United Stnn
Environmental Protection
Aqcncy
Off to of
Pastickfes md Tonic Subfancn
WuhinjtonOC 20460
January 1982
3EPA
Oxyfiuorfen (Goal 2E
Position Document No. 4
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CHOFIECRFEN
POSITICN DOCUMENT
Office of Pesticide Programs
Environmental Protection Agency
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- flCKNDWLEDGEMEMTS -
EPA OXYFLUORFEN TEAM
Frank Beck, Agronomist, BFSD
Jolene Chinchilli, Project Manager, SPRD
Katharine Devine, Econonist, 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, Product Manager, RD
R.B. Perfetti, Chemist, HED
Richard Petrie, Agronomist, BFSD
Emil Regelman, Environmental Chemist, HED
Joseph Reinert, Chemist, HED
Amy Rispin, Environmental Chemist, HED
Dudley E. Thompson, Attorney Advisor, SPRD
OTHER AQCNOWLEDGEMENTS
Vickie Vaughn-Dellarco, REAG
Bernard HaJberman, GAG
Robert McGaughy, CAG
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Oxyfluorfen
PD 4
Table of Contents
Page
I. Introduction 1
A. Sunmary of Position Document 1/2/3 1
1. Risk 2
2. Benefits 2
3. Risk/Benefit Analysis and Regulatory Options 2
4. Proposed Regulatory Decision 4
B. Request for Garments 7
II. Revisions and Amendments to PD 1/2/3 - Exposure and Risk 8
III. Analysis of Garments 12
A. Comments Relating to Risk 12
B. Garments Relating to Benefits 13
C. Garments Relating to Regulatory Options - Respirator
Requirement for Mixer/Loader/Applicators 13
Appendix A - Revised Exposure and Risk Tables from the Oxyfluorfen
Position Document 1/2/3
Appendix B - Comments from Scientific Advisory Panel and USDA
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List of Tables
Page
1. Carcinogenic Risk to Agricultural Workers and to the General
Population Associated with the Use of PCE-Contaminated
Qxyfluorfen 3
2. Adjusted Lifetime Average Daily Worker Exposure to PCE from
Uses of Qxyfluorfen 9
3. Adjusted Maximum Dietary Exposure to PCE from Uses of
Qxyfluorfen 10
4. Carcinogenic Risk to Agricultural Workers and the General Public
Associated with the Uses of PCE-Contaminated Qxyfluorfen 11
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Executive Summary
Oxyfluorfen (Goal 2E) was referred for Rebuttable Presumption
Against Registration (RPAR) review in January, 1980, because
pesticide products containing oxyfluorfen were shown to be
contaminated with perchloroethylene (PCE), a demonstrated
liver carcinogen in B6C3F1 mice. The review was initiated
because of the potential for human risk via dietary and
applicator exposure.
Goal 2E is the only registered product containing oxyfluorfen.
It is registered as a herbicide for both pre-emergence and
post emergence control of certain weed species on conifer
seedbeds and transplants, bearing and nonbearing tree fruits
and nuts, soybeans and field corn (USDA Witchweed Eradication
Program). The sole producer and registrant is the Rohm and
Haas Company of Philadelphia, Pennsylvania.
In March 1981, the Agency issued a position document
integrating the presumption against registration and the
risk/benefit analysis (position document 1/2/3). In this
document, the Agency proposed to limit the level of the PCE
contaminant to 200 ppm or less. This reflected the level
the registrant had stated was both economically and technically
feasible. Risks estimated by the Agency at the 200 ppm
level for the PCE contaminant were not large and were considered
to be outweighed by the benefits of the use of oxyfluorfen.
The risk estimate for applicators was based on a very
conservative model of inhalational exposure rather than
actual field measurements. Because of the risk estimates
associated with this model, the Agency proposed to require,
within six months of the final decision, the use of respirators
by mixer/loader/ applicators for currently registered and
proposed uses to reduce inhalational exposure, unless the
registrant submitted actual monitoring data showing levels
of inhalational exposure significantly lower than those
estimated.
The Agency recommended in the PD 1/2/3 the continuation of
registration for use on conifers and nonbearing tree fruits
and nuts, since the relatively small risks to applicators
for these uses were determined to be exceeded by the benefits.
The pending registration actions for Goal at the initiation
of the RPAR review were for soybeans, field corn and bearing
tree fruits/nuts. The recommended decision in the PD 1/2/3
was to approve these proposed registrations on condition
that the registrant provide necessary data required to
support full registration. These conditional registrations
were subsequently approved.
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During this review, the Agency also determined that for uses
of Goal, data are currently inadequate to properly assess
certain possible adverse effects of oxyfluorfen itself.
These possible adverse effects include oncogenicity,
mutagenicity, teratogenicity, persistence and bioaccumulation
in the aquatic environment, and avian reproduction. The
request for these data is independent of the Agency's RPAR
determination. The registrant is currently engaged in
discussions with the Agency concerning these data
requirements.
The Agency also determined that the risk to aquatic plants,
aquatic invertebrates, wildlife and fish from all uses of
oxyfluorfen could be reduced by labeling without adverse
impact on benefits. For the soybean use, additional labeling
to protect certain species of endangered aquatic molluscs
from the possible hazard posed by the erosion of oxyfluorfen-
bound soil was proposed. The registrant has subsequently
filed label amendments to include these changes.
The Scientific Advisory Panel and the United States Department
of Agriculture have both concurred on the proposed decision
in the PD 1/2/3. Their comments on the auxiliary issues have
been addressed in the PD 4.
The Agency has decided that the final determination
regarding oxyfluorfen will remain unchanged from that
proposed in the PD 1/2/3.
