Fluoroacetamide (Compound 1081)
Position Document 2
Special Pesticide Review Division
Office of Pesticide Programs
U.S. Environmental Protection Agency
-------
CONTENTS
Page
I. Introduction.... 1
A. Background 2
B. Regulatory History. 3
C. Basis of Rebuttable Presumption. 3
1. Lack of Emergency Treatment 4
2. Acute Toxicity to Mammalian and Avian Species.... 4
3. Significant Reduction to Populations of Nontarget
Organisms and Fatalities to Members of Endangered
Species • • 5
II. Rebuttal Analysis 5
A. Risk Criterion: Lack of Emergency Treatment 7
1. Availability of Emergency Treatment 7
2. Time Factor 9
3* Dose Likely to be Consumed in an Accident 10
4. Likelihood of Exposure to Compound 1081... 11
B. Risk Criteria: Acute Toxicity to Mammalian and
Avian Species; Significant Reduction of Nontarget
Populations and Fatalities to Members of Endangered
Species • • 12
C. Amendment of the Label 13
1. Site Clarification 13
2. Other Restrictions 14
a. Use by Certified Commercial Applicators 14
b. Preparation, Storage, and Disposal 14
III. Discussion: Rationale for Label Amendments 15
A. Site Clarification • 15
B. Other Restrictions 16
IV. Conclusions •• 16
Appendix I. References 18
Appendix II. Rebuttal Submissions • 19
-------
Acknowledgements
Writing Staff 024279
Henry Craven, (formerly Project Manager), EEB, HED, OPP
Bill Coniglio, formerly Project Manager, SPRD, OPP
Carol Lang ley, Project Manager, SPRD, OPP
Karen O'Steen, formerly Writer/Editor, SPRD, OPP
Paul Parsons, Writer/Editor, SPRD, OPP
EPA Project Support Team
Richard Bozof, OGC
Tom Edwards, TB, HED, OPP
Tim Gardner, SPRD, OPP
Roger Holtorf, EAB, BFSD, OPP
Jim Horst, EAB, BFSD, OPP
Cara Jab Ion, OGC
Al Jackson, formerly C&E, OPP
John Leitzke, EEB, HED, OPP
Ray Matheny, EEB, HED, OPP
C. Dudley Mattson, EAB, BFSD, OPP
Bill Miller, RD
Dan Peacock, RD
Dick Schmidt, RGB, HED, OPP
Dick Tucker, OPTS
EPA Pesticide Chemical Review Committee (PCRC)
Marcia Williams, Chairperson, SPRD, OPP
Richard Hill, OPTS
Allen Jennings, 3RD, 0PM
Donna Kuroda, OHEE, ORD
John Neylan, PTSED, OE
Michael Winer, OGC
-------
I. Introduction
The Federal Insecticide, Fungicide, and Rodenticide
Act (FIFRA) as amended, September 30, 1978, and its
regulations require the Environmental Protection Agency
(EPA) to review the risks and benefits of the uses of
registered pesticides. This review process is set forth
in 40 CFR 162.11. These regulations describe various
risk criteria and provide that a Rebuttable Presumption
Against Registration (RPAR) or continued registration shall
arise if the Agency determines that any of these criteria
have been met. Once a rebuttable presumption has arisen,
registrants, applicants, and interested persons may submit
evidence in rebuttal or in support of the presumption.
These people may also submit evidence on the economic,
social, and environmental benefits of any use of the
pesticide. The Agency then determines whether the pesticide
may be regulated so as to achieve a balance between risks
and benefits.
The Agency formally initiated this review for all
products containing fluoroacetamide (Compound 1081) by
publishing an RPAR notice in the Federal Register [41 FR
(232): 52792-809, December 1, 1976]. This document presents
the Agency's analysis of information submitted by concerned
individuals on the risks from the continued use of Compound
1081 and presents a discussion of label amendments proposed
by the sole-remaining registrant.
