homer Hall, Branch Chief, SPRD
Robert Hitch, Fish and Wildlife Biologist, HED
Cara Jablon, Attorney, OGC
Van Kozak, Chemist, HED
Irving Mauer, Geneticist, HED
Tom Miller, Project Manager, SPRD
Richard Mountfort, Project Manager, RD
R.B. Perfetti, Chemist, HED
Richard Petrle, Agronomist, BFSD
Emil Regelman, Environmental Chemist, HED
Amy Rispin, Science Policy Analyst, HED
Dudley E. Thompson, Attorney Advisor, SPRD
PESTICIDE CHEMICAL REVIEW COMMITTEE
Elizabeth Anderson, ORD
Henry Seal, 0PM
Ed Gray, OGC
Charles Gregg, OWWM
Richard Hill, OPTS
Lois Jacobs, OE
Allen Jennings, 0PM
Donna Kuroda, ORD
Fran Pollack, 0PM
Ray Smith, OANR
Marian Thompson, OWWM
Ed Tuerk, OANR
Marcia Williams, Chairperson, SPRD
Richard Wilson, OE
Michael Winer, OGC
OTHER ACKNOWLEDGEMENTS
Vickie Vaughn-Dellarco, REAG
Bernard Haberman, GAG
Robert McGaughy, CAG
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Oxyfluorfen
PD 1/2/3
Table of Contents
Page
I. INTRODUCTION 1
A. Legislative Background 1
B. The RPAR Process 2
C. Regulatory History 4
1. Existing Registrations A
2. Experimental Use Permits 5
3. Specific Exemptions 6
4. Application for Registration 6
5. RPAR Action 7
D. Chemical Background 8
1. Oxyfluorfen 8
2. Perchloroethylene (PCE) 8
E. Uses and Production 9
1. Registrations and Use 9
2. Production 9
i
F. Tolerances 10
1. Oxyfluorfen 10
2. Perchloroethylene 10
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Page
II. RISK ANALYSIS 13
A. Environmental Occurrence 13
B. Exposure Analysis - PCE 14
1. Method of Estimating Exposure 14
2. Applicator/Mixer/Loader Exposure 15
a. Inhalatlonal Exposure 15
b. Dermal Exposure 15
3. Dietary Exposure 20
C. Cancer Risk Assessment 23
1. Introduction 23
2. Evaluation of Cancer Data 23
a. Perchloroethylene 23
b. Oxyfluorfen 28
3. Cancer Risk 29
a. Introduction 29
b. Applicator/Mixer/Loader 30
c. Dietary Risk 30
d. Reduction of Risk by the Use of 32
Protective Equipment 33
D. Other Possible Adverse Effects 33
1. Mutagenicity 33
a. Introduction 33
b. Oxyfluorfen Mutagenicity Data 33
c. PCE Mutagenicity Data 37
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Page
2. Teratogenicity 40
a. Introduction 40
b. Oxyfluorfen Teratogenicity Data 40
c. PCE Teratogenicity and Fetotoxicity Data 40
3. Chronic Toxicity 41
E. Environmental Risk 41
1. Persistence and Bioaccumulation in Aquatic Habitats 41
2. Toxicity to Molluscs 44
3. Possible Hazard To Wetlands 46
4. Avian Reproduction Study 46
III. BENEFITS ANALYSIS 47
A. Introduction 47
B. Soybeans 48
1. EPA Registration of Oxyfluorfen and Otber Soybean 48
Herbicides
2. Recommendations for Using Oxyfluorfen and Other Soybean 51
Herbicides
3. Performance Evaluation of Oxyfluorfen and Other Soybean 51
Herbicides
a. Pest Infestation and Damage . 51
b. Comparative Performance Evaluation 51
4. Economic Impact Analysis 54
a. Profile of Impacted Area 54
b. User Impacts 54
c. Market and Consumer Impacts 61
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Page
C. Corn 61
1. EPA Registrations of Oxyfluorfen and Other Herbicides 61
2. Recommendations for Use of Oxyfluorfen 62
and Other Herbicides
3. Performance Evaluation of Oxyfluorfen 62
and Alternatives
a. Pest Infestation and Damage , 62
b. Comparative Performance Evaluation 64
4. Economic Impact Analysis 65
a. Profile of Impacted Area 65
b* User Impacts 65
c* Market and Consumer Impacts 67
d. Social/Community/Macroeconomlc Impacts 67
D. Bearing and Nonbearing Tree Fruit/Nuts and Vineyards 67
1. EPA Registration of Oxyfluorfen and Other Herbicides 67
2. Performance of Goal 2E Herbicide 68
3. Comparative Performance Evaluation 71
4. Economic Impact Analysis 71
a. Profile of Impacted Area 71
b. User Impacts 72
E. Conifers 72
1. EPA Registration of Oxyfluorfen and Other Herbicides 72
a. Conifer Seedbeds 73
b. Conifer Transplants and Outplantings 73
c. Other Registered Herbicides 74
2. Performance of Goal 2E Herbicide 74
3. Comparative Performance Evaluation 76
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Page
4. Economic Impact Analysis 77
a* Profile of Impacted Area 77
b. User Impacts 77
IV. RISK/BENEFIT ANALYSIS 79
A. Introduction 79
1. Rationale for Development of Regulatory Options 79
2. Salient Risk/Benefit Considerations 80
B. Regulatory Options Considered 81
C. Risk/Benefit Analysis and Proposed Decision 83
1. Nonbearlng Tree Fruits/Nuts 83
2. Conifers 85
3. Soybeans 87
4. Corn 90
5. Bearing Tree Fruits/Nuts 92
D. Summary of Proposed Regulatory Decision 94
APPENDICES A-E
BIBLIOGRAPHY
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Tables
1. Maximum PCE Exposure Recommendations Based Upon the
Acute Toxicity of PCE 12
2. Daily PCE Inhalational Exposure to Applicator/Mixer/Loaders
from Goal 2E Use 16
3. Daily PCE Dermal Exposure for Applicator/Mixer/Loader
Using Goal 2E 18
A. Adjusted Lifetime Average Daily Worker Exposure to PCE
Exposure to Workers from Use of Goal 2E 19
5. Adjusted Lifetime Average Daily Worker Exposure to PCE
From Use of Goal 2E - Protective Clothing Scenario 21
6. Theoretical Maximum Dietary Exposure to PCE 22
7. Adjusted Maximum Dietary Exposure to PCE 24
8. Incidence of Hepatocellular Carcinomas in B6C3F1 Mice
Fed PCE 26
9. Carcinogenic Risk to Applicator/Mixer/Loaders and the
General Population Associated with the PCE Contaminant
of Goal 2E 31
10. Adjusted Lifetime Average Daily Worker Exposure to and
Associated Risk from PCE in Goal 2E 32
11. Comparison of Applicator Risk With and Without the Use of
Protective Equipment 34
12. Goal Residue Analyses from Samples Taken in the Witchweed
Quarantine Area 43
13. States and Counties Providing Habitat for Federally
Designated Endangered Mussel Species 45
14. Weed Species Controlled, by Goal 2E 49
15. Selected Major Registered Herbicides for Control of Annual
Broadleaf and Grassy Weeds in Soybeans 50
16. Comparative Costs of Goal 2E and Selected Preemergence
Herbicides for Control of Annual Broad Leaf and Grassy
Weeds in Soybeans 56
17. Comparative Costs of Goal 2E Combinations and Selected
Preemergence Herbicide Combinations Used for Control
of Annual Broadleaf aand Grassy Weeds in Soybeans 57
18. Comparative Costs of Goal 2E and Selected No Till Herbicide
Uses for Control of Annual Broadleaf and Grassy Weeds
in Soybeans 59
19. Comparative Cost of Goal 2E and Selected Post Emergence
Directed Herbicides for Control of Annual and Broadleaf
Grassy Weeds in Soybeans 60
20. State Herbicidal Recommendations for Control of Grassy
Weed Hosts of Witchweed in Corn 63
21. Total Per Acre Cost Increases of Using Other Herbicides
for Control of Witchweed in Field Corn in North and
South Carolina • 66
22. Other Registered Herbicides Used for Weed Control In Tree
Fruit/Nuts and Vineyards 69
23. Other Registered Herbicides for Weed Control in Conifers 75
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I. INTRODUCTION
A. Legislative Background
The Federal Insecticide, Fungicide, and Rodenticide Act (7 U.S.C.
Section 136 et_ seq.), as amended, gives the Environmental Protection
Agency (EPA or the Agency) the authority to regulate pesticide products.
In order to obtain a registration for a pesticide under FIFRA, a
manufacturer must demonstrate that the pesticide satisfies the statutory
standard for registration. That standard requires (among other things)
that the pesticide perform its intended function without causing "unreason-
able adverse effects on the environment" [Section 3(c)(5)]. The term
"unreasonable adverse effects on the environment" is defined as "any
unreasonable risk to man or the environment, taking into account the
economic, social, and environmental costs and benefits of the use of any
pesticide" [FIFRA, Section 2(bb)]. In effect, this standard requires a
finding that the benefits of each use of the pesticide exceed the risks of
use, when the pesticide is used in accordance with commonly recognized
practices. The burden of proving that a pesticide satisfies the standard
for registration is on the proponents of registration and continues as long
as the registration remains in effect. Under Section 6 of FIFRA, the
Administrator is required to deny or cancel the registration of a pesticide
or modify the terms and conditions of registration whenever he determines
that the pesticide does not satisfy the statutory standard for
registration.—
Section 3(c)(7)(B) of FIFRA allows the Administrator to condition-
ally amend the registration of a pesticide to permit additional uses of
such pesticide notwithstanding that data concerning the pesticide may be
insufficient to support an unconditional amendment, if the Administrator
determines that:
— the applicant has submitted satisfactory data pertaining to
the proposed additional use, and
— amending the registration in the manner proposed by the
applicant would not significantly increase the risk of any
unreasonable adverse effect on the environment.
\J Another part of the statutory standard for registration is that the
pesticide must satisfy the labeling requirements of FIFRA. These require-
ments are set out in the statutory definition of "misbranded" [FIFRA
Section 2(q)]. Among other things, this section provides that a pesticide
is misbranded if
"the labeling * * * does not contain directions for use which are
necessary for effecting the purpose for which the product is
intended and if complied with, together with any * * *
(restrictions) imposed under Section 3(d) * * * are adequate to
protect health and the environment."
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The Agency can require changes to the directions for use of a
pesticide in most circumstances either by finding that the pesticide would
cause unreasonable adverse effects on the environment, unless labeling
changes are made which accomplish risk reductions [Section 6(b) or by
finding that the pesticide is misbranded if the labeling is not changed
[Section 3(c)(5)].
Section 3(c)(7)(B) states that ...
"-- no registration of a pesticide may be amended to permit an
additional use of such pesticide if the Administrator has issued
a notice stating that such pesticide, or any ingredient thereof,
meets or exceeds risk criteria associated in whole or in part
with human dietary exposure enumerated in regulations issued
under this Act, and during the pendancy of any risk-benefit
evaluation initiated by such notice, if (1) the additional use of
such pesticide involves a major food or feed crop, or (ii) the.
additional use of such pesticide Involves a minor food or feed
crop and the Administrator determines, with the concurrence of
the Secretary of Agriculture, there Is available an effective
alternative pesticide that does not meet or exceed such risk
criteria."
In order for a pesticide to be sold and used to produce a crop, the
pesticide must not only be registered for the particular use under FIFRA,
but also must have a tolerance or an exemption from a tolerance for each
individual crop on which it will be used. Under section 402 of the Federal
Food Drug and Cosmetic Act (FFDCA), a raw agricultural commodity or a
processed food or feed which contains a pesticide residue is "adulterated"
unless a tolerance (maximum allowable limit of pesticide residue) or an
exemption from a tolerance, or a food additive regulation has been
established for the pesticide in question. The authority for establishing
tolerances and exemptions from tolerances for residues of pesticide
chemicals on raw agricultural commodities, and food additive regulations
allowing pesticide residues in processed food is found in sections 408 (raw
agricultural commodities) and 409 (processed food) of the FFDCA. In 1970,
pursuant to the Reorganization Plan No. 3 of 1970, 84 Stat. 3086, the
authority for establishing tolerances and exemptions from tolerances under
sections 408 and food additive regulations under 409 of the FFDCA was
transferred from the Food and Drug Administration to the Administrator of
EPA.
B. The RPAR Process
The Agency created the Rebuttable Presumption Against Registra-
tion (RPAR) process to facilitate the identification of pesticide uses
which may not satisfy the statutory standard for registration and to
provide a public, informal procedure for the gathering and evaluation of
information about the risks and benefits of these uses.
The regulations governing the RPAR process are set forth in
40 CFR 162.11. This section provides that a rebuttable presumption shall
arise if a pesticide meets or exceeds any of the risk criteria set out in
the regulations.
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The Agency generally announces that an RPAR has arisen by
publishing a notice in the Federal Register. After an RPAR is issued,
registrants and other interested persons are invited to review the data
upon which the presumption is based and to submit data and information to
rebut the presumption. Respondents may rebut the presumption of risk by
showing that the Agency's initial determination of risk was in error, or by
showing that use of the pesticide is not likely to result in any signifi-
cant exposure to humans or to the animal or plant of concern with regard to
the adverse effect in question.— Further, in addition to submitting
evidence to rebut the risk presumption, respondents may submit evidence as
to whether the economic, social, and environmental benefits of the use of
the pesticide subject to the presumption outweigh the risks of use.
The regulations require the Agency to conclude an RPAR by issuing
a Proposed Notice of Determination in which the Agency states and explains
its position on the question of whether the risk presumptions have been
rebutted. If the Agency determines that the presumption is not rebutted,
it will then consider information relating to the social, economic, and
environmental costs and benefits which registrants and other interested
persons submitted to the Agency, and any other benefits information known
to the Agency.
A primary purpose of the RPAR process is to screen for those
pesticide uses which pose risks which are of sufficient concern to require
the Agency to consider whether offsetting benefits justify the risks.
Accordingly, the Agency's approach to rebuttal determinations concentrates
on whether the risk concerns which are central to each RPAR proceeding have
in fact been answered.
After weighing the risks and benefits of a pesticide use, the
Administrator may conclude the RPAR process by issuing a proposed notice of
intent to cancel or deny registration, or to change the classification of a
pesticide pursuant to FIFRA Section 6(b)(l) and Section 3(c)(6) or by
Issuing a notice of Intent to hold a hearing pursuant to Section 6(b)(2) of
FIFRA to determine whether the registrations should be cancelled or
applications for registration denied.
T/40 CFR Section 162.11(a)(A) provides that registrants and applicants
may rebut a presumption against registration by sustaining the burden of
proving: (i) in the case of a pesticide which meets or exceeds the
criteria for risk set forth in paragraphs (a)(3)(i) or (ill) that when
considered with the formulation, packaging, method of use, and proposed
restrictions on and directions for use, and widespread and commonly
recognized practices of use, the anticipated exposure to an applicator or
user and to local, regional, or national populations of nontarget organisms
is not likely to result in any significant acute adverse effects; or (ii)
in the case of a pesticide which meets or exceeds the criteria for risk set
forth in paragraph (a)(3)(ii) that when considered with proposed
restrictions on use, the pesticide will not concentrate, persist or accrue
to levels in man or the environment likely to result in any significant
chronic adverse effects; or (ill) that the determination by the Agency that
the pesticide meets or exceeds any of these criteria for risk was in error.
3
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In determining whether the use of a pesticide poses risks which
are greater than benefits, the Agency considers modifications to the terms
and conditions of registration which can reduce risks, and the impacts of
such modifications on the benefits of the use. Of the many risk reduction
measures short of cancellation which are available to the Agency, two
examples are changes in the directions for use on the'"pesticide's labeling
and classification of the pesticide for "restricted use" pursuant to FIFRA
Section 3(d).
FIFRA requires the Agency to submit the proposed notices issued
pursuant to Section 6 to the Secretary of Agriculture for comment and to
provide the Secretary of Agriculture with an analysis of the impact of the
proposed action on the agricultural economy [Section 6(b)]. If the
Secretary of Agriculture comments in writing within 30 days after receiving
the notice, the Agency is required to publish the Secretary's comments and
the Administrator's response. FIFRA also requires the Administrator to
submit Section 6 notices to a Scientific Advisory Panel for comment on the
impact of the proposed action on health and the environment, at the same
time and under the same procedures as those described above for review by
the Secretary of Agriculture [Section 25(d)].
Although not required to do so under the statute, the Agency has
decided that it is consistent with the general theme of the RPAR process
and the Agency's overall policy of open decisionmaking to afford
registrants and other interested person's an opportunity to comment on the
bases for the proposed action during the time that the proposed action is
under review by the Secretary of Agriculture and the Scientific Advisory
Panel. Accordingly, appropriate steps are taken to make copies of the
position document available to registrants and other interested persons at
the time the position documents are transmitted for formal external review,
through publication of a notice of availability in the Federal Register, or
by other means. Registrants and other interested persons are usually
allowed the same period of time to comment—30 days—that the statute
provides for receipt of comments from the Secretary of Agriculture and the
Scientific Advisory Panel. The Agency will formally extend this comment
period in cases where the issues are extremely complex, or where new data
are in the process of being generated.
After completing these external review procedures and making any
changes in the proposed action which are deemed appropriate as a result of
the comments received, the Agency will proceed to implement the desired
regulatory action by preparing appropriate documents and releasing them in
the manner prescribed by the statute and by the Agency's rules.
C. Regulatory History
1. Existing Registrations
Rohm and Haas is the sole producer of the herbicide Goal
(oxyfluorfen) in the United States. There is one unconditionally
registered product containing the active Ingredient oxyfluorfen marketed
under the trade name Goal 2E. This product has two unconditionally
registered uses. Goal 2E was registered on May 17, 1979, for preemergence
and postemergence weed control in nonbearlng almonds, nectarines, peaches,
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grapes, plums and prunes in California only. Subsequently, Goal 2E
was registered on March 25, 1980, for preemergence and postenergence
weed control in conifer seedbeds throughout the United States, and for
preemergence and postemergence weed control in conifer transplants and
outplantlngs. Conditional registration of Goal 2E for use on bearing tree
fruits/nuts (as mentioned above) was approved by the Agency on December 18,
1980. The conditions of this registration will be defined in later
sections of this document.
2. Experimental Use Permits
Under Section 5 of FIFRA, any person may apply to the
Administrator for an experimental use permit (EUP). The Administrator may
issue an EUP only if he/she determines that the applicant needs such a
permit to accumulate information necessary to register the pesticide under
Section 3 of FIFRA.
If the pesticide use under the experimental use permit Is
likely to result in residues on or in food or feed, the applicant must also
petition for the establishment of temporary tolerance levels for the
pesticide. Such a temporary tolerance must be established before the
experimental permit may be issued. Permits and associated temporary
tolerances may be renewed or extended upon request if circumstances, such
as providing additional testing, warrant. The Administrator may also
revoke an EUP at any time if he determines that Its terms or conditions are
not being met, or if the terms and conditions are not adequate to avoid
unreasonable adverse effects on the environment.
On December 27, 197A, Rohm and Haas submitted an application
for the experimental use of Goal 2E on 70,000 acres of soybeans (707-EUP-
83) and a petition for a temporary tolerance for residues of oxyfluorfen of
0.05 ppm In soybeans (5G1581). The Agency first issued this permit on June
6, 1975, and has extended It annually since that time. The registrant
requested that the current permit, effective for the period June 5, 1979 to
June 5, 1980, be extended. This request was granted on March 20, 1980.
On October 13, 1975, Rohm and Haas submitted an application for
the experimental use of Goal 2E on certain tree fruits (707-EUP-85) and a
petition for a temporary tolerance for residues of oxyfluorfen of 0.05 ppm
in almonds, apricots, grapes (intended for the fresh fruit market only),
peaches, nectarines, and plums (fresh prunes, intended for the fresh fruit
market only) (6G1690). The Agency first Issued this permit on May 7, 1976,
and has extended it annually since that time. The most recent permit
expired on January 9, 1981. Permanent tolerances for these commodities
were established December 24, 1980, (45 FR 85021) and conditional
registration was approved December 18, 1980.
On December 7, 1977, Rohm and Haas submitted an application for
the experimental use of Goal 2E on cotton (707-EUP-91) and a petition for a
temporary tolerance for residues of oxyfluorfen of 0.05 ppm in cottonseed,
eggs, milk, and meat, fat, and meat by-products of cattle, goats, hogs,
horses, poultry, and sheep (8G2028). The Agency Issued this permit and the
temporary tolerances for the above-mentioned products with effective dates
from July 11, 1979 to July 11, 1981. Permanent tolerances for eggs, milk,
meat, fat and meat by-products of cattle, goats, hogs, horses, poultry and
sheep were established December 24, 1980 (45 FR 85021).
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3. Specific Exemptions
Section 18 of FIFRA authorizes the Agency to "... exempt any
Federal or State Agency from any provision of this Act if [The Adminis-
trator] determines that emergency conditions exist which require such
exemption."
On May 11, 1979, the Agency granted a specific exemption
pursuant to Section 18 of FIFRA and 40 CFR 166.1 to the U.S. Department of
Agriculture, Animal Plant Health Inspection Service, to apply Goal 2E on
corn in a witchweed eradication program in 30 counties in the states of
North and South Carolina. Some of the conditions for the use under this
specific exemption were:
—A maximum of two applications per year could be made as a directed
ground spray.
—The first application was restricted to the months of May and June
and the second to July and August.
—The total quantity applied should not exceed 2.0 pounds active
Ingredient per acre per year.
—A maximum of 3,000 pounds active ingredient could be applied on a
maximum of 2,000 acres in these two states.
—^Application was restricted to USDA, Animal, Plant, Health Inspection
Service (APHIS), Plant Protection and Quarantine personnel or
certified commercial applicators under their supervision.
—Application closer than 60 feet to fish habitat and 120 feet to
oyster habitat was prohibited.
—Analysis of water, hydrosoil, and young fish for oxyfluorfen
residues in limnetic or estuarine habitat adjacent to a treated
field was required.
This specific exemption expired on August 31, 1979. The
Agency granted the USDA request for an exemption for 1980. This exemption
allowed the use of up to 4,000 pounds of Goal (active ingredient) on a
maximum of 2,000 acres of field corn in the Carolinas.
4. Application for Registration
On March 14, 1978, the Rohm and Haas Company submitted an appli-
cation for the registration of Goal 2E (oxyfluorfen) for use on soybeans,
bearing tree fruit/nuts, and corn and3at the same time petitioned for
establishment of permanent tolerances— for oxyfluorfen residues of
0.05 ppm in soybeans, bearing tree fruits/nuts, and corn.—•
T/ This was later amended to include establishment of permanent toler-
ances on the meat, fat, and meat by-products of cattle, goats, hogs,
horses, poultry, and sheep, eggs and milk at the 0.05 ppm level.
4/ The corn use is restricted to application In conjunction with the
USDA, Plant Protection and Quarantine Program's Witchweed Eradication
Project in North and South Carolina.
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5. RPAR Action
Oxyfluorfen was referred to the Special Pesticide Review
Division for Rebuttable Presumption Against Registration (RPAR) review in
January 1980 because pesticide products containing oxyfluorfen as an active
ingredient were shown to be contaminated with perchloroethylene (PCE), a
liver carcinogen In B6C3F1 mice (NCI, 1977), which may pose a risk to human
health via dietary and work-related exposures. On the basis of the
carcinogenic potential of perchloethylene, the Agency determined that
oxyfluorfen met or exceeded the RPAR criteria for oncogenicity. This
contamination has been reduced by Rohm and Haas from the initial level of
1680 ppm (parts per million) (2-E formulation) to 200 ppm when the Agency
performed its exposure and risk analyses for this document.
PCE is a process solvent used in one or more steps in the
production of oxyfluorfen. The capabilities of PCE in this regard are
unique. During the course of this RPAR review, the registrant was able to
reduce the PCE contamination from 1680 ppm to 200 ppm by amending the
production process. The registrant asserts that any further reduction in
the amount of PCE would also remove an inordinate amount of oxyfluorfen.
In the interest of achieving an expedited review of the uses of
oxyfluorfen, the Agency decided to issue a position document which
integrated the PD 1 presumption against registration and the PD 2/3
risk/benefit analysis (PD 1/2/3). This approach was possible and desirable
in this situation because much of the information which the registrant
would have submitted at the PD 2/3 RPAR rebuttal stage was submitted during
the current review of oxyfluorfen. It seemed reasonable, therefore, to
focus public discussion on the risk/benefit analysis by presenting the
Agency's proposed position in a single document followed by a public
comment period during Which time the registrant and other interested
persons may submit comments in response to the Agency's proposed
risk/benefit conclusions regarding oxyfluorfen. The Agency believes that
neither the registrant nor any other Interested person has been prejudiced
by this procedural modification since they will not be deprived of their
opportunity to participate meaningfully in the administrative
decisionmaking process affecting the registration of this pesticide.
This document considers the potential risks and benefits
associated with oxyfluorfen use relevant to the proposed issuance of
oxyfluorfen tolerances and product registrations either currently
registered or proposed.— This review was based upon exposure, risk,
and benefits information obtained from readily available published
literature on PCE and data supplied by the registrant, Rohm and Haas, the
U.S. Department of Agriculture, and various weed scientists throughout the
United States.
Information on the potential benefits of registering
oxyfluorfen for new uses was obtained by the Agency from the U.S.
Department of Agriculture, various state plant scientists, and the
applicant for registration.
57Currently registered uses includes conifers (seedbeds, transplants
and outplantings) and nonbearing and bearing fruit and nut trees In
California (almonds, peaches, prunes, plums, and nectarines). Proposed
uses include: soybeans in the U.S., and field corn (USDA Witchweed
Program only).
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D. Chemical Background
1. Oxyfluorfen
Oxyfluorfen is the common name for [2-chloro-l-(3-ethoxy-4-
nitrophenoxy)-4-(trifluoromethyl)-benzene], the selective herbicide sold
under the trade name "Goal".
Some of oxyfluorfen's physical-chemical properties are (WSSA, 1979):
Melting point 65 - 80°C
Boiling point 250 - 3gO°C
Vapor pressure 2 x 10 mm of Hg at 25 C
Water solubility 0.1 ppm
Physical state Solid at room temperature
Color Deep red-brown to yellow
The empirical formula for Oxyfluorfen is C.-H..C1F.NO,,
its molecular weight 361.7, and its structural formula:
2. Perchloroethylene (PCE)
\ •
PCE contaminates Oxyfluorfen at 0.02% in the formulation
marketed as Goal 2E. PCE has a molecular weight of 165.85 and a structural
formula of:
Cl Cl
^ C = C
Cl -" ^ Cl
Some of PCE's physical-chemical properties are:
Melting point -23.35°C
Boiling point 121.2 C at 769 mm Hg
Vapor pressure 19 mm Hg at 25 C
Water solubility . 0.1 percent at 25°C
Color Colorless
At high concentrations, PCE has induced toxic effects such as
liver and kidney damage, neurophysiological effects, central nervous system
depression, and primary eye and skin irritation (NIOSH, 1978). The Agency
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has reviewed readily available studies— relevant to these effects of
PCE and has determined that a human health hazard for the effects
enumerated above is not indicated for those uses of oxyfluorfen discussed
in this document due to the relatively low exposure levels which result
from the use of Goal 2E (Dykstra, 1980c).
E. Uses and Production
1. Registrations and Use
There is one unconditionally registered product containing
the active ingredient oxyfluorfen marketed under the trade name Goal 2E.
This product contains 23.5% oxyfluorfen and is labeled for use in the
preemergence and postemergence control of certain weeds in nonbearing
almonds, nectarines, peaches, plums, and prunes grown in California, the
preemergence and post emergence control of various weeds in conifer
seedbeds (nationwide), and conifer transplants and out-plantings.
Additional registration applications for Goal 2E are pending for use in
soybeans, and field corn (for wltchweed control only). Goal is
conditionally registered for use on bearing tree fruits/nuts (as
mentioned above). This registration is subject to the conditions outlined
in this position document.
2. Production
a. Oxyfluorfen'
Oxyfluorfen is manufactured solely by the Rohm and Haas
Company of Philadelphia, Pennsylvania. Information concerning the actual
manufacturing process and the amount of oxyfluorfen produced is considered
confidential under Section 7 and protected under Section 10 of FIFRA.
b. Perchloroethylene
PCE is a heavily used chemical in commercial dry cleaning
and industrial metal degreasing. The chemical has additional uses as an
industrial solvent, and as a veterinary antihelmintic. About 700 million
pounds of PCE are currently produced in the U.S. each year (NIOSH, 1978).
6>/ In addition, the Agency is aware of a number of other reviews of PCE's
risk potential. These include reviews by: NIOSH (1976, 1978); US EPA
(1979, 1979a, 1980); NCI (1977); CPSC (1976); and Fuller (1976).
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F. Tolerances
1. Oxyfluorfen
Section 5(b) of FIFRA states that the Administrator nay
establish a temporary tolerance level for the residue of a pesticide before
issuing an experimental use permit, if he determines that the use of the
pesticide may reasonably be expected to result in residues on or in food or
.feed. Temporary tolerances were established for 0.05 ppm oxyfluorfen in
corn and soybeans (Petition No. 5G1581); almonds, apricots, grapes,
peaches, nectarines, and plums (all 6G1690); and cottonseed, eggs, milk,
meat, fat, and meat by-products of cattle, goats, hogs, horses, poultry,
and sheep (Petition No. 8G2028). In addition, there is a temporary
tolerance established at 0.2 ppm in cottonseed oil (Petition No. 9H5199).