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I. Introduction
Under the Federal Insecticide, Fungicide, and Rodenticide Act, as amended
(FIFRA) (7 U.S.C. Section 136 et seoj the Environmental Protection Agency
(EPA or the Agency) regulates all pesticide products. Section 6(b) of FIFRA
authorizes the Administrator of the EPA to issue a notice of intent to cancel
the registration of a pesticide or to change its classification if it appears
to him that the pesticide or its labeling "does not comply with the provisions
of [FIFRA] or, when used in accordance with widespread and commonly recognized
practice, generally causes unreasonable adverse effects on the environment"
Section 3(c)(6) authorizes the Administrator to deny applications for
pesticide registration if the statutory standards for registration are not met.
The Agency designed the Rebuttable Presumption Against Registration (RPAR)
process to gather risk and benefit information about problem pesticides and to
make balanced decisions concerning them in a manner which allows all interested
groups to participate. This process is set forth in 40 CFR 162.11.
A. Summary of Position Document 1/2/3
Cxyfluorfen was referred to the Special Pesticide Review Division of the Office
of Pesticide Programs in January of 1980 because pesticide products containing
oxyfluorfen as an active ingredient are contaminated with perchloroethylene
(PCE). PCE was demonstrated to be a liver carcinogen in mice in a National
Cancer Institute (NCI) carcincgenicity bioassay (1977). Because of the
carcinogenic potential of PCE shown in the NCI study, the Agency determined
that PCE-contaminated oxyfluorfen met or exceeded the rebuttable presumption
against registration (RPAR) criterion for oncogenicity as set forth in 40 CFR
162.11.
In the interest of achieving an expedited review of the uses of oxyfluorfen,
the Agency decided to issue a position document which integrated the position
document 1 presumption against registration and the position document
2/3 risk/benefit analysis. It seemed reasonable to focus public discussion on
the risk/benefit analysis by presenting the Agency's proposed position in a
single document, the Position Document 1/2/3, (PD 1/2/3).
Currently, there is one registered product containing the active ingredient
oxyfluorfen. This product is marketed under the trade name Goal® 2E,
contains 23.5 percent oxyfluorfen, and, along with technical oxyfluorfen,is
manufactured solely by the Rohm and Haas Company of Philadelphia, Pennsylvania.
At the initiation of this review, Goal® 2E had already been registered for use
on conifer seedbeds, transplants and outplantings, and certain nonbearing tree
fruits/nuts in California; and conditional registrations were pending for
soybeans, certain bearing tree fruits/nuts and field com. The field corn use
applies only to those 38 counties in North and South Carolina which are part of
the U.S. Department of Agriculture Witchweed Eradication Program. The
conditional registrations were subsequently granted in an action separate from
the PD 1/2/3, with the conditions described in the PD 1/2/3.
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1. Risk
Based upon "worst case" exposure situations and the current maximum level of
PCE in formulated oxyfluorfen products (200 ppm), the Agency estimated the
carcinogenic risk associated with PCE-contaminated oxyfluorfen to both the
agricultural worker and the general public.
The carcinogenic risk associated with each of the uses of PCE--
contaminated oxyfluorfen is presented in Table 1. These values show slightly
higher levels of risk than those presented in the PD 1/2/3. This discrepancy
is discussed further in Section II of this document.
Five other areas of concern were also addressed in the PD 1/2/3, related to
oxyfluorfen itself. The areas of concern were oncogenicity, mutagenicity,
teratogenicity, and subchronic effects. The potential for adverse
environmental effects was also examined in light of the pending registrations
for the corn and soybean uses. Valid data concerning the chronic toxicity of
oxyfluorfen in the above-mentioned categories are necessary to support
registration of all uses of oxyfluorfen.
2. Benefits
The benefits associated with each use of oxyfluorfen were discussed at length
in the PD 1/2/3. In summary, the benefits of oxyfluorfen use include the
following.
o Oxyfluorfen possesses both pre- and post emergence activity. This
increases herbicide utility and allows for season-long control of
certain weeds.
o Oxyfluorfen is less dependent on soil and moisture conditions than
some otherwise comparable herbicides.
o Oxyfluorfen appears to be uniquely effective for control of certain
problem weeds (e.g. cheeseweed, witchweed).
o Oxyfluorfen is competitively priced with respect to other herbicides
registered for the same use pattern.
o Oxyfluorfen, when applied as directed, will not cause injury to
conifers or crops specified on the label.
3. Risk/Benefit Analysis and Regulatory Options
The Agency developed various regulatory options with respect to oxyfluorfen
products and has evaluated each option for its impact on risks and benefits.
The regulatory options considered in the PD 1/2/3 for conclusion of the
oxyfluorfen RPAR focused on methods to reduce levels of human exposure to the
PCE contaminant, and to reduce environmental risk associated with the uses of
oxyfluorfen.
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i
U)
I
Table 1
Carcinogenic Risk-'to Agricultural Workers and to the General Population
Associated with the Use of PCE-'-Contaminated Oxyfluorfen.
CROP RISK
Worker~General Public
(Inhalational + Dermal)-' (Dietary)
Soybeans 4.20 x 10~6 5.30 x 10~8
Field Corn 1.10 x 10~4 3.03 x 10"8
Tree Fruits/Nuts 1.70 x 10~5 1.00 x 10~6
Conifers 1.80 x 10~5
a/ Based on multistage model.
b/ Assumes 200 ppm in formulated product.
£/ Inhalation is estimated to be the primary route of
~~ exposure. See revised Table 4.
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The Agency considered the following six regulatory options.
a. Specify a maximum PCE contamination level of 200 ppm in formulated
oxyfluorfen products.
b. Require protective equipment (suitable respirators) to be worn
during the mixing, loading, and application of oxyfluorfen products.
c. For the pending registration for soybean use, prohibit use of
oxyfluorfen products in counties providing habitat for endangered
molluscs.
d. Require labeling for the pending registration for soybean use in
order to protect aquatic molluscs.
e. Require labeling for all uses of oxyfluorfen for the protection of
aquatic plants, aquatic invertebrates, wildlife and fish.
f. Require development of certain data on the possible adverse effects
of oxyfluorfen en 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, mutagenicity,
teratogenicity, subchronic effects, persistence and bioaccumulation
in the environment, and toxicity to fish and wildlife.