-------
With these new use restrictions on the label, Compound
1081 does not meet or exceed any of the risk criteria set
forth in 40 CFR 162.11. Therefore, the Agency has determined
that the presumption against Compound 1081 has been rebutted
and the registration of Compound 1081 should be continued*
A. Background
Sodium fluoroacetate (Compound 1080) was first used
as a rodenticide in the 1940's. Fluoroacetamide, or Com-
pound 1081, was developed in the early 1950's. Although
Compound 1080 and Compound 1081 are different compounds, the
chemical and pharmacological similarities of these two
chemicals suggest that they would present similar hazards.
Some of the Agency's conclusions about the hazards of
Compound 1081 are based in part on data available for
Compound 1080. The chemical formulas for Compound 1080 and
Compound 1081 are:
HO HO
t n i it
F-C-C-ONa F-C-C-NH
» ' 2
H H
Compound 1080 Compound 1081
Although both compounds are systemic insecticides,
Compound 1080 and Compound 1081 are currently registered in
the United States only as rodenticides. In other countries
Compound 1081 has been used to control aphids on sugarbeets,
beans, and strawberries.
-2-
-------
B. Regulatory History
When Position Document 1 was issued, Compound 1081 was
registered for use in two products. In 1978, the manufacturer
of one, Fluorakil 100, requested a voluntary cancellation.
There is currently one Federally-registered Compound
1081 product, Fluorakil 90, which is used with cereal grain
as bait to kill Norway rats and roof rats. It is manufactured
by the ArCHEM Corporation and was originally registered
on May 6, 1972 only for use against rats in sewers. The
label specified that the product was effective against rats
in sewers, but did not specifically restrict use of the
product to a particular site. The registrant submitted to
the Registration Division a proposed label with amendments
which would clarify the use site restrictions and which
would modify the use directions on the original label. This
proposed label was approved by the Registration Division
November 2, 1979.
C. Basis of Rebuttal Presumption
The rebuttable presumption of Compound 1081 was
based on the Agency's determination that products containing
Compound 1081 met or exceeded three risk criteria: lack of
emergency treatment [40 CFR 162.ll(a)(3)(ill)], acute
toxicity to mammalian and avian species [40 CFR 162.11
(a)(3)(1)(B)(1) and (2)], and significant reduction of
-3-
-------
populations of nontarget organisms and fatalities to members
of endangered species [40 CFR 162.11(a)(3)(11)(C)].
The following three sections explain each criterion
further.
1. Lack of Emergency Treatment
The primary factors cited by the Agency as supporting
an RPAR based on this risk criterion were:
- The Compound 1081 labels did not specifically prohibit
use of the product around domestic dwellings where
children are likely to be exposed to it.
• If ingested, symptoms of poisoning might not occur
until after Compound 1081 has been absorbed into the
bloodstream. Once a substantial dose of Compound 1081
is absorbed into the bloodstream, the victim inevitably
dies despite emergency treatment attempts.
- Monoacetin, a potentially effective drug for treating
Compound 1081 poisoning, is not generally available
for medical use In the United States.
2. Acute Toxlclty to Mammalian and Avian Species
The Agency determined that lethal amounts of Compound
1081 bait may be consumed by mammals or birds and therefore
-4-
-------
Compound 1081 is hazardous Co nontarget species. In addition,
the Agency determined that Compound 1081 poses a hazard to
predators which feed on sick or dead animals that have
consumed the poisoned bait. These determinations were
based on LD... data for Compound 1080.
3. Significant Reduction of Populations of Nontarget
Organisms and Fatalities to Members of Endangered
Species
The Agency concluded that the use of Compound 1081
reduces populations of nontarget organisms and kills members
of endangered species because:
- Compound 1081 is extremely toxic to vertebrates.
- Baits treated with Compound 1081 might be applied over
a fairly large geographic area and might be consumed
by many types of animals.
- Poisoned bait might be applied in areas known to be
inhabited by endangered species.
II. Rebuttal Analysis
After the Compound 1081 RPAR was issued, registrants and
other interested people were invited to review the data upon
which the RPAR was based and to submit information to
-5-
-------
support or refute the Agency's findings; respondents could
also submit information on the economic, social, and
environmental benefits derived from the use of Compound
1081.
According to 40 CFR 162.11(a) (4) (i), and (ii), a
presumption against registration may be rebutted either by
proving that anticipated exposure to the pesticide, when
considered with proposed restrictions and directions for
use, is not likely to result in any significant acute
effects in applicators, users, or non-target animals or is
not likely to result in significant chronic adverse effects
in humans or the environment.