Temporary tolerances are extended or renewed in association with the
respective renewals or extensions of experimental use permits.
Rohm and Haas petitioned the Agency on March 8, 1978, for
the establishment of permanent tolerances in or on a number of commodities
(Petition No. 8F2058) including: soybeans; corn; the meat, fat, and meat by-
products of cattle, goats, hogs, horses, poultry, and sheep; eggs; and milk
at 0.05 ppm and soybean oil at 0.25 ppm (FAP 9H5230). With the exception
of corn, soybeans and soybean oil, permanent tolerances for these
commodities were established on December 24, 1980 (45 FR 85021).
2. Perchloroethylene (PCE)
PCE is used as a solvent or cosolvent in a number of
pesticide products. As a result of an Agency review (US EPA, 1974), PCE
was exempted from the requirement of a tolerance when used in accordance
with good agricultural practice as an inert (or occasionally active)
ingredients in pesticide formulations applied to growing crops or to raw
agricultural commodities after harvest when present in the pesticide
formulation at not more than 0.6% [40 CFR 180.1001(c)].— In addition,
PCE was exempted fVom the requirements of a tolerance when used in
accordance with good agricultural practice as inert (or occasionally
active) ingredients in pesticide formulations applied to animals at all
concentrations [40 CFR 180.1001(e)l.
Various agencies and groups have evaluated potential human
and environmental effects associated with PCE exposure. Table 1 shows a
number of PCE concentrations that have been recommended by these groups as
the maximum exposure levels for man or the environment that will not
produce harmful effects. It should be noted that these levels were based
on the acute effects of PCE and do not consider recent data Indicating that
PCE is carcinogenic in the B6C3F1 mouse. Current NIOSH Interim guidelines
indicates that occupational exposure to PCE should be reduced and that a
reduction in the number of employees exposed to PCE should also be
considered because of PCE's carcinogenic potential.
TJ These exemptions were established prior to the determination in
September, 1977, that PCE is a carcinogen in B6C3F1 mice.
10
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A number of other groups in addition to those listed in
Table 1 have endorsed the exposure limits shown in that table, have
established their own maximum exposure levels, or are currently evaluating
effects of PCE on humans. A number of foreign governments have also set
maximum exposure levels for PCE ranging from 2 ppm in Czechoslovakia to
100 ppm in the Federal Republic of Germany (US EPA, 1979a).
11
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TABLE 1
Maximum PCE Exposure Recommendations Based Upon the Acute Toxicity of PCE
STANDARD,
RECOMMENDATION,
OR MAXIMUM PCE
EXPOSURE
ORIGINATOR
MEDIUM
EPA, Office of Water /
and Waste Management^
Freshwater
Chronic Toxic Effect
Acute Toxic Effect
Saltwater
Chronic Toxic Effect
Acute Toxic Effect
EPA, Office of Water and
Waste Management
Human Health Effects
EPA, Office of Drinking
Water
NIOSH:
10-hour time weighted
average
Ceiling
OSHA:
8-hour time weighted
average
Acceptable Ceiling
Maximum (5 minutes in
3 hours)
ACGIH^/
Threshold Limit Value
840 ug/1 Water
5280 ug/1 Water
450 ug/1 Water
10,200 ug/1 Water
8.0 ug/1 Water
(for a cancer
risk of 10"5)
0.5 ug/1b/ Drinking
Water
50 ppmc/ Air
100 ppm Air
100 ppm Air
200 ppm Air
300 ppm Air
100 ppm Air
US EPA, 1980
US EPA, 1980
US EPA, 1980
US EPA, 1980
US EPA, 1980
43 PR 5756
NIOSH (1976)
NIOSH (1976)
29 CFR 1910.1000
29 cm 1910.1000
29 CFR 1910.1000
ACGIH (1976)
Maximum level which will not harm aquatic organisms
Ty A maximum was not set specifically for PCE, however, maximum
concentration of volatile halogenated organic compounds must not
exceed 0.5 ug/liter.
cj As a result of an NCI bioassay indicating that PCE is carcinogenic to
B6C3F1 mice NIOSH has recommended that exposure to PCE"...should be
limited to as few employees as possible, while minimizing workplace
exposure levels (NIOSH, 1978)."
d/ American Conference of Governmental Industrial Hygienists.
12
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II. RISK ANALYSIS
A. Environmental Occurrence
A brief survey of published literature resulted in the following
information on background levels of PCE in the environment.
Monitoring has been carried out for PCE residues in the
environment. PCE was detected in 9 of 105 drinking water samples analyzed
between November 1976 and January 1977 at a range from <0.2 to 3.1 ug/liter;
median <0.2 ug/liter; mean 0.81 ug/liter (US EPA, 1978). In addition,
Dowty et al. (1975) detected PCE among a number of organic compounds in
drinking water before, during, and after processing at a municipal water
treatment facility in New Orleans, Louisiana.
Pearson and McConnell (1975) determined the concentration of PCE
in Liverpool Bay and other areas of the United Kingdom using gas chromato-
graphy. This study found PCE levels as follows:
Atmosphere <0.1 ppb to 40 ppb
Freshwater 0.15 ppb to 0.38 ppb
Seawater 2.6 ppb maximum,
0.12 ppb average
Marine sediments 4.8 ppb maximum
.Marine invertebrates 0.05 ppb to 15 ppb
Marine algae 13.0 ppb to 22 ppb
Fish <0.1 ppb to 41 ppb
Sea and Freshwater Birds 0.7 ppb to 39 ppb
Mammals 0.0 ppb to 19 ppb
McConnell et al. (1975) reported PCE levels In the following
materials: in meat ranging from 0.9 to 5.0 ug/kg, in oils and fats from
0.01 to 7.0 ug/kg.
Singh (1977) reported an average northern hemispheric background
concentration of 30.7 ppt (parts per trillion). Monitoring was done at a
"clean air continental site" (Badger Pass—Yosemite, California) at an
elevation of 2,360 meters, which was well above the inversion layer.
Slmmonds et al. (1974) found an average PCE concentration of
1.25 ppb (parts per billion) in the air over the Los Angeles Basin In
California. The range of PCE contamination in this study was reported to
be from <0.01 ppb to 4.2 ppb. These measurements were made at an altitude
of 3,200 meters.
Jensen and Ingvordsen (1977) found residues as high as 1,200 ppm
In freshly cleaned clothing in self-service dry cleaning machines in
Denmark. Air around the machines was found to contain 35 to 250 ppm of PCE.
NIOSH (1976) presented data taken from a study by Kerr (1972)
indicating that the average concentration of PCE in various commercial dry
cleaning plants ranged from 31 to 270 ppm with the highest level measured
being 990 ppm. The same study found concentrations of PCE around the area
used by the customers In coin-operated dry cleaners to range from 28 to
121 ppm. The maintenance area of these establishments contained from 93
to 378 ppm PCE.
13
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It should be noted that the Agency is presently examining other
non-pesticide uses of PCE and will address their significance under
appropriate statutes.
B. Exposure Analysis - PCE
Since Goal was referred to SPRD on the basis of oncogenic risk
from PCE contamination, this review will focus on exposure to PCE from use
of Goal 2E in soybeans, tree fruits/nuts, field corn and conifers.
Exposure from use on cotton will not be considered at.this time because no
application for use on cotton has been submitted. The exposure analysis
prepared by the Agency (Kozak, 1980 as modified by Regelman, 1981) provides
much of the basis for the information summarized in this section.
1. Method of Estimating Exposure
The registrant submitted an exposure analysis for £CE which
could theoretically result from use of Goal 2E on field corn, tree
fruit/nuts and soybeans. No analytical data were provided. This analysis
was modified as described below in order to arrive at the Agency's exposure
estimates.
Goal is presently registered for use as a pre- and post
emergence herbicide in tree fruits/nuts in California and conifer
seedbeds, transplants, and outplantings. Registration is pending for use
in field corn, and soybeans. Application is by tractor-mounted low boom
spray methods for all uses. Both inhalational and dermal exposures will be
considered. The inhalation estimate was derived from a model that assumed
total vaporization of the PCE in Goal since data on actual PCE levels
during application were not available.
While it is recognized that the above approach yields an
extremely conservative estimate of inhalational exposure, a number of
physical and chemical properties of PCE support this approach.' PCE is
highly volatile and even though it is photolabile, its reported two-day
half-life (Fuller, 1976) suggests that significant photodegradation will
not occur during the time required for Goal application. In addition,
since PCE has a vapor density 5.5 times greater than that of air,
it might tend to spread laterally (Instead of upward) under stagnant
conditions (Fuller, 1976).
Evaporation of PCE from aqueous solutions is known to be
rapid, even in the presence of adsorbing contaminants. In a study by
Dilling et al. (1978), a solution of PCE in water at a concentration gf
1 ppm was allowed to stand open to the atmosphere at approximately 25 C
and stirred gently. The PCE concentration of this solution decreased by 50%
after 26 minutes and by 90% after 83 minutes. It is likely that much more
rapid evaporation would occur under conditions in which the surface-to-
volume ratio of the solution was much greater, such as when the compound
was sprayed onto the soil surface in an agricultural spray operation.
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2. Applicator/Mixer/Loader Exposure
a. Inhalational Exposure
Daily inhalational exposure levels for applicator/
mixer/loaders were calculated— assuming that the average worker
weighs 70 kg, applies Goal 2E for 8 hours per day, inhales 14,400 liters of
air during a working day, that 100% of inhaled PCE is absorbed (Rohm and
Haas, 1978), and that all PCE in the formulated product is volatilized into
a rectangular prism of air six feet"high above the treated field. The
detailed calculation of inhalational exposure along with parameter values
for each use is presented in Appendix A.
The estimated daily inhalation Exposures to PCE are
summarized in Table 2.
The inhalational model did not consider an increment of
exposure to PCE during' the process of mixing/loading. Instead, it
presented PCE exposure assuming a full eight hours of spraying, since a
reliable method of quantifying PCE exposure during the mixing/loading
operation could not be found. However, based on the physical and chemical
characteristics of PCE, as well as on the limited time involved in the
mixing/loading operation (less than one hour), it is expected that the
quantity of PCE vaporized during mixing/loading operations would be less
than that which would occur during application. The Agency estimate,
therefore, further tends toward the conservative side, where "conservative"
is defined to be protective of human health.
b. Dermal Exposure
Dermal exposure data for applicator/mixer/loaders using
tractor-mounted low-boom spray apparatus is limited in the literature. The
registrant has, however, developed an estimate of this exposure using the
model which takes into account the amount of liquid contacting applicators'
skin during spraying (Rohm and Haas, 1978). The registrant assumed that
0.048 pint of diluted spray could contact an applicator's skin during an
8-hoiir day and that' 10% of this amount would be absorbed.
a/
87Inhalation - Grams PCE/Acre x Volume Air Inhaled/Day—
Exposure Volume of Air/acre-- x Average Body Weight
(soybeans)
* 0»064Sg PCE/Acre x 14,400 liters/day x 1000 mg/gm
, . • . 7.4 x 10 liters/Acre x 70 kg Body Weight
- 1.804 x 10~3 rag/kg/day
^( 1.8 m3/hr x 1000 1/m3 x 8 hr/day » 14*400 liters/day 3
—' volume of air/acre - 6 ft x 43,560 ft /acre x 28.3,I/ft
« 7.4 x 10 liters of air/acre
15
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TABLE 2.
Daily PCE Inhalation Exposure for . .
Applicator/Mixer/Loaders Using Goal 2E-'—'
CROP (mgAg bw/day)
Soybeans 1.804 x 10"3
Field Corn 7.211 x 10"3
Tree Fruits/Huts 7.211 x l(f3
Oonifers 7.211 x 10"3
a/ Assumes 200 ppm PCE in Goal 2E.
by Assumes an 8-hour day of spraying,
16
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These values were originally derived from an applicator
exposure study for paraquat, conducted by Staiff et al. (1975). The study
was performed with workers using tractor-mounted low-boom spray equipment,
the method also recommended for Goal 2E. The applicators in that study
used a liquid concentrate formulation. Exposure was calculated on the
basis of workers wearing short-sleeved, open-necked shirts, no gloves, and
no hats. It was further assumed that the clothing worn protected the skin
beneath the covered areas.
Use patterns, maximal use conditions and the amount of
Goal 2E/PCE in the applied spray were estimated, and were used to compute
the dermal exposure estimates— which are summarized in Table 3. The
estimates assume that the typical applicator/mixer/loader weighs 70 kg, and
spends one hour/day in mixing/loading and 7 hours/day in spraying. The
detailed calculation of dermal exposure, along with parameter values for
each use is presented in Appendix A.
Since worker exposure does not occur daily throughout the
year, nor does it occur throughout the lifetime of an applicator,
adjustments to the estimates were made to allow for these variations in
exposure. Using an average applicator exposure time of 10 days/year,
(62.5 days/year for corn), assuming a working life of 40 years, and a 70-
year life-span, the daily average lifetime exposure estimates were
calculated, — and are summarized in Table A. These estimates were
9/ Daily dermal exposure to PCE through use of Goal 2E in soybeans was
calculated as follows:
Dermal •= PCE Concentration ,x Diluted Spray x .Weight per Pint of Water x
Exposure in Diluted Spray^- Contacting Skin—
(soybeans)
Percent Skin «_ Average Body
Penetration • Weight
- 0.86 ug/g x 0.048 pints x .4.54 g/pint x 0.1 x 1 mg/1000 ug
70 kg bw
= 2.7 x 10" mg/kg bw/day
a/ PCE Concentration - PCE Weight Rate (grams/acre)
Spray Weight Rate (grams/acre)
• 0.0645 g/acre x 10 ug/g
8.34 Ibs/gal H20 x 454 g/lb x 20 gal H20/acre
• 0.86 ug PCE/g H20
Jb/ Rohm and Haas, 1978.
10/ 10 days/year x AO yaflts - 0.0156 for soybeans, tree fruit/nuts
70 years x 365 days and conifers
17
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TABLE 3.
Dally PCE Dermal Exposure for ,, , ,
Applicator/Mixer/Loaders Using Goal --
CROP (rag/kg bw/day)
Soybeans 2.7 x 10
Field Corn 2.1 x 10~4
Tree Fruits/Nuts 2.8 x 10
Conifers 1.1 x 10~4
a/ Assumes 200 ppm PCE in Goal 2E.
b/ Assumes 1-hour mixing/loading and 7-hour spraying,
c/ Based on Staiff, et al. (1975) work on paraquat.
18
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TABLE 4.
Adjusted Lifetime Average Daily Worker Exposure
to PCE from Use of Goal 2E3-'
Crop
Inhalation
mg/kg bw/day
Dermal Total
mg/kg bw/day mg/kg bw/day
Soybeans
Tree Fruit/touts
Conifer
2.814 x 10
.-5
Field Cornk/ [1981] 7.013 x 10"
1.125 x 10
1.125 x 10"
.-4
4.2 x 10
,-7
2.0 x 10
,-5
4.4 x 10
-7
1.7 x 10'
,-6
2.8 x 10
,-5
7.2 x 10'
,-4
1.1 x 10"
1.1 x 10
,-4
a/ Assumes 200 ppm PCE in Goal 2E.
b/ Soybean, tree fruit/nuts, and conifer estimates are based on 10
working days per year. Field corn estimates were further adjusted
to reflect the number of days that applicators are estimated (Petrie,
1980c) to be treating field corn as part of the USDA Witchweed Eradication
Program during 1981 (62.5 days). It is estimated that 100,000 acres of
field corn will be treated in 1981.
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used by the Agency as the basis for estimating individual lifetime
carcinogenic risk (Section II.C. of this document). Further reductions in
the level of PCE contamination of Goal 2E would produce proportional
decreases in the estimate of worker exposure.
In order to reduce applicator exposure to PCE, a number of
protective measures may be taken. Severn (1978), in evaluating citrus use
of chlorobenzllate, estimated the reduction in applicator exposure by the
use of both protective clothing and respirators. Under the assumptions
that the exposed skin surface, in the absence of protective clothing, is
0.29 m (face, neck and "v" of chest, forearms and hands), and that
clothing which covers these areas (except the face) completely protect
them, the exposed skin surface area of a pesticide applicator is estimated
to be reduced from 0.29 m to 0.065 m . In addition, the wearing of
the respirator during application would be expected to further reduce
exposed skin surface to 0.042 m . Finally, assuming that a suitable
respirator were used, inhalational exposures would be expected to be
reduced to extremely low levels.
Table 5 summarizes estimated applicator exposure under
these assumptions, reflecting a nearly 85% reduction in dermal exposure
(0.042m /0.29 m - 0.145), and a 100% reduction in respiratory
exposure.
3. Dietary Exposure
While current data show no PCE residues in crops at the
limit of detection, the Agency still considers that residues of PCE in
Goal-treated commodities may exist below this level* Accordingly, the
Agency estimated the theoretical maximum level of PCE in soybeans, field
corn grain, and bearing tree fruit/nuts.
Rohm and Haas submitted data indicating the results of
analysis for PCE in corn grain, various tree fruit/nuts, and soybeans grown
on Goal-treated soil. These analyses indicated that PCE was not detected
in these commodities at 0.05 ppm (the analytical sensitivity of the method
used) (Perfetti,.1979a). The theoretical maximum dietary exposure was
then calculated, — and is summarized in Table 6. Calculations of
dietary exposure and parameter values for each use are presented in
Appendix A.
IT/Dietary - Daily Consumption— x Sensitivity of
Exposure of commodity analytical method
(Soybeans) Human Body Weight
0.01819 kg x 0.05 tag/kg^- 1.30 x 10"5 mg/kg bw/day
70 kg
o_l Daily consumption of commodity in kg/person/day is based on
the average consumption figures for each commodity (Schmitt, 1977).
b_/ Assumes that 0.05 ppm level of analytical sensitivity is equivalent
to 0.05 mg/kg of commodity.
20
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TABLE 5.
Adjusted Lifetime Average Daily Worker Exposure /
to PCE from Use of Goal 2E - Protective Clothing Scenario^'
Crop
Soybeans
Field Corn [1981]
Tree fruit/Huts
Conifer
Inhalation
rag/kg bw/day
0
0
0 .
0
Dermal
rag/kg bw/day
6.1 x 10"8
2.9 x'lO"6
6.4 x 10"8
2.5 x l(f 7
•total
mgAg bw/day
6.1 x 10"8
2.9 x 10" 6
6.4 x 10~8
2.5 x 10"7
a/ Assumes applicators wear protective clothing and suitable respirator.
21
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TABLE 6.
Theoretical Maximum Dietary Exposure to PCE
Soybeans
1.30 x 10~5 mgAg bw/day
Field Corn
3.57 x 10"5 mgAg bw/day
Tree Fruits/Nuts
1.90 x 10~5 mgAg bw/day
22
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The Agency recognizes that these estimates are conservative,
since they assume that all consumed corn, tree fruit/nuts and soybeans
contain PCE residues from Goal-treatment. Therefore, further downward
adjustments must be made to take into account the percentage of these
commodities likely to be treated with Goal.
Estimates of percentage of crop treated are currently 8% for
soybeans and 1.6% for corn. In addition, the field corn that will receive
Goal treatment under this registration is limited to that grown in witch-
weed infested areas of North and South Carolina, treated in conjunction
with the USDA's Witchweed Eradication Program. These adjustments to the
maximum dietary exposure are summarized in Table 7. It is estimated that
50-90% of bearing tree fruits/nuts might possibly be treated with Goal, so
that no downward adjustment was made for these commodities.
C. Cancer Risk Assessment
1. Introduction
The Agency's Interim Cancer Assessment Guidelines (Cancer
Guidelines) (41 FR 21402) state that when a chemical is judged to be a
potential human carcinogen, the Agency will estimate its possible impact on
public health at current and anticipated levels of exposure. The Cancer
Guidelines also recognize that the available techniques for assessing the
magnitude of cancer risk to human populations based on animal data are at
best very crude; this is due to uncertainties in the extrapolation of dose-
response data to very low dose levels and to differences in levels of
susceptibility of animals and humans. Accordingly, these risk estimates
are neither scientific certainties nor absolute upper limits on the risk of
cancer from use of PCE contaminated Goal. Rather, these estimates should
be viewed as a health hazard index that incorporates the degree of
carcinogenic activity and hunan exposure to the compound.
2. Evaluation of Cancer Data
The Agency has prepared an estimate of the carcinogenic risk
to agricultural workers and to the U.S. population associated with the use
of PCE contaminated Goal 2E. This evaluation was based upon data submitted
by the registrant, Rohm and Haas, and studies acquired by the Agency from
the open literature. These studies are discussed in the following
sections.
a. Perchloroethylene
The following discussion (a.l) through a.6)] was
taken from the EPA Carcinogen Assessment Group's risk assessment for PCE
(CAG, 1979).
Two long-term animal bioassays have been performed to
assess the carcinogenic potential of PCE. In one study (NCI, 1977) in
which mice and rats were exposed to PCE by gavage, the National Cancer
Institute (NCI) reported the induction of a highly significant number of
hepatocellular carcinomas in male and female mice, but concluded that the
test with rats was inconclusive due to excessive mortality.
23
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TABLE 7.
Adjusted Maximum Dietary Exposure to PCE
Soybeans 1.04 x 10 mgAg bw/day
Field Corn [1981]a/ 4.96 x 10"8 mgAg bw/day
Tree Fruits/touts 1.90 x 10~5 mgAg bw/day
a/ Up to 100/000 acres of field corn are expected to be treated.
-------
In the other study (Rampy et al., 1978) In which
Sprague-Dawley rats were exposed by inhalation of PCE, the authors reported
no evidence for the carclnogenicity of the chemical.
1) National Cancer Institute Bioassay (1977)
PCE was one of several halogenated hydrocarbon
compounds tested for possible carcinogenicity in male and female (Osborne-
Mendel) rats and male and female (B6C3F1) mice by NCI. PCE was
administered to the animals in a corn oil vehicle by gastric intubation 5
days a week for 78 weeks. The vehicle control animals were Intubated with
an amount of pure corn oil equal to the amount given to the high dose
animals. At the end of 90 weeks (mice) or 110 weeks (rats), surviving
animals were killed, necropsied, and submitted to an extensive gross and
microscopic examination.
The summary of tumor incidence in male and female
mice at low and high dose levels of PCE is described in Table 8. The
results indicate that PCE Induced a highly significant increase in the
incidence of hepatocellular carcinomas in both sexes of mice as compared
to untreated controls or vehicle controls.
In rats, PCE-related chronic nephropathy occurred
in exposed groups. The animals were also afflicted with chronic respira-
tory disease* Survival of PCE-exposed rats was poor, and the decrease In
survival was significantly associated with increasing dose levels. No
hepatocellular carcinomas were observed In any of the exposed rats. No
significant changes in the structure of the liver were observed, and no
statistically significant tumor incidence was observed at any anatomical
site other than the liver* The National Cancer Institute concluded that
the high mortality among rats detracted from the usefulness of the
experiment in detecting carcinogenic potential with that species.
In summary, perchloroethylene Induced a
statistically significant Incidence of hepatocellar carcinomas in both
sexes of mice at low and high dose levels. However, the bloassay for
rats was considered Inadequate due to early mortality of many of the study
animals (GAG, 1979).
2) Rat Inhalation Study (Rampy et al., 1978)
Male and female.Sprague-Dawley rats were exposed
to 300 or 600 ppm (2034 or 4068 mg/m ) PCE in the air five days a week
for 12 months. Although many tumors were found both in treated and control
animals, there was no statistically significant increase in tumor Incidence
at any anatomical site.
\
Increase^ mortality occurred in the male rats
exposed to 600 ppm (4068 mg/m ). Earlier onset of advanced chronic renal
disease appeared to be a contributing factor to the Increased mortality
rate of this group which also had a statistically significant increase in
kidney tumor or tumor-like changes observed in gross pathology. However,
light microscopic observation of kidney lesions did not reveal a statis-
tically significant tumor incidence Increase as compared to controls. Both
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TABLE 8.
Incidence of Hepatocellular Carcinomas in
B6C3F1 Mice With PCE Administered by
by Gavage (NCI, 1977).
Dose (mg/kg/day) Hepatocellular Carcinomas
Male
untreated 2/17 (12%)
vehicle control 2/20 (10%)
536 32/49 (65%)
1072 27/48 (56%)
Female
untreated 2/20 (10%)
vehicle control 0/20 (0%)
386 19/48 (40%)
772 19/48 (40%)
26
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groups of female rats exposed to PCE showed liver atrophy, and high
exposure-level females had an increased incidence of fluid filled cysts in
the liver.
The authors of the report concluded that there was
no evidence of tumor reponse to PCE because the incidence of tumors was
similar for exposed and control rats. However, this study had the follow-
ing drawbacks: (1) the period of exposure was only 12 months; (2) dose
levels employed in this study were not high enough to provide maximum
sensitivity. Because of these limitations, this study is inconclusive and
not appropriate to use in assessing the carcinogenicity or noncarcinoge-
nicity of PCE (CAG, 1979).
3) Intraperitoneal Administration
Theiss et al. (1977) injected six to eight-week-
old, male strain Amice intraperitoneally (i.p.) with doses of 80 mg/kg, or
400 mg/kg PCE. The i.p. injections were given three times a week until 14
injections at 80 mg/kg or 24 injections of 200 or 400 mg/kg were completed.
The survivors were sacrificed 24 weeks after the initial injection of PCE.
There was no statistically significant increase in lung tumor incidence in
treated animals as compared to controls.
4) Skin Painting Study of PCE by Van Duuren
et al. (1979)
Van Duuren and his co-workers performed mouse skin
bioassays of several halogenated hydrocarbons including PCE in groups of
mice (ICR/Ha Swiss) for about one year.
A total of seven papillomas developed on 4 of 30
mice receiving PCE application followed by applications of phorbol
myristate in acetone to the skin of the back. Of 90 mice receiving only
applications of phorobol myristate acetate, six developed a total of seven
skin papillomas. Two of these mice also developed squamous cell
carcinomas. However, the results of this study are not statistically
significant and this study does not provide evidence of positive
carcinogenic effects by this mode of administration (CAG, 1979).
5) Cell Transformation
Price et al. (1978), using a highly sensitive j£
vitro cell system, demonstrated the transformation of Fischer rat embryo
cells (F1706) to tumor-producing cells upon exposure to PCE. When these
morphologically-altered cells were injected subcutaneously into newborn
(Fischer) rats, tumors developed at the injection sites in all animals in
less than two months. Based on this observation, the author concluded that
PCE had a carcinogenic potential.
27
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b. Oxyfluorfen
Two long-term rodent feeding studies were performed to
assess the carcinogeriicity of oxyfluorfen (Bio-Dynamics, 1978; IRDC, 1977).
1) Rat Study (Bio-Dynamics, 1978)
In this study, male and female (Long - Evans) rats
were fed oxyfluorfen in the diet at levels of 2 ppm, 40 ppm and 800 ppm
(raised to 1600 ppm at week 57 of the test) for 24 months. Interim
necropsy was performed on a number of control and high dose animals at 12
months. Terminal sacrifice and necropsy for all surviving animals was
performed at 24 months. The oxyfluorfen used in this study contained 5 to
60 ppm PCE (Rohm and Haas, 1978).
The 40 ppm dose level was considered to be the highest
dose level giving no observable effect (NOEL). This was the middle dose
level of the study. The high-dose level exhibited a mild treatment effect
which microscopically was observed as minimal hypertrophy of centrilobular
hepatocytes of the liver (1 male and 2 females). The liver cell change
seen after 24 months of treatment was histomorphologically similar to that
seen in rats examined from 12-month interim necropsy. There was no
indication of any tumorigenic activity in any of the tissues examined in
rats. The incidence of the neoplastlc processes encountered generally was
similar among the control and compound-treated groups or occurred in a
single animal or at a very low incidence in rats of the various groups.
However, further evaluation of this study indicated that the high dose
was not reflective of the maximum tolerated dose (MTD) In this species.
Therefore the study may be inadequate to determine the oncogenic potential
of oxyfluorfen (Albert, 1980; Dykstra, 1981).
2) Mouse 20-Month Feeding Study (IRDC, 1977)
Male and female Charles River CD-I mice were fed diets
containing 2, 20, and 200 ppm Goal (85.7% active Ingredient) for 20
months. The following discussion of the results is taken from the EPA
Carcinogen Assessment Group (CAG) report on Goal (Albert, 1980).
The results of this study indicate that there was a
dose-related toxic response In the livers of both male and female mice and
that this was most pronounced in males (Squire, 1980). With respect to
carcinogenic!ty, hepatocellular neoplasms were found In both treated and
control animals. The Increase in the incidence of liver tumors (carcinomas
and adenomas combined) was not statistically significant even In the high
dose males (p » 0.068) where the largest liver tumor incidence occurred.
However, a statistically significant dose trend (p • 0.008) was
demonstrated for liver tumors (adenomas and carcinomas combined). The
Agency therefore determined that the evidence for carcinogeniclty in this
study is only marginal (Albert, 1980).
The potential carcinogenic role of the perchloro-
ethylene (PCE) contamination of oxyfluorfen in this particular study was
o examined in this review. Although the current level of PCE In Goal 2E
is 200 ppm, the PCE content of the recrystalllzed oxfluorfen used in this
study ranged from 5 to 60 ppm (Rohm and Haas, 1978). The mg/kg/day of PCE
consumed by the high dose mice was calculated and related to animal tumor
28
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Incidence based on the NCI bioassay in B6C3F1 mice for oral PCE. Using
this information, it was then determined that the incidence of tumors due
to PCE contamination would be approximately 8.27 x 10 . Since this is
too small to have been detectable in this study, it is likely that PCE is
not the cause of the small incidence of tumors observed (Albert, 1980).