The risks and benefits for each use were compared under each appropriate
option listed above. This use-by-use risk/benefit analysis was detailed in the
PD 1/2/3.
4. Proposed Regulatory Decision
Based on the use-by-use risk/benefit analysis, the Agency proposed the
following regulatory decision.
For all uses of oxyfluorfen products (currently registered and proposed) the
Agency proposed that:
o The PCE contamination of formulated oxyfluorfen products (Goal® 2E)
may 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 perchloroethylene must be used during
the mixing, loading and application of all oxyfluorfen products.
Labelling of all oxyfluorfen products must be amended to include this
statement. 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 inhalational exposure for the maximum application rate for
each registered use is significantly lower than the inhalational
exposure estimated by the Agency.
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o Labeling for the protection of wetlands and other aquatic resources is
required as part of the conditions for registration. Specific
label statements are to read as follows.
For Soybeans:
"This product is highly toxic to freshwater clams, oysters, aquatic
invertebrates and aquatic plants. Do not apply where visible
erosion to aquatic habitats and wetlands occurs."
For all other uses;
"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 bodies by cleaning of equipment or disposal of wastes."
The Agency also determined that with the adoption of the above-mentioned
provisions, amending the existing Goal 2E registration to include use on
soybeans, field corn, and bearing tree fruits/nuts would not significantly
increase the risk of unreasonable adverse effects on man or the environment.
The Agency, however, recommended that subsequent registrations for these
proposed uses (field com, soybeans, bearing tree fruits/nuts and any other
uses to be proposed) include the following condition due to oxyfluorfen's
persistence and potential to bioaccumulate.
Extensive field monitoring for oxyfluorfen residues in each proposed
use pattern area would be required. The registrant would submit these
data to the Agency within two years of the date of conditional
registration.
The detailed rationale for the proposed decision is presented in the PD 1/2/3.
In summary, those options which would result in maximum risk reduction or
incremental risk reduction with minimum impact on the benefits of oxyfluorfen
use. During the course of this review the registrant reduced the PCE
contamination of oxyfluorfen from 1680 ppm to 200 ppm or less in the formulated
product. The Agency based its risk assessment on the current level (200 ppm)
of PCE in oxyfluorfen and "worst case" exposure conditions. Based on the
resulting "worst case" risk figures, the Agency determined that to allow PCE
levels higher than 200 ppm would increase the risk without a concomitant
increase in benefits. Limiting PCE levels to 200 pcm would not affect the
benefits adversely, because oxyfluorfen is currently produced with levels of
200 ppm or less PCE.
The "worst case" exposure estimates resulted in risk estimates for
mixer/loader/applicators which the Agency believed warranted the use of
protective equipment. Because inhalational exposure appears to be the major
component of worker risk, respirators would be required unless actual
monitoring data submitted by the registrant demonstrate that exposure to PCE
during application of oxyfluorfen is significantly less than that estimated by
the Agency. This course of action will reduce risk, not adversely affect the
benefits, and provide the registrant with the option of supplying additional
information to the Agency so that the risk assessment and consequently the
regulatory decision may be modified as indicated by these data.
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The environmental hazard labeling, as part of the conditions for registration,
is designed to reduce the possible hazard to the environment, in particular to
aquatic habitats, without major use restrictions. For the soybean use pattern,
specific labeling has been developed. This labeling has been coupled with a
requirement for extensive field monitoring for oxyfluorfen residues. If levels
in aquatic habitats are .found in monitoring studies to approach toxic levels,
the Agency may reconsider the option of restricting use of oxyfluorfen from
those counties providing habitat for endangered molluscs. This monitoring
requirement has also been required as a condition of registration for the field
corn and tree fruit/nut uses.
In an action independent of the RPAR under authority of FXFPA section
3(c)(2)(B), the Agency stated in the PD 1/2/3 that the registrant would be
required to submit the following oxyfluorfen studies to the Agency in support
of all registrations.
o The registrant is to be 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
before initiation of testing.
o A battery of mutagenicity tests are to be submitted to the
Agency. Protocols should be submitted to the Agency prior to the
initiation of testing.
o The registrant is to be required to submit an oxyfluorfen oncogenicity
study in mice and an oxyfluorfen oncogenicity study in rats.
Protocols for these studies are to be submitted prior to initiation
of testing.
o The registrant is to be required to submit a 6-month (or longer) dog
feeding study which demonstrates a no-observed-effect level (NOEL).
Protocols for this study have been published in 43 FR 37536,
August 22, 1978.
o The registrant is to be required to submit avian reproduction studies
with mallard ducks and bobwhite quail.
The registrant is currently engaged in discussions with the Agency concerning
these proposed actions for testing of oxyfluorfen. In the course of these
discussions, the Agency has determined that the information needed to evaluate
the human health effects of oxyfluorfen can be obtained without requiring the
registrant to perform all of the studies specifically detailed in the PD 1/2/3.
As a result of clarification of data in the existing dog chronic feeding study,
the Agency has found the study demonstrates an acceptable no-observed-cffect
level and the registrant will not be required to repeat the study. The Agency
has also determined that, since the acceptability of earlier rodent
oncogenicity studies hinges on whether the highest experiment dose was near the
maximum tolerated dose (MTD), the registrant will first conduct short-term
studies to determine the MTD. Unless this MTD is significantly higher than the
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high dose in the earlier experiments, the Agency will not require further
oncogenicity testing. All proposed testing requirements are currently under
discussion with the registrant. Final determination of the studies to be
required will be made when discussions with the registrant are completed, and
the Agency will issue a letter to the registrant, under authority of FIFRA
section 3(c)(2)(B), requesting the studies. At that time, the Agency will
specify a value of the NOEL for teratogenicity data that indicates acceptable
safety, based on calculated exposure and an adequate magin of safety.