Fourteen respondents, listed in Appendix II of this
document, submitted information on Compound 1081. Eight
respondents [#24, #5, #46, #32, #40, #36, #41, and #48
(30000/8)] expressed support for the continued registration
or reregistration of Compound 1081 for commensal rodent
control and attempted to rebut the risk criteria. Six
respondents C#6l, #50, #55, #57, #56, and #42 (30000/8)3
stated that the registration of Compound 1081 should be
cancelled because it poses a hazard to nontarget wildlife
species, but they provided no new information in support of
their position.
The Agency concluded that the eight respondents supporting
continued registration or reregistration of Compound 1081 did
not successfully rebut any of the risk criteria. Nevertheless,
-6-
-------
the Agency determined that if certain restrictions on use
and modifications of use directions on the label were agreed
to by the registrant, anticipated exposure of humans and
nontarget species of wildlife and domestic animals would be
reduced to insignificant levels* Since the registrant
voluntarily agreed to, these label revisions, the Agency
concludes that the presumption has been rebutted.
A discussion of the Agency's analysis of the rebuttals
is given below according to risk criteria. Then the new
restrictions on use and modification of use directions on
the label will be described.
A. Risk Criterion; Lack of Emergency Treatment
Respondents did not show that commonly available medical
treatment in the U.S. can prevent persons from dying
after accidental ingestion of Compound 1081. Those rebuttal
submissions which addressed this risk criterion will now be
discussed.
1. Availability of Emergency Treatment
One respondent asserted that many persons who received
prompt first aid treatment have recovered after Ingesting
supposedly lethal amounts of Compound 1080 [Fitzwater, 1977
(46:30000/8)]. This assertion warrants some consideration
because it could indicate that people receiving prompt
first aid treatment after ingesting lethal amounts of
Compound 1081 might also recover, since Compound 1080 and
-7-
-------
Compound 1081 are pharmacologically similar. However, in
the recoveries cited, the doses were not documented, so the
amounts of Compound 1080 ingested may have been sublethal,
thus making successful treatment possible. In addition, not
only have the majority of people who have ingested Compound
1080 died, but in the only documented incident of Compound
1081 poisoning, all three victims died. Therefore, while
there have been some recoveries from Compound 1080 poisoning,
the overall case history indicates that first aid treatment
is not effective for Compound 1081 poisoning.
The same respondent suggested that monoacetin and
acetamide may be effective emergency treatments for Compound
1081 poisoning. The Agency has recognized that monoacetin is
potentially effective for treating Compound 1081 poisoning,
but the respondent did not attempt to refute the Agency's
finding that this treatment is not readily available in
emergency situations. In addition, the respondent failed to
demonstrate that acetamide is effective in treating human
cases of Compound 1081 poisoning. One cited article
(Phillips and Worden, 1957) demonstrated only that acetamide
may be effective in treating Compound 1081 poisoning in
rats. The respondent cited a second reference (Moore, 1950)
to support the contention that acetamide has been effective
in Japan for treating humans poisoned with Compound 1081.
However, the reference contained no information which
actually supported this contention.
-8-
-------
Another respondent indicated that antidotes are described
in the literature [National Pest Control Association, Inc.,
1977 (48:30000/8)]. A more recent edition of the clinical
toxicology text cited in support of this statement (Clinical
Toxicology of Commercial Products, 4th Edition) indicated
'that monoacetin has proved to be an effective antidote for
Compound 1080 poisoning in monkeys, but stated that this
treatment is not available for the pharmaceutical market
(Gosselin et alt, 1976). In addition, this reference
indicated that while acetamide and ethyl alcohol may be of
value in treating Compound 1080 poisonings, these treatments
have not been clinically tested and no treatment protocol
has been established for using these chemicals. In conclusion,
no rebuttal submissions refuted the Agency's determination
that emergency treatment for Compound 1081 poisoning was not
readily available.