Certain inconsistencies in the protocol and conduct of
the mouse feeding study make it of questionable value for the evaluation of
the carcinogenic potential of oxyfluorfen (Albert, 1980). The 200 ppm dose
groups were administered 800 ppm during weeks 57 and 58 of the study.
Also, the high dose (200 ppm) does not appear to be representative of a
maximum tolerated dose (MTD), as evidenced by a lack of change In body
weight, food consumption, mortality, or other in-life observations due to
compound adminstration. It appears, therefore, that the level of
oxyfluorfen used in this study was too low to be of toxicological
significance (Albert, 1980).
The Agency considers this study to be inadequate for
the accurate evaluation of carcinogenic potential of oxyfluorfen, because
of the Inconclusiveness of the results and the inconsistencies In the
protocol and conduct of this study.
3. Cancer Risk
a. Introduction
The Agency based Its estimate of human exposure to the
PCE contaminate of Goal 2E on a model which assumed total vaporization of
PCE Into a stagnant atmosphere during application operations. PCE exposure
was calculated for Goal 2E contaminated with 200 ppm PCE (see Tables 2
through 7). In this model, worker exposure can be further reduced in
proportion to reductions in PCE contamination in the formulated product and
by measures which reduce exposure to workers and to the general
population. A complete discussion of the exposure estimate is given in
Section II.B. of this document.
Based upon this exposure estimate, the Agency
calculated the individual lifetime risk of cancer to agricultural workers
and the general population assuming that the risk was a function of the PCE
contaminant of oxyfluorfen alone. The Agency calculated the risk
associated with exposure levels using the multistage model for risk
assessment and based upon the male mouse data from the NCI bioassay for
carclnogeniclty (discussed earlier in Section II.C.2.b.).
29
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For the multistage model the relationship between dose and
risk is as follows:—'
P =
where P = the lifetime probability (risk) of cancer
q = coefficient
d = dose
b. Applicator/Mixer/Loader Risk
Table 4 summarizes the Agency's estimate of applicator/
mixer/loader exposure to PCE from the use of Goal 2E in soybeans, field
corn (witchweed eradication), various tree fruit/nuts and conifers. These
exposure estimates were then used in the multistage model. Table 10
presents the risk estimates using the multistage model. These estimates
assume a 40-year working life, a 70-year lifespan, 200 ppm PCE
contamination of Goal 2E, application of 10 days per year in soybeans and
tree fruit/nuts, .and conifers and 62.5 days per applicator in 1981 for corn.
c. Dietary Risk
Table 9 shows the estimate of maximum carcinogenic risk
to the general population through the potential ingestion of PCE residues
associated with treatment of agricultural sites used for the production of
soybeans, field corn (witchweed eradication) and certain tree fruit/nut
(Dykstra, 1931b). Although actual PCE residues have not been detected at a
0.05 ppm level of analytical sensitivity in samples of corn grain and
soybeans treated with Goal 2E, the Agency assumed that PCE residues could
exist in these crops at the level of analytical sensitivity for the purpose
of estimating the worst-case dietary risk that might be associated with use
of PCE contaminated Goal 2E in these food crops. Therefore, actual
residues of PCE in these commodities may be much lower than 0.05 ppm. The
Agency calculated the risk associated with exposure levels using the
multistage model and based upon the male mouse data from the NCI bioassay
for carcinogenicity (discussed earlier in Sections II.C.2.b. and II.C.3.a.).
12/ See Appendix B for sample risk calculation.
30
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TABLE 9.
Carcinogenic Risk to Applicator/Mixer/Loaders and to the
General Population Associated with the FCE Contaminant
of Goal 2E (Dykstra, 1981b)
Crop Exposure Estimate Risk Estimate
(mg/kg/day)
Worker;
Soybeans 2.8 x l(f5 1.48 x l(f6
Field Corn . 7.2 x 10~4 3.82 x 10~5
Tree Fruit/Nuts , ,
(bearing; 1.1 x 10 5.84 x 10
nonbearing)
Conifers 1.1 x 10~4 5.84 x 10~6
Dietary;
Soybeans 1.0 x 10~6 5.30 x 10"8
Field Corn 5.0 x 10~8 2.65 x 10~9
Tree Fruit/Nuts
(bearing only) 1.9 x 10"° 1.00 x 10~°
31
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00
NJ
TABLE 10.
Adjusted Lifetime Average Daily Worker Exposure to and
Associated Risk from PCE in Goal-
Inhalation Dermal Total Risk
Crop (mg/kg bw/day) (mg/kg bw/day) (rag/kg bw/day)
Soybeans 0 6.1 x 10~8 6.1 x 10~8 3.24 x 10~9
Field Corn [1981] 0 2.9 x 10~6 2.9 x 10~6 1.54 x 10~7
Tree Fruit/Nuts 0 6.4 x 10~8 6.4 x 10~8 3.39 x 10~9
Conifers 0 2.5 x 10~7 2.5 x 10~7 1.33 x 10~8
a/ Assumes applicators wear protective clothing and suitable respirator.
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d. Reduction of Risk by the Use of Protective Clothing and
Equipment
The protective equipment and clothing scenario described
in Section II.B.2.b. of this document reduces applicator exposure to PCE
for all uses of oxyfluorfen. This results in a concomitant reduction in
the risk associated with each of the uses. The estimated applicator
exposure to PCE and associated risk under the protective equipment scenario
are presented In Table 10. Table 11 presents a comparison between risk
without protective equipment and the risk to applicators when protective
equipment is employed.
D. Other Adverse Effects
1. Mutagenicity
a. Introduction
40 CFR 162.11(a)(3)(ii)(A) provides that a "....
rebuttable presumption shall arise If a pesticide's Ingredlent(s),
metabolite(s), or degradation product(s) ... induces mutagenic effects, as
determined by multitest evidence."
The importance of protecting humans against exposure to
environmental rautagens is twofold. First, it is essential to protect
against germinal mutations which may pose a threat to the health of future
generations (i.e., expression of genetic disease) and secondly, to protect
against somatic mutations which may be a possible cause of cancer or other
genetically mediated disease.
b. Oxyfluorfen Mutagenlcity Data
The following mutagenicity review is based on the Repro-
ductive Effects Assessment Group's (REAG) Preliminary Report on the
Mutagenlcity of Oxyfluorfen (1980).
All oxyfluorfen mutagenicity data reviewed by the Agency
have been submitted by the registrant. The submitted studies included
tests which examined the ability of oxyfluorfen to cause point mutations
and primary DNA damage in bacteria, mitotic recombination in yeast, and
chromosome aberrations in rats. Also, attempts were made by the Agency to
locate published mutagenicity studies by conducting several literature
surveys. No references pertinent to the mutagenicity of oxyfluorfen were
found.
33
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TABLE 11.
Comparison of Applicator Risk With and Without the Use of
Protective Equipment
Risk Without Risk When Protective
Crop Protective Equipment Equipment is Employed
Soybeans 1.48 x 10~6 3.24 x 10~9
Field Corn [1981] 3.82 x 10~5 1.54 x 10~7
Tree Fruit/Nuts 5.84 x 10~6 3.39 x 10~9
Conifers 5.84 x 10~6 1.33 x 10~8
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The Nomura Research Institute (NRI, 1980) evaluated the
mutagenicity of Technical Goal (RH-2915, lot number 2-3985) with the
Salmonella /microsomal activation system, the Escherichia coli
tryptophan reversion assay, and the Rec-assay in Bacillus subtilis. The
purity of oxyfluorfen used in these studies was reported as 72.0% (nine
kinds of'impurities were indicated but were not identified except 0 to 1%
perchloroethylene). In the NRI study, Salmonella tests were carried out
using the standard plate assay over-a 500 fold concentration range (0, 10,
50, 100, 500, 1000, 5000 ug/plate — ) of Technical Goal with base-
pair substitution sensitive strains TA 1535, TA 100, TA 92, and with
frameshift sensitive strains TA 1537, TA'1538, TA 98, and TA 94.
In the absence of in vitro microsomal activation, dose-
related positive responses were found with strains TA 100, TA 98, and
TA 1538. When revertant counts at the highest concentration tested
(5000 ug/plate)are compared to the spontaneous control revertant counts,
TA 100 and TA 98 were weakly reverted (2.4 and 1.9 - fold increases in
spontaneous revertant counts respectively) and TA 1538 showed a 7-fold
increase in the number of spontaneous revertants. The mutagenic activity
(expressed as the slope of dose-response curve) of Technical Goal in the
presence of rat liver S-9 mix for metabolic activation, appeared to be
increased about three-fold over the induced mutagenic activity observed
without S-9 mix for TA 100, TA 98, and TA 1538. Strain TA 1537 was weakly
reverted by Goal but only after S-9 activation (2.1-fold increase in the
negative control value at 5000 ug/plate). Negative results were observed
with strains TA 94, TA 92, and TA 1535 when tests were carried out with
and without rat-liver enzyme activation. These results indicate the
mechanism of genetic activity of Technical Goal for Salmonella is by
frameshift mutation.
The Rec-assay (a differential growth inhibition test)
conducted by NRI used a strain of Bacillus subtilis which is repair
deficient (M45 Rec-) and a strain which is repair competent (HI7 Rec+).
Tests were carried out in the absence of in vitro mammalian metabolic
activation. No growth inhibition in either Rec+ strain or Rec- was
observed at concentrations up to 1000 ug/plate well of Technical Goal.
Growth inhibition was observed at 5000 ug/well; a 4 to 5 mm difference in
growth of Rec- and Rec+ strains was found. At the next concentration
tested, 20,000 ug/well, a 3 mm difference was shown. Because this
indicates that Technical Goal is causing damage to bacterial DNA that can
be repaired, these results are considered to support the positive results
reported in Salmonella.
The Escherichia coll WP2 tryptophan reversion assay was
also used in the NRI study. The same concentration range (0 to 5000
ug/plate) was examined. Reversion of E. coli WP2 Her- by Technical Goal
was not observed in the presence or absence of S-9 metabolic activation.
It should be pointed out that this test system does not effectively detect
frameshift mutagens. In addition, there have been known mutagens which
test positive in the Salmonella assay, but which test negative in I5._ coli
WP2 assay (Sugimura et al., 1976; McMahon et al., 1979). .Therefore, these
negative results do not reduce the weight of the positive results obtained
in the Salmonella /microsome test system.
Following the NRI studies in Japan, the registrant
initiated another Salmonella /microsome assay (Smith, 1980) using both
J^3_/At 5000 ug/plate crystal formation occurs.
35
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recrystallized oxyfluorfen (99.7% purity, lot TTF-0685) and Technical Goal
(72.5% purity, lot 2-3985). It should be noted that the lot of Technical
Goal used in this study was the same lot tested by NRI. Oxyfluorfen was
examined at a concentration range of 1 to 7500 ug/plate for both technical
and recrystallized preparations in strains TA 98 and TA 100 with and
without metabolic activation. Briefly, when TA 98 and TA 100 were treated
with Technical Goal, dose-related responses, similar to those reported in
the NRI study, were observed In both strains. Therefore, these results
corroborate the results described in the NRI report for Technical
Goal. In contrast, analytical Goal was not detected as mutagenic when
tested in TA 98 and TA 100 with and without S-9 activation at 1 to 7500
ug/plate. Because Technical Goal produced point mutations in Salmonella
but recrystallized Goal did not, the possibility of an impurity with
mutagenic activity, in the technical product should be considered. Although
perchloroethylene is one of the impurities which is present in Technical
Goal, the available evidence suggests that PCE Is not detected as mutagenic
in bacteria (REAG, 1981).
Highly purified oxyfluorfen was initially examined for
mutagenicity In earlier studies submitted by the registrant (Litton
Bionetics, 1973). These tests included a bone marrow assay for detecting
cytogenetic effects and a host-mediated assay for detecting point
mutations. The purity of oxyfluorfen was 99+% (Krzeminski, 1980). In the
bone marrow assay, male rats (Sprague-Dawley) were dosed orally by
intubation per day at 0.1 mg/kg, 1 mg/kg, and 10 mg/kg of Goal (RH915, BRL
652) for five consecutive days. Five animals were used at each dose. The
investigators examined fifty metaphases per animal at the end of treatment
for chromosomal effects (chromatid gaps and breaks, chromosome gaps and
breaks, reunions, cells with greater than 10 aberrations, polyploidy,
pulverization). No detectable aberrations were reported. The criteria
used to establish the dosage levels are not clearly defined in the report
except that they were based on the registrant's knowledge of the LDcn of
RH 915 and the anticipated human exposure. Thus, it is possible that the
dose levels used were not high enough to induce chromosomal effects to a
detectable level (i.e., the maximum tolerated dose may not have been
approached). Therefore, the significance of the results is difficult to
interpret.
Litton Bionetics, Inc. (1973) also conducted in vivo
subacute host-mediated assays with parallel J.n vitro tests using the
mitotic recombination system In Saccharomyces and the histidine reversion
assay in Salmonella. In the in vitro Saccharomyces D3 assay, 5% Goal
(99 4- % purity) tested in liquid suspension for four hours did not
demonstrate any genetic activity. At this concentration no appreciable
cell killing (9%) occurred. The low toxicity may indicate that this
treatment condition was not sufficient to significantly increase mitotic
recombination. Negative results were also observed when "pure" Goal (0.1
ml of a saturated solution) was examined in the Ames spot test using the
base-pair substitution sensitive strains TA 1530 and G-46 without S-9
activation. Frameshift - sensitive strains were not evaluated in this
study. In addition, the spot test is not particularly sensitive for
detecting weak mutagenicity due to its qualitative nature. Since the
report did not provide information on the number of revertants
(experimental and control) and toxicity of dose used, the reported negative
result cannot be considered evidence supportive of the nonmutagenlclty of
oxyfluorfen.
36
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Host-mediated assays using Saccharomyces and Salmonella as
indicator organisms and Flow Laboratory ICR random-bred male mice as the
host to activate the test substance were conducted. The dosage levels used
were 0.1 mg/kg, 1 mg/kg, and 10 mg/kg per day for five days. Mice were
dosed by stomach tube and 30 minutes after the last dose the indicator
organism was injected into the peritoneum. Goal (99+% purity) did not
significantly increase the incidence of recombination or histidine .
independent revertants in Saccharomyces or Salmonella, respectively.
Although a weak response (3.4-fold increase in control value) was observed
at 1 mg/kg for yeast, the response was not dose-related. In addition,
there are several deficiencies in this report which make the Interpretation
of the results tenuous. The number of indicator organisms recovered was
not given and the standard deviation of the results was not reported. In
addition, the criteria used to establish'the dose levels to arrive at a
maximum tolerated dose are not clearly indicated, thus it is not known if
the test material was available at concentrations sufficient to increase
the mutation frequency of the indicator organism. It shouldbe noted that
in order for Goal to produce mutations in the indicator organism, it (or
its active form) must be absorbed and transported to the peritoneum of the
host animal.
In summary, results from two independent studies indicated
that Technical Goal (72% to 72.5% oxyfluorfen) produced point mutations in
Salmonella typhimurium. In addition, a Rec-assay using Bacillus
indicated the ability of Technical Goal to damage bacterial DNA. Because
recrystallized Goal (99.7% oxyfluorfen) was not detected as mutagenic in
Salmonella in the Rohm and Haas study, the possibility of an impurity with
mutagenic activity .present in the technical grade product cannot be
ignored. Nevertheless, the technical product is mutagenic to bacteria and
may cause mutations in other organisms as well, including mutations in
humans. However, further testing in other organisms should be conducted
with Technical Goal to confirm its mutagenic activity.
With respect to mutagenicity testing of highly purified
Goal (99+% oxyfluorfen), negative results were reported in the Salmonella/
microsome assay (Rohm and Haas, 1980), the bone marrow assay, and the
in vivo host-mediated assay with parallel JLri vitro tests using Salmonella
and Saccharomyces (Litton, 1973). The negative results found in these
studies do not permit a final judgment on the potential rautagenicity or non-
mutagenicity of oxyfluorfen because of the experimental deficiencies found
in the studies conducted in 1973 and because the genetic end-points, point
mutations, and chromosomal mutations have not been adequately examined.
Therefore, additional studies are needed to refute or confirm the reported
negative results for "pure" oxyfluorfen.
c. PCE Mutagenicity Data
Perchloroethylene has been tested for its ability to cause
point mutations in bacteria, point mutations and recombination in yeast,
and for chromosome aberrations in rodents. These studies are discussed
below.
Henschler (1977) found that PCE was not mutagenic when
tested using Escherichia coll K._ with metabolic activation. The lack of
mutagenicity demonstrated for PCE was theorized to be due to the formation
of a stable symmetrical configuration of the oxiranes derived from this
compound (CAG, 1979).
37
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Greim et al. (1975) reported negative results in a
preliminary report of testing employing jin vitro metabolic activation of
analytical grade PCE at 0.9mM (survival 99 + 1%) for two hours in
Escherichia coli K12 (Mauer, 1980).
Bartsch et al. (1979) investigated the mutagenicity of a number of
haloethylenes including PCE. PCE was evaluated in a plate incorporation
assay adapted for testing volatile chemicals. Negative results were
reported with concentrations up to 4 x 10 M PCE using TA 100 in the
absence and presence of liver-enzyme activation.
Margard (1978) tested both stabilized and unstabilized PCE
in the Ames plate incorporation assay using TA 1535, TA 1537, TA 1538, TA
98, and TA 100. The unstabilized material was identified as purified PCE
and the stabilized material was identified as an industrial, degreasing
grade of PCE containing 0.07% epichlorohydrin and other stabilizer
components (Schlossberg, 1981). Positive responses were reported using the
frameshift sensitive strains TA 1538 and TA 98, and the base-pair
substitution sensitive strain TA 100 with 0.1 ml (concentration not given)
of stabilized PCE per plate both in the presence and absence of liver
enzyme activation. It should be stressed, however, that the stabilized
test material contained epichlorohydrin which has been shown to be strongly
mutagenic in Salmonella (McMahon et al.,1979; Andersen et al., 1978).
Unstabilized PCE (purified) was not detected as mutagenic in either the
presence or absence of metabolic activation up to 0.1 ml per plate.
Because stabilized PCE appears to produce point mutations in Salmonella and
"pure" PCE appears not to be mutagenic, this suggests that an impurity
(epichlorohydrin) may be producing the observed mutagenic activity in the
stabilized test material. However, with respect to mutagenicity testing of
highly purified PCE, it should be emphasized that a negative result in a
bacterial point mutation test does not preclude the mutagenic activity of
the chemical evaluated. For example, several factors such as the toxicity
of the test agent, differences between in vitro liver enzyme activation and
in vivo metabolic activation, and the relative reactivity (e.g., highly
reactive intermediates) of the metabolites could result in a chemical not
being detected as positive in an in vitro test system.
Cerna and Kypenova (Abst. 1977) reported increased
mutagenic activity in Salmonella typhimurium with PCE (both base-pair
substitution as well as frameshift mutation) in the presence and absence
of liver microsomal activation. The authors also reported that in the host-
mediated assay using tester strains TA 1950, TA 1951, and TA 1952, PCE
induced significant increases in the number of revertants (CAG, 1979).
However, this report was an abstract which did not include information on
the protocol used, did not present data to substantiate the conclusions,
and did not report the purity of the test material, or the concentrations
used.
Callen et al. (1980) evaluated the ability of PCE
(containing 0.01% thymol as a stabilizer) and six other halogenated
aliphatic hydrocarbons to cause gene conversion at the trp-5 locus, mitotic.
recombination at the ade-2 locus, and reversion at the ilv-1 locus in
Saccharomyces cerevisiae D7. In this organism, a marginal increase in
the frequency of gene conversion (19 convertants/10 survivors versus 14
convertants/10 survivors in the control) and mitotic recombination (530
mitotic recombinants/10 survivors versus 330 mitotic recombinants/10
survivors in the control) were produced by a one hour treatment at 4.9 mM
38
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(84% survival). When the concentration of PCE was increased to 6.6 mM (58%
survival), increases in gene conversion and tnitotic recombination (83 con-
vertants/10 survivors and 5260 mltotic recombinants/10 survivors,
respectively) were found., A marginal increase in reversion was observed at
4.9 mM (3.8 revertants/10 survivors versus 2.9 revertants/10 sur-
vivors in control). The reversion frequency was not determined at 6.6 mM.
Although concurrent positive controls were not included in this study, the
results indicate that PCE (with 0.01% thymol) is genetically active in
yeast. However, because there was no concurrent thymol control, the
activity of PCE needs to be re-examined in yeast using the "pure" chemical.
Rampy et al. (1978), in a chronic rat study, examined
three male and three female rats for chromosome aberrations after the
animals had been exposed to 300 or 600 ppm (2.03 or 4.07 rag/1) PCE formula-
tion by inhalation 6 hours/day, 5 days/week, for one year. The authors
reported no chromosome or chromatid aberrations in the bone marrow cells of
male rats, and indicated that the data for female rats were inadequate for
a clear Interpretation because of the low number of scorable metaphases.
The cytogenetic data and details of the protocol were not provided in this
report. Therefore, the negative conclusions forwarded cannot be
evaluated. In addition, it does not appear that the highest exposure level
is near the maximum tolerated dose for females because no weight loss was
reported and no mortality was observed. In males, however, the maximum
tolerated dose may have been approached because significant increases in
mortality above control values was observed at the highest dose tested. It
should be noted that it is not apparent that the investigators determined
the toxicity of the test material to arrive at a maximum tolerated dose for
this study in that dose levels were based on the threshold limit value of
100 ppm for PCE.
Cerna and Kypenova (1977) reported in ah abstract that,
male-mice (ICR) given an acute intraperitoneal dose or dosed intraperi-
toneally for five applications did not show cytogenetic effects in the bone
marrow cells. Details of the protocol and the cytogenetic data are not
available for an evaluation. In addition, purity of the chemical was not
reported.
In summary, PCE has not been clearly demonstrated to cause
point mutations in bacteria. However, a negative result in a particular
bacterial system does not preclude the mutagenic activity of a chemical in
other organisms. Only two positive reports were found in the available
literature and both utilized the Salmonella system; one was an abstract by
Russian authors where the purity of the test material was not reported and
the data were not provided to substantiate the reported results (Cerna and
Kypenova 1977), and the other indicates that only stabilized test material
[the mutagen epichlorohydrin (0.07%) reported to be present] was active and
nonstabillzed (purified) was not active (Margard, 1978). There is sugges-
tive evidence in yeast, however, that PCE may be genetically active.
However, since PCE contained 0.01% thymol as a stabilizer, this
positive response needs to be confirmed or refuted by re-examining PCE in
yeast using the "pure" chemical. Therefore, to date the bacterial tests
14/ A written request has been made to Dow Chemical Company to secure
these data.
39
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appear to be negative and the positive response reported in yeast does not
allow for a determination of PCE mutagenicity but emphasizes the need for
further studies to evaluate its mutagenicity*
The Agency considers the data base discussed above to be
insufficient to characterize PCE or Goal for mutagenicity.
2. Teratogenicity
a. Introduction
40 CFR 162.11(3)(ii)(B) provides that a rebuttable
presumption shall arise if a pesticide ingredient(s), metabollte(s), or
degradation product(s) ... "produces any chronic or delayed toxic effect
in test animals at any dosage up to a level ... which is substantially
higher than that to which humans can reasonably be anticipated to be
exposed ..."
b. Oxyfluorfen Teratogenicity Data
A rat teratogenicity study which has been submitted by the
registrant indicates that the active ingredient of Goal 2E, oxyfluorfen, is
not teratogenic at a dosage of 1000 mg/kg (Dykstra, 1979a). The Agency has
also reviewed a rabbit teratogenicity study with oxyfluorfen which it
determined was unacceptable (Dykstra, 1980d).
The possibility that oxyfluorfen might behave as a
teratogen was carefully considered because of the similarity in chemical
structure of oxyfluorfen to nitrofen,a known teratogen. However, studies
submitted to and reviewed by the Agency failed to detect any teratogenic
activity attributable to oxyfluorfen (Dykstra 1980). The data obtained
from these studies were not entirely adequate to assess the teratogenic
potential of oxyfluorfen because no post-natal evaluations were done in the
oxyfluorfen studies. Post-natal observations are of particular importance
in the case of oxyfluorfen because observation of the teratogenic effects
produced by nitrofen requires a test protocol which includes post-natal
evaluation.
Because the rabbit study was not acceptable and because
studies submitted to this date did not include post-natal evaluation, the
data available are considered to be inadequate to determine the teratogenic
potential of oxyfluorfen.
c. PCE Teratogenicity and Fetotoxicity Data
The Agency is not aware of any studies indicating .that PCE
is a teratogen.
A study done by Schwetz et al. (1975) reports reduced
fetal body weight and a slightly elevated fetal resorption incidence for
female rats which had inhaled 300 ppm PCE for 7 hours/day on days 6 through
IS of gestation.
At the exposure level of 300 ppm for 7 hours a day, the
rat would be exposed to 313 mg/kg/day. This exposure level is higher by a
ko
-------
factor of 6,788 than the highest human exposure calculated here for
oxyfluorfen contaminated by 200 ppm PCE (Dykstra, 1981a).
3. Chronic Toxicity
A two year dog feeding study (Hazleton, 1980) submitted by the
registrant has been reviewed by the Agency. A no-observed effect level
(NOEL) was not established in this study. At the lowest dose tested
(100 ppm) the effects observed consisted of the following: bile pigmented
hepatocytes, dose-related liver weight increases, dose-related alkaline
phosphatase, renal tubular exithelial vacuolization, and lymphocytic
thyroiditis (Dykstra, 1980ft. In order to establish a NOEL for oxyfluorfen
in dogs, the Agency believes that this study would need to be repeated at
lower dose levels.
E. Environmental Risk
The Agency has evaluated the potential environmental risks
associated with use of the active ingredient of Goal 2E (oxyfluorfen).
Although data are not currently adequate for determining whether use of
this compound would exceed the criteria for risk to wildlife at 40 CFR
162.11(a)(3)(i)(B) or 162.ll(a)(3)(ii)(C), Agency scientists have indicated
concern over four separate issues with respect to wildlife risks (Hitch,
1980).
1. Persistence and Bioaccumulation in Aquatic Habitats
The Agency has conducted a computer simulation of the
expected aquatic environmental concentration of oxyfluorfen. A small,
unstratified lake receiving input from a five acre watershed was simulated
with the Exposure Analysis Monitoring System (EXAMS) developed by the EPA,
Athens, Ga., Environmental Research Laboratory.
Results of this simulation indicate that oxyfluorfen loading
to such an aquatic system would be 0.046 kg per year. The sediment residue
after 1 year of loading is predicted to be 30 ppb.
Over the long term, based on model predictions, oxyfluorfen
can be expected to persist and accumulate in certain aquatic environments
(Hitch, 1980). The EXAMS simulation predicts a half-life for oxyfluorfen
in the model aquatic system to be 127.3 days, and that there will be
increases in the hydrosoil sediment concentration every year that the
pesticide is applied.
The possibility of annual increases in oxyfluorfen
concentrations in aquatic habitats limits the accuracy of exposure level
predictions for aquatic organisms and consumers of aquatic organisms.
The Agency believes that field monitoring of actual oxyfluorfen residues in
aquatic habitats is necessary to accurately evaluate the persistence,
bioaccumulation and hazard to aquatic organisms.
a. Preliminary Survey of Possible Monitoring Sites
The computer simulation indicating that oxyfluorfen might
be transported from treated fields thereby reaching environmentally
hazardous levels in aquatic habitats can be evaluated with field monitoring
-------
of actual treatment sites. To begin this evaluation, Agency personnel
conducted, from August 13, 1980 to August 15, 1980, a field survey designed
to select sites with physical parameters comparable to those used in the
computer simulation or with parameters more likely to cause runoff.
The preliminary survey sites were located within the
witchweed (Striga asiatica) quarantine area on the coastal plain of
North Carolina. Cooperating U.S. Dept. of Agriculture personnel selected
three farm sites having soils similar to those of Midwestern corn and
soybean fields. Each farm had corn acreage within the watershed of a swamp
or pond-like body of water. The R.S. Hilburn farm in Fender County was
treated with Goal in 1979 and 1980. The C.E. Quinn farm in Duplin County
received Goal treatments in the four years of 1977 thru 1980. Samples from
the third site provided controls for other samples. This farm—belonging
to P.P. Fensel—was located in Fender County. Corn fields on this farm had
not been treated with Goal. Aquatic organisms, soil samples, and hydrosoll
samples were collected from all three sites for residue analysis.
Because Goal may be expected to be more rapidly assimilated by the aquatic
organisms living in or near the hydrosoil, benthic organisms were collected
at each site. No, one, suitable, benthic organism taxon was common to any
two of the sites. Three different taxa were, therefore, collected: adult
crayfish (family: Astacidae), tadpoles (order: Anura), and freshwater
clams (class: Pelecypoda).
The EXAMS model simulation was made with the assumption
that only the uppermost hydrosoil strata would be reactive with
oxyfluorfen. A hydrosoil coring device was, therefore, employed which had
been designed by the cooperating USDA personnel to sample the top strata.