B. Request for Comments
FIFRA requires the Agency to submit notices issued pursuant to section 6 to the
Secretary of Agriculture for comment en the proposed action [section 6(b)] and
to a Scientific Advisory Panel (SAP) for comment on the impact of the proposed
action en health and the environment [section 25(d)]. The Secretary of
Agriculture and SAP are invited to comment, as required by the statute, in
writing within 30 days of receiving the notice and the Agency is required to
publish their comments and the Administrator's response with publication of the
notice of final determination.
The Agency presented its proposed decision to the SAP at a public meeting held
on May 13 and 14, 1981. Notice of the meeting was published in the Federal
Register on April 27, 1981, indicating the availability of the PD 1/2/3 and
describing the procedures for making oral and written comments. In addition,
the SAP contacted, by mail, members of the general public who had previously
expressed an interest in the Panel's activities. The SAP meeting was attended
by the registrant and other interested parties.
The Agency has received three sets of comments in response to the March, 1981,
Oxyfluorfen Position Document 1/2/3. Responses from the SAP, the U.S.
Department of Agriculture, and the registrant have been analyzed and are
addressed in Section III of this document. The responses from the SAP and the
USDA are presented in Appendix B in their entirety.
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II. Revisions and Amendments to PD 1/2/3 - Exposure and Risk
Since publication of the PD 1/2/3, the estimates of PCE exposure have been
revised. Refinements in calculation have demonstrated that exposure to PCE
from use of oxyfluorfen products had been underestimated by a factor of three
in the initial review. As a result, it was also necessary to revise the risk
figures, which are a function of the exposure.
Tables 2 and 3 present the original and revised PCE exposure estimates for all
uses of oxyfluorfen. Revised risk estimates are presented in Table 4.
All tables relating to exposure and risk estimates which were presented in the
PD 1/2/3 have been corrected and the revised editions appear in Appendix A of
this document.
From a review of Tables 2, 3, and 4, of this docunent, the Agency concludes
that the revised risk figures are not significantly different from those which
appear in the PD 1/2/3. However, the Agency wishes to present the most
accurate evaluation possible in its final decision. The Agency has determined
that these revisions do not affect the proposed regulatory action. The means
for reducing risk to applicators have already been proposed, and these are
sufficient to take into account the slightly higher revised risk figures.
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Table 2
Adjusted Lifetime Average Daily Worker .Exposure
to PCE-'from Use of Oxyfluorfen-'
10
I
Route
Crop
Exposure—'
(mg/kg/day)
Original
Inhalational-/
Dermal-
Total
Soybeans
Field corn
Tree fruits/nuts
Conifers
Soybeans
Field corn
Tree fruits/nuts
Conifers
Soybeans
Field corn
Tree fruits/nuts
Conifers
0.
7.
1.
1.
0.
20.
0.
1.
0.
7.
1.
1.
3
0
1
1
4
0
4
7
3
2
1
1
X
X
X
X
X
X
X
X
X
X
X
X
10
10
10
10
10
10
10
10
10
10
10
-4
-4
A
~
-6
-6
-6
-6
-4
_ »
10~"
0.
20.
3.
3.
1.
60.
1.
4.
0.
21.
3.
3.
Revised
8
6
3
3
2
0
3
8
8
0
3
4
X
X
X
X
X
X
X
X
X
X
X
X
10
10
10
10
10
10
10
10
10
10
10
-4
-4
-4
^t
~
-6
-6
-6
-4
_ *
10—
a/ Assumes 200 ppm in formulated product.
b/ Assumes exposure time of 10 days/year (62.5 days for corn),
a working life of 40 years and a 70-year life span.
c/ See Appendix A, Tables 2 and 3 for individual daily dermal and
~ inhalation figures.
d/ Based on an 8-hour day of spraying.
e/ Based on 1 hour mixing/loading and 7-hours spraying.
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Table 3
Adjusted Maximum Dietary Exposure to
PCE— 'from Uses of Oxyfluorfen
Exposure^'
Crop (mg/kg/day)
Original Revised
Soybean 1.04 x 10~6 1.04 x 10~6
Field Corn 0.05 x 10"6 0.57 x 10"6
Tree Fruit/Nuts 19.00 x 10~6 19.00 x 10~6
a/ Assumes that 0,05 ppm level of analytical sensitivity is
equivalent to 0.05 mg/kg of commodity.
b/ Daily consumption of commodity in mg/person/day based on
average consumption figures for each commodity (U.S. EPA,
1981, PD 1/2/3).
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Table 4
Carcinogenic Risk-/to Agricultural Workers and the General
Public Associated with the Uses of PCE-'-Contaminated Oxyflurofen
Crop
Risk Estimate
Original
a/ Uses multistage model for calculations.
b/ Assumes 200 ppm PCE in formulated product.
c/ Uses revised exposure figures from Tables 2 and 3,
Revised—'
c/
WORKER:
Soybean
Field Corn
Tree Fruits/Nuts
Conifers
DIETARY:
Soybeans
Field Corn
Tree Fruits/Nuts
1.5 x 10"|
3.8 x 10~j?
5.8 x 10":!
5.8 x 10~b
5.30 x 10"?
2.65 x 10";:
1.00 x 10~b
4.2 x 10"^
1.1 x 10~J
1.7 x 10~j?
1.8 x 10"*
5.30 x 10~J
3.03 x 10"?