2. Time Factor
No respondent successfully refuted the Agency's
determination that it is important to obtain emergency
treatment Immediately after ingestion of Compound 1081 and
that a time delay could be fatal. The Agency indicated in
Position Document-1 that time delays could be expected to
cause fatalities because: first, Compound 1081 is rapidly
absorbed from the gastrointestinal tract; second, once a
lethal dose is absorbed into the bloodstream, treatment is
invariably unsuccessful; and third, lack of symptoms prior
to absorption of a fatal dose into the bloodstream may
prevent the victim from obtaining treatment in time.
-9-
-------
One respondent indicated that the time lag between
ingesting the poison and the appearance of symptoms is
greater for Compound 1081 than Compound 1080 [Fitzwater,
1977 (46:30000/8)]. The references cited verify this for
laboratory animals (Phillips and Worden, 1957). They indicated
that no information regarding the time lag in humans was
available at the present time. However, even if the
greater time lag were present in humans,this would not
necessarily mean that Compound 1081 is absorbed more slowly
from the gastrointestinal tract than Compound 1080. Phillips
and Worden indicated that the slower action of Compound 1081
is due to a slower biochemical conversion to a physiologically
poisonous intermediate product rather than a delay in its
absorption into the bloodstream. Since no effective antidote
is readily available, the Compound 1081 must be flushed from
the gastrointestinal tract before absorption into the
bloodstream or the victim will die. Because symptoms do
not appear immediately, a victim may delay seeking treatment .
until a fatal dose has already been absorbed into the
bloodstream. Therefore, no rebuttal submission refuted the
presumption regarding the time factor involved in seeking
emergency treatment*
3. Dose Likely to Be Consumed in an Accident
No respondent attempted to rebut the Agency's determi-
nation that a typical dose of Compound 1081 which could be
accidentally Ingested would be fatal.
-10-
-------
4. Likelihood of Exposure to Compound 1081
Two respondents maintained that accidental exposure
to Compound 1081 has been very rare [Fitzwater, 1977
(46:30000/8); Spear, 1977 (48:30000/8)]. They pointed out
that during the last 22 years only one incident resulting in
death is known to have occurred in the United States; in
1976 three children died after eating Compound 1081-treated
cookies, which they obtained from the unlocked truck of a
pest control operator* Nevertheless, the Agency is concerned
about even very infrequent human exposure to this pesticide
because it is so highly toxic and because an effective
emergency treatment is not available. Non-applicators,
especially children, could come into contact with Compound
1081 if the pesticide were stored, transported, or applied
negligently. Applicators could also be exposed if storage,
mixing, or application was not performed according to
appropriate safeguards*
In its rebuttal submission, the National Pest Control
Association indicated that any risk of exposure posed
by use of Compound 1081 was due to the fact that the Agency
had not restricted the pesticide to use by Certified Commercial
Applicators only, and that the Agency had not specifically
limited the use of the pesticide for sewer rat control
[Spear, 1977 (48:30000/8)]. The Agency subsequently classified
Compound 1081 for restricted use by Certified Commercial
Applicators [43 FR (28):5782-91, Feb. 9, 1978]. In addition,
Compound 1081 is in fact registered only for control
-11-
-------
of rats in sewers* However, the Agency agrees that the
original label for Compound 1081 was unduly vague about the
permissible site and pest.
At the time the Agency reviewed these rebuttal sub-
missions, the Agency concluded that the possibility of
exposure to Compound 1081 was still cause for concern unless
additional use restrictions and directions were prescribed.
B* Risk Criteria; Acute Toxicity to Mammalian and
Avian Species; Significant Reduction of Nontarget
Populations and Fatalities to Members of Endangered
Species
Respondents did not submit any data to show that
Compound 1081 is not acutely toxic to mammalian and avian
species. However, three respondents maintained that
Compound 1081 does not pose a substantial hazard to nontarget
organisms, including members of endangered species, when
used to control rats in sewers [Arbaugh, 1976 (24:30000/8);
Fitzwater, 1977 (46:30000/8); and Spear, 1977 (48:30000/8)].
However, because the labels for Compound 1081 products
which were in effect when the RPAR was issued did not
clearly describe the registered use, it was possible that
these products could have been used at sites other than
sewers under the false impression that such use was permissible.