Table 12 shows the number of samples of each type, the average
residue concentration and the range of residue measurements.
b. Conclusions
The 50 ppb mean hydrosoil concentration found at the Quinn
farm exceeds the 30 ppb concentration projected with the EXAMS computer
model. This correspondence and the fact that the Quinn farm does have
treated fields in close proximity to a natural aquatic habitat indicates
that a definitive monitoring program at this site might help the Agency
determine if unreasonable harm to aquatic organisms is posed by the
witchweed use.
In general, however, the fields of the witchweed
quarantine areas were found to be of low gradient and to be comprised of
sandy soil. Portions of the soybean and bearing fruit use-pattern areas
are more highly sloped and contain finer, more organic soils. It is
recommended that oxyfluorfen monitoring, in the future, within the
witchweed control area include only fields where runoff to valuable aquatic
habitats is likely. Monitoring should, in addition, be conducted at
aquatic sites within the other major use pattern areas where runoff and
transport may be likely.
Some observations made during the survey have given rise
to an unexpected concern. Although no field soil residues were found at
the 10 ppb detection level at the Hilburn site, Goal apparently was still
providing control of the witchweed. This raises the question of whether or
not the observed hydrosoil cooncentrations of 50 ppb may'not be lethal to
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TABLE 12.
Goal Residue Analyses from Samples Taken in the Witchweed
Quarantine Area (August 13-15, 1980)
Farm
Quinn
(Treated)
,
Hilburn
(Treated)
Fensel
(Control)
Sample Type
Hydrosoil
Field Soil
Benthic Organism
Hydrosoil
Field Soil
Benthic Organism
Hydrosoil
Field Soil
Benthic Organism
Number of
Samples
6
2
2
2
2
2
2
2
2
Mean
(ppb)
50
72
20
*
*
*
*
*
Range
(ppb)
10-70
42-102
20
*
*
*
*
* Below 10 ppb detection limit.
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aquatic plants residing in the wetlands of the corn and other use pattern
areas (Hitch, 1981).
2. Toxicity to Molluscs
Oxyfluorfen has been shown to be toxic to certain aquatic
molluscs (Grassestrea virginica) at concentrations which may be
expected in the hydrosoil. The oyster larvae water column no effect level
has been determined to be 3.2 ppb (Vilkas, 1978). In addition,
pelecypode— may assimulate significant amounts of pesticides
directly from the sediments (Hauer and Morales-Alamo, 1978). Sediment
residues were predicted by the EXAMS model to be 30 ppb after one year of
loading. Preliminary monitoring data indicate that residue levels
predicted by the model can occur in the environment.
The Agency believes that these data are a cause for concern
with regard to certain endangered freshwater molluscs. Twenty species of
freshwater clams found throughout the Great Mississippi River Basin are
on the Department of Interior Endangered Species List (FR Notice 45-99,
1980). A large scale use pattern for oxyfluorfen in this area of the
United States may present,a hazard to these molluscs. The eight major
soybean producing states— are drained by the Mississippi River and
its' tributaries.
Section 7 of the December 28, 1973 Endangered Species Act
states that:
"All...Federal departments and agencies shall...insure that
actions authorized... by them do not jeopardize the
continued existence of... endangered species and threatened
species..."
The U.S. Environmental Protection Agency is, by this portion
of section 7, prohibited from authorizing actions—including pesticide
usages—which jeopardize endangered and threatened species. In order to
remove the jeopardy to endangered molluscs posed by the application of Goal
to soybeans, the Agency could request that the registrant provide
monitoring data during the conditional registration period. If the
monitoring data indicate that lethal concentrations are being approached,
then registrations for this use could be cancelled in the counties
providing habitat for the endangered clams. The counties providing habitat
for endangered clams are listed in Table 13.
15/ Pelecypoda is a class of aquatic mollusc which includes clams,
oysters, mussels and scallops.
16/ The eight major soybean producing states in the U.S. are Indiana,
Illinois, Missouri, Arkansas, Minnesota, Iowa, Mississippi, and Ohio.
kk
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TABLE 13.
States and Counties Providing Habitat for Federally Designated
Endangered Mussel Species.
States
Counties
Alabama
Arkansas
Illinois
Indiana
Iowa
Kentucky
Minnesota
Missouri
Ohio
Tennessee
Virginia
West Virginia
Wisconsin
Jackson/ Limestone/ Madison/ Marshall/ Morgan
Arkansas, Craighead/ Cross/ Greene/ Independence/ Izard/
Jackson/ Lee, Monroe/ Poinsett, Prairie/ St. Francis/ Stone/
White/ Woodruff
Carrol/ Gallatin, Hardin/ Henderson/ Jo Daviess, Massac,
Mercer/ Pope, Pulaski, Rock Island, White, Whiteside
Gibson, Knox, Pike, Posey
Allamakee, Clayton, Clinton/ Des Moines, Dubuque, Jackson,
Louisa, Muscatine, Scott
Ballard, Butler, Crittenden, Edmonson, Hart, Laurel,
Livingston, McCracken, Pulasky, Union/ Warren
Washington
Bolinger, Butler, Carter/ Cedar, Cole, Dunklin, Franklin,
Gasconade, Jefferson, Maries, Miller, Osage, Pike Rails,
Reynolds, Ripley, St. Clair, St. Louis, Stoddard, Wayne
Licking, Morgan, Mushingum, Washington
Bedford, Claiborne, Coffee, Decatur, Franklin, Grainger,
Greene, Hardin, Jackson, Lincoln/ Madison/ Marshall/ Maury,
Morgan, Perry, Robertson, Smith, Washington, Wayne
Washington
Fayette
Crawford, Grant, Iowa, LaCrosse, Richland, Sauk, St. Croix,
Vernon
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3. Possible Hazard to Wetlands
Some observations made during the Agency's preliminary survey
of monitoring sites have given rise to an unexpected concern. Although no
field soil residues were found at the 10 ppb detection level at the
Hilburn site, Goal apparently was still providing control of witchweed.
This raises the question of whether the observed hydrosoil concentrations
of 50 ppb might be lethal to aquatic plants residing in the wetlands of the
corn and other use pattern areas.
7
The ecological importance of the nation's wetlands is widely
recognized. Oxyfluorfen appears to be herbicidally active at soil
concentrations below 10 ppb. During the preliminary monitoring survey
conducted by the Agency in North Carolina, hydrosoil concentrations of up
to 70 ppb were found. If oxyfluorfen is as toxic to beneficial aquatic
plants as to target weeds, wetlands might be threatened by the use of Goal
on nearby fields or orchards. Monitoring studies may indicate that harm
would only occur over an area which is geographically insignificant in
size or that exposure of wetlands could be reduced by certain management
practices. Until such a demonstration is made, the Agency could require
labeling to protect wetlands for all proposed Goal uses.
4. Avian Reproductive Study
The Agency has determined that the results of avian
reproductive studies submitted by the registrant are inconclusive due to
high variability in the controls and significant failure to comply with
standard protocols (Hitch, 1980). Therefore, data are currently inadequate
to determine whether use of Goal 2E would result in a significant hazard
to birds.
1*6
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Ill, BENEFITS ANALYSIS
A. Introduction
The applicant for registration, Rohm and Haas, has proposed that
oxyfluorfen be registered for control of certain weed species in soybeans
and for witchweed control in field corn. In this section, the Agency
examines the potential usage of oxyfluorfen on these crops, costs of other
pest control programs, and the projected impacts on producers of these
commodities if oxyfluorfen were not available. The information in this
Section is based upon the analysis provided by the Economic Analysis Branch
of the Office of Pesticide Program's, Benefits and Field Studies Division
(Devine, 1980a; 1980b). In addition, the Agency is including a qualitative
benefits discussion of the currently registered oxyfluorfen uses on bearing
and nonbearing tree fruit/nuts, and conifers (seedbeds, transplants and
outplantings).
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B. Soybeans
1. Soybeans: EPA Registration of Oxyfluorfen and Other Soybean
Herbicides-^'
The manufacturer of oxyfluorfen, Rohm and Haas, is
seeking registration for Goal 2E use on soybeans to control certain annual
broadleaf and grassy weeds, which are listed in Table 14. Numerous
herbicides are currently registered for use on soybeans. Major registered
soybean herbicides selected for cost comparisons are listed in Table
15.—'
17/Limitations of Analysis
a. Application rates for oxyfluorfen and alternatives are estimated
from product labels and state recommendations.
b. Alternative herbicide treatments are based on state
recommendations, information provided by the Plant Sciences
Branch/BFSD, and other sources.
c. For this analysis, it is assumed that no differences exist in
application methods or application costs for oxyfluorfen and
other soybean herbicides.
d. Calculations of the comparative costs of oxyfluorfen and other
herbicides do not reflect any signicant differences in
comparative efficacy and performance that may exist.
e. The degree of growers' acceptance of oxyfluorfen over time is
unknown.
18/ This analysis mentions four types of soybean herbicide use:
preplant incorporated, preemergence, no till and postemergence. Preplant
incorporated herbicides are applied to the soil surface and incorporated or
mixed into the top two to four inches of soil before or during planting,
within a specified period on the herbicide label. Preemergence herbicides
are applied to the soil surface during or soon after planting, before the
emergence of the crop or weeds. No till herbicides are used in cropping
systems in which crops are planted directly into plant residue with a
minimum of soil disturbance. Finally, post emergence herbicides are
applied after emergence of the crop, weeds, or both (Beck and Petrie,
1981).
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TABLE 14.
Weed Species Controlled by Goal 2E (Rohm and Haas, 1979).
Broadleaf
Weeds Grasses
Black nightshade Barnyard grass
Common Lambsquarters Fall Panicum
Common ragweed Giant foxtail
Cutleaf groundcherry Large crabgrass
Jimsonweed Broadleaf signalgrass—'
Pennsylvania smartweed Seedling johnsongrass3-'
Prickly sida Yellow foxtail-
Fed root pigweed
Velvetleaf
Common cocklebur—'
Morning ^'
a/ Under certain conditions, Goal may give sufficient benefit
(suppression) to be of value against these weeds.
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TABLE 15.
Selected Major Registered Herbicides for Control, of Annual
Broadleaf and Grassy Weeds in Soybeans-
Application Methods
Herbicides
Preemergence
Single Herbicide
Tank Mix Combinations
Following Preplant - Incorporated
Trifluralin Treatment
Alachlor
Chloramben
Linuron
Metribuzin
Chloramben/alachlor
Linuron/alachlor
Metribuzin/alachlor
Trifluralin 4- Metribuzin
No Till
Postemergenee
Linuron/alachlor/paraquat
Metribuzln/alachlor/paraquat
Glyphosate/alachlor/linuron
Glyphosate/alachlor/metribuzin
2,4-DB
2,4-DB/linuron
Dinoseb
a/ Devine, 1980a
50
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2. Soybeans: Recommendations for Using Oxyfluorfen and Other
Soybean Herbicides
Since 197A, oxyfluorfen has been used experimentally on
soybeans under Section 5 of FIFRA (Malak, 1980). Although oxyfluorfen use
on soybeans is currently permitted only on an experimental basis, the
Missouri, Ohio, and Wisconsin Extension Services currently recommend its
use as an experimental herbicide for the preemergence control of annual
broadleaf weeds and grasses. The proposed label for Goal 2E recommends
that it be applied on soybeans in one of three ways: preemergence during
or soon after planting, no till after emergence of weeds but before
emergence of the crop, or postemergence-directed (sprayed between rows to
avoid crop Injury) after emergence of both crop and weeds. Soybean
herbicide recommendations of selected soybean-producing states for those
weeds listed on the oxyfluorfen label are presented in Appendix E. USDA
recommendations are also shown in Appendix E.
3. Soybeans: Performance Evaluation of Oxyfluorfen and Other
Soybean Herbicides
a. Pest Infestation and Damage
Table 1A presents the weed species listed as controlled
by oxyfluorfen on the Goal 2E label. The majority of these weeds infest
the entire eastern half of the United States and many are widespread
throughout the country. The major soybean-producing states, Arkansas,
Illinois, Indiana, Iowa, Minnesota, Mississippi, Missouri and Ohio (USDA,
1980a and 1978), are included in the major infested areas of weeds listed
on the oxyfluorfen label. Many other soybean-producing states are also
affected by several of these weeds (USDA, 1978).
One especially troublesome weed in soybeans, listed as
controlled by Goal 2E on the proposed label, is black nightshade (Solanum
nigrum) (Table 14). The tough stems of black nightshade can jam the
cylinders of combines; and nightshade berries, which are poisonous to
humans and animals, are difficult to separate from the harvested soybeans.
t*hen crushed by harvesting, the berries produce a sticky juice that stains
the soybeans and makes dust and debris adhere to them, reducing
marketability of the crop (Seim, 1981).
Other examples of problem weeds in soybeans include weedy
vines such as morning glory, which can cause lodging of soybeans. Lodging
Interferes with harvesting and requires extra drying of the crop because of
moisture from the excess green material harvested. Grasses can also hinder
harvesting operations because their tough stems are difficult for combines
to cut (Caldwell, 1973). The Goal 2E label claims control of morning glory
and control or suppression of several grass species (Table 1A).
b. Comparative Performance Evaluation
Since 197A, a limited amount of field testing has been
done on oxyfluorfen as an experimental soybean herbicide under section 5 of
FIFRA. The manufacturer has submitted sufficient efficacy, phytotoxicity
and yield data for soybean use to satisfy EPA performance data requirements
as they existed prior to the Agency's efficacy data waiver policy, and thus
to support initial registration of label-claimed uses of Goal 2E on
51
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soybeans (Petrie, 1980a). Extensive performance evaluations comparing
oxyfluorfen with other currently registered soybean herbicides will not be
available until after oxyfluorfen is registered and becomes more widely
available. Several weed researchers have indicated that there are too many
newly registered products in need of performance testing to extensively
test all unregistered products at this time (Beck and Petrie, 1980b).
Currently insufficient data are available to make a
thorough quantitative comparative performance evaluation of oxyfluorfen and
other soybean herbicides. Enough information exists, however, to make a
qualitative analysis that identifies a number of situations where
oxyfluorfen compares favorably with certain other soybean herbicides.
Because of the small amount of comparative efficacy
information available, the comparative performance evaluation analysis was
not limited to comparisons of oxyfluorfen with herbicides applied by the
same methods. However, in the economic impact analysis oxyfluorfen was
only compared to herbicides applied by the same methods: preemergence, no
till or postemergence. This greatly reduced the number of comparative
cost calculations without sacrificing the usefulness of those calculations
in the analysis or altering the Agency's decision (see footnote 19). The
same purpose would not be accomplished by making the same limiting
assumption in the comparative efficacy discussion. The many possible
herbicide treatment programs to control the weeds listed on the Goal 2E
label are illustrated in Appendix E.
The manufacturer, Rohm and Haas, characterizes Goal 2E as
a specialty herbicide for use where problems of poor weed control or crop
phytotoxicity may exist if currently registered herbicides are used (Rohm
and Haas, 1980a). Performance data in EPA Registration Division files
generally confirm this statement, and agricultural researchers expect
oxyfluorfen to occupy such a niche in the soybean herbicide market
(Petrie, 1980a; Beck and Petrie, 1980b).
Several advantageous properties and uses of oxyfluorfen
are indicated by the manufacturer's registration data and are supported by
the experience of agricultural experts. These are described below:
a) Soil texture and organic matter content affect the
performance of most soil-applied herbicides. As clay and organic matter
content increase, there is greater adsorption of certain of these
herbicides by the soil. Soils with more clay and organic matter require
higher application rates to offset adsorption, and soils with more sand and
less organic matter need lower rates to avoid phytotoxicity or burning of
the soybean crop. The labels of several Important preplant-lncorporated
herbicides Instruct users to adjust application rates according to soil
texture and organic content. Alachlor, chloramben, linuron, metribuzin and
trifluralin are examples of such herbicides. Linuron and metribuzin labels
do not recommend use of those herbicides in soils of coarse texture and
extremely low organic content (sand) in order to avoid phytotoxicity to
the crop. Since soil organic matter and texture may vary in different
parts of a single field, a uniform application rate for herbicides such as
those listed above may cause poor weed control in some areas of the field
and crop injury in others (Beck and Petrie, 1980b; Rohm and Haas, 1980a).
Unlike most soil-applied soybean herbicides, the application rate and weed
control performance of oxyfluorfen does not depend on soil texture or
organic matter content, and a single application rate can be used on soils
52
-------
of any texture with organic matter content ranging from 0-8% (Beck and
Petrie, 1980b; Petrie, 1980a; Rohm and Haas, 1980a). Most soybeans are
grown in soils containing 8% or less organic matter (Knake, 1980a).
b) Highly alkaline or calcareous soils may prevent use of
metribuzin, a major soybean herbicide, which, like oxyfluorfen, lists pre-
emergence, no-till and postemergence directed spray uses on its label.
Labels of metribuzin products state that crop injury may result from use
in soils with a pH of 7.5 or more. In tests of oxyfluorfen on soils of
varying pH, its performance was not significantly affected by soil acidity
or alkalinity (Petrie, 1980a; Rohm and Haas, 1980a).
c) According to label instructions, the major
preemergence soybean herbicides alachlor, chloramben, linuron and
metribuzin require moisture for activation, in the form of rainfall or
irrigation within one or two weeks after application. This post-
application moisture distributes the herbicide into the weed germination
layer of the soil (Caldwell, 1973). In the case of alachlor, soil
incorporation may be used to activate the herbicide if the soil is
sufficiently moist, and may serve as a substitute for post-application
rainfall or irrigation. Oxyfluorfen does not require rainfall, irrigation
or soil incorporation after application, since soil moisture adequate for
soybean germination is also enough for activation of the herbicide (Beck
and Petrie, 1980b; Petrie, 1980a; Rohm and Haas, 1980a).
d) Oxyfluorfen has been reported to be less phytotoxic
than other soybean herbicides at normal use levels (Beck and Petrie, 1980b;
Knake, 1980). Metribuzin, a major soybean herbicide, causes injury to
several soybean varieties, and its label cautions against use on these
varieties (Beck and Petrie, 1980b). Oxyfluorfen may be used on these
metribuzin-sensitive soybeans (Petrie, 1980a). Some of the other soybean
herbicides can also be phytotoxic under extremely wet field conditions,
where leaching of the herbicide damages soybean root systems (Beck and
Petrie, 1980b) For example, the Lorox (linuron) label warns users about
crop injury when fields are very wet. Some herbicides will leach so
rapidly In low organic, coarse-textures soils that they have a potential
for either harming the crop or providing little weed control (Caldwell,
1973; Rohm and Haas, 1980a). Oxyfluorfen is not prone to leaching due to
Its low solubility in water and It affinity for soil exchange sites
(Petrie, 1980a; Rohm and Haas, 1980a). However, too much rainfall or
irrigation immediately after oxyfluorfen preemergence application can cause
splashing of the chemical onto newly emerged soybean leaves, and cause
contact chemical burning (Ryan, 1978). Yield reduction, crop maturity
delay, or both have occasionally resulted from heavy rainfall between
application and crop emergence. Significant yield reductions were not
found, and the magnitude of this potential problem has not been determined
(Petrie and Beck, 1980b; Petrie, 1980a).
e) Oxyfluorfen has a combination of attributes that are
well adapted to use in no till systems„ Preemergence residual activity of
oxyfluorfen is good, and weeds may be controlled up to three months after
application (Beck and Petrie, 1980bj Petrie, 1980a; Rohm and Haas, 1980a)o
In addition, oxyfluorfen is not readily.de-activated by the crop trash and
stubble present in no till use (Rohm and Haas, 1980a). Agricultural
researchers have Identified a specific need for oxyfluorfen in a no till
53
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tank mix with alachlor for use in double cropping systems in Kentucky and
Illinois (Beck and Petrie, 1980b).
f) The limited field research comparing oxyfluorfen with
other soybean herbicides indicates that oxyfluorfen helps control certain
problem weeds that infest soybeans. Black nightshade is a particularly
troublesome weed in soybeans that is controlled by oxyfluorfen. In field
studies, preemergence application of oxyfluorfen has been shown to be more
effective than alachlor or trifluralin against black nightshade, and
preemergence spraying of an oxyfluorfen/alachlor mixture gave better
control over nightshade species than an alachlor/linuron mixture (Petrie,
1980a).
Cutleaf groundcherry is considered to be a problem weed
in Arkansas, a major soybean-producing state, and oxyfluorfen has been
effective as a post emergence directed spray for control of groundcherry in
that state (Petrie, 1980a). In Arkansas tests, oxyfluorfen provided
better control than alachlor, and provided residual preemergence control of
groundcherry plants germinating after spraying (Petrie, 1980a). Other
studies found oxyfluorfen alone to be superior to an alachlor/netribuzin
tank mix for groundcherry control (Petrie, 1980a).
Annual morning glory is another weed that is poorly
controlled by presently registered herbicides (Petrie, 1980a). The Goal 2E
label lists morning glory species among the weeds suppressed by its use,
and researchers have identified a need for oxyfluorfen to control
annual morning glory in Illinois, Kentucky, and North Carolina (Petrie,
1980a).
A. Soybeans: Economic Impact Analysis
a. Profile of Impacted Area
In 1979, there were approximately 2.3 billion bushels
of soybeans harvested from 70.5 million acres in the U.S (USDA, 1980b).
The value of soybean production in 1979 was estimated to be about $13.8
billion (Matthews, 1980). The eight largest soybean-producing states
(previously listed) accounted for about 70% of the total U.S. soybean
production in 1975-79 (USDA, 1980b and 1978).
b. User Impacts
It is assumed for this analysis that if oxyfluorfen is
registered, a farmer will continue to use his current method of herbicide
application, substituting oxyfluorfen or oxyfluorfen combinations for the
herbicides currently used.— Therefore, economic impacts would be
limited to differences in herbicide material cost between oxyfluorfen and
other soybean herbicides.
19/ The Agency recognizes that farmers may in reality choose among a
wide variety of soybean herbicides and application methods, as illustrated
in Appendix E. However, the limited economic analysis chosen by the Agency
is sufficient to establish that some soybean herbicides are more costly
than oxyfluorfen, while others are less costly. Further cost comparisons
would not alter the conclusion that oxyfluorfen is competetlve in price.
-------
In a typical soybean weed control program, herbicides
are initially applied to the soil in a preplant-incorporated, preemergence,
or no till (a combination of a nonselective and preemergence herbicides)
treatment* This is done either before, during or soon after planting, and
before emergence of the crop. If weed problems persist, postemergence
herbicides may be applied after emergence of both crop and weeds (Petrie,
1980a). The Goal 2E label allows one application of oxyfluorfen each year,
which may be either a preemergence (including no till) or post emergence
directed treatment.
1) Preemergence Use
Oxyfluorfen can be applied as either a band or
broadcast treatment (Rohm and Haas, 1980a). In this analysis, only
broadcast application rates are used to calculate herbicide cost since the
majority of preemergence herbicides are applied in this manner (Devine,
1980a). Although the herbicide cost per acre is less for band application,
cost differences between herbicides would be relatively the same for both
band and broadcast application.
The major preemergence herbicides used for weed
control in soybeans include alachlor, chloramben, linuron and metribuzin
(Table 15). All of these can be applied by either band or broadcast
techniques. The cost associated with the application of oxyfluorfen is
compared to these four herbicides in Table 16, and range a ..from $1.56 to
$9.60 per acre less for oxyfluorfen than for the others.—
Oxyfluorfen can also be applied preemergence In a
tank mix with alachlor. Other major herbicides that are applied preemer-
gence in a tank mix combination with alachlor include chloramben, linuron
and metribuzin (Table 15). Comparisons between oxyfluorfen/alachlor
and the other tank mix combinations indicate that the oxyfluorfen/
alachlor combination treatment ranges from $0.30 to $2.88 less per
acre than the other combinations (Table 17).
Oxyfluorfen can also be applied after preplant
incorporation of trifluralin (Rohm and Haas, 1980a). Metribuzin is one of
the major herbicides applied after trifluralin is preplant incorporated.
(Table 15). A treatment of preplant-incorporated trifluralin followed by
preemergence oxyfluorfen costs $2.04 more per acre than the comparable
trifluralin/metribuzin treatment (Devine, 1980a) (Table 17).
20/Since application rates may vary according to the soil type and
organic content, a midpoint of the recommended range of application rates
(for medium soils, if listed) from the eight major soybean-producing states
was determined. Averages of the midpoints were calculated in order to
estimate the per acre costs of other herbicides.
55
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TABLE 16.
Comparison Costs of Goal 2E and Selected Preemergence
Herbicides for .Control of Annual Broadleaf and
a/
Grassy Weeds in Soybeans—
Herbicides
oxyfluorfen
alachlor
chloramben
linuron
metribuzin
Per Acre
Herbicide
Cost
($)
8.96
10.88
18.56
15.07
10.52
Per Acre Difference
in Cost Between
Oxyfluorfen and
Selected Preemergence
Herbicides
($)
+1.92
+9.60
+6.11
+1.56
a/ Devine, 1980a
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TABLE 17.
Comparison Costs of Goal 2E Combinations and Selected
Freemergence Herbicide Combinations Used for Control of
Annual Broadleaf and Grassy Weeds in Soybeans—
Per Acre Per Acre
Herbicides Herbicide Differences
Combinations Cost in Cost
($) ($)
Tank Mixes
oxyfluorfen/alachlor 8.96 + 7.04 = 16.00
chloramben/alachlor 11.84 + 7.04 = 18.88 +2.88
linuron/alachlor 9.61 + 8.80 = 18.41 +2.41
metribuzin/alachlor 7.50 + 8.80 = 16.30 +0.30
Preemergence Spray Following Preplant - Incorporated Trifluralin
trifluralin + oxyfluorfen 6.99 + 8.96 = 15.95 ___
trifluralin + metribuzin 5.31 + 8.60 = 13.91 -2.04
a/ Devine, 1980a
57
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2) No Till Use
Oxyfluorfen can also be applied in no till systems
as a tank mix with either paraquat 'or paraquat plus alachlor.—
The major alternative herbicide combinations applied to no till systems
include: linuron/alachlor/paraquat, metribuzin/alachlor/paraquat,
glyphosphate/alachlor/linuron, and glyphosphate/alachlor/raetribuzin
(Table 15).
The per-acre chemical cost of oxyfluorfen/paraquat/
surfactant ranges from $6.57 to $25.29 less per acre than alternative tank
mixes. The per-acre chemical cost difference between oxyfluorfen/alachlor/
paraquat/surfactant and the other tank mixes ranges from $5.29 to $24.01
less per acre for the oxyfluorfen-containing treatment (Table 18) (Devine,
1980a).
3) Postemergence Use
Oxyfluorfen can also be applied as a postemergence-
directed spray. Table 15 lists selected postemergence-directed herbicides
and Table 19 lists their comparative costs per acre. The cost of
oxyfluorfen treatment per acre falls between the extremes of the per acre
herbicide costs calculated. Dinoseb costs $2.32 more per acre, but 2,4-
D/linuron and 2,4-DB cost $1.23 and $5.85 less per acre respectively
(Devine, 1980a) (Table 19).
4) Summary of User Impacts
Taken as a whole, calculations of comparative cost
per acre of oxyfluorfen (used alone, in icombination, or in sequence with
other herbicides) indicate that it will he competitive in cost with other
herbicide treatments used in soybeans. In a number of instances,
oxyfluorfen use is less costly than use of other herbicides selected for
this analysis: single herbicide preemergence spray, tank mix combination
preemergence spray and no till treatment (Tables 16, 17, and 18). For
other methods of application, use of oxyfluorfen results in a more
expensive treatment program than some of the others selected: sequential
program of preplant-incorporated trifluralin and preemergence spray and
postemergence directed spray (Tables 17 and 19). The cost figures used to
calculate user impacts do not include increased yield, Improved crop
quality, Increased ease of harvesting, or other presently unquantifiable
benefits that may result from use of oxyfluorfen in special situations,
such as soil composition or problem weeds, that are outlined in the
comparative efficacy discussion.
21/The paraquat label specifies use of x-77 surfactant with all
paraquat soybean tank mixes.
58
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TABLE 18.
Comparison Costs of Goal 2E and Selected No Till Herbicides
Tank Mixes for Control of Annual Broadleaf and Grassy Weeds
in Soybeans3/
Per Acre Cost Differences
Between Other Tank Mixes and:
Herbicides
Combinations
oxyfluorf en/paraquat/surfactant
oxyfluorfen/alachlor/paraquat/
surfactant
1 inuron/alachlor/paraquat/
surfactant
me tr ibuz in/alachlor/paraquat/
surfactant
glyphospha te/alachlor/1 inuron
glyphosphate/alachlor/metr ibuz in
Per Acre
Herbicide
Cost
($)
19.74
21.02
28.91
26 .-31
45.03
43.55
Qxyfluorfen/
Paraquat
($)
+9.17
+6.57
+25.29
+23.81
Oxyfluorfen/
Alachlor/Paraquat
($)
+7.89
+5.29
+24.01
+22.53
a/ Devine, 1980a
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TABLE 19.
Comparison Costs of Goal 2E and Selected Fostemergence-Directed
Herbicides for Control of Annual Broadleaf and Grassy Weeds
in Soybeans—
Herbicides/
Herbicide
Combinations
oxyfluorfen
2,4-DB
dinoseb
2,4-DB/linuron
Per Acre
Herbicide
Cost
($.)