1.00 x 10"b
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III. Analysis of Garments
The Agency received comments from the Secretary of Agriculture, the Scientific
Advisory Panel (SAP) and the registrant. These comments are organized by topic
and discussed below. As indicated in the following discussion, the Agency has
revised some aspects of its assessment of risks, benefits, and regulatory
requirements in accordance with USDA, SAP, and other recommendations. Except
as discussed below and in Section II, other aspects of the analysis presented
in the Position Document 1/2/3 are unchanged.
A. Comments Relating to Risk
The Agency has received no comments on its assessment of the carcinogenic risk
from PCE associated with the uses of oxyfluorfen. Minor revisions in exposure
and risk figures have been made by the Agency and have been presented and
discussed in Section II of this document.
The SAP has concurred with the Agency's assessment of risk from PCE but has
stated that it has "a number of serious concerns with oxyfluorfen not
related to the oncogenic hazard from PCE«.." (30000/36:#3). These concerns
relate to the following issues.
1. The persistence and possible bioaccumulation of oxyfluorfen
in the food chain.
2. The adequacy of testing of oxyfluorfen's potential teratological
effects given its structural resemblance to nitrofen.
3. The identification and potential adverse effects of the various
inert ingredients in oxyfluorfen.
With regard to issue (1) above, the Agency shares the SAP's concern regarding
the persistence of oxyfluorfen in the environment. This concern was discussed
in the PD 1/2/3 and the Agency has proposed that extensive field monitoring for
oxyfluorfen residues in the major use pattern areas be required as part of the
conditions for registration. The field monitoring outlined by the Agency in
the PD 1/2/3 includes provisions for evaluating the potential of oxyfluorfen to
bioaccumulate in aquatic organisms.
Issue number (2) pertains to oxyfluorfen's potential to cause teratogenic
effects. This concern arises from the fact that oxyfluorfen is structurally
similar to nitrofen, a known teratogen. Therefore, the SAP believes that an
especially careful evaluation of oxyfluorfen is warranted.
The Agency agrees with the SAP that a special effort should be made to
determine that no teratological problem exists with oxyfluorfen. The PD 1/2/3
discussed the information available at the time and highlighted the need for
some further study. Along with the rat teratology study submitted by the
registrant (negative for teratogenic effects at 1000 mg/kg/day), the registrant
is currently conducting a second teratology study with rabbits which will be
submitted in late 1981. Additional teratogenic evaluation of oxyfluorfen is
being conducted by EPA at its Research Triangle Park (RTP), N.C. facility. The
EPA scientist in charge of this research has also evaluated the teratogenic
effects of nitrofen and acifluorfen (two diphenyl ethers similar to
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oxyfluorfen). Therefore, any teratogenic effects of oxyfluorfen similar to
those of nitrofen should be recognized. Also, the Agency points out that
structurally similar chemicals do not necessarily possess the same
toxicological characteristics. Evidence of this in the case of diphenyl ethers
cones from the above-mentioned EPA studies being done at FTP. Data from these
studies indicate that nitrofen is teratogenic but that acifluorfen is negative
for teratogenic effects (Dykstra, 1981).
Following the evaluation of the rabbit teratology study, to be submitted in
late 1981 by the registrant, and the results of EPA testing of oxyfluorfen, the
Agency will then determine whether further testing is warranted, or whether the
information to date is sufficient to accurately evaluate the teratogenic
potential of oxyfluorfen.
SAP's third concern relates to the level of impurities in technical oxyfluorfen
and the possible adverse effects of these impurities on the environment.
Although not specifically discussed in the PD 1/2/3, the identification of and
toxicological information on the impurities in technical oxyfluorfen have been
submitted to and reviewed by the Agency (Rohm and Haas, 1978; Perfetti, 1978;
and Dykstra, 1978). Unless an impurity or inert ingredient of a pesticide is
judged to pose an unreasonable adverse effect on man or the environment, it is
illegal to disclose such product information in a public document. The Agency
has addressed the issue of the impurities in technical oxyfluorfen and the
relevant reviews are on file. These reviews were provided to the SAP. The
panel expressed their satisfaction with the adequacy of these reviews.
B. Comments Relating to Benefits
The only comments relating to oxyfluorfen benefits were received from USDA
(30000/36:#2). Essentially, the USDA concurs with the Agency assessment of
benefits and adds that oxyfluorfen is particularly beneficial for witchweed
control and use in forest nurseries. The Agency agrees and believes that the
benefits of oxyfluorfen for use in corn and forest nurseries have been
adequately discussed in the PD 1/2/3.
C. Comments Relating to Regulatory Options - Respirator Requirement for
Mixer/Loader/Applicators
The USDA (30000/36:#2) has agreed with the Agency's proposal to require
respirators during the mixing, loading, and application of oxyfluorfen
products. The USDA commented, however, that this requirement does not take
into account different methods of application. The USDA stated that in many
forest nurseries, pesticides are applied through automatic watering systems
which would result in little or no applicator exposure.
In assessing applicator exposure to PCE from use of oxyfluorfen products, the
Agency assumed spray application as indicated on the Goal© 2E conifer label.
The Goal® 2E label does not currently provide rates, metering instructions,
limitations, precautions D-r y-)f-r directions for use of Goal® 2E through
automatic watering systems. As indicated in the PD 1/2/3, oxyfluorfen
performance and exposure data are extremely limited.
-13-
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The USDA. also ccranented that use of respirators in many areas of the United
States poses problems of discomfort due to heat and humidity and that in
certain high temperature situations the hazards associated with the use of
respirators may be more immediate and dangerous than the hazard due to
pesticide exposure. The USDfc, suggests that research is needed to devise
protective measures suitable for hot weather.