Such use could pose a risk to nontarget or endangered
species. In addition, even if Compound 1081 were used only
in sewers, exposed rat carcasses could pose some hazard to
-12-
-------
domestic cats and dogs. Therefore, the Agency concluded that
this risk criterion was not rebutted, unless additional use
restrictions and directions were prescribed.
C. Amendment of the Label
After completion of its review of the rebuttals, the
Agency determined that the presumption against Compound 1081
had not been rebutted even though the pesticide had been
classified for restricted use by Certified Commercial
Applicators. The Agency concluded, however, that if the
registrant agreed to certain use restrictions and modified
use directions on the label, the presumption would be
rebutted because the likelihood of exposure to humans,
nontarget mammals and birds, and endangered species would
then be very remote. The rationale for the label restrictions
is discussed in Section III of this document.
The use restrictions and modified use directions
are:
1. Site Clarification
The labels should be modified so that it is clear that
Compound 1081 may only be used in sewers to control roof
rats and Norway rats. The label should also indicate
that the location of application inside the sewers should be
selected such that entry by unauthorized personnel is
unlikely.
-13-
-------
2. Other Restrictions
a* Use by Certified Commercial Applicators
The label should be amended to indicate that Compound
1081 may not be made available to or used by anyone other
than Certified Commercial Applicators or persons under the
supervision and in the physical presence of a Certified
Commercial Applicator.
b. Preparation, Storage, and Disposal
The label should indicate that baits must be prepared
and mixed at the facility of the applicator and that baits
must not take the form of any food normally consumed by
humans. (Baits were previously in the form of wafers or
cookies.) Persons preparing the formulation from the dry
concentrate must wear gloves and a respirator. Equipment
used to handle and mix Compound 1081 must be identified and
used only for this purpose.
All Compound 1081 baits and containers must be clearly
labeled and kept locked during storage and transport.
Sewer exits in the treatment area must be inspected daily,
and dead animals collected and disposed of by the Certified
Applicator. Control efforts must cease if there is evidence
of unauthorized use of the sewer. At the end of operations,
all unused baits and containers must be picked up and
disposed of by the Certified Applicator. All containers
(which must be triple-rinsed and empty), solutions, baits,
-14-
-------
and poisoned animals muse be disposed of in a landfill which
has been approved by the appropriate local Health or
Environmental Department*
The Agency concluded that these specific label restric-
tion would make exposure of humans and of nontarget mammalian
or avain species including endangered species very remote.
III. Discussion; Rationale for Label Amendments
A. Site Clarification
Position Document 1 implied that the labels in effect
at that time permitted Compound 1081 to be used against
rodents in locations other than sewers. The Agency reevaluated
the scope of permissible uses of Compound 1081 and concluded
that the pesticide was registered only for use against rats
in sewers, since this was the only pest and site Indicated
on the labels and proposed in the original applications from
both registrants. However, the Agency determined that much
confusion would be eliminated if the label were amended to
state clearly that the product could be used only for rat
control in sewers. The Agency determined that this restriction
would significantly reduce the risks to nontarget organisms
and endangered species, since these animals, not generally
being found in sewers, would have little or no exposure to
it. Although raccoons and opossums do frequent sewers, no
significant impact on their population at large would be
-15-
-------
expected. Human exposure would be unlikely, since use
around domestic dwellings or barns would be specifically
prohibited.
B. Other Restrictions
The Agency also concluded that the risk of secondary
poisoning to nontarget species, including domestic dogs and
cats, would be significantly reduced by the label amendment
requiring that dead animals be collected dally and dis-
posed of by the Certified Applicator. Secondary poisoning
could occur by chance if a poisoned rat moved outside a
sewer before dying and if the carcass was not found by the
Certified Applicator. However, the Agency concluded that
this situation is unlikely to happen often enough to be of
concern. The risk of accidental human exposure would also
be reduced by the label amendment restricting the use of
Compound 1081 to Certified Applicators.
Restrictions on preparing the formulation and storing
and disposing of baits and poisoned animals would also
contribute to reducing the risk of human exposure to an
insignificant level. The acute toxicity of the chemical
would be the same, but the likelihood of accidental human
exposure would be very low.