7.28
1.43
9.60
1.30 + 4.75 - 6.05
Per Acre Differences
in Cost Between
Oxyfluorfen and
Selected Postemergence -
Directed Herbicides
($)
-5.85
+2.32
-1.23
a/ Devine, 1980a
60
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c. Market and Consumer Impacts
It is not currently possible to determine oxyfluorfen's
market acceptance if it is registered. Some state extension personnel
estimate that the herbicide could eventually claim up to eight percent
of the market if accepted by growers (Coble, 1980; Burnside, 1980).
Advantageous characteristics of oxyfluorfen (i.e., less application rate,
dependence on soil organic matter content and less soil moisture dependence
than many other herbicides) and Its competitive price will influence its
marketability. The magnitude of such economic impacts cannot be estimated
without improved information about comparative cost and performance, as
well as the degree of the soybean growers' acceptance of oxyfluorfen
over time (Devine, 1980a).
C. Corn
1. Corn: EPA^Beglstrations of Oxyfluorfen and Other
Herbicides^-7
The manufacturer of oxyfluorfen, Rohm and Haaa, is currently
seeking registration for product use in the USDA/State Cooperative
Witchweed Eradication Program. The Eradication Program consists of three
main activities: surveys of the infested area and surrounding noninfested
areas, quarantines to prevent translocation of the infestation by farm
equipment, and weed control by the use of herbicides and. germination
stimulation techniques (USDA, 1978a). USDA currently holds a section
18—(FIFRA) exemption for use of Goal 2E in the Witchweed Program.
The primary herbicides currently being used in the
Eradication Program are oxyfluorfen (under section 18 of FIFRA), 2,4-D, and
paraquat (Sand, 1980). Other chemicals, such as ethylene gas, are used to
22/ Limitations of the analysis.
a. A large range in the number of acre treatments per year Is
possible since the level of Eradication Program support is
influenced by the availability of USDA or state financial
resources.
b. The future success of the Eradication Program could not be
evaluated.
c. The analysis was based on statements by the manufacturer that a
Federal registration of the product for corn/witchweed is for
USDA use only.
d. Comparative yield data between crops treated with oxyfluorfen and
the other major herbicides were not available.
e. The USDA's standard application rates for oxyfluorfen and the
other herbicides were used.
23/ This section, "Exemption of Federal Agencies" allows for the
exemption of a Federal or State Agency from any provisions of FIFRA If
warranted by emergency conditions.
61
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force germination of witchweed seeds. Methyl bromide can be used to
fumigate the soil or contaminated farm equipment (USDA, 1979a and 1978a).
2. Corn: Recommendations for Use of Oxyfluorfen and Other
Herbicides .
In 1978 and 1979, oxyfluorfen was used for witchweed control
under section 18 of FIFRA as amended (Sand, 1980). Approximately 1,073
acres of corn were treated in 1978 (USDA, 1979b). The 1979 published
exemption for this use limited treatment to a maximum of 2,000 acres (see
Section I.C.4. of this document). Of this, about 1,821 acres were actually
treated (USDA, 1980a).
Witchweed (Striga asiatica) is a problem weed in a rela-
tively small area of the country (38 counties of the Carolinas) (Langston,
1980). Since certain grasses are host to witchweed, North and South .
Carolina State recommendations are directed to removal of host species and
thereby indirectly reduce witchweed infestation. Herbicides recommended by
the Carolinas for this use are presented in Table 20.
The standard application rate for oxyfluorfen is 0.5 pounds
active ingredient per acre (Langston, 1980). The major alternative
herbicide treatments are: 5-6 applications of 2,4-D (1.0 pound active
ingredient per acre), or one treatment of 2,4-D (1.0 pound active
ingredient per acre) followed by three paraquat treatments (0.25 pound
active ingredient per acre), or four to five applications of a tank mix of
2,4-D (0.50 pound active ingredient per acre) and paraquat (0.10 pound
active ingredient per acre) (Langston, 1980).
3. Corn: Performance Evaluation of Oxyfluorfen and Alternatives
a. Pest Infestation and Damage
Witchweed (Striga asiatica) is a parasitic weed that
is native to India, first discovered in the United States during 1956 in
the eastern parts of North and South Carolina; it now infests about 380,000
acres (Langston, et al., 1979; Sand, 1979).
Witchweed can reproduce wherever a host crop or grassy
weed is present. The weed is a parasite of more than 60 different plants
in the grass family, including corn, sorghum, rice, sugarcane, crabgrass
and Johnsongrass. Infestations in corn, sorghum, sugarcane and rice can
contribute to yield reductions of up to 90% (Langston et al., 1979).
Host plant root secretions stimulate witchweed
germination. Upon germinating, the seed attaches a rootlike growth to the
host and withdraws nutrients. The most serious witchweed damage occurs
during the below-ground stage; parasitic action contributes to a drought
stricken appearance in an infested field (USDA, 1980a).
Warm temperatures, light soils and high soil moisture
content are optimal witchweed growing conditions. However, the conditions
prevalent in the major corn/sorghum-producing regions of the United States
are also suitable for witchweed growth (USDA 1980a). Therefore, if this
pest is not geographically contained, it could cause serious economic
damage to U.S. corn, sorghum and other crop production.
62
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TABLE 20.
State Herbicldal Recommendations for Control of
Grassy Weed Hosts of Witchweed in ^-
Preemergence
Use
Pre-plant Soil
Incorporated
Post Emergence-
Directed Use^-'
Alachlor
Alachlor/atrazine
Alachlor/cyanazine
Atrazine
Atrazine/cyanazine
Atrazine/simazine
Cyanazine
Metolachlor/atrazine
Pendemethalln
Pendemethalin/atrazine
Pendemethalin/cyanazine
Simazine
Butylate Ametryn
Butylate/atrazine Atrazine
Butylate/cyanazine 2,4-D
EPTC Linuron
a/ Devine, 1980b
b/ For use in corn up to the last cultivation
63
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b. Comparative Performance Evaluation
Witchweed currently infests about 380,000 acres
(Langston et al., 1979). The Eradication Area is the periphery of the
infested area and accounts for approximately 50,000 acres (Langston, 1980).
The Program consists of moving the periphery inward as the target weed is
eliminated from each eradication area (Sand, 1980).
The Program's chemical control consists of: (1)
elimination of witchweed seed in the soil and (2) prevention of new
witchweed seed production. Stimulants, such as ethylene gas, injected into
infested soils induce the seeds to germinate in the absence of host plants.
Oxyfluorfen and other herbicides are used to kill existing plants in order
to prevent new seed production (Langston et al., 1979).
During 1958-1970, the major herbicide used for
witchweed control was 2,4-D. This herbicide was annually applied to some
400,000 to 500,000 acres. However, because of 2,4-D's limitations,
witchweed continued to proliferate in soybeans, cotton and other broadleaf
crops due to the presence of hosts, such as crabgrass (Langston et al.,
1979).
In 1964, the introduction of dinitroaniline herbicides
(e.g., trifluralin, nitralin, fluchloralin) increased host grass control
greatly (Langston and Eplee, 1974). These chemicals suppressed witchweed
emergence from 60-100% (Langston, 1975).
Paraquat, a postemergence herbicide introduced in the
late 1960's, kills witchweed as well as grassy hosts. Paraquat's usage
reduced the number of 2,4-D applications that were required. Applications
of 2,4-D occur every three to four weeks, from June until frost if a grassy
weed is present. Paraquat treatments cease when the corn senesces, thereby
reducing the number of total applications from six to four (Langston et
al., 1979).
Application of 2,4-D alone, 2,4-D followed by paraquat,
or 2,4-D/paraquat tank mixes are the major herbicide control methods
currently employed by the witchweed Plant Quarantine Program (Langston,
1980; Sand, 1980). Use of 2,4-D alone requires five to six applications.
When 2,4-D is followed by paraquat, the number of treatments can be reduced
to one application of 2,4-D and three applications of paraquat; the tank
mix is applied four or five times (Langston, 1980).
One disadvantage of 2,4-D or paraquat use is that only
those weeds that the herbicides contact are killed; therefore, retreatment
would be required to control plants emerging after treatment (Beck and
Petrie, 1980a). In addition, 2,4-D and paraquat spray operations are not
possible if wind lodges the corn or if fields become too wet (Sand, 1980).
Oxyfluorfen has residual preeraergence soil activity
from preemergence and postemergence treatment (Rohm and Haas, 1980a).
Unlike 2,4-D and paraquat, which have no soil preemergence activity,
Oxyfluorfen can kill witchweed plants that are present at spraying as well
as newly germinating witchweed plants (Beck and Petrie, 1980b).
-------
Corn yields differ, depending upon whether oxyflubrfen
or the other major herbicides are used (Beck and Petrie, 1980b). By the
time witchweed is easily visible and can be treated with a post emergence
spray, crop root damage has progressed to the extent that full recovery is
not possible. Preemergence treatment with oxyfluorfen reduces damage since
the seedling is killed as it emerges through the treated soil.
Preemergence and postemergence oxyfluorfen treatments reportedly cause
reproductive failure in witchweed plants that survive treatment and thereby
effectively reduce those seeds produced by the treated witchweed plant.
Oxyfluorfen continues to provide preemergence weed control under conditions
that prohibit application of 2,4-D and paraquat (Beck and Petrie, 1980b).
4. Corn: Economic Impact Analysis
a. Profile of Impacted Area
As of November 27, 1979, there were 27 counties in
North Carolina and 11 counties in South Carolina that were infested with
witchweed (Langston, 1980). The majority of these counties were in North
Carolina's Central Coastal and Southern Coastal Crop Reporting Districts
and in South Carolina's Eastern Crop Reporting District.
In the infested counties, there were an estimated
907,000 acres of grain corn harvested in North Carolina and 203,600 acres
in South Carolina during 1978. In 1978 this area produced an estimated
80,205,000 bushels of grain corn valued at $190.4 million (North Carolina
Crop and Livestock Reporting Service, 1980; Rogers, 1980).
b. User Impacts
In order to determine user impacts, the cost of the
herbicides as well as the costs of application must be considered. The
user, in this case, is the Federal/State Government. In the Eradication
Area, the farmer is not involved with herbicide application; all
application work is government contracted (Sand, 1980).
To calculate the total treatment cost, the cost of the
herbicide as well as the cost of application must be considered. Since the
same equipment is used regardless of the herbicide applied, application
costs per treatment will not change (Sand, 1980). However, the number of
treatments varies with the herbicide used (Table 21).
Oxyfluorfen is normally applied only once. If any
witchweed appears after treatment, oxyfluorfen is reapplied. However,
reappearance of the weed has occurred on only 9-10% of the oxyfluorfen
treated acres (Sand, 1980). Treatments with 2,4-D alone must be applied
five to six times during the season. One application of 2,4-D followed
by three paraquat applications is another standard treatment. Treatment
with a 2,4-D/paraquat tank mix requires four to five applications
(Langston, 1980).
Comparison of the total per acre treatment costs
indicates that oxyfluorf«n ($26.78 per acre) is the least expensive. The
per acre cost increases associated with 2,4-D alone, 2,4-D followed by
paraquat, or 2,4-D/paraqua.t tank mix treatments instead of oxyfluorfen are
$41.97, $31.98 and $35.19| respectively (.Table 21). If oxyfluorfen were
65
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TABLE 21.
Total Per Acre Cost Increases of Using Goal 2E Alternatives for Control of Witchweed
in Field Corn in North and South Carolina
Herbicides
Goal 2E +
surfactant
2,4-D
2,4-D +
Total Herbicide Costs
Per Acre Treated
a/
Per Season—
($)
13.03
8.25
14.76
Total Application
Costs Per Acre
Treatment Per Season—
($)
13.75
60.50
44.00
Total Per Acre
Treatment Costs
($)
26.78
68.75
58.76
Per Acre Cost
Increase
($)
41.97
31.98
paraquat + ,
surfactant—
2,4-D/paraquat +
surfactant—
12.47
49.50
61.97
35.19
a/ See Devine (1980b).
b/ Based on total number of treatments per season and $11.00 application cost per acre treated
which includes a $6.00 per acre contractor charge for the application (Langston, 1980) plus
$5.00 per acre USDA monitoring cost (Beck & Petrie, 1980b).
c/ Standard treatment consists of 1 application of 2,4-D followed by 3 applications of paraquat
(Langston 1980).
d/ Tank mix.
-------
unavailable, the Federal/State Eradication Program would experience
increased treatment costs. Using other herbicides on 1,000 to 2,000
acres (the amount allowed under the current exemption) would increase total
costs by about $32,000 to $84,000 (Devine, 1980b). If larger acreage, such
as 80,000 to 100,000 acres were treated as desired by USDA, the increase
would range from about $2,600,000 to $4,200,000 (Devine, 1980b).
c. Market and Consumer Impacts
A short term reduction in corn yield in witchweed-
infested areas (at least 10%) could be expected if oxyfluorfen were no
longer available. This reduction would vary depending upon the herbicide
employed in control programs by APHIS. Oxyfluorfen is considered the most
useful selective herbicide for witchweed control in corn. Without
preemergence oxyfluorfen treatment, poor weather conditions in any year
could have adverse effects upon witchweed control efforts (Beck and Petrie,
1980a).
Long term economic impacts upon corn and other crop
producers as well as consumers could be quite severe if the Eradication
Program is not successful in containing witchweed. The magnitude of long
term economic,impacts are highly conjectural and dependent on the success
of the Eradication Program over time.
d. Social/Community/Macroeconomic Impacts
With continuance of a successful Eradication Program in
the area presently infested, no social/community/macroeconomic impacts are
expected in either the long or short term.
D. Bearing and Nonbearing Tree Fruits/Nuts and Vineyards
1. Fruit/Nut Orchards and Vineyards: EPA
Registration of Oxyfluorfen and Other Herbicides
Oxyfluorfen, hereafter referred to as Goal 2E, was,,
registered on May 17, 1979, for preemergence and post emergence—
weed control in nonbearing almonds, nectarines, peaches, plums and prune-s
in California only. (Registration Number: 707-145). Efficacy, crop injury
and trunk diameter data of these crops were submitted to the Agency in
support of this registration prior to the December 1978 waiver of efficacy
data. Four times the maximum label rate of Goal 2E was used to evaluate
crop injury and trunk diameter growth rates. No injury or adverse effects
were noted on almond, nectarine, peach, plum and prune orchards that were
treated with Goal 2E immediately after transplanting (the growth stage at
which these young plants would be most susceptible to herbicide injury).
Efficacy data were found acceptable by Registration Division (R.D.) in
24/ Preemergence Goal 2E herbicide treatments are applied to the soil
surface prior to emergence of weeds from the soil. Post emergence Goal 2E
herbicide treatments are applied directly to the surface of emerged weeds
growing underneath the tree or vine.
67
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support of those claims on the 707-145 label for Goal 2E alone, Goal 2E
plus Paraquat CL and Goal 2E plus Paraquat CL plus Surflan 75W.
Conditional registration for use of Goal on bearing tree
fruits/nuts was approved December 18, 1980.
Table 22 presents the other major registered preemergence,
postemergence and-preemergence and/or post emergence herbicides considered
in this analysis.—
20 Tree Fruits/Nuts and Vineyards: Performance of Goal 2E
Herbicide
There are an estimated 1.4 million acres of commercially
grown tree fruits, tree nuts and vineyards in California. The first
harvest from newly planted orchards/vineyards occurs approximately four to
five years after transplanting. During this nonbearing to bearing
interval, annual weeds can reduce growth of young orchards/vineyards by up
to 50 percent where weeds are dense and irrigation is limited. Mechanical
methods of weed control such as discing or mowing can compact and
mechanically harm the delicate root systems. Biennial and perennial weeds
are even more harmful to new transplants than annual weeds due to their
persistent hard-to-control nature (Lange, 1976).
Goal 2E is considered an effective herbicide in orchards and
vineyards in California for the following reasons:
a) Goal 2E is uniquely effective for control of the
following problem weeds in California fruit and nut orchards and vineyards:
cheeseweed9 henbit, fiddleneck, filaree spp., and nettle. Goal 2E is
currently the only herbicide available that effectively controls cheeseweed
(Malva parviflora) (Elmore, 1980). Cheeseweed is widely distributed
throughout the coastal and inland orchards and vineyards in California.
Cheeseweed is a biennial weed that frequently reaches 4 feet in height. By
the second year, cheeseweed can reach a stem diameter of 1/2 inch which
becomes woody. Cheeseweed has a large taproot and is virtually impossible
to pull by hand and must be dug out with a shovel (which is injurious to
the tree or vine root system) or flail mowed. After being mowed,
cheeseweed will rapidly resprout at the base and continue to rob the
tree/vine of moisture, nutrients8 and space. If no herbicides are used,
growers must flail mow 10 to 12 times per year. Growers are encouraged
25/ Information used in this analysis is taken from the Agency
Preliminary Analysis of Oxyfluorfen (Goal 2E) Use for Weed Control in Tree
Fruit/Nut and Vineyards in California (Petrie, R. C., 1980c).
68
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TABLE 22
Other Registered Herbicides Used for Weed Control in
Tree Fruits/Nuts and Vineyards
Class • Herbicides
Preemergence Napropamide
Napropamide/Simazine
Frincep (Simazine)
Devi no I/ S imaz ine
Oryzalin
Eptam (EPTC),
Trifluralin*-'
(incorporated)
Diphenamid
Norflurazon
Postemergence Glyphosate
Paraquat—
Dalapon
2,4-D
MSMA plus surfactant
Preemergence . Diuron
and/or Postemergence Diuron/Terbacil
DNBP or Dinoseb
Paraquat/Simazine
a/ Trifluralin is currently under RPAR review by the US EPA.
b/ Paraquat is currently under RPAR review by the US EPA.
69
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not to cultivate (disc or harrow) under the trees/vines in order,to prevent
the spread of diseases<. Further, the use of berras— by most growers
makes cultivation and mowing under the tree and within the row difficult.
Similarly, weeds are difficult to remove from under a trellis (vine support
for grapes) without damaging vines and roots (USDA, 1977).
b) Goal 2E is versatile because it provides preemergence and
postemergence contact weed control from one application of 1 Ib Al/acre or
more. Based on data in EPA Registration Division files, Goal 2E will
control those emerged weeds listed on the label by contact activity. Any
Goal that reaches the soil surface will provide three to four months
residual control of those germinating weeds listed on the label. Research
done by the University of California extension service with Goal
demonstrated 99% preemergence control of cheeseweed for 236 days.
c) Goal 2E is more easily used than preplant incorporated
herbicides. Preplant incorporated herbicides are applied before weed
emergence as are preemergence herbicides, however, most preplant
incorporated herbicides must be immediately mechanically mixed into the
soil surface top two to four inches after application. The mechanical
incorporation operation is difficult to accomplish between the trees/vines
due to emerged weeds and benns, thus resulting in loss of herbicide
effectiveness.
d) Efficacy data in EPA Registration Division files support
the Rohm and Haas claim that "Goal 2E can remain on the ground for up to
three to four weeks after application without moisture incorporation with
no loss of effectiveness." Therefore, Goal 2E can be used in areas of
limited rainfall or where no sprinkler irrigation exists.
e) Goal 2E is not injurious to newly-planted almond,
apricots, nectarine, peach, plum or prune trees, nor does it appear to be
injurious to vineyards established for three years or more. Due to the
efficacy waiver policy, phytotoxicity and efficacy data for apricots and
grapes are limited. In the case of apricots, only one test in one growing
season in one soil-type climatic area was submitted. For grapes, Goal 2E
was evaluated on only 6 of 67 California grape varieties.
f) Goal 2E can be used on all soil textures (sands, silts,
clays) and on soils with 0-8% organic matter content with no loss of
activity or selectivity. Goal 2E can be used as a preemergence herbicide
on low organic matter soils, and where irrigation practices are utilized,
without excessive leaching or herbicide injury to crop roots (Lange, 1977).
26/A berra is a raised mound or ridge on which the tree vine is
planted to improve drainage, reduce salt damage and reduce disease
problems.
70
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3. Tree Fruits/Nuts and Vineyards: Comparative Performance
Evaluation
Goal 2E herbicide is unique in California fruit and nut
orchards and vineyards because it provides contact control of label-claimed
weeds emerged at the time of treatment (postemergence), as well as long-
lasting residual preemergence control of later-germinating seeds. Further,
Goal 2E is the only available herbicide that will provide season-long
control of the problem weed cheeseweed. Napropamide and norflurazon
provide some residual preemergence control of cheeseweed but are
ineffective for control of cheeseweed emerged at the time of application
and for control of later-germinating cheeseweed.
Of the 14 herbicides other than Goal 2E available for use in
the Goal 2E label-claimed orchard/vineyard crops, only paraquat,
trifluralin and MSMA plus surfactant are labeled for use on all of the same
orchard/vineyard sites as Goal 2E. Trifluralin and MSMA plus surfactant
labels do not claim control of cheeseweed. Paraquat will only top kill
cheeseweed, resulting in resprouting at the base of the plant.
In contrast with other available herbicides, Goal 2E is
ineffective for control of many grassy weeds and, therefore, is recommended
for use in tank mix combination with paraquat (for postemergence annual
grass control) and/or Devrinol (for preemergence residual grass control).
A drawback of Goal 2E on vineyards is that the grower must wait at least
three years before applying Goal 2E to new grape plantings. However, only
four of the 13 herbicides and herbicide combinations listed for use on
grapes can be used soon after planting before grapes are "established"
(approximately three years after planting). Of the four, paraquat and MSMA
plus surfactant are postemergence directed sprays. A four-week wait after
planting is required before applying dichlobenil for preemergence weed
control, and trifluralin can be applied for preemergence weed control with
no wait after planting. Trifluralin, however, requires mechanical
incorporation Immediately after application.
Goal 2E has proven especially effective for control of label-
claimed weeds in the Compositae family such as sowthistle, prickly lettuce
and common groundsel (Elmore, 1980). As a postemergence herbicide, Goal
2E is superior to paraquat and dinitro products for control of cheeseweed,
filare and nettle (Elmore, 1980).
Nonherbicidal alternatives include mechanical methods of weed
control such as discing or mowing. Such methods can result in damage to
vines and delicate root systems. Use of berms by most growers makes mowing
under trees and within rows difficult. Hand hoeing involves high labor
costs and may still result in root damage.
4. Tree Fruit/Nuts and Vineyards: Economic Impact Analysis
a. Profile of Impacted Area
California accounted for 50-100% of the total U.S.
production in 1979 of each of the following: peaches, nectarines, pluins,
grapes, apricots and .almonds (USDA, 1980). Commercial orchards and
vineyards make up 1.4 million acres in this state. It is estimated that
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80% of the coastal orchards and vineyards and 70% of the Northern
California acreage is infested with cheeseweed.
b. User Impacts
It is assumed that oxyfluorfen's registration for use on
bearing tree fruit/nuts will result in a farmer applying it using his
current application method. Therefore, economic impacts would be limited
to cost differences between oxyfluorfen and other herbicides. Total cost
will also vary because the number of treatments vary with the herbicide
used. Goal 2E is normally applied only once per season. Since Goal has
both preemergence and postemergence activity, use of Goal 2E may reduce
the need for application of a second, postemergence herbicide.
E. Conifers —'
1. Conifers: EPA Registration of Oxyfluorfen and Other
Herbicides
Oxyfluorfen (Goal 2E), was federally registered by the Agency
on March 25, 1980, for preemergence and postemergence weed control in
conifer seedbeds throughout the U.S.—— and for preemergence and post-
emergence weed control in certain conifer transplants.—
Conifer transplants, as referred to on the Goal 2E label, are
conifer seedlings that are taken from the seedbed after one year's growth
and are re-planted (transplanted) into a well-tilled, weed free bed. When
transplanted, they are "lined-out" or evenly spaced in rows.
27J Information used in this analysis is taken from the Agency
Preliminary Analysis of Oxyfluorfen Use for Weed Control in Conifer
Seedbeds throughout the U.S.; and for Weed Control in Conifer Transplants
(Petrie, R.C., 1980d).
Limitations of this analysis include:
a. No benefits or efficacy data were available in Agency files
because of the efficacy data waiver policy. (Dec., 1978).
b. Where label claims have been compared, it is assumed that
these claims are accurate and in conformance with agency-
industry performance standards.
28/ Preemergence treatment is made after seeding into the seed bed but
before conifer and weed seed germination. Postemergence treatments are
made after conifer seedlings are at least five weeks old and after weeds
have emerged from the soil.
29/ Preemergence treatment refers to application of Goal 2E immediately
after transplanting before weeds emerge from the soil. Postemergence
refers to application of Goal 2E after weeds have emerged from the soil.
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a. Conifers - Seedbeds:
Goal 2E can be used at up to 1 Ib.AI per acre as a
preetnergence treatment and up to three times at a maximum rate of 0.5 Ib.
Al/per acre per each treatment as a postemergence spray (for a maximum
possible total of 2.5 Ib. AI per acre per season) without injury to
loblolly pine, slash pine, longleaf pine, shortleaf pine, eastern white
pine, Virginia pine, ponderosa pine, lodgepole pine, Douglas fir and
Colorado blue spruce.
Conifer seeds are planted into well tilled, weed free
seedbeds. Most seedbeds are either fumigated before or receive herbicide
treatments before and after planting. The decision of whether or not to
fumigate is, in most cases, determined by the relative value of the
conifers and on the need for disease and/or fungus control. The fumigant
formulation selected varies with the seriousness of the disease and/or
fungus problem. Therefore, herbicide seedbed treatments may be necessary
after seedling emergence even if a fumigant is used before planting.
b. Conifers - Transplants and Outplantings:
On spring transplanted conifers, up to 2 Ib. AI per acre
Goal 2E can be applied as a preemergence or postemergence treatment (one
treatment per season). On fall transplanted conifers, Goal 2E can be
applied at up to 2 Ib. AI per acre as a preemergence or postemergence
treatment up to two times per season (for a maximum possible total of 4
Ib. AI per acre per season). At the recommended rates, Goal 2E will not
injure: pyramid arborvitae, golden pfitzer juniper, tarn juniper, mugho
pine, dwarf Alberta spruce, bird's nest spruce, Himalayan pine, scotch
pine, noble fir, Norway spruce and Colorado spruce.
The conifer seedbed and transplant uses were approved by
Registration Division after the agricultural herbicide efficacy data waiver
policy took effect. Therefore, there are no benefits data in Agency files
to support the registered Goal 2E label claims (Reg. No. 707-145).
The conifer transplants are dormant at the time they are
transplanted. If fall transplanted, they remain dormant all winter and
break dormancy (resume growth) in late May or early June the following
spring. If transplanted in the spring (usually March to April), the
conifer transplants break dormancy approximately 30 days later (late May to
early June). Fall herbicide applications are desirable because (1) labor
is usually more available in the fall and (2) fall herbicide treatments
prevent weed infestations during the early spring digging and transplanting
season. Fall herbicide treatments are usually followed by treatments in
late spring to control summer weeds. Goal 2E is recommended for use only
while the conifer transplants are still in dormancy. The dormancy period
soon following transplanting is the most critical period concerning the
need for effective weed control. Weeds start germinating soon after the
bed has been prepared and can quickly outgrow the conifer transplants
(which are only six to eight inches tall and still dormant) and eventually
kill them by shading. Hand pulling of weeds is not possible for up to two
years after transplanting (most transplants are in the transplant bed for
only one year). Because the transplants are planted in light-sandy soil
for drainage and aeration purposes and because the conifer transplants have
such delicate root systems (especially while still dormant), the pulling up
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of weeds results in the pulling up of conifer transplants as well. Hand
weeding can be done on a limited scale between rows. However, labor costs
are usually prohibitive.
Most conifer transplants stay in the transplant bed one
year before being "outplanted" (transplanted to the field). Conifer
transplant species listed on the Goal 2E label are used primarily along
interstate highways and for other landscaping purposes.
Conifer transplants are considered "established" only
after the new growth is fully expanded and has hardened off (soft growth
becomes hardened with age) and after the root system has expanded. If
transplanted around the first of April, it would take approximately 2.5
months for the transplants to break dormancy and become "established."
Having to wait this late after transplanting, before application of
preemergence herbicides usually defeats their purpose because the weeds
have already emerged and are vigorously growing. Most of the preemergence
herbicides have no postemergence weed control activity, as does Goal 2E.
The Goal 2E label does not recommend use on "established" transplants.
c. Other Registered Herbicides
Major registered preemergence and postemergence
herbicides other than Goal 2E, for weed control in conifers are presented
in Table 23.
2. Conifers: Performance of Goal 2E Herbicide
A qualitative analysis of the benefits of Goal 2E use on
conifers follows.
a) With the exception of soil fumigants, there are currently
only two-barbieides registered for use on conifer seedbeds beside
Goal 2E.— They are bifenox and diphenamid. Neither bifenox nor
diphenamid can be used on all of the same conifer species that are listed
on the Goal 2E label.
b) Of the herbicides listed in Table 31 under transplants,
only chlorpropham, naptalam, and DCPA can be used on all of the same
conifer species that are listed on the Goal 2E label. None of the three
herbicide labels claim control of all the Goal 2E label claimed species.
c) Goal 2E can be applied as a preemergence treatment for
residual control of label claimed weeds or as a postemergence treatment
for contact control of label claimed species. Most growers prefer to use
Goal 2E preemergence before weeds can become established and do damage.
30/ State Recommendations (Ark., Wash., Kans., La., Miss., Va., New
England) (Petrie, 1980d) and 1980 Weed Control Manual - Agricultural
Consultant and Fieldman.