In the case of oxyfluorfen, inhalational exposure accounts for 98 percent or
more of the total applicator exposure to the PCE contaminant, according to
Agency estimates. Reducing inhalational exposure is therefore the most
effective method of reducing total exposure of applicators to PCE in
oxyfluorfen. Respirator use dramatically decreases total exposure and
resultant risk, as illustrated in revised Table 11.
The Agency recognizes the reluctance of applicators to wear respirators in hot
and humid weather situations. The Agency is not aware, however, of any data
which indicate that the use of respirators in high temperature situations
results in "more immediate and dangerous hazards than exposure to the
chemical."
With respect to oxyfluorfen specifically, the Agency believes (as stated in the
PD 1/2/3) that its exposure estimates for applicators are, of necessity, "worst
case" values and has invited the registrant to submit data demonstrating that
actual exposure to PCE is significantly lower than Agency estimates. These
data are not anticipated to be costly to generate and could successfully rebut
the respirator requirement. Until such time as these data are available or
other protective methods are developed, the Agency will require the currently
available means of reducing inhalational exposure (respirators) to be used
during mixing, loading, and application of oxyfluorfen products.
The registrant has also submitted conroents (30000/36:#1) on implementation of
the respirator requirement. Rohm and Haas believes that "the actual inhalation
exposure to PCE from Goal® formulations is significantly less than that
calculated by the Agency and the company will obtain actual field monitoring
data to substantiate its contention."
After reviewing comments frcm the Departnent of Agriculture, the Scientific
Advisory Panel, and the registrant on the Agency's findings and recommendations
concerning oxyfluorfen as set forth in the PD 1/2/3, the Agency has decided to
implement its proposed decision without modification.
-14-
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Bibliography of Comments
FIFRA Scientific Advisory Panel. June 19, 1981. Gray, P.H. (30000/36:#43).
Rohm and Haas Company. May 11, 1981. Krzemenski, S.F. (30000/36:11).
USDA, United States Department of Agriculture. July 6, 1981. Flamm, B.R.
(30000/36:ft2).
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References
CFR, 40. 1980. Protection of the Environment. Subchapter E—Pesticide
Programs. CFR 40, Part 162—Regulations for the Enforcement of the
Federal Insecticide, Fungicide and Rodenticide Pet. Subpart A—
Registration, Reregistration and Classification Procedures. CFR 40, Part
162.11—Criteria for determinations of unreasonable adverse effects.
Dykstra, W. 1981. Personal ccnraunicaticn with Neil Chernoff. Concerning
teratogenicity testing at Research, Triangle Park, N.C., May 6, 1981.
Dykstra, W. 1978. Request for establishment of permanent tolerances on
soybeans and corn at 0.05 ppm for oxyfluorfen and its metabolites
containing the diphenyl ether linkage. Memo to Robert Taylor RD, OPP,
OPTS, EPA. November 7, 1978.
Federal Register. 1978. Proposed Guidelines for Registering Pesticides in the
United States. Federal Register Vol. 43 No. 132. Pages 29709-10, July 10,
1978.
Federal Register. 1978. Proposed Guidelines for Registering Pesticides in the
United States. Federal Register Vol. 43. No. 163, Page 37536. August 22,
1978.
Federal Register. 1980. Endangered and Threatened Wildlife and Plants.
Federal Register Vol. 45, No. 99. pg 33768, May 20, 1980.
Federal Register. 1980. Proposed Guidelines for Mutagenicity Risk
Assessments. Federal Register Vol. 45, No. 221, pg. 74984, November 13,
1980.
FIFRA. 1978. The Federal Insecticide, Fungicide and Rodenticide Act as
Amended. Public Lavs 92-516, 94-140, 95-396. 7 U.S.C. 136 et seq
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.
National Cancer Institute. 1977. Bioassay of tetrachloroethylene for possible
carcinogenicity. Carcinogenesis Technical Report Series No. 13,
NCI-CG-TR-13, DHEW Publication No. (NIH) 77-813.
Perfetti, R.B. 1978. Oxyfluorfen on soybeans and corn. Memo to R. Taylor RD,
OPP, OPTS, EPA. July 12, 1978.
Rohm and Haas Co. 1978. Petition for Establishment of Permanent Tolerances for
Goal® 2E on Soybeans and Corn, September 29, 1978. Pesticide Petition
8F2058, Ace. No. 097425.
U.S. Environmental Protection Agency. 1981. Oxyfluorfen (Goal 2E®) Position
Document 1/2/3, Project Manager, Jolene Chinchilli.
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.
(confidential)
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APPENDIX A
Revised Exposure and Risk Tables from the
Oxyfluorfen Position Document 1/2/3
TABLE 2.
Daily PCE Inhalation Exposure for
Applicator/Mixer/Loaders Using Goal
CROP (mg/kg bw/day)
Soybeans 5.282 x 10"3
Field Corn 21.127 x 10~3
Tree Fruits/Nuts 21.127 x 10~3
Conifers 21.127 x 10~3
a/ Assumes 200 ppm PCE in Goal 2E.
b/ Assumes an 8-hour day of spraying.
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TABLE 3.
Daily PCE Dermal Exposure for ... .
Applicator/Mixer/Loaders Using Goal 2E3-' —'£f
CROP (mg/kg bw/day)
—4
Soybeans 0.78 x 10
Field Corn 6.20 x 10~4
Tree Fruits/Nuts 0.83 x 10~4
Conifers 3.10 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.
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TABLE 4.
Adjusted Lifetime Average Daily Worker Exposure
'
to PCE from Use of Goal
Crop
Inhalation
mg/kg bw/day
Dermal
mg/kg bw/day
Total
mg/kg bw/day
Soybeans
0.8 x 10
-4
Field Corn [1981] 20.6 x 10~4
Tree Fruit/Nuts
Conifer
3.3 x 10
-4
3.3 x 10
-4
1.2 x 10
-6
60.0 x 10
1.3 x 10
-6
-6
4.8 x 10
-6
0.8 x 10
-4
21.0 x 10
3.3 x 10
-4
-4
3.4 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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TABLE 5.