IV. CONCLUSIONS
A presumption against registration may be rebutted
by proving that anticipated exposure to a pesticide,
when considered with proposed restrictions and directions
-16-
-------
for use, is not likely to result in any significant acute or
chronic effects in humans, nontarget animals, or the environment,
[40 CFR 162.11(a)(4).J
The registrant for Fluorakil 90 voluntarily proposed
that the restrictions and modified directions for use be
incorporated in the labels of new stocks of the product*
The proposed label was approved November 2, 1979* With
these new use restrictions and modified directions for
use, the presumption concerning the lack of emergency
treatment is rebutted, since the risk of accidental human
poisonings is now very remote and therefore insignificant*
The presumptions concerning acute toxicity to nontarget
avlan and mammalian species, significant reduction in
populations of nontarget species, and fatalities to members
of endangered species are also rebutted because the risk of
exposure to nontarget species, including endangered species,
is now very unlikely. Therefore, the Agency concludes
that the presumption against the registration of Compound
1081 has been rebutted.
If, in the future, other people submit applications
to register a product containing Compound 1081, they will
be required to comply with these new restrictions.
-17-
-------
Appendix I. REFERENCES
1* Federal Register, December 1, 1976. Notice of
presumption against registration and continued registra-
tion of pesticide products containing Compound 1080 and
Compound 1081; 41(232):52792-52809.
2. Federal Register, February 9, 1978. Optional
Procedures for Classification of Pesticide Uses by
Regulation; Pesticide Use Restrictions; 43(28):5782-91.
3. Gosselin, R.E. et al., 1976. Clinical Toxicology
of Commercial Products, 4th Edition. The William
and Wilkins Co., Baltimore, MD.
4. Markley, Merle H., (CED), 1977. EPA memo of November
14, 1977 to William Coniglio (SPRD); Analysis of Adequacy
of 1081 Rebuttal.
5. Moore, R., 1950. Summary of "1080" accidents. Rodent
Control Conference, Dallas, Texas. January 31 -
February 2; 4 p.
6. Phillips M.A. and Alastair N. Worden, 1957. The
Mammalian Oral Toxicity of Fluoroacetamide. J. Sci.
Food Agrlc., 8:653-657.
7. Tippens, T.W., September 29, 1978. Letter to Wm.
Miller; Cancellation of registration.
-18-
-------
Appendix II. REBUTTAL SUBMISSIONS COMPOUND 1081
1. Arbaugh, Howard, December 31, 1976; ArChem Corporation,
Portsmouth, Ohio; (24:30000/8).
2. Deck, Errett, March 7, 1977; U.S. Department of Agricul-
ture, Washington, D.C.; (5A:30000/8).
3. Deck, Errett, March 9,, 1977; U.S. Department of Agricul-
ture, Washington, D.C.; (58:30000/8).
4. Edmiston, Beula, March 3, 1977; Committee for the
Preservation of the Tule Elk, Los Angeles, California;
(61:30000/8).
5. Fitzwater, William D., March 2, 1977; BioLOGIC Consultants,
Albuquerque, New Mexico; (46:30000/8).
6. Grant, Allan, December 28, 1976; American Farm Bureau
Federation, Park Ridge, Illinois; (32:30000/8).
7. Harkness, Bernard J., December, 31, 1976; Montana
Farm Bureau Federation, Bozeman, Montana; (40:30000/8).
8. Hinkle, Maureen K. , March 7, 1977; Environmental
Defense Fund, Washington, D.C.; (50:30000/8).
9. Kopecky, Edward F., March 1, 1977; Cedar Rapids,
Iowa; (55:30000/8).
10. Lavigne, J.H., January 4, 1977; Fike Chemicals,
Incorporated, Nitro, West Virginia; (36:30000/8).
11. Randall, Dick, March 7, 1977; Defenders of Wildlife,
Washington, D.C.; (57:30000/8).
12. Senske, William M., February 8, 1977; Senske Weed
and Pest Control, Spokane, Washington; (41:30000/8).
13. Smerdon, Glenn E., March 10, 1977; State Department
of Agriculture, Olymphia, Washington; (56:30000/8).
14. Spear, Philip J., March 4, 1977; National Pest Control
Association, Vienna, Virginia; (48:30000/8).
15. Weber, William J., February 9, 1977; Leesburg, Florida,
(42:30000/8).
-19-
------- |