United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508W)
EPA738-F-99-019
December 1999
&ERA R.E.D. FACTS
Isofenphos
Pesticide
Reregistration
All pesticides sold or distributed in the United States must be registered
by EPA. Registration decisions are based on scientific studies showing that the
pesticide can be used without posing unreasonable risks to people or the
environment. Because of advances in scientific knowledge, the law requires
that pesticides which were first registered before November 1, 1984, be
reregistered to ensure that they meet today's more stringent standards.
In evaluating pesticides for reregi strati on, EPA obtains and reviews
studies from pesticide producers that are conducted to elucidate the human
health and environmental effects of each pesticide. To implement provisions of
the Food Quality Protection Act of 1996 (FQPA), EPA considers issues
specific to infants and children, the aggregate exposure of the public to
residues of the pesticide from all sources, and the cumulative effects of the
pesticide and other compounds with a common mechanism of toxicity. The
Agency develops mitigation measures or regulatory controls needed to reduce
each pesticide's risks. EPA reregisters pesticides that meet the safety standard
of FQPA and can be used without posing unreasonable risks to human health
or the environment.
Isofenphos, an organophosphate (OP) pesticide (known in chemical
nomenclature as 1-methylethyl 2-((ethoxy((l-
methylethyl)amino)phosphinoyl)oxy)benzoate and designated as EPA case
number 0105), was scheduled for a reregi strati on decision in 1999.
Accordingly, EPA reviewed the existing database and developed preliminary
human health and ecological risk assessments. In 1998, a public docket was
opened and initial steps were taken to review Isofenphos along with the other
organophosphate pesticides. Before EPA could complete the reregi strati on
process, however, the basic producer of the pesticide gave official notification
that they would no longer support Isofenphos through reregistration. EPA
then took the necessary administrative steps to process a request to voluntarily
cancel a pesticide, as discussed below in the History section.
The following information is based on an abbreviated review of the
existing information on Isofenphos. As a result of the voluntary cancellation of
the technical grade product, a final review for reregistration was not
completed. The preliminary risk assessments were not revised, for example, as
has been the case for the other organophosphate pesticides undergoing
reregistration and tolerance reassessment.
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Use Profile
History
Human Health
Assessment
Isofenphos, marketed under the basic producer's trade name Oftanol, is
currently used in the United States on turf and ornamental trees and shrubs to
control white grubs, mole crickets, and other insects (mostly subterranean
species). According to recent usage data, about 60% of the Isofenphos active
ingredient produced annually is used on golf courses; the remainder is used on
residential and public turf sites.
Isofenphos, the common name for this phenyl derivative,
organophosphorus insecticide, was first registered in the United States in 1980
by Bayer Corporation for use on corn for control of the corn rootworm. In
recent years, all of the food uses and the various residential indoor uses
(including the termiticide use) were dropped by the basic producer. As
mentioned above, the remaining turf and ornamental uses of the pesticide are
now no longer supported. The Agency was informed that the availability of
pesticide alternatives persuaded the basic producer to discontinue
manufacturing the technical material.
As required under the pesticide law, EPA announced in the Federal
Register on January 15, 1999 (64 FR 2642), that the registrant who supports
Isofenphos had requested voluntary cancellation. A second notice published in
the Federal Register on May 26, 1999 (64 FR 28471), finalized that action and
approved the registrant's phase out plan. The public, given 60 days to
comment on the request for voluntary cancellation and the proposed phase out
plan, provided no objection. The registrant has been granted various existing
stocks provisions, as detailed in the final Federal Register cancellation notice.
All food tolerances for Isofenphos have been revoked (effective January 1999).
Toxicity
Although the human health assessment was not completed for
Isofenphos, some preliminary conclusions were reached during the toxicology
review. The toxicological database is otherwise adequate to support the
reregistration of Isofenphos. Acute oral toxicity studies in male and female
rats indicate that, like other organophosphate pesticides, oral exposure to
Isofenphos induces cholinesterase inhibition. Acute toxicity categories, which
are classified as I (most toxic) through IV (least toxic), included Category I for
acute oral and dermal toxicity; Category II for inhalation toxicity; Category III
for acute eye irritation; and Category IV for acute dermal irritation.
Isofenphos is classified as a Group E carcinogen (that is, there was no evidence
of carcinogenic potential in long-term studies in rats and mice).
Dietary Exposure
In the preliminary human health risk assessment, acute and chronic
dietary (food source) evaluations were not conducted because at that time
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there were no Isofenphos products registered for food or feed uses.
Although there are no food or feed residue concerns, EPA was concerned
about the potential for exposure to humans through the consumption of
drinking water containing Isofenphos residues. The Agency evaluated the
acute and chronic exposure possibilities. Using cholinesterase inhibition in the
rat as the toxicological endpoint, EPA initially established the acute reference
dose (RfD) (also commonly referred to as the population adjusted dose
(PAD)) at 2 mg per kilogram of body weight per day (mg/kg/day). The
purpose of the endpoint was to assess the acute dietary risk resulting from
exposure to potentially contaminated drinking water. This value was based on
the lowest observed effect level (LOEL) of 2.0 mg/kg/day from an acute
neurotoxicity study in the rat. The study had not determined the conventional
no observed effect level (NOEL). Additionally, in the absence of a
developmental neurotoxicity study the Agency initially decided to retain the
10X FQPA safety factor, resulting in a total uncertainly factor of 3000.