Adjusted Lifetime Average Daily Worker Exposure /
to PCE from Use of Goal 2E - Protective Clothing Scenario—7
Inhalation
Crop mg/kg bw/day
Soybeans 0
Field Corn (1981] 0
Tree Fruit/Nuts 0
Conifer 0
Dermal Total
mg/kg bw/day mg/kg bw/day
1.8 x 10~7 1.8 x 10"7
88.0 x 10"7 88.0 x 10~7
1.9 x 10~7 1.9 x 10~7
7.0 x 10~7 7.0 x 10~7
a/ Assumes applicators wear protective clothing and suitable respirator,
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TABLE 9.
Carcinogenic Risk to Applicator/Mixer/Loaders and to the
General Population Associated with the PCE Contaminant
of Goal 2E (Dykstra, 198Ib)
Crop Exposure Estimate Risk Estimate
(mg/kg/day)
Worker;
Soybeans 0.8 x 10"4 4.2 x 10~6
Field Corn 21.0 x 10~4 1.1 x 10~4
Tree Fruit/Nuts . _
(bearing; 3.3 x 10~4 1.7 x lO'3
nonbearing)
Conifers 3.4 x 10~4 1.8 x 10"5
Dietary;
Soybeans 1.0 x 10~6 5.30 x 10"8
Field Corn 5.7 x 10~7 3.03 x 10~8
Tree Fruit/Nuts _
(bearing only) 1.9 x 10"3 1.00 x 10"b
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TABLE 10.
Adjusted Lifetime Average Daily Worker Exposure to and
Associated Risk from PCE in Goal-7
Inhalation Dermal Total Risk
Crop (mg/kg bw/day) (mg/kg bw/day) (mg/kg bw/day)
Soybeans 0
Field Corn 11981] 0
Tree Fruit/Nuts 0
Conifers 0
1.8 x 10~7 1.8 x 10~7 9.5 x 10~9
88.0 x 10~7 88.0 x 10"7 4.7 x 10~7
1.9 x 10~7 1.9 x 10~7 1.0 x 10"8
7.0 x 10~7 7.0 x 10~7 3.7 x 10~8
a/ Assumes applicators wear protective clothing and suitable respirator.
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TABLE 11.
Comparison of Applicator Risk With and Without the Use of
Protective Equipment
Crop
Risk Without
Protective Equipment
Risk When Protective
Equipment is Employed
Soybeans
4.2 x 10
~6
9.5 x 10
~9
Field Corn [1981]
1.1 x 10
~4
4.7 x 10
~7
Tree Fruit/Nuts
1.7 x 10
~5
1.0 x 10
~8
Conifers
1.8 x 10
~5
3.7 x 10
~8
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The Following Tables and Sample Calculations Are
Revisions of Appendix A of the Oxyfluorfen Position
Document 1/2/3, pp. 96-101.
Maximal PCE Applied Under Goal 2E Use Conditions-'
a/
Soybeans
Field Corn
Tree Fruit/Nuts
Conifers
Goal
Pounds
A.I.
per acre
0.5
2.0
2.0
2.0
Application Rate
(lb/A)
Gallons
GoalK2E
per acre
0.25
1.00
1.00
1.00
Perchlorethylene
lb/acre-/
0.00042
0.00167
0.00167
0.00167
gm/acre^'
0.19
0.76
0.76
0.76
a/ Rohm and Haas, 1978. p. 580 (modified). Assumes 200 ppm PCE in GoalR2E.
b/ 8.34 Ib./gallon/acre x 2 x 10~4 = 1.67 x 10"3 Ib PCE/acre.
c/ 1.67 x 10~3 Ib PCE/acre x 454 gm/lb. = 0.76 gms PCE/acre.
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Goal 2E and PCE Spray Rates, by Crop—'
a/
Goal Spray Rate
Crop
Soybeans
Field
Tree Fruit/Nuts
Conifers
Volume
(gal. /acre)
20
10
75
20
Weight-/
(gm/acre)
7.57 x 104
3.79 x 104
2.84 x 105
7.57 x 104
PCE Spray Rate
Weight
(gm/acre)
0.19
0.76
0.76
0.76
Concentration
(gm/mg H2O)
2.51 x 10~6
20.05 x 10~6
2.68 x 10"6
10.04 x 10"6
(ppm)
2.5
20.1
2.7
10.0
a/ Rohm and Haas, 1978 (modified). Assumes 200 ppm PCE in Goal 2B.
b/ 1 gallon of H2O weighs 8.34 pounds.
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2. Sample calculations for inhalational, dermal, dietary exposure estimates,
Inhalational grams PCE/acre x volume air inhaled/day-^
Exposure = ~~
(soybeans) volume of air/acre-/ x average body weight
0.19 gm PCE/acre x 14.400 liters/day x 1000 mg/gm
7.4 x 106 liters/acre x 70 kg body weight
5.282 x 10~3 mg/kg bw/day
a/ 1.8 m3 hr x 1000 1/m3 x 8 hr/day = 14.400 liters/day
b/ volume of air/acre = 6 ft x 43,560 ft2 acre x 28.3 I/ft3
= 7.4 x 106 liters of air/acre
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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
2.51 ug/q x 0.048 pintsa/ x 454 g/pint x O.la/ x 1 mg/1000 ug
70 kq bw
7.8 x 10 5 mg/kg bw/day
a/ Values for the amount of liquid contacting applicator's skin (0.048 pints) and
percentage skin penetration (10%) were estimated by the registrant (Rohm and Haas,
1978).