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TABLE 23
Other Registered Herbicides Used for Weed Control In Conifers
Use
Class
Herbicide
Seedbeds
Preeoergence
Methyl Bromide5/
Methaa5-'
Blfenox
Dlphenamld
Transplants
Preemergence Weed
Control - Applied
before transplanting
conifers
Methyl Bromide
Methan
Naptalam
Trifluralln^7-'
Transplants
Preemergence Weed
Control - Applied
Immediately after
transplanting during
conifer dormancy
(similar to
oxyfluorfen)
Alachloi
f/
Chloramben— .
Chlorpropham^
DCPA!/
Napropamide^'
Naptalan^
Oxadiazon—
Pronamlde—
Transplants
Preemergence Weed
Control - Applied
after transplants
are "established"
Alachlor^
Bensullde^
Chloramben—
Mchlobenili'
Dlpenamld
Napropamide—
Naptalao£/
Oryzalln^-'
Oxadlazon^-'
Transplants
Post Emergence Weed
Control
Glyphosat^
Paraquat^'
Pronamlde—
a/ Fumlgants
¥/ Requires mechanical or moisture Incorporation
c/ Postemergence control of creeping speedwell
"it Presently under RPAR review by US EPA
e/ Applied as a directed treatment
f_/ Applied as a broadcast
fj Limited post emergence control of seedling pigweed and smartweed,
chlckweed, purslane and field dodder. (These claims taken from 1979
"Herbicide Handbook", WSSA; not from registered labels)
ti/ Applied as a directed treatment anytime after transplanting and after
conlferu are established
ij Applied after conifers are "established"
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Also, Goal 2E provides season-long weed control (until fall
dormancy in November) from the preemergence application. The preemergence -
postemergence utility virtually ensures season-long control of the Goal
2E label claimed weed species (Comegys, 1980).
d) Goal 2E is not injurious to the label claimed conifer
species and therefore can be applied just before and soon after seeding and
immediately after transplanting into a bed when weeds can be the most
damaging to conifer seedlings and transplants. Goal 2E can be applied as a
postemergence spray directly over-the-top of label claimed conifer species
with no injury (when applied as directed by the label). Many other
herbicides cannot contact the conifer foliage without causing Injury, or
must be directed to the middle of the rows. This type of restriction
prevents the treatment of weeds growing close to the transplant and in the
row.
e) Goal 2E is more easily used than preplant incorporated
herbicides. Use of Goal 2E preemergence eliminates the need for mechanical
incorporation (rototilling or .hand-hoeing) required immediately after
application of most preplant incorporated herbicides.
f) Goal 2E can be used on all soil textures (sands, silts,
clays) and on soils with 0-8% organic matter content with no loss of
activity or selectivity.
g) Sandy soils used in seedbeds and transplant beds, and
continuous irrigation increase the chances for herbicide injury to young
conifers by leaching into the root zone. Rohm and Haas has previously
reported that Goal 2E does not leach through soil due to Its low water
solubility (0.1 ppm) and Goal's affinity for soil exchange sites.
3. Conifers: Comparative Performance Evaluation
Goal 2E is considered a unique herbicide for the following
reasons: (1) Goal 2E provides preemergence residual and/or postemergence
contact control of label claimed weed species. This preemergence/post-
emergence utility virtually ensures season-long control of the label
claimed weed species at a time in conifer growth when weed control is
essential; (2) Goal 2E can be applied over-the-top of five week old
seedlings of label claimed conifers without causing injury. Up to three
over-the-top applications are allowed per season; (3) Goal 2E can be
applied over-the-top of newly transplanted label-claimed conifers while
they are still dormant without causing injury. Effective weed control is
critically needed after transplanting while conifers are dormant because
weeds can very quickly outgrow the six to eight inch tall dormant
conifers.
Futaigants such as methyl bromide or metham are used primarily
for disease and fungus control in seedbeds and transplant beds. Their use,
however, is quite often limited by their high human toxicity and the high
labor costs associated with their use. Weed control by these products is
considered incidental to disease and fungus control. Most weed seeds
present at the time of fumigation are killed, but there is no residual
protection from weed seeds deposited later.
-------
Bifenox and dlphenamid are herbicides that can be used for
preeraergence weed control in conifer seedbeds. However, these herbicides
cannot be used on all Goal 2E label claimed conifer species nor do they
claim control of all weed species claimed on the Goal 2E label.
Of the 12 herbicides other than Goal 2E that can be used for
weed control in newly transplanted conifers, only three (DCPA, chloro-
propham -and naptalam) are registered for use on all of the same conifer
species as Goal 2E. None of the labels for these three herbicides claim
control of the following 18 weed species claimed on the Goal 2E label:
annual morning glory, scarlet pimpernel, mayweed, wild mustard, lesser
bittercress, sticky chickweed, bull thistle, fireweed, prickly lettuce,
ladysthumb, common groundsel, hairy nightshade, annual sowthistle, corn and
sand spurrys, red and white clovers and birds eye speedwell.
Nonherbicidal methods of weed control, used to a limited
extent in small nurseries, include (1) mulching with organic materials such
as peat, bark, wood chips, sawdust, straw, cattle manure, waste newsprint
and pine needles and; (2) plastic sheeting. A one to two inch deep mulch
reduces water loss from the soil, tends to insulate the soil to prevent
wide temperature fluctuations and shades out small weedy seedling plants.
A fresh sawdust mulch, however, can rapidly deplete the soil of nitrogen
needed for plant (rowth. Also, the temperature under black plastic mulch
can sometimes raise the soil temperature to a lethal level. Mulch Is not
effective for control of emerged weeds at the time it is applied.
Hand pulling of weeds in seedbeds or in transplant beds has
proven injurious to the conifer seedlings/transplants because of the
tendency to pull up the weak-rooted conifers as well.
No comparative efficacy or phytotoxiclty data are currently
available due to the efficacy data waiver policy which took effect in
December 1978.
4. Conifers: Economic Impact Analysis
a. Profile of Impacted Area
Goal 2E is registered for weed control in certain conifer
seedbeds throughout the entire United States. State.recommendations
include Arkansas - 1980, Washington - 1980, Kansas - 1978, Louisiana -
1980, Mississippi - 1980, Virginia - 1980, New England - 1979, and Idaho -
1979. Goal 2E is registered for weed control in certain conifer
transplants throughout the United States.
b. User Impacts
Nurserymen have very limited experience with Goal 2E for
weed control in conifer seedbeds and conifer transplants because 1980 was
the first year that most were able to use it. Goal 2E was first registered
for use on these sites on March 25, 1980. Those that have used the
chemical under experimental permit (Dr. IIlo Gauditz and Dr. William Morris
of Weyerhauser; Mr. John Grim of Industrial Forest Association, Dr. Clyde
Elmore, Weed Scientist of the University of California, Davis) report
excellent control of label claimed weeds with no conifer phytotoxicity when
used as directed by the label in small nursery plots.
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Weyerhauser almost always fumigates their Pacific N.W.
seedbeds. Weyerhauser's southern (Hot Springs, Arkansas) loblolly pine
seedbeds are fumigated every other year for disease control. Weyerhauser
grows only loblolly pines on their 600 acres of seedbeds in Arkansas.
Unlike the Pacific N.W. conifer species, loblolly pine seedlings remain in
the seedbed for only ten months and are then transplanted directly to the
field (outplanted). Goal 2E was used preemergence and postemergence on
200 of the 600 total acres of southern seedbeds this year with no injury to
the loblolly pine seedlings. Dr. Morris reported excellent control of
crabgrass, goosegrass and dallisgrass from the low rate of 0.25 Ib. AI per
acre applied preemergence.
No comparative performance data are currently available
to compare most differences between Goal 2E and other herbicides. For
nonherbicidal alternatives, Dr. Gauditz of Weyerhauser estimated that hand
weeding would cost Weyerhauser $50,000.00 to $100,000.00 per year if no
herbicides were used, due to the need to hand weed carefully and often
(this figure does not include the cost of replacing trees pulled out with
the weeds).
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IV. RISK/BENEFIT ANALYSIS: DEVELOPMENT OF REGULATORY OPTIONS
A. Introduction
In the previous Sections II and III, the potential human risks
associated with the proposed use of oxyfluorfen were examined, and the
potential benefits associated with each use were identified in light of
available data. FIFRA requires the Agency to achieve a balance between the
competing considerations of risks and benefits. To carry out that mandate,
the Agency has developed various regulatory options and has evaluated each
option for its impacts on risks and benefits.
This section of the Position Document describes the rationale for
the development of regulatory options and discusses the options which were
selected for consideration.
1. Rationale For Development Of Regulatory Options
In its simplest terms, FIFRA provides for two basic options
concerning the regulation of pesticides: to grant or to deny
registration. For new pesticide products, these options are represented in
terms of the approval or the denial of applications for registration. For
previously registered products, they are framed in terms of a decision
either to allow continued registration or to cancel registration.
Denial/cancellation of registration represents an absolute
regulatory response which means that the sale or the distribution of the
pesticide for the use(s) at issue is prohibited. Registration, on the
other hand, represents a range of regulatory options, since the
Administrator may specify the terms and conditions of registration for some
or all uses. He may, among other things, require the label and the
labeling of a pesticide product to contain certain language which he
considers necessary for the adequate protection of health and the
environment, or he may classify the use of a pesticide product for
restricted use, and limit its application to certified applicators or
persons under their direct supervision.
While cancellation/denial and unrestricted registration fall
at opposite ends of the regulatory spectrum, the development of
intermediate regulatory options involves the formulation (and/or
modification) of the terms and conditions of registration which are
intended to reduce the risks attendant to the use(s) of the pesticide.
The concept of incremental unreasonable risk also comes into play in
assessing whether the use of a pesticide causes unreasonable adverse
effects on the environment. Under this concept, a risk which is small
or marginal is still not acceptable if risk reduction measures can be
implemented without an adverse impact on the benefit of use. Thus, for any
given use situation, the Agency seeks to reduce the risk to the lowest
possible level without reducing the benefits of use. Each option is then
evaluated on a use-by-use basis to determine whether it achieves an
adequate reduction in risk without causing unacceptable economic
consequences, so that the remaining benefits of each use exceed the
remaining risks.
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2. Salient Risk/Benefit Considerations
The Agency has determined that both technical and formulated
oxyfluorfen meet or exceed the criterion for carcinogenic risk under 40 CFR
162.ll(a)(3)(ii) since they both contain the carcinogenic contaminant PCE.
The carcinogenic risk to humans associated with this PCE contaminant of
oxyfluorfen was the primary risk consideration in the regulatory decision
recommended In this Position Document. No other human or environmental
risk criteria as described in 40 CFR 162.ll(a)(3) have been met or exceeded
by the proposed uses of oxyfluorfen or its PCE contaminant at this time.
However, with respect to oxyfluorfen itself, there are certain areas for
which information is currently inadequate for the Agency to determine
hazard potential. These areas were discussed in Section II and include
oncogenicity, teratogenicity, mutagenicity, persistence and bioaccumulation
in aquatic habitats and hazard to aquatic molluscs and wetlands.
The Agency identified a number of situations which have the
potential to cause human exposure to the PCE contaminant of oxyfluorfen.
These situations include the mixing, loading, and application of oxyfluor-
fen to crops. During these activities both dermal and inhalational
exposure to PCE are to be expected. In addition, PCE exposure to the
general population through ingestion of residues on oxyfluorfen-treated
crops was considered possible (see Section II.B.).
The benefits of oxyfluorfen were assessed in terms of the
economic impact which would result if the Agency did not register the
proposed uses and cancelled the currently registered, uses of this
herbicide. For this assessment the Agency assumed that oxyfluorfen would
be as efficacious as the herbicides now registered for these proposed
uses. The Agency considers that there may be an efficacy differentia]
between oxyfluorfen and certain of these other herbicides especially for
the control of witchweed in field corn. However, data have not been
developed to quantify these differences. Benefits estimates are therefore
expressed in terms of treatment costs differences between oxyfluorfen and
those alternatives, or qualitative descriptions of the utility of
oxyfluorfen in these use patterns. A quantitative analysis of the benefits
was not available for tree fruits/nuts and conifer uses, making qualitative
descriptions particularly necessary for the appraisal of these uses.
In Section III of the this document, herbicides which may be
considered alternatives to Goal 2E were presented for each use pattern.
The Agency has, in the past, often considered the risks of alternative
pesticides in its risk/benefit determinations. In the case of Goal 2E data
currently available to the Agency are inadequate to predict what, if any
Impact the availability of Goal 2E will have on the use of other
herbicides. Market acceptence of Goal 2E is still relatively unknown for
most uses. Also, for most uses, Goal is likely to be used in conjxinction
with other herbicides rather than in place of them.
The Agency does believe that it is important to note that some
of the alternatives listed in Section III currently are under review by the.
Agency. There alternatives have a number of possible adverse effects and
data gaps which are being evaluated. However, no final determination has
been made by the Agency on these herbicides.
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Therefore, in this Instance the Agency did not perform a
formal comparative risk analysis hetween Goal and other weed control
treatments.
The Agency has determined that the lifetime individual
cancer risk to agricultural-workers using oxyfluorfen in soybeans, field
corn (Witchweed Eradication Program only), and tree fruit/nuts and conifers
would range from about 1.48 x 10 to 3.82 x 10 and that the _q
maximum dietary cancer risk estimate would range from 2.65 x 10 " to
1.0 x 10 . The benefit to agricultural producers from
registering oxyfluorfen on soybeans would range from about -$6.00 per acre
to + $24.00 per acre and for corn £Witchweed Eradication Program only) from
about +$32.00 to +$42.00 per acre.— Goal's preemergence and post-
emergence effectiveness, its selective control of cheeseweed, and its lack
of phytotoxic effects on conifer species are among the qualitative benefits
to agricultural producers from registering Goal for use on tree fruits/nuts
and conifers.
B. Regulatory Options Considered
The regulatory options considered for the present action on
oxyfluorfen focused on methods to reduce levels of human exposure to the
PCE contaminant. The Agency also considered requiring the submission, by
Rohm and Haas, of additional risk data for oxyfluorfen itself. The Agency
considered basic regulatory options for each use. The specific regulatory
options for each use are explained in the following sections.
Option 1: Specify a maximum PCE contamination level of 200 ppm
in formulated oxyfluorfen products (Goal 2E).
The choice of this option would indicate that:
o The Agency accepts the registrants assertion that 200 ppm is
the lowest PCE level which is technologically and econo-iically
feasible. Further risk reduction, if warranted could be
accomplished via other means, such as requiring the use of
protective equipment.
o Allotting greater than 200 ppm PCE in formulated oxyfluorfen
products wold increase the risk from use of these products to
unacceptable levels.
Option 2: Require the protective equipment scenario described
in Section II.C.3.d.
The choice of this option would indicate that:
o The Agency has concluded that the risk from the uses of
oxyfluorfen products outweighs the benefits, but that the use of
protective equipment by applicators will significantly reduce
the risk from PCE associated with these uses.
31/ A negative value indicates that oxyfluorfen per acre-treatment
costs are greater than that of the currently registered alternatives; a
positive value indicates the opposite.
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Option 3: Prohibit use of oxyfluorfen products In counties
providing habitat for species of endangered clams.
The choice of this option would indicate that:
o The Agency has concluded that based on current information the
use of oxyfluorfen products in certain counties poses a threat
to federally designated endangered species (clans).
Option 4: Require labeling for the soybean use in order to
protect aquatic molluscs.
The choice of this option would indicate that:
o The Agency has concluded that the risks from PCE associated
with the use if oxyfluorfen are outweighed by the benefits of
such uses, but that the incremental risk to aquatic molluscs
from oxyfluorfen can be reduced by labeling without an adverse
impact on benefits.
Option 5: Require labeling for all uses for the protection of
aquatic plants, aquatic invertebrates, wildlife and fish.
The choice of this option would indicate that:
o The Agency has concluded that the risks from PCE from the use of
oxyflurofen products are outweighed by the benefits of such
uses, but that the incremental risk to aquatic plants and
animals from oxyfluorfen itself can be reduced by labeling
without an adverse impact on benefits.
Option 6: Require certain data on the possible adverse effects
of oxyfluorfen on man and the environment to be submitted to the
Agency by the registrant. The areas of concern for which the
data would be required include: oncogenicity, rautagenicity,
teratogenicity, persistence and bioaccumulation in the
environment, and toxicity to fish and wildlife. '
The choice of this option would indicate that:
o The Agency believes that currently available data are
inadequate to accurately evaluate the possible adverse effects
of oxyfluorfen in the areas listed above.
Option 7: Cancel and/or deny registrations for oxyfluorfen uses.
The choice of this option would Indicate that:
o The Agency has concluded that the risks from PCE associated
with the uses of oxyfluorfen outweigh the benefits of such
uses and that there are no viable means* short of cancellation
or denial of registration which would reduce these risks to an
acceptable level.
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C. Risk/Benefit Analysis and Proposed Decision
The purpose of this section is to compare the risk and benefits
for each use under each of the options considered. Since the risks and
benefits have been discussed in detail in Section II and III the following
evaluation will be presented in general terms. Following the risk benefit
evaluations under each option, is the proposed regulatory decision for that
particular use.
1. Nonbearing Tree Fruit/Nuts
a. Risk/Benefit Analysis
If continued use of Goal in nonbearing tree fruit/nuts were
allowed, lifetime cancer risk to agricultural workers, assuming a 200 ppm
contamination level of PCE, would be 5.8 x 10- . It is assumed that
continued registration presents no cancer risk (dietary) to the general
population.
Benefits for use of Goal on nonbearing tree fruit/nuts cannot
be quantified from available data. However, the general performance of
Goal compared to other currently available registered herbicides has been
judged to be quite good (Section III.D.). Goal is apparently the most
effective herbicide treatment for preemergent control of cheeseweed in
orchards and vineyards and its persistence indicates that it would be
effective against annual weeds that threaten new transplants, and other
crops that would otherwise require extensive cultivation. Goal, in
combination with other chemicals (e.g., paraquat, devrinol), would provide
maximal .control of cheeseweed and grassy weeds. Mechanical weeding as an
alternative would damage vines and root systems and it. Is estimated that
hand hoeing would prove more expensive than use of Goal. Cost differences
between Coal and other herbicidal alternatives would vary according to the
number of treatments, and treatment and application methods.
If continued use in nonbearing tree fruit/nuts were allowed
with additional requirements for protective clothing the following would
result. Agricultural workers would be required to wear hats, gloves,
forearm protection, shirt with the collar buttoned and long pants during
mixing/loading and application of Goal. Since inhalational exposure is
higher then dermal exposure, respirators would also be required.
Reduction of total cancer risk fromthe use of bo£|j protective
clothing and a respirator would be from 5.8 x 10 to 3.4 x 10 . The
benefits postulated for use of Goal (Section III.D.) would not be affected
by this option.
If registration of Goal (oxyfluorfen) use on nonbearing tree
fruit/nuts were cancelled, lifetime cancer risks to agricultural workers
would be reduced from 5.8 x 10 to 0. The nonavailability of Goal would
prevent the farmer from obtaining effective herbicidal control of
cheeseweed and would force him to Incur the costs of hand hoeing or
experience damage to his crops from mechanical weeding. No quantitative
amounts can be calculated to predict costs of other herbicides for control
of other weeds (Section III.Do).
83
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Specific labeling to protect endangered molluscs was not
considered because the nonbearing tree fruit/nuts use pattern area
(California) does not provide habitat for these species.
If labeling to protect aquatic plants, aquatic invertebrates,
wildlife and fish were required, risk to the environment would be reduced
with no concurrent reduction in the benefits of oxyfluorfen use on tree
fruit/nuts.
b. Proposed Regulatory Decision
Having evaluated both the carcinogenic risk posed to
agricultural workers in conjunction with PCE-contatninated oxyfluorfen use
on nonbearing tree fruit/nuts and the benefits of such use, the Agency has
determined that, with a maximum PCE level of 200 ppm, the benefit of use
outweigh the risk from PCE.
Benefits of Goal 2E are discussed fully in Section III.D.
Briefly, Goal is particularly effective in the control of cheeseweed in
California orchards and vineyards and is preferable to mechanical weeding
and less expensive than hand hoeing.
The Agency recognizes that the risk estimated for this use
pattern is based upon estimates of the worst case exposure (See section
II.C.). However, in the absence of field monitoring data indicating actual
PCE exposure levels during the mixing, loading, and applying of formulated
oxyfluorfen products under typical conditions, the Agency must base its
regulatory decision on the worst case estimate of,exposure. Therefore, the
use of a respirator to reduce the risk (5.8 x 10 to 3.4 x 10 ) to
agricultural workers is justified. Because dermal exposure contributes
very little to the total risk to applicators/mixers/loaders, protective
clothing will not be required.
Cancellation of this use is not justifiable since the Agency
has determined that the benefits outweigh the risk.
The Agency proposes that the folloi^ing be implemented:
o Continue the registration of Goal 2E for use on nonbearing
tree fruits/nuts in California with the requirement that the.
PCE level in the formulated product not exceed 200 ppm.
o A pesticide respirator jointly approved by the Mining
Enforcement and Safety Administration (formerly the U.S.
Bureau of Mines) and by the National Institute for
Occupational Safety and Health under the provisions of
30 CFR Part II for perchloroethylene must he vised during the
mixing, loading and application of all oxyfluorfen
products. This requirement will take effect six months
after the date of publication of the Notice announcing the
final determination concluding the oxyfluorfen RPAR, unless
by that time the registrant submits field monitoring data to
the Agency establishing that the inhalation exposure for the
maximum application rate for each registered use is
significantly lower than the inhalation exposure estimated
by the Agency.
-------
o Require labeling to protect aquatic plants, aquatic
invertebrates, wildlife and fish. This labeling will take
the form of the following statement:
"This pesticide is highly toxic to aquatic plants, aquatic
invertebrates, wildlife and fish. Use with care when
applying in areas frequented by wildlife or adjacent to any
body of water or wetland area. Do not apply when weather
conditions favor drift or erosion from target area. Do not
contaminate water by cleaning of equipment or disposal of
wastes."
o Require the registrant to submit to the Agency data in a
number of areas where current information is inadequate to
accurately evaluate the hazard potential, of oxyfluorfen.
These areas include oncogenic.ity, mutagenicity,
teratogenicity, chronic toxicity, and toxicity to wildlife.
The studies required in each of these areas are listed in
the summary of the Agency's proposed decision at the end of
this Section.
2. Conifers
a. Risk/Benefit Analysis
If the Agency were to allow continued use of Goal
(oxyfluorfen) on conifers assuming a 200 ppm or less level of PCE
contamination, total cancer risk for mixer/loader/applicators would be
5.0 x 10 .
The continuation of Goal use In conifer seedbeds would be
considered advantageous to growers because only bifenox and diphenamid are
registered for preemergence weed control in conifer seedbeds. However,
these herbicides cannot be used on all Goal 2E label claimed weed species.
The continuation of Goal 2E use in conifer transplant beds is also
advantageous in that of the 12 herbicides registered for weed control In
newly transplanted conifers, only three (DCPA, chloropropham, and naptalnm)
are registered for use on all the same conifer species as are listed on the
Goal ?.E label. Hand weeding without the use of currently registered
herbicides to control weeds in conifer transplant beds would cost
substantially more than the use of chemicals, according to estimates of
Weyerhauser personnel.
If the Agency were to allov; continued use of Goal
(oxyfluorfen) on conifers with additional requirements for protective
equipment the following would result. Mixer/loader/applicators would be
required to wear hat, gloves, forearm protection, shirt \Jlth the collar
buttoned and long trousers. If the Agency were to Impose the additional
requirement of a respirator along with protective clothing for _,
mixer/loader/applicators, cancer risk would be reduced from 5.8 x 10 to
1.3 x 10 ' . The provisions of this option would not he expected to
affect the benefits for Goal use on conifers.
85
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If the Agency were to cancel the use of Goal 2E on
conifers the risk to applicators from PCE would be reduced to 0.
The nonavailability of Goal would deprive growers of an
effective pre- and post emergence herbicide for use on seedbeds,
transplants and outplantings. There are only two alternative herbicides
registered for use on seedbeds and neither of these can be used on all
conifer species listed on the Goal label.
Fumigants such as methyl bromide, are used on seedbeds
primarily for disease and fungus control with weed control being
incidental. Also, fumigants are associated with high acute toxicity to
humans and incur high labor costs.
For transplants and outplantings, loss of Goal would
deprive growers of herbicidal control of certain weed species not
controlled by other herbicides registered for use or the same conifer
species. Hand weeding is injurious to transplants and costs substantially
more than chemical control.
Labeling for the protection of fish and wildlife would
serve to reduce the risk to the environment from oxyfluorfen without an
adverse impact on the benefit of Goal use on conifers:
b. Proposed Regulatory Decision
Regarding the use of Goal 2E on conifers, the Agency has
examined both the risk from PCE contamination and the benefits associated
with this use of oxyfluorfen. Based on_a maximum PCE level of 200 ppm the
risk has been determined to be 5.8 x 10 . The Agency has determined
that the benefits of this use of Coal on conifers (discussed in Section
III. E.)outweigh the risk. Therefore, cancellation of the registration of
Goal for use on conifers, is not justifiable.
The Agency recognizes that the worker risk estimates for this
use pattern (5.8 x 10 ) is based on a worst case estimate of exposure to
PCE. However, in the absence of field monitoring data indicating actual
PCE exposure levels during the mixing, loading, and applying of
formulated oxyfluorfen products under typical conditions, the Agency must
base its regulatory decision on the worst case estimate exposure.
Therefore, the use of respirators to reduce the risk to agricultural
workers is justified. Because dernal exposure contributes very little to
the total risk to applicators/mixers/loaders, protective clothing will not
be required.
The Agency therefore proposes that the following be
implemented for the use of oxyfluorfen on conifers.
o Continue the registration of Goal 2E for use on conifers
with the requirement that the PCE level in the formulated
product not exceed 200 ppm.
86
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o A pesticide respirator jointly approved by the Mining
Enforcement and Safety Administration (formerly the U.S.
Bureau of Mines) and by the National Institute for
Occupational Safety and Health under the provisions of
30 CFR Part II for perchloroethylene must be used during the
mixing, loading and application of all oxyfluorfen
products. This requirement will take effect six months
after the date of publication of the Notice announcing the
final determination concluding the oxyfluorfen RPAR, unless
by that time the registrant submits field monitoring data to
the Agency establishing that the inhalation exposure for the
maximum application rate for each registered use is
significantly lower than the inhalation exposure estimated
by the Agency.
o Require labeling to protect aquatic plants, aquatic
invertebrates, wildlife and fish. This labeling will take
the form of the following statement:
"This pesticide is highly toxic to aquatic plants, aquatic
invertebrates, wildlife and fish. Use with care when
applying in areas frequented by wildlife or adjacent to any
body of water or wetland area. Do not apply when weather
conditions favor drift or erosion from target area. Do not
contaminate water by cleaning of equipment or disposal of
wastes."
o Require the registrant to submit to the Agency data in a
number of areas where current information is inadequate to
accurately evaluate the' hazard potential of oxyfluorfen.
These areas include oncogenicity, mutagenicity,
teratogenicity, chronic toxicity, and toxicity to wildlife.
The studies required in each of these areas are listed In
the summary of the Agency's proposed decision at the end
of this Section.
3. Soybeans
a. Risk/Benefit Analysis
If the Agency were to register Goal 2E for use on
soybeans, lifetime cancer risk for agricultural workers (based on 200 ppm
PCE in the formulated product) from use on soybeans would be 1.5 x 10 .
Lifetime cancer risk to the general public (via dietary exposure) is
estimated to be 5.3 x 10 . The choice of this option would make
available to the grower a herbicide which can be used in situations where
soil conditions or special weed problems make the use of other herbicides
undesirable or ineffective. In some cases, use of oxyfluorfen in weed
control would be less expensive than alternative treatments.
87
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If registration for use of Goal on soybeans were granted
with the additional requirement for protective equipment cancerrisk to
applicators from exposure to PCE would he reduced from 1.5 x 10 to
3.2 x 10 (see Table 11). This option would have no impact on the risk
to the general public from dietary exposure. This option would also not be
expected to affect the benefits of Goal use on soybeans.
If registration of Goal for use on soybeans were denied,
all risks from PCE contamination of oxyfluorfen would be eliminated. This
option would deny the soybean grower another soybean herbicide which could
be particularly effective in certain situations. The economic impact of
the nonavailability of Goal for use on soybeans would range from a cost of
$24.00 more per acre to $6.00 less per acre depending upon the weed control
treatment being considered. The actual impact of the nonavailability of
Goal cannot be quantified because it has never been registered for use on
soybeans.
Labeling to protect freshwater clams, oysters, aquatic
invertebrates and aquatic plants would r ."'vice the risk to the environment
from oxyfluorfen without an adverse impact on the predicted benefits
associated with the use of Goal 2E on soybeans.
If the option to prohibit the use of Goal 2E in counties
providing habitat for endangered freshwater clams were chosen, possible
hazard to these animals would be significantly reduced. The benefits of
using Goal on soybeans in these counties cannot be determined at this time,
because the market acceptability of Goal 2E is not yet known. (See Section
III).
b. Proposed Regulatory Decision
Having evaluated the risk to both applicators and the
general public from the potential benefits associated with the use of Goal
on soybeans, the Agency has determined that the benefits outweigh the
risk. Therefore, denial of registration for soybeans is not justifiable.