EPA also established the chronic dietary RfD using the NOEL of 0.08
mg/kg/day from a 2-generation reproductive toxicity study in the rat. As
before, the toxic effect observed in test animals was cholinesterase inhibition
and the preliminary risk assessment described the use of an uncertainly factor
of 1000, resulting in a chronic dietary RfD (or chronic PAD) of 0.00008
mg/kg/day.
Subsequent to the public release of the preliminary risk assessments,
EPA reevaluated the selection of the 10X safety factor required by FQPA for
Isofenphos in a comprehensive report for all organophosphates. While the
preliminary human health risk assessment chapter retained the 10X factor, the
comprehensive report recommended retaining only a 3X factor. This would
have resulted in an adjustment to the RfDs or PADs discussed above.
In the drinking water risk assessment, modeling data were used for
estimating surface and ground-water exposure. The modeled values from the
preliminary assessment suggest that Isofenphos could pose a drinking water
concern. However, the Agency concluded that the limited use associated with
Isofenphos was not expected to impact water resources through labeled uses.
Thus, EPA does not expect Isofenphos exposure to humans through drinking
water.
Occupational and Residential Exposure
In the preliminary human health risk assessment, the Agency used the
same acute oral neurotoxicity study as was used for the acute dietary
assessment for assessing the short-term or residential dermal exposure risk (1-7
days)(see the previous discussion). For the intermediate term occupational or
residential risk (one week to several months), a NOEL of 0.06 mg/kg/day
(males) was obtained using a subchronic neurotoxicity screening study in the
rat. These assessments assumed that 100% of Isofenphos would be dermally
absorbed. The inhalation component of exposure was also added to derive a
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total or aggregate exposure value for short and intermediate term exposure
situations. No long-term/chronic exposures were expected from the use of
Isofenphos. EPA used surrogate exposure data to estimate occupational and
residential exposure to Isofenphos.
In general, EPA found that most occupational and residential exposure
scenarios were of concern. The preliminary risk assessment provided exposure
estimates to mixer/loaders, applicators and residents of such a magnitude that
EPA would have pursued extensive exposure mitigation had the registrant not
voluntarily canceled the pesticide. Post-application exposure scenarios were
also of concern.
Environmental
Assessment
Additional Data
Required
The preliminary ecological risk assessment found that Isofenphos is toxic
to birds, mammals, beneficial insects, freshwater and estuarine/marine fish, and
aquatic invertebrates. When considering the pesticide's toxicity and exposure
potential to non-target organisms, EPA found that acute and chronic levels of
concern were exceeded for terrestrial animals and aquatic invertebrates.
Chronic levels of concern were also exceeded for freshwater and
estuarine/marine fish.
The environmental fate of Isofenphos is understood relatively well, but
the Agency's knowledge of some aspects is still incomplete. While sufficiently
persistent (with soil half-lives up to one year and field dissipation half-lives
ranging from weeks to months), Isofenphos is not likely to move appreciably
through the soil to ground water (unless ground water is particularly shallow).
On the other hand, EPA believes that Isofenphos can be expected to move to
surface water via runoff. As mentioned earlier, however, EPA does not believe
that the limited use of the pesticide would lead to residues in drinking water.
Isofenphos' major degradate, Isofenphos oxon, is likely to be as toxic as
the parent chemical. However, the persistence and fate of Isofenphos oxon is
not known.
There are a number of outstanding data requirements for Isofenphos. At
a minimum, a developmental neurotoxicity study, a 21-day dermal toxicity
study in the rat (or dermal absorption study), an aerobic soil metabolism study
(on a range of soil types), an aerobic aquatic metabolism study, additional
environmental fate studies on the degradate Isofenphos oxon, and an
estuarine/marine invertebrate chronic toxicity study would have been required
if this chemical were to have continued with reregi strati on.
Conclusion
Voluntary cancellation is being accomplished in 3 steps:
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For More
Information
- Certain product registrations were canceled effective May 26, 1999. Sale
and use of existing stocks is permitted until stocks are exhausted.
- One product registration (Oftanol 2 insecticide) was canceled effective
September 30, 1999. The registrant may sell and distribute existing stocks for
one year after that date. Existing stocks already in the hands of dealers and
users can be distributed, sold, and used until these stocks are exhausted.
- Oftanol Technical will be canceled effective December 31, 1999. The
registrant (Bayer) will discontinue any further sales or distribution of the
technical product after that date. Sales in 1999 are limited to the level of 1998
sales.
For more information about EPA's pesticide reregi strati on program or
the pesticide Isofenphos, please contact Dean Monos at the Special Review
and Reregistration Division (7508C), OPPTS, U.S. EPA, Washington, DC
20460; telephone 703-308-8074.
Electronic copies of this fact sheet and other REDs are available on the
Internet. Please see http://www.epa.gov/REDs. The Isofenphos preliminary
human health and ecological risk assessments are available at
http://www.epa.gov/pesticides/op/isofenphos.htm.
For information about the health effects of pesticides, or for assistance in
recognizing and managing pesticide poisoning symptoms, please contact the
National Pesticides Telecommunications Network (NPTN). Call toll-free
1-800-858-7378, between 9:30 am and 7:30 pm Eastern Standard Time, seven
days a week. The NPTN website is http://www.ace.orst.edu/info/nptn.
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