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Appendix B
The comments of the Scientific Advisory Panel and the United States Department
of Agriculture on the Preliminary Notice of Determination Concluding the
Rebuttal Presumption gainst Registration of Pesticide Containing Oxyfluorfen
are presented below in their entirety.
FEDERAL INSECTICIDE, FUNGICIDE, AND RODENTICIDE ACT (FIFRA)
SCIENTIFIC ADVISORY PANEL
Review of Preliminary Notice of Determination
Concluding the Rebuttable Presumption Against
Registration (REAR) of Pesticide Products Containing
Cxyfluorfen (GOAL 2E)
The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific
Advisory Panel has completed review of plans by the Environmental Protection
Agency (EPA) for initiation of regulatory action on pesticide products
containing oxyfluorfen (GOAL 2E) under the provisions of Section 6(b)(2) of
FIFRA, as amended. The review was completed in an open meeting held in
Arlington, Virginia on March 13-14, 1981. The following Panel members were
present for the review: Drs. Torgeson, Doull, Metcalf, and Davies.
Maximum public participation was encouraged for the review. Public notice of
the meeting was published in the Federal Register on Wednesday, April 27,
1981. In addition, telephone calls were received from and mailings sent to the
general public who had previously expressed an interest in activities of the
Panel.
Written and oral statements were received from technical staff and
representatives of the Environmental Protection Agency. A written statement
was received from Rohm and Haas Company, the registrant for oxyfluorfen.
Company representatives also participated extensively in the discussion.
In consideration of all matters brought out during the meeting and careful
review of all documents presented by the Agency and other parties, the Panel
unanimously submits the following report:
Scientific Advisory Panel Report on
Oxyfluorfen (GOAL 2E)
The Panel concurs with the Agency's proposed decision to conclude the
Rebuttable Presumption Against Registration (RPAR) of Oxyfluorfen (GOAL 2E)
on the grounds that the oncogenic hazard from perchloroethylene (PCE) contained
in the compound is no longer sufficient to warrant the denial of a conditional
registration for various uses.
-------
However, the Panel has a number of serious concerns with oxyfluorfen not
related to the oncogenic hazard of PCE and wishes to bring these to the
attention of the Agency. These concerns are:
1. The persistence of oxyfluorfen and its possible bio-magnification in the
food chain* This concern is based on Japanese data on related compound's"
which indicate a bioaccumulation effect.
2. The adequacy of testing of oxyfluorfen's potential teratological effects.
The Panel expresses the belief that it is necessary to make special efforts
to determine that no teratological problems exists with all the diphenyl
ether class of chemicals. The Panel thus recommends that additional
teratological testing be conducted, with e.g. nitrofen being used for a
positive control as a comparison.
3. The identification of the various inert ingredients in oxyfluorfen and
their potential adverse effects on the environment. The Panel notes that
there is an impurities level of 28 percent in oxyfluorfen technical
material, and states its belief that considerably more information is
needed on the potential effects of these impurities.
The Panel further notes that although oxyfluorfen is intended initially as
a specialty herbicide with relatively low usage planned, nonetheless,
the potential exists for much greater use, e.g. as a replacement for
nitrofen, and therefore one must be concerned over potential health effects
on a broader scale.
In conclusion, the Panel reconmends that monitoring studies be designed
and carried out in order to clarify any adverse environmental effects of
the use of oxyfluorfen.
FCR THE CHAIRMAN:
Certified as an accurate Report of Findings:
Philip H. Gray, Jr.
Executive Secretary
FIFRA Scientific Advisory Panel
DATE: June 19, 1981
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July 6, 1981
Mr. Edwin L. Johnson (TS-766C)
Acting Deputy Administrator for
Pesticide Programs
U. S. Environmental Protection Agency
Washington, D. C. 20460
Dear Ed:
This is the U. S. Department of Agriculture's response to
the U. S. Environmental Protection Agency's (EPA) Preliminary
Notice of Determination Concluding the Rebuttable Presumption
Against Registration of the pesticide chemical oxyfluorfen
(GOAL).
We concur with the Agency's conclusions that the benefits
from the use of this chemical are biologically and economically
meaningful to agricultural production. We have used Goal in
our witchweed program over the past three years. Where it
has been used, control of witchweed has been excellent
lasting from six weeks to full season without observable
adverse effects on corn or other aspects of the environment.
Goal is rated as the best of the new herbicides for use in
forest nurseries. The indications are that it will become a
very important tool because it can be applied over the top
of five-week old seedlings without any noticeable phytotoxicity
and because of the season-long control the material provides.
We agree with the requirement to use a respirator during the
mixing, loading and application of oxyfluorfen until the
registrant can more accurately assess inhalation exposure;
however, we are concerned that the requirement for respirators
makes no differentiation between methods of application. In
many forest nurseries, pesticides are applied through
automatic watering systems which would result in little or
no applicator exposure. In less sophisticated nurseries the
material is applied with a directed spray which should
result in low inhalation exposure. We are hopeful that the
additional toxicology studies that the agency has requested
from the registrant will demonstrate that the use of respirators
is not necessary. If it is determined that the use of
respirators is necessary, we suggest that consideration be
given to evaluating protective equipment that poses minimal
discomfort in hot, humid climate. As we have pointed out in
the past, the use of respirators in many areas of the U. S.
poses problems of discomfort due to heat and humidity.
In these climatic conditions applicators and other support
personnel are often reluctant to use them, regardless of
regulatory requirements. It has been suggested that in
certain high temperature situations the hazards associated
with the use of respirators may be more immediate and
dangerous than the hazard due to chemical exposure which the
use is intended to prevent.
-------
We would recommend followup action that would substantiate
that respirators significantly lower exposure during application
and that they are mitigating the problem. Research is
needed to devise protective measures suitable for hot
weather.
If we can be of assistance in developing needed exposure
data, please advise.
Sincerely,
Barry R. Flamm
Director
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