Requiring protective equipment for applicators would
reduce risk from PCE from 1.5 x 10 to 3.2 x 10 ' . The Agency
recognizes that the worker risk estimates for this use pattern (1.5 x
10 ) is based on a worst case estimate of exposure to PCE. However, in
the absence of field monitoring data indicating actual PCE exposure levels
during the mixing, loading, and applying of formulated oxyfluorfen products
under typical conditions, the Agency must base its regulatory decision on
the worst case estimate exposure. Therefore, the use of respirators to
reduce the risk to agricultural workers is justified. Because dermal
exposure contributes very little to the total risk to applicators/
mixers/loaders, protective clothing will not be required.
Since actual field monitoring data from the soybean use
pattern area are not currently available to accurately determine the
hazard to endangered clams, prohibiting the use of Goal 2E in counties
providing habitat for these species is not warranted at this time.
However, protective labeling can reduce the potential risk to these
molluscs while appropriate field studies are being conducted.
88
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The Agency, therefore, nas determined that amending the
terms and conditions of the Goal 2E registration to include use on soybeans
does not significantly increase the risk of unreasonable adverse effects on
man or the environment. The Agency has, however, identified certain
measures which can be taken to further reduce risk and has also
identified areas where data are currently inadequate to accurately assess
possible risk. Therefore, the Agency recommends that the following
restrictions and/or conditions apply to subsequent registration actions
regarding the use of Goal 2E on soybeans.
o Require that the level of PCE in the formulated product
not exceed 200 ppm. Permanent tolerances will be
established in conjunction with this registration,
\ o A pesticide respirator jointly approved by the Mining
Enforcement and Safety Administration (formerly the
U.S. Bureau of Mines) and by the National Institute for
Occupational Safety and Health under the provisions of
30 CFR Part II for perchloroethylene must be used during
the mixing, loading and application of all oxyfluorfen
products. This requirement will take effect six months
after the date of publication of the Notice announcing
the final determination concluding the oxyfluorfen
RPAR, unless by that time the registrant submits field
monitoring data to the Agency establishing that the
inhalation exposure for the maximum application rate
for each registered use is significantly lower than the
inhalation exposure estimated by the Agency,,
o Require labeling to protect aquatic invertebrates and
plants. The labeling will take the form of the
following statement:
"This product is highly toxic to freshwater clams,
oysters, aquatic invertebrates and aquatic plants- Do
not apply Goal where visible erosion to aquatic habitats
and wetlands occurs."
o Require the registrant to submit to the Agency
data from field monitoring studies conducted in the
soybean use pattern area. The studies should be
submitted within two years of the date of
conditional registration. A fuller discussion of the
required data appears in Appendix D. Protocols for
these studies should be submitted to the Agency prior
to the initiation of these studies,
o Require the registrant to submit to the Agency data in a
number of areas where current information is inadequate
to accurately evaluate the hazard potential of
oxyfluorfen. These areas include oncogenicity,
mutagenicity, teratogenicity, chronic toxicity, and
toxicity to wildlife. The studies required in each of
these areas are listed in. the summary of the Agency's
proposed decision at the end of this Section,
89.
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4. Corn
a. Risk/Benefit Analysis
Based upon a PCE level of 200 ppra In formulated Goal 2E,
the lifetime cancer risk from PCE for applicators has been estimated to be
3.8 x 10 for theq1981 season. Risk to the general public (dietary)
would be 2.7 x 10~ .
The availability of Goal 2E would provide the USDA program
with the. most versatile selective herbicide currently available for .
witchweed control in corn. Also, use of Goal in the Witchweed Eradication
Program would cost $32.00 to 42.00 less per acre than other herbicidal weed
control treatments.
If registration for use of Goal 2E on corn (in conjunction
with the USDA Witchweed Eradication Program) were granted with the
additional requirement for protective clothing equipment, total cancer risk
from PCE for agricultural workers would be reduced from 3.8 x 10 to
1.5 x 10 (See Table 11).
Requiring protective clothing and a respirator would not
be expected to affect the benefits of Goal 2E use on corn.
If registration of Goal for use on corn for the Witchweed
Eradication Program were not granted, all risks from PCE contamination of
oxyfluorfen would be eliminated. The nonavailability of Goal for this use
could have adverse effects on witchweed control efforts (See Section III
C). Also, it has been estimated that it would cost $32.00 to $42.00 more
per acre to use Goal. The major alternative witchweed control treatment is
the repeated (four to five times) application of 2,4-D and/or paraquat.
These herbicides are currently being reviewed by the Agency for a number of
possible adverse effects.
Labeling to protect aquatic plants, aquatic invertebrates,
wildlife and fish would reduce the risk to the environment without an
adverse impact on benefits.
Because there are no counties providing habitat for
endangered mussel species within the witchweed Eradication Program area,
the option to prohibit the use of Goal in certain counties was not
considered for this use.
b. Proposed Regulatory Decision
Having evaluated both the risks ,and the benefits of the
use of Goal 2E on field corn in conjunction with the USDA Witchweed
Eradication Program, the Agency has determined that the benefits of such
use outweigh the risk from PCE. Therefore, the Agency has rejected the
Option to deny the application for registration of Goal on corn.
90
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The risk to applicators of Goal 2E in the field corn use
has been estimated to be 3.8 x 10 , based on a total of 100,000 acres
expected to be treated in 1981. The Agency recognizes that this risk
estimate is based on a model of the "worst case" exposure. However,
in the absence of field monitoring data indicating actual PCE exposure
levels during the mixing, loading, and applying of formulated oxyfluorfen
products under typical conditions, the Agency must base its regulatory
decision on the worst case estimate exposure. Therefore, the use of-
respirators to reduce the risk to agricultural workers from 3.8 x 10 to
1.5 x 10 is justified. Because dermal exposure contributes very
little to the total risk to applicators/mixers/loaders, protective clothing
will not be required.
As discussed above, the option to prohibit the use of
Goal 2E in certain counties is not relevant to this use.
The Agency therefore has determined that amending the
terms and conditions of the Goal 2E registration to include use on field
corn in conjunction with the USDA Witchweed Eradication Program does not
significantly increase the risk of unreasonable adverse effects on man or
the environment. The Agency has, however, Identified certain measures
which can be taken to further reduce risk and has also identified areas
where data are currently inadequate to accurately assess possible risk.
Therefore, the Agency recommends that the following restrictions and/or
conditions apply to subsequent registration actions regarding the use of
Goal 2E on field corn in the USDA Witchweed Program.
o Conditionally register Goal 2E for use on field corn in
conjunction with the USDA Witchweed Eradication Program
with the requirement that the level of PCE in the
formulated product not exceed 200 ppm. Permanent
tolerances will be established in conjunction with this
registration.
o A pesticide respirator jointly approved by the Mining
Enforcement and Safety Administration (formerly the
U.S. Bureau of Mines) and by the National Institute
for Occupational Safety and Health under the provisions
of 30 CFR Part II for perchloroethylene must he used
during the mixing, loading and application of all
oxyfluorfen products. This requirement will take
effect six months after the date of publication of the
Notice announcing the final determination concluding
the oxyfluorfen RPAR, unless by that time the
registrant submits field monitoring data to the
Agency establishing that the Inhalation exposure for
the maximum application rate for each registered use Is
significantly lower than the inhalation exposure
estimated by the Agency.
o Require labeling to protect aquatic invertebrates,
aquatic plants, wildlife and fish. The labeling will
take the form of the following statement:
91
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"This pesticide is highly toxic to aquatic plants,
aquatic Invertebrates, wildlife and fish. Use with care
when applying in areas frequented by wildlife or
adjacent to any body of water or wetland area. Do not
apply when weather conditions favor drift or erosion
from target area. Do not contaminate water by cleaning
of equipment or disposal of wastes."
o Require the registrant to submit to the Agency, data
from field monitoring studies conducted in the corn use
area. These studies should be submitted within two
years of the date of conditional registration. A
further discussion of the required data is presented in
Appendix D. Protocols for these studies should be
submitted to the Agency prior to the initiation of
these studies.
o Require the registrant to submit to the Agency data in
a number of areas where current information Is
inadequate to accurately evaluate the hazard potential
of oxyfluorfen. These areas Include oncogenlclty,
mutagenicity, teratogentcity, chronic toxicity, and
toxicity to wildlife. The studies required in each of
these areas are listed in summary of the Agency's
proposed decision at the end of this Section.
5. Bearing Tree Fruits/Nuts
a. Risk/Benefit Analysis
If continued registration of Goal ?.E in bearing tree
fruits/nuts were allowed, assuming a 200 ppm contamination level of_PCE,
the lifetime cancer risk to agricultural workers, would be 5.8 x 10 .
Lifetime cancer risk (dietary) to the general population is estimated to be
1.0 x 10 .
Benefits for use of Goal on bearing tree fruits/nuts
cannot be quantified from available data. However, the general performance
of Goal compared to other currently available herbicides has been judged to
be good (See Section III. D.). Goal is apparently the most effective
herbicide treatment for preemergent control of c.heeseweed in orchards and
vineyards. Cost differences between Goal and other registered herbicide
treatments would vary according to the number of treatments and application
methods. Since Goal has both preemergence and post emergence activity, use.
of Goal many reduce the need for application of a second, post emergence
herbicide.
If registration of Goal 2E for use on bearing tree
fruits/nuts were allowed with additional requirements for protective
equipment (as described in Section II.C.) cancer risk to agricultural,
workers would be reduced from 5.H x 10 to .3.4 x 10 . The general
population would experience no change in the level of cancer risk (dietary)
from the choice of this option. The benefits from this use of Goal 2E
(Section III. D.) would not be affected by this option.
92
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If the Agency were to cancel the use of Goal 2E on
bearing tree fruits/nuts, cancer risks to both applicators and the general
public from PCE would be eliminated. The nonavailability of Goal would
deprive growers of an effective herbicide treatment for control of
cheeseweed in orchards and vineyards. Choice of this option would also
depriye growers of a herbicide which provides control of label claimed
weeds at the time of treatment (post emergence) as well as long-lasting
residual preemergence control of later germinating seeds. Mechanical
methods of weed control can damage vines and root systems and hand-hoeing
involves high labor costs.
Labeling to protect aquatic plants, aquatic
invertebrates, wildlife and fish would reduce the risk to the environment
without an adverse impact on benefit of this use.
Because there are no counties providing habitat for
endangered mussel species in this use pattern area, the option to prohibit
the use of Coal 2E in such counties was not considered for this use.
b. Proposed Regulatory Decision
Having evaluated the carcinogenic risk posed to both
agricultural workers and the general public in conjunction with the use of
PCE-contaminated oxyfluorfen (Goal) on bearing tree fruits/nuts, the
Agency has determined that the benefits associated with this use outweigh
the risk. Therefore, cancelling the registration of Goal for use on
bearing tree fruit/nuts is not justifiable. The Agency recognizes that the
worker risk (5.8 x 10 ) estimated for this use pattern is based on a
worst case estimate of exposure to PCE. However, in the absence of fie.ld
monitoring data indicating actual PCE exposure levels during the mixing,
loading, and applying of formulated oxyfluorfen products under typical
conditions, the Agency must base its regulatory decision on the worst case
estimate exposure. Therefore, the use of respirators to reduce the risk to
agricultural workers is justified. Because dermal exposure contributes
very little to the total risk to applicators/mixers/loaders, protective
clothing will not be required.
Since the Agency has determined that the benefits of this
use discussed in Section III.D. outweigh the risk associated with the use,
the Agency proposes that the following be implemented:
o Continue the conditional! registration for the use of
Goal 2E on bearing tree fruit/nuts with the requirement
that the level of PCE In the formulated product not
exceed 200 ppm.
o A pesticide respirator jointly approved by the Mining
Enforcement and Safety Administration (formerly the
U.S. Bureau of Mines) and by the National Institute for
Occupational Safety and Health under the provisions of
30 CFR Part II for perchloroethylene must be used
during the mixing, loading and application of all
oxyfluorfen products. This requirement will take
effect six months after the date of publication of the
Notice announcing the final determination concluding
the oxyfluorfen RPAR, unless by that time the
93
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registrant submits field monitoring data to the Agency
establishing that the inhalation exposure for the
maximum application rate for each registered use is
significantly lower than the Inhalation exposure
estimated by the Agency.
o Require labeling to protect aquatic invertebrates,
aquatic plants, wildlife and fish. The labeling will
take the form of the following statement:
"This pesticide is highly toxic to aquatic plants,
aquatic invertebrates, wildlife and fish. Use with care
when applying in areas frequented by wildlife or
adjacent to any body of water or wetland area. Do not
apply when weather conditions favor drift or erosion
from target area. Do not contaminate water by cleaning
of equipment of disposal of wastes."
o Require the registrant to submit to the Agency, data
from field monitoring studies conducted in the bearing
, tree fruit/nuts vise pattern area. These studies should
be submitted within two years of the date of the
Agency's final decision. A fuller discussion of the
required data is presented in Appendix D. Protocols for
these studies should be submitted to the Agency prior to
the initiation of testing.
o Require the registrant to submit to the Agency data in a
number of areas where current information Is inadequate
to accurately evaluate the hazard potential of
oxyfluorfen. These areas include oncogenicity,
mutageniclty, teratogenicity, chronic toxlcity, and
toxicity to wildlife. The studies required in each of
these areas are listed in the summary of the Agency's
proposed decision at the end of this Section.
D. Summary of Proposed Regulatory Decision
For all uses of Goal 2E (currently registered and proposed") the
Agency has determined that:
o The PCE contamination of formulated oxyfluorfen products
''Coal 2E) nay not exceed 200 ppm and that a statement to
that effect be added to the confidential statement of
formula for each registered oxyfluorfen product.
o A -pesticide respirator jointly approved by the Mining
Enforcement and Safety Administration (formerly the
U.S. Bureau of Mines) and by the National Institute for
Occupational Safety and Health under the provisions of
30 CFR Part II for perchlorocthylene must he used during
the mixing, loading and application of all oxyfluorfen
products. This requirement will take effect six months
after the date of publication of the Notice announcing
the final determination concluding the oxyfluorfen
RPAR, unless by that time the registrant submits field
-------
monitoring data to the Agency establishing that the
inhalation exposure for the maximum application rate
for each registered use is significantly lower than the
inhalation exposure estimated by the Agency.
•
o Labeling for the protection of wetlands and other aquatic
resources is required. Specific label statements have
been presented in the Proposed Regulatory Decision Section
for each use.
v
*
The Agency has also determined that with the above
mentioned provisions, amending the existing Goal 2E registration to include
use on soybeans, field corn, and bearing tree fruits/nuts would not
i " ! j
significantly increase the risk of unreasonable adverse effects on man or
the environment. The Agency, therefore, recommends that subsequent
registrations for the proposed uses include the following conditon:
^
w
o Extensive field monitoring for oxyfluorfen residues in
each proposed use pattern area is required. The
registrant will submit these data to the Agency within two
years of the date of conditional registration.
In an action independent of the RPAR, the Agency will require the
registrant to submit the following oxyfluorfen studies to the Agency in
support of all registrations.
+
o The registrant is required to submit to the Agency an
oxyfluorfen oncogenicity study in mice and an oxyflurofen
oncogenicity study in rats. Protocols for these studies
*
are to be submitted before initiation of testing.
o The registrant is required to submit to the Agency an
oxyfluorfen teratogenicity study in rabbits. The protocol
of this study should include post-natal evaluation and
should be submitted to the Agency prior to initiation of
testing.
o A tiered series of mutagenicity tests must be submitted to
the Agency. An outline of the testing scheme is presented
in Appendix C. Protocols should be submitted to the
Agency prior to the initiation of testing.
t
i
o The registrant is required to submit a 6-month (or longer)
dog feeding study which demonstrates a NOEL. Protocols
for this study have been published in 43 FR 37536,
August 22, 1978.
o The registrant is required to submit avian reproduction
studies with mallard ducks and bobwhite quail.
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Appendix A
Parameter Values and Exposure Calculations for Uses of Oxyfl uorf en
lo Parameter Value for each Use of Goal 2E.
Maximal Goal 2E Use Parameters
a/
Quarts
Pounds b/ Goal 2E/
Al/acre-' acre
Soybeans 0»5 1
Field Corn 2 4
Tree Fruit/Nuts 2 4
Conifers 2 4
dilution
volume pounds
(gal ./acre) applied
20 1
10 1 (or 2)
75 1
20 1 (or 2)
•_a/ Rohm and Haas, 1978«
]>/ The combined amount of Goal 2E applied annually may not exceed
2 Ib Al/acre.
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a/
Maximal PCE Applied Under Goal 2E Use Conditions—
Crop
Application Rate
Goal (Ib/A) .
A.I. Goal 2E-'
Perchloroethylene
Ib/acre— gm/acre—
Soybeans
Field Corn
Tree Fruit/Nuts
Conifers
0.5
2.0
2.0
2.0
0.71
2.86
2.86
2.86
0.000143
0.000571
0.000571
0.000571
0.0645
0.2594
0.2594
0.2594
a/ Rohm and Haas, 1978. (modified). Assumes 200 ppm PCE in Goal 2E,
W 70% A.I. minimum.
c/ 0.7Mb. Goal 2E/acre x 0.0002 [200 PPm] = 0.000142 Ib. PCE/acre.
At 454 gm = 1 Ib.
97
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a/
Goal 2E and PCE Spray Rates, by Crop—'
Goal
Spray Rate PCE Spray Rate
Volume Weight^- Weight Concentration
Crop (gal. /acre) (gm/acre) (gm/acre) (gm/gm H-0) (ppm)
Soybeans 20
Field Corn 10
Tree Fruit/Nuts 75
Conifers 20
7.57 x 104 0.0649 8.57 x 10~7 0.86
3.79 x 104 0.2594 6.84 x 10~6 6.84
2.84 x 105 0.2594 9.13 x 10~7 0.91
7.57 x 104 0.2594 3.43 x 10"6 3.43
a/ Rohm and Haas, 1978. (modified). Assumes 200 ppm PCE in Goal 2E.
t>/ 1 gallon of H«0 weighs 8.34 pounds
-------
2. Sample calculations for inhalational, dermal, dietary exposure estimates,
Inhalational Grams PCE/Acre x Volume Air Inhaled/Day^
Exposure = u,
(soybeans) Volume of Air/acre^x Average Body Weight
0.065 gm PCE/Acre x 14,400 liters/day x 1000 mg/gm
7.4 x 106 liters/Acre x 70 kg Body Weight
1.804 x 10"3 mg/kg bw/day
1.8 m3hr x 1000 1/m3 x 8 hr/day = 14,400 liters/ day
volume of air/acre = 6 ft x 43,560 ft2 acre x 28.3 I/ft3
= 7.4 x 10 liters of air/acre
99
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o
o
Dermal Exposure = PCE Concentrations x Diluted Spray ;x Weight per x Percent Skin
(soybeans) in Diluted Spray Contacting Skin Pint of Water Penetration
Average Body Weight
= 0.86 ug/g x 0.048 pints^x 454 g/pint x 0.1-^/x 1 mg/1000 ug
7 Q j^g j.jw —
_ c
. = 2.7 x 10 mg/kg bw/day
a/ Values for the amount of liquid contacting on applicator's skin (0.048 pints) and
percentage skin penetration (10%) were estimated by the registrant (Rohm and Haas, 1978)
-------
Dietary . 'Daily consumption^ sensitivity of
Exposure = o£ commodity x analytical method
(soybeans) Human Body Weight
0.01819 kg x 0.05 mg/kg^ = 1.30 x 10~5 mg/kg bw/day
70 kg
£/ Daily consumption of commodity in kg/person/day is based on the average
consumption figures for each commodity (Schmitt, 1977).
b/ Assumes that 0.05 ppm level of analytical sensitivity is equivalent to
0.05 mg/kg of commodity.
101
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(CAG, 1980)
Appendix B
Calculation of Cancer Risk from PCE Using the Multistage Model,
The NCI bioassay of tetrachloroethylene showed that 32/49 (65%)
and 27/A8 (56%) of male mice had hepatocellular carcinomas of the liver after
oral intubation of tetrachloroethylene at an average dose level of 536 and 1072
mg/kg/day, 5 day/week, for 78 weeks during the 90-week study period. The
vehicle control male mice had 10% (2/20) incidence rate of the same tumor type.
The lifetime average dose for the animals in the low dose
group is
78 _5
536 x 90 x 7 - 322 mg/kg/day
The equivalent human lifetime dose is
(0.03)
332 x (70) = 25.031 mg/kg/day
assuming the average human body weight of,70 kg and the average male mice body
weight of 0.03 kg. The value (0.03 - 70) is a factor converting the
effective dose from nice to humans assuming that the amount of the direct-
acting agent is proportional to the body surface.
The unit risk calculation is based on the hepatocellular
carcinoma from the male mice. The data from the highest dose group is excluded
in fitting the multistage model due to the lack of fit.
The 95% confidence upper limit for the carcinogenic potency
(slope) for the human' is
.qj*- 5.31 x 10~2 (mg/kg/day)"1
For exposures (mg/kg/day) lower than those used in the animal
study
Risk = qj* x exposure
Using the soybean situation as an example, the lifetime cancer
risk from PCE associated with the application of Goal 2E on soybeans is
5.31 x 10~2 (mg/kg/day)"1 x 2.5 x 10~5 mg/kg/day = 1.48 x 10 ~6
102
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Appendix C
Proposed Testing for Assessing the Mutagenic Potential of Goal
.To adequately evaluate the rmtagenic risk posed by human exposure to a chemical
substance, a rautagenicity testing program should incorporate tests which
evaluate both the intrinsic potential of a chemical or its metabolites to cause
mutations and its ability to reach the germinal tissue of whole mammals in an
active form. The most direct tests for determining germinal mutagenicity are
the whole mammal test systems (e.g. mouse specific locus test) which are
capable of demonstrating the. ability of a chemical substance to reach the
germinal tissue and cause heritable mutations. However, these tests are not
only time consuming and expensive to perform, but also only a few laboratories
have the experienced personnel and facilities to conduct these tests. Thus,
for practical purposes, short-term mutagenicity test systems may be chosen as
an alternative. Short-term tests, which detect mutagenic activity, can
adequately address the issue of germinal mutagencity if they are utilized in
combination with tests which determine the ability of a chemical to reach
mammalian gonads. This approach is in accordance with the Agency's recently
published Proposed Mutagenicity Guidelines for Risk Assessment (45 FR 749R4-
74988).
The testing Strategy described below is considered necessary to better
characterize the mutagenic potential of the pesticide Goal.
Because human exposure is to the commercial product containing Technical Goal,
the proposed testing scheme is described for technical Goal. If an impurity in
the technical material is found to be mutagenic and the registrant attempts to
alter the manufacturing process to eliminate the mutagenic contaminant(s), the
proposed testing strategy would also be applicable to the "alteredir~Technical
Goal product. In addition, because the proposed approach is a general one, it
may be useful to confirm or refute the negative results reported for "pure"
oxyfluorfen. Of course, it is not possible to rigidly establish a testing
scheme and modifications may be necessary for the testing of altered technical
material or "pure" Goal.
The testing strategy is illustrated in Figure 1 and involves an approach where
the sequence of testing to be followed depends on the results of the previous
test. The short-term genetic tests which can be used in this scheme are listed
in the FIFRA's Proposed Rules for Mutagenicity Testing (4.3 FR 163.84 pp. 37388-
37394).
Because the results generated by the required testing will be used to support
potential regulatory action for Goal, it is essential that careful attention be
given to the design and conduct of the proposed studies (See FIFRA's Proposed
Rules for Mutagenicity Testing; 43 FR 163: pp. 37388-37394). In addition,
because this testing approach provides general guidance only, the Registrant
(Rohm and Haas) should submit the details of testing protocols to the Agency
for review prior to the initiation of testing.
103
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A. Tests to Determine Mutagenic Activity
B. Tests to Determine Whether the Chemical
Reaches the Germinal Tissue of Whole
Mammals in an Active Form
Known Positive in
Salmonella and in the Rec Assay using Bacillus subtilus
Second Point Mutation
Test System
(eukaryotic)
I
negative
Third Point Mutation
Test System
Positive
Positive
(eukaryotic and different
from second test system)
negative
Two Cytogenetic Assays )
I J,
both negative one positive-^ or
Test Indicative of
Primary DNA Damage
(eukaryotic)
Agency Decision on
the Necessity of
Further Testing
Test may include the detection of labeled
chemical in the gonads, or bioassays for
unscheduled DNA synthesis, sister chromatid
exchange or chromosome damage in germinal
tissue of whole mammals
.Figure 1. Test strategy to assess the ability of Goal to be a potential human mutagen.
-------
TESTING FOR MUTAGENIC ACTIVITY
To insure that the positive response reported in Salmonella was not a species-
specific positive or a false-positive result, it is necessary to conduct a
point mutation test other than bacteria (e.g. mammalian cells in culture,
Drosophila, yeast). If positive results are obtained in this second test, then
this plus the positive response obtained in Salmonella are considered to be
sufficient evidence to classify the chemical as having mutagenic activity.
However, if Goal is not demonstrated to be a mutagen by the second confirmatory
point mutation test, the limitations and strengths of this second assay and the
previously employed test system (Salmonella/ microsome assay) should be re-
evaluated to choose a third point mutation test system to further examine the
ability of the chemical to cause point mutations. The third point mutation
test should be a eukaryotic test system different from the second confirmatory
system. As described above, if the test agent proves positive In this third
assay, it is considered to have mutagenic activity.
If the chemical is adequately tested in the proposed point mutation systems and
results are negative, unlike the first test in Salmonella, two additional tests
which assay for numerical and morphological chromosome aberrations should be
performed. This step will screen for another kind of genetic damage. The test-
ing can either include two different in vivo somatic cellcytogenetic tests or
an in vivo somatic cell cytogenetic test system plus an Jji vitro cytogenetic
test system (e.g. mammalian cells in vitro). If the test material is positive
in both assays, it is designated as a potential mutagen. When a positive
result is obtained in only one of the cytogenetic tests, depending on the
nature of the test and the response, the Agency will decide whether to classify
the chemical as a rautagen or to recommend additional primary DNA damage assay
(nonbacterial). The inclusion of a nonbacterial primary DNA damage assay
(efg. unscheduled DNA synthesis in mammaliam cells in vitro^ may determine the
ability of the chemical to interact with eukaryotic DNA. When both cytogenetic
tests are negative, additional eukaryotic primary DNA damage assay will be
required. At this stage, the Agency will examine the weight of evidence and
decide whether further testing will be warranted, or whether to provlsionaly
classify the chemical as a nonmutagen.
TESTING FOR THE ABILITY OF THE CHEMICAL TO REACH THE GERMINAL TISSUE OF WHOLE
MAMMALS
In the event the short-term tests establish that the chemical has mutagenic
activity further studies should be conducted to determine whether or not the
active form of the chemical reaches the germinal tissue of whole mammals. If
the observed mutagenic activity can be attributed to a chemical which can be
radioactively labeled, radiotracer studies should be conducted. However, if
the chemical responsible for the mutagenic activity cannot be identified or
labeled, then other studies which are considered to provide evidence that a
chemical reaches mammalian germinal tissue and causes DNA damage will be
required. These may involve examination of the germinal, tissue of mammals for
evidence of unscheduled DNA synthesis, chromosome damage, or sister chromatid
exchange formation.
105
-------
The test substance will be classified as a mutagen with the potential to cause
heritable genetic effects in bunans if i-t is shown to possess mutagenic
activity and is demonstrated to reach the mammalian gonad. If the chemical has
intrinsic rautagenicity but cannot be shown to reach namraalian germinal tissue,
and thus is not likely to cause germinal mutations, it will be operationally
designated as a mutagen which may have the potential to cause somatic cell
mutations which may be involved in the etiology of a cancer or genetically
mediated disease.
If Goal is shown to have the potential for being a germ-cell mutagen to
humans, the Agency may require supplementary tests to quantitatively estimate
the mutagenic risk posed to humans. The approaches for quantitatively
assessing mutagenic risk are described in the Agency's Proposed Guidelines for
Risk Assessment (45 FR 221:74984-74988).
106
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Appendix D
a/
Field Monitoring during the Conditional Registration Period
Preliminary field monitoring and exposure modeling indicate that harmful
residues of oxyfluorfen may accrue in aquatic habitats. The registrant is,
therefore, requested by the Agency to submit the results of field monitoring
studies within the first two years of the conditional registration period.
The purpose of the field studies will be to .determine the tendency of lethal
pesticide residues to be transported away from the site of application.
Chemical analyses of water courses and aquatic habitats adjacent to the treated
fields will provide some indication of pesticide movement. Because oxyflourfen
may be detrimental to nontarget plants at residue levels below the analytical
detection limit, the Agency requests that the productivity and density of
aquatic plants adjoining the treated fields also be monitored. These
productivity and density parameters will be compared to those for similar plant
populations adjacent to untreated fields. The comparison will form 'a field
bioassay to determine the presence or absence of herbicidal pesticide residues.
The field study sites should be selected within the soybean, corn, and bearing
fruit and nut use pattern areas. Each study site should adjoin a small
limnetic habitat containing submerged aquatic plants including members of the
grass family (Gramineae). Submerged aquatic plant populations in untreated
watersheds should also be located within close commuting distances. One of the
soybean field study sites should be located within the Chesapeake Bay Drainage
area, as persistent herbicides have been implicated in the apparent depletion
of submerged aquatic vegetation in the bay.
The registrant may wish to augment the natural rainfall with irrigation at any
or all of the study sites. An abnormally low natural rainfall, might otherwise
necessitate that the studies be repeated.
It is well known that good soil management practices can reduce the runoff of
sediment-bound pesticides. If such practices are used during this field runoff
study, they should be practices already in general use or practices which could
be readily understood by agricultural workers after having read label
instructions. That is, if this field study Indicates that certain management
practices are required to reduce runoff to safe levels, then those practices
should be described and required by future Goal labels.
a/ Due to the expected stability of oxyfluorfen the registrant will be
expected to monitor for the parent chemical only. If metabolites are present
they will be expected to be below the detection limit of the analytical
method. The detection limit should be 0.01 ppm.
107
-------
Specific items to be included in the registrants's field study protocol for
each use pattern include:
Meteorological
1. Pan evaporation - daily
2. Temperature monitoring - continuous
3. Rainfall monitoring - continuous
(rainwater itself should be analyzed for oxyfluorfen)
A. Volume of runoff water - per rujioff event.
Soil
5. Soil profile description to one meter - once per season
6. Soil density - once per season
7. Soil organic matter content - once per season
8. Soil moisture holding capacity - once per season
9. Soil in'f i Itratin rate - once per season
Biological
10. Comparison of the productivity and density of indigenous submerged
aquatic plant populations growing adjacent to treated fields to the
productivity and density of such populations growing adjacent to
untreated fields. The protocol for this comparison should include an
estimation of the real differences that can be detected by the test at
the 95% confidence level. Pesticide residue analyses of hydrosoil
surrounding the roots of these plants should be provided monthly.
Pesticide Residues. (10% of these analyses should be duplicated by mass
spectrometry where appropriate).
11. Hydrosoil concentrations - Measurements in top 5 cm may be combined
with hydrosoil measurements described under "Biological" above, where
appropriate - monthly.
12. Benthic invertebrate's tissue residue (oligochaetes, burrowing
mayflies, chironomids) - monthly.
13.° Concentration of dissolved residues in runoff - per rainfall event.
14. Concentration of sediment-bound residues - per rainfall event (Analyses
of spiked samples should be submitted to demonstrate percentage
recovery.)
15. Treated soil pesticide concentrations - should be measured from 0 to
8cm in 2cm increments monthly. (Analyses of spiked samples should be
submitted for each sampling interval to demonstrate percentage
recovery.)
«
16. Total discharge of bound and unbound pesticide from treated fields. -
estimated monthly.
108
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Some references may be of aid to the registrant when writing the protocol.
Field plot statistical design is discussed, generally, by LeClerq et al.
(1962). Specific runoff monitoring protocols were detailed-by the Agency
(U.S. Environmental Protection Agency, 1978) as were collecting techniques for
benthic organisms (U.S. Environmental Protection Agency, 1973).
The above study should extend for one year after the last appplication of Goal.
109
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Appendix E
The following tables indicate the variety of herbicides and herbicide combinations
recommended for use on soybeans for control of the weeds listed on the proposed
Goal 2E soybean label (Table 14). Herbicides are recommended by at least one of
the states listed, and control at least one of the weed species listed on Goal 2E
label. None of the herbicides listed controls the same weed spectrum as oxyfluorfen
(Beck and Petrie, 1981).
Table El.
a/
State Herbicide Recommendations for Weed Control in Soybeans: Preemergence—
Herbicide
Also Used in Combination With:
Alachlor^
Bifenox
Chloramben
c/
Chlorbromuron—
c/
Chlorpropham—
DCPA
c/
Dinitramine11-'
Dinoseb
Dinoseb/Naptalam
Diphenamid
Linuron—
Acifluorfen, Bentazon, Bifenox,
Chloramben, Chlorpropham, Dinoseb
Dinoseb/Naptalam, Linuron, Linuron/
Paraquat or Metribuzin
Alachlor or Trifluralin
Alachlor, Dinoseb, Linuron,
Metolachlor, Metribuzin or
Trifluralin
Linuron
Alachlor
Metribuzin
Alachlor, Diphenamid or Naptalam
Alachlor, Metolachlor, Oryzalin,
Profluralin or Vernolate
Alachlor, Chloramben,
Chlorbromuron, Metolachlor,
Metolachlor/Paraquat, Oryzalin,
Oryzalin/Paraquat, Pendimethalin,
Profluralin, Propachlor,
Trifluralin or Vernolate
110
-------
Metolachlor Chloramben, Dinoseb/Naptalam,
Linuron, Linuron/Paraquat,
Metribuzin or Metribuzin/
: Paraquat
Metribuzln .Alachlor, Alachlor/Paraquat
Chloramben, Dinitramine,
Metolachlor, Metolachlor/
Paraquat, Oryzalin, Pendimethalin
or Trlfluralln
Naptalam/Dlnoseb Alachlor, Metolachlor, Oryzalin,
Profluralin or Vernolate
Oryzalin Chloramben, Dinoseb/Naptalam,
Linuron, Linuron/Paraquat
Metribuzln or Metrlbuzln/Paraquat
Oxyfluorfen^'
Pendimethalin Chloramben, Linuron or Metribuzln
Propachlor
c/
Trifluralin— Bentazon, Bifenox, Chloramben,
Chlorpropham, Dinitramine,
Linuron or Metribuzln
c/
Vernolate— Dinoseb/Naptalam, Linuron
a/ Taken from 1979 or 1980 state recommendations for Alabama, Arkansas,
Delaware, Illinois, Iowa, Indiana, Kansas,1 Kentucky, Louisiana, Michigan,
Mississippi, Missouri, Ohio, and Wisconsin (Beck and Petrle, 1981).
these states have been chosen to represent a variety of soybean growing practices
and herbicide recommendations.
b/ Most frequently recommended. \
C/ Recommended in combination with other herbicides only.
d_/ Experimental use only.
111
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Table E2.
State Herbicide Recommendations for Weed Control in Soybeans:
Preplant Incorporated—
Herbicide Also Used in Combination With:
Alachlor Blfenox, Metribuzin
Dinitramlne Metribuzin
Fluchloralin Metribuzin
Metolachlor Chloramben, Metribuzin
Pendimethalin Metribuzin
Profluralin Chloramben, Metribuzin or Chlorpropham
Trifluralin Bifenox, Chloramben, Chlorprophan,
Metribuzin
Vernolate Chlorpropham, Trifluralin
aj From 1979 or 1980 state recommendations for Alabama, Arkansas, Delaware,
Illinois, Indiana, Iowa, Kansas, Kentucky, Louisana, Michigan, Mississippi,
Missouri, Ohio, and Wisconsin (Beck and Petrie, 1981). These states have been
chosen to represent a variety of soybean growing practices and herbicide
recommendations.
112
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Table E3.
State Herbicide Recommendations for Weed Control in Soybeans:
a/
Preplant Incorporated Followed by Preemergence Overlay Treatment—
Preplant Incorporated Herbicide
Preemergence Overlay Herbicide
Fluchloralin
Dinitramine
Metolachlor
Pendimethalin
Profluralin
Trifluralin
Vernolate
Metribuzin
Metribuzin
Chloramben, Metribuzin
Chloramben, Linuron or
Metribuzin
Chlorpropham, Linuron or
Metribuzin
Bifenox, Chloramben,
Chlorpropham, Linuron or
Metribuzin
Chloramben, Chlorpropham or
Linuron
a/ Taken from 1979 or 1980 state recommendations for Arkansas, Iowa, Kansas,
Kentucky, Michigan, Mississippi, and Wisconsin (Beck and Petrie, 1981).
These states have been chosen to represent a variety of soybean growing
practices and herbicide recommendations.
113
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Table E4.
State Herbicide Recommendations for Weed Control in Soybeans:
Post Emergence-
Broadcast
Directed Spray
Acifluorfen
Acifluorfen/Alachlor
Alachlor/Dinoseb/Naptalam
Bentazon—
Chloramben
Chloroxuron
2,4-DB
Dichlofop
/'
Dinoseb
Dinos eb/Alachlor
Dinoseb/Naptalam—
Fluchloralin/Bentazon
Metolachlor
Metolachlor/Acifluorfen
Metolachlor/Dinoseb/Naptalam
Oryzalin/Acifluorfen
Chloroxuron
2,4-DB^
Dinoseb—'
Glyphosate—
Linuron
Linuron/2,4-DB
Linuron/Paraquat
Metribuzin
Metribuzin/2,4-DB
Paraquat—
/
Paraquat/2,4-:
a/ Taken from 1979 or 1980 state recommendations for Alabama, Arkansas,
Delaware, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana,
Michigan, Mississippi, Missouri, Ohio, and Wisconsin (Beck and Petrie, 1981).
These states have been chosen to represent a variety of soybean growing practices
and herbicide recommendations.
b/ Most frequently recommended.
c/ Arkansas recommendations only.
-------
Table E5.
State Herbicide Recommendations for Weed Control in Soybeans:
No Till-/
Herbicide or Herbicide Combination
Alachlor/Glyphosate/Linuron—
Alachlor/Linuron
Alachlor/Linuron/Metribuzin
Alachlor/Linuron/Paraquat—
Alachlor/Metribuzin
Alachlor/Metribuzin/Paraquat
Glyphosate
Glyphosate/Linuron/Oryzalin
Glyphosate/Linuron/Metolachlor
Glyphosate/Metolachlor/Metribuzin
Glyphosate/Metribuzin/Oryzalin
Linuron/Paraquat
Linuron/Metolachlor/Paraquat
Linuron/Oryzalin/Paraquat—
Metolachlor/Linuron
Metolachlor/Metribuzin
Metolachlor/Metribuzin/Paraquat
Metribuzin/Oryzalin/Paraquat
Paraquat
a/ Taken from state recommendations for Alabama, Kentucky, Illinois,
Indiana and Iowa (Beck and Petrie, 1981). These states have been chosen
£o represent a variety of soybean growing practices and herbicide
recommendations.
b/ Most frequently recommended.
115
-------
Table
USDA Herbicide Recommendations for Weed Control in
Preplant
Incorporated
Preemergence
Post Emergence
Dinitramine
ELuchloralin
Pendimethalin
Trifluralin
Vernolate
Alachlor
Bifenox
Chloramben
Chlorbromuron
Chlorpropham
Dalapon-'
Glyphosate-'
Linuron
Metribuzin
Naptalam-^
Naptalam/Dinoseb
Oryzalin
Paraquat
Bentazon
Chloroxuron
2,4-DB
Dinoseb
Linuron
Naptalam/Dinoseb
Paraquat
a/ USDA, 1980c
b/ Recommended for use in Arkansas, Kentucky, Louisiana and Mississippi
only.
£/ Applied preplant, post emergent to weeds.
d/ Recommended for use in Nebraska only.
116
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water sources tested by gas chromatography-mass spectroraetry.
Environ Sci and Technol. 9(8);762-765.
Dykstra, William, Ph.D. 1978. Request for establishment of permanent
tolerances on soybeans and corn at 0.05 ppm for the herbicide Goal 2E
(formerly RH-2915). Memo to Robert Taylor, RD, OPP, OPTS, EPA. •
May 5, 1978.
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Price, P.J.,.Hassett, C.M., and Mansfield, J.I. 1973. Transforming
. activities of trichlo.roethylene-and proposed industrial alternatives.
In Vitro 14:290.
Rampy, L.W.,,. Quast,. J.F.^ Leong, M.F. B.K.J.,, Gehrlng, P.J. 1973. Results
of-a long-term inhalation.toxicity study. Perchloroethylehe in rats.
Toxicology Reseach Laboratory. Health and Environmental Research.
The Dow Chemical Company. Midland, Michigan.
REAG. 1980 The Reproductive Assessment Group's (REAG) Preliminary Report on
the Mutagenicity.of Oxyfluorfen. EPA. November 21, 1980.
Regelman, E. 1981. Goal/PCE Exposure Analysis. EPA memo to J. Chinchilli,
SPRD, OPP, OPTS, EPA. January 28, 1981.
Rogers,.Melvin. 1980. North Carolina Crop and Livestock Reporting Service.
Raleigh, North Carolina. Personal Communication. February 22, 1930.
Rohm, and Haas. 1978.. Goal 2E Herbicide (Formerly RH-2915> 2-chloro-l-
(;3-ethoxy-4-nitrophenoxy)r4-(trifluoromethyl) benzene. Pesticide
Petition 8F2058.. Petition for establishment of permanent tolerances
for Goal 2E on soybeans and corn. Rohm and Haas Company.
Philadelphia, PA. Accession No. 097425. (Proprietary).
Rohm; and .Haasi. Company.; 1979. Proposed label for oxyfluorfen for use on
soybeans. EPA Registration No. 707-145-AA. Philadelphia,
Pennsylvania.
"Rohm and Haas Company. 1980a. Benefits to the public.:. Goal 2E herbicide-
use on soybeans. Philadelphia, Pennsylvania. (Proprietary).
Rohm and Haas Company. 1980b* Microbial Mutagen Test. Protocol Number 30p-
385. July, 1980. Submitted to EPA August 13, 1980. (Proprietary)
Ryan, J. 1978. Rohm and Haas Company. Philadelphia, Pennsylvania.
Personal communication with Richard Petr.ie of Efficacy and Ecological
• Effects Branch, RD, OPP, OPTS, EPA. Accession Numbers 096387, 196880,
097035. April 24, 1978. .
Sand, P.F. 1979. Witchweed.:- Will it invade the Midwest? Weeds Today.
. Winter.
Sand, P.F. 1980. Economist. Staff Officer. Pest Programs Development
Staff. National Program Planning Staff. Plant Protection and
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communications. February 8 - February 19, 1980.
Schlossberg, L. 1981 (January 5), Detrex Chemical Industries Inc. Detroit,
Michigan^ Letter to Dr. V. Vaughan-Dellarco, EPA, REAG.
Schmitt, R. D. 1977. Food Factors. EPA memo to O.E. Paynter,
HED, OPP, OPTS, EPA. October 4, 1977.
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Schwetz, B.A., Leong, B.K.J., Gehring, P.J. 1975. The effect of
maternally inhaled trichloroethylene, perc.hl.oroethyl.ene, methyl
chloroform, and methylene chloride on embryonal and fetal development
in mice and rats. Toxicology and Applied Pharmacology. 32:84-96.
Seim, R. 1981. It's Sticky...It Clogs Augers...It Stops Comhines
Cold...It's Nightshade. Farm Journal, Vol. 1.05 No. 2. Mid-January,
1981.
Severn, D.J., Ph.D. 1978. Evaluation of comments on the chlorohenzilate
position document submitted by Florida Citrus Mutual. EPA memo to Joe
Boyd, SPRD, OPP, OPTS, EPA. September 13, 1978.
Simmonds, P.C., Kerrin, S.L., Lovelock, J.E., and Shair, F.H. 1974.
Distribution of atmospheric -halocarbons in the air over the Los
Angeles Basin. Atmospheric Environment. 8:209-216.
Singh, H.B. 1977. Atmospheric halocarbons: Evidence in favor of reduced
average hydroxyl radical, concentration in the troposphere.
Geophysical Research Letters 4(3):101-104.
Squire, R.A. 1980. Histopathologic Evaluation of Mouse Livers from Rohm
and Haas Goal (Oxyfluorofen) Chronic Study. Submitted to EPA Cancer
Assessment Group. November 6, 1980.
Staiff, D.C., Comer, S.W., Armstrong, J.F., and Wolfe, H.R., 1975.
Exposure to the herbicide paraquat. Bull. Environ. Contam. and
Toxicol. 14:(3), 334-340.
Sugimura, T.S.; Sato, M.; Nagao, T.; Yahagi, T.; Matsushima, Y.; Selno, M.;
Takeucht, and T. Kawachi. 1976. Overlapping of Mutagens and
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Prevention. Univ. of Tokyo Press, Tokyo/univ. Park Press. Baltimore,
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Tests for carcinogenicity of organic contaminants of United States
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1978. Washington, D.C.
United States Department of Agriculture. 1978a. Plant Protection and
Quarantine Programs. APHIS Program Aid No. 1212. Watch out for
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1978.
United States Department of Agriculture. 1979a. Plant Protection and
Quarantine Programs. APHIS. Domestic Program Manual: Witchweed
(Striga asiatica Lour.) Rev. June, 1979.
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United States Department of Agriculture. 1979h. Plant Protection and
Quarantine Programs. APHIS. Summary Report: Control of witchweed
with Goal.
United States Department of Agriculture. 1980a. Plant Protection and
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with Coal. January, 1980.
United States Department of Agriculture. 1980b. Crop Reporting Board.
Economics, Statistics, and Cooperatives Service. Crop Production:
1979 Annual Summary: Acreage, Yield, Production. Washington, D.C.
January 15, 1980.
United States Department of Agriculture, 1980c. Suggested Guidelines for
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US EPA 1973. Biological Field and laboratory methods for measuring the
quality of surface waters and effluents. U.S. EPA National
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particularly the "Marcroinvetebrate" Chapter.
i
US EPA 1974. Perchloroethylene, EPA Accession No. 000580A. Use as an
inert solvent, cosolvent. Exemption from a tolerance - review for.
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US EPA 1978. Transport of agricultural chemical from shell upland
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Environmental Protection Agency, Athens, Georgia. Publication Number
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US EPA 1980. Tetrachloroethylene. Ambient Water Quality Criteria.
Criteria and Standards Division, Office of Water and Planning and
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US EPA 1979a. An assessment of the need for limitations on
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Van Duuren, B. 1975. On the possible mechanism of carcinogenic action of
vinyl chloride. N.Y. Acad. Sci. 246:258.
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I. Seidman, and D. Roth. 1979. Carci.nogenicity of halogenated
alefinic and aliphatis hydrocarbons in mice. J. Natl. Cancer Inst.
63(6):1433-1439.
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Vilkas, A.G. 1978. Unpublished study done by Union Carbide Environmental
Services for Rohm and Haas Co. The acute toxicity of RH 2915 to the
Eastern Oyster, Crassostea virginica. Ace. # 096881, July 1, 1978.
(Proprietary)
W.S.S.A. 1979. Herbicide Handbook of the Weed Science Society of America.
4th edition. W.S.S.A., 309 West Clark Street, Champaign, IL; 61820.
AU.S. GOVERNMENT PRINTING OFFICE: 1981 341-082/238 1-3
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Dykstra, W. 1979a. EPA Reg. No. 707-145. Goal 2E risk assessment
for possible perchloroethylene residues in soybeans, corn grain and
cottonseed. Memo to R. Taylor, RD, OPP, OPTS, EPA. August 27, 1979.
Dykstra, W. 1979b. PP#9F2197; Oxyfluorfen (Goal) in or on almonds,
grapes and certain stone fruits. Memo to M. Nelson, RGB, OPP,
OPTS, EPA. December 17, 1979.
Dykstra, W. 1930a. Calculation of slope coefficient for the one-hit
method using perchloroethylene NCI data. Mamo to Tom Miller, SPRD,
OPP, OPTS, EPA. March 18, 1980.
Dykstra, W. 1980b. Goal 2E Herbicide; 104-Week Tbxicity Study in Dogs
with RH-2915. Memo to R. Mountfort RD, OPP, OPTS, EPA, October 30,
1980.
Dykstra, W. 1980c. Perchloroethylene. Review of lexicology Data.
Memo to T. Miller, SPRD, OPP, OPTS, EPA. February 1, 1980.
Dykstra, W. 1980d. Goal 2E; Rabbit teratology study. Memo. TB, HED,
OPP, OPTS, EPA. March 3, 1930.
Dykstra, W. 1931. Oxyfluorofen; Goal 2E; Mouse and Rat Oncogenicity
Studies. EPA memo to J. Chinchilli, SPRD, OPP, OPTS, EPA. February 2,
1981.
Dykstra, W. 1981a. Perchloroethylene Tbxicity; Goal 2E; Oxyfluorfen. Memo
to J. Chinchilli, SPRD, OPP, OPTS, EPA, February 2, 1981.
Dykstra, W. 1981b. Revised PCE Risk Assessment. Memo to J. Chinchilli,
SPRD, OPP, OPTS, EPA, March 4, 1981.
Elmore, C.L. 1980. Weed Scientist, College of Agriculture and
Environmental Sciences, University of California, Davis, Cal.
Personal communication with R. C. Petrie, Agronomist, PSB, BFSD, OPTS,
EPA. May 15, 1980.
Federal Register. 1976. Health Risks and Economic Impact Assessment of
Suspected Carcinogens. Federal Register \fol. 41 No. 102. Page 21402,
May 25, 1976.
Federal Register. 1978. Proposed Guidelines for Registering Pesticides in
the United States. Federal Register \fol. 43 No. 132. Pages 29709-10,
July 10, 1978.
Federal Register. 1980. Endangered and Threatened Wildlife and Plants.
Federal Register \fol 45, No 99. pg 33768, May 20, 1980.
Federal Register, 1980. Proposed Guidelines for Mutagenicity Risk
Assessments. Federal Itegister Ntol. 45, No. 221, pg. 74984,
November 13, 1980.
Federal Register. 1980. Tolerances and Exemptions from Tolerances for
Pesticide Chemicals in or on Raw Agricultural Commodities;
Oxyfluorfen. Federal Register Vol. 45, No. 249. pp. 85021,
December 24, 1930.
FFDCA. 1978. Federal Food, Drug and Cosmetic Act, as amended.
21 U.S. Code.
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FIFRA. 1978. The Federal Insecticide, Fungicide and Rodenticide Act as
Amended. Public Laws 92-516, 94-140, 95-396. 7 U.S.C. 136 et.'seq.
Fuller, B.B., 1976. Air pollution assessment of tetrachloroethylene. EPA
Contract No. 68-02-1495, February 1976.
Creira, H., Bonse, G., Radwan, Z., Reichprt, D., Henscbler, D. 1975.
Mutagenicity in vitro and potential carcinogenicity of chlorinated
ethylenes as a function of metabolic oxirane formation. Biocbem.
Pharmacol. 24:2013. . • '
Hauer, Dexter S. and Reginaldo Morales - Alamo, 1978. Uptake of Kepone
from suspended sediments by Oysters, Rangia and Hacoma in The
Kepone Seminar II. Sponsored by the U.S. EPA. Chesapeake Bay Program
and the National Marine Fisheries Service, NOAA. U.S. EPA publication
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a comparison of structure and activity. Environ. Health Persp. 21:61.
Henschler, D., Bonse, G., Greira, H. Carcinogenic potential of chlorinated
ethylenes—tentative molecular rules. Proc. Third WHO-IARC
Meeting. Lyon, France.Held November 3, 1975.
Henschler, D., Eder, E., Neudecker, T., Metzler, M. 1977. Short
communication. Carcinogenicity of trichloroethylene: Fact or
artifact? Arch. Toxicol. 37:233.
Hitch, R.K. 1980. Comments concerning the EEB risk assessment status for
Goal. Memo to T. Miller from EEB, HED, OPP, OPTS, EPA, February 8,
1980.
Hitch, R. 1981. Conditions to the Registrations of Goal for PD 1/2/3. EPA
memo to J. Chinchilli, SPRD, OPP, OPTS, EPA. January 12, 1981.
IRDC, 1977. Twenty-month dietary feeding study in mice. International
Research and Development Corporation, Final Report. April 25, 1977.
Jensen, S. and C. Ingvordsen. 1977. The perchloro-ethylene content of
garments from dry-cleaning machines. Ugcskrift for Laeger
(Physician'sWeekly) 139:293-297.
Kerr, R.E. 1972. Environmental exposure to tetrachloroethylene in the dry-
cleaning industry. Cincinnati, University of Cincinnati. M.S.
thesis, 112 pages.
Knake, E.L. 1980. Professor of Weed Science Extension. University of
Illinois. Urbana-Champaign, Illinois. Personal communication with
Frank^Beck, PSB, BFSD, OPP, OPTS, EPA. January 30, 1980.
Kozak, V. 1980. Review of Goal/Perchloroethylene exposure assessment
submitted by the Rohm and Haas Company. EFB, HED, OPTS, EPA.
February 6, 1980.
Krzeminski, S. F. 1980. Letter to R. Mountfort, RD, OPP, OPTS, EPA.
November 13, 1980.
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Lange, A.H. et al. 1976. Devrinol and Surflan: New selective weed control
in young orchards and vineyards. California Agriculture, March 1976.
Lange, A.H. et ai. 1977. Weed Control in grapes: A special kind of
problem. Weeds Today, February - March 1977.
Langston, Marion, A. 1975. Witchweed control in horticultural crops.
Proceedings Southern Weed Society, Volume 28.
Langston, Marion A. 1980. Researcher. Plant Protection and Quarantine
Programs. APHIS-USDA. Little Rock, South Carolina. Personal
communication. February-April 1980.
Langston, Marion A. and R.E. Eplee. 1974. Herbicides effective in the
control of wltchweed (Striga asiatica). Proceedings Southern Weed
Society, volume 27.
Langston, Marion A., English, T.J., Eplee, R.E. 1979. Witchweed
(Striga aslattca). Eradication in the United States of
America - Herbicides. Proceedings of the Second International
Symposium on Parasitic Weeds. Musseman, L.J., A.D. Worsham and
R.E. Eplee. North Carolina State University. Raleigh, North
Carolina.
LeClerq, E.L., W.H. Leonard, A.G. Clark. 1962. Field Plot Technique.
Burgess Publishing Co., Minneapolis, 373 pp.
Liebman, K.C. .and E, Ortiz. 1970. Epoxide intermediates in microsomal
oxidation of olefins to glycols. J. Pharraacol. Exptl. Therap. 173:242.
Litton Bionetic, Inc. 1973. Cytogenetic Studies; Compound RH 915. Submitted
by Rohm and Haas, March 1978. EPA accession minber 096872.
(Proprietary)
Malak, V.S. 1980. Plant physiologist. RD, OPP, OPTS, EPA. Personal
communication with T. Miller, SPRD, OPP, OPTS, EPA. February 25, 1980.
Margnrd, W. 1978. In vitro bioassay of chlorinated hydrocarbon solvents.
Report from Battelle Columbus Lab., 505 King Ave. Columbus, OH 43201.
Matthews, W. 1980. Crop reporting board. Economics, Statistics and
Cooperative Services. USDA. Personal communication. February 21,
1980.
Mauer, I. 1980. Mutagenicity studies on the perchloroethylene contaminant
of Goal (Cursory review). Toxicology Branch memo to T. Miller,
February 21, 1980.
McConnell, G., Ferguson, D.M., Pearson, C.R. 1975. Chlorinated hydro-
carbons and the environment. Endeavor 34:13-18.
McMahon, R.E., J.C. Cline and C.Z. Thompson. 1979. The Assay of 855 test
chemicals in 10 Tester Strains Employing a New Modification of the
Ames Test for Bacterial Mutagens. Cancer Research 39:682-693.
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National Cancer Institute. 1977. Bioassay of tetraehloroethylerte for
possible carcinogeniclty. Carcinogenesis technical Report Series
No. 13, NCI-CG-TR-13i DREW Publication No. (NlH) 77-813.
NIOSH. 1976. Criteria for a recommended standard occupational exposure to
tetrachloroethylene (perehloroethylene). Agatha dorp*, Cincinnati,
Ohio. Prepared for the National institute for Occupational Safety arid
Health.
NIOSH. 1978. Tetrachloroethylene (perchloroethylene). Current
Intelligence Bulletin 20. DHEW, Public Health Service Center for
Disease Control, National Institute fot Occupational Safety and
Health.
North Carolina, Crop and Livestock Reporting Service. 1980. Raleigh,
North Carolina. Personal communication with t* Miller* SPRD, OPP,
OPTS, EPA. February 1980. '
Nomura Research Institute (NRI). 1980. In Vitro Micfobi.il Assays for
Mutageniclty Testing of RH-2915* Study Number NRI 80-7256. July,
1980. Submitted to EPA by Rohm and Haas Company, August 13, 1980*
(Proprietary).
Pearson, C.R. and C. McConnell. 1975. Chlorinated C. aiid C0
hydrocarbons in the marine environment. Pfoc., Royal Soc* of, London
(B) 189:305-332.
Perfetti, R.B. 1979. Oxyfluorfen on soybeans and corn* Evaluation of
analytical methods and residue data. EPA memo to R. TaylorY RD» OI>P»
OPTS, EPA. February 13, 1979.
Perfetti, R.B. 1979a. Oxyfluorfen on soybeans and corn. Amendments of
March 6, 1979 and July 18, 1979* EPA memo to R* Taylor, Registration
Division, OPTS, EPA. August 31, 1979.
Perfetti, R.B. 1980. Oxyfluorfen on corn and soybeans. PP# 852058
and FAP//* 9H5230. Amendment of Febfuary 6, 1980. Memo front RCB, HED,
OPP, OPTS, EPA. February 8, 1980.
Petrie, R. 1980a. Agronomist. Section 3, PSB, BFSD, OPP, OPTS, EPA* Memo
entitled "Review of Goal 2E efficacy, phytOtoXiCity, and yield data In
Registration Division files *• filed under Reference No.: 8F2658;
dated March 8, 1978, May 5, 1978 arid September 29, 1978* Memo dated
March 11, H'?0.
Petrie, R. 1980b. Personal communication with ton Miller, SPRD, OPP* OPTS,
EPA. April 1980.
Petrie, R. 1980c. Preliminary analysis of oxyfluorfen (Goal 2E) use for
weed control in fruit, nut orchards and Vineyards in California.
PSB, BFSD, OPP, OPTS, EPA. June 5, 1980*
Petrie, R. 1980d. Preliminary analysis of oxyfluorfen (Goal 2E) use for
weed control in conifer seedbeds throughout the U.S*, and for weed
control in conifer transplants in the Pacific Northwestern U.S* PSB,
BFSD, OPP, OPTS, EPA. June 19, 1980.
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