United States
Environmental Protection
Agency
Office of Prevention, Pesticides
And Toxic Substances
(7508W)
EPA-738-F-93-007
September 1993
R.E.D. FACTS
Pesticide
Reregistration
Use Profile
Regulatory
History
Daminozide
All pesticides sold or distributed in the United States must be
registered by EPA, based on scientific studies showing that they 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 years ago be reregistered to ensure that they meet
today's more stringent standards.
In evaluating pesticides for reregistration, EPA obtains and reviews a
complete set of studies from pesticide producers, describing the human
health and environmental effects of each pesticide. The Agency imposes
any regulatory controls that are needed to effectively manage each
pesticide's risks. EPA then reregisters pesticides that can be used without
posing unreasonable risks to human health or the environment.
When a pesticide is eligible for reregistration, EPA announces this and
explains why in a Reregistration Eligibility Decision (RED) document. This
fact sheet summarizes the information in the RED document for
daminozide, or butanedioic acid mono (2,2-diemthylhydrazide), also known
by the trade name Alar.
Daminozide is a systemic growth regulator registered for use on
ornamentals, including potted chrysanthemums and poinsettias, and bedding
plants in enclosed structures such as greenhouses, shadehouses and
interiorscapes. It is formulated as a soluble concentrate and applied as a
pre-plant dip and/or foliar spray.
Daminozide was initially registered as a pesticide in the United States
in 1963 for use on potted chrysanthemums. The first food use, apples, was
registered in 1968. EPA issued a Registration Standard for daminozide in
June 1984 (NTIS PB87-104782), requiring additional product and residue
chemistry, toxicology, worker exposure, ecological effects and
environmental fate data.
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Human Health
Assessment
In July 1984, EPA initiated a Special Review of pesticide products
containing daminozide based on findings that daminozide and its degradate
and metabolite, unsymmetrical dimethylhydrazine (UDMH), were
oncogenic (caused the growth of tumors) at multiple organ sites, in multiple
species and strains of test animals. The Agency issued a Data Call-in in
1986 requiring additional toxicology and worker exposure data. As a result
of the Special Review, the registrant, Uniroyal Chemical Company,
voluntarily cancelled all food use registrations of daminozide on November
14, 1989. EPA revoked the tolerances (maximum residue limits) for these
food uses in March 1990.
EPA continued to evaluate the risks to workers (mixers, loaders and
applicators) posed by the remaining non-food uses of daminozide, and found
that those uses did not pose an unreasonable risk. The Agency allowed the
non-food uses to continue in completing the Special Review of daminozide
in October 1992.
Currently, four products (two end-use, one technical and one
formulation intermediate) containing daminozide are registered in the U.S.
Toxicity
Daminozide is of very low acute and subacute toxicity. It is placed in
Toxicity Category IV, indicating the lowest level of acute toxicity, for oral
and inhalation effects, and is placed in Toxicity Category III, indicating a
slightly greater degree of acute toxicity, for dermal effects. A subchronic
feeding study using rats did not produce any discernable toxic effects.
In carcinogenicity studies using mice, daminozide caused some
increase in the incidence of malignant and benign tumors. UDMH caused a
slight increase in liver tumors in rats, and produced liver vascular tumors
and lung tumors in mice. EPA has classified UDMH as a Group B2,
"probable human carcinogen." Since UDMH is dependent on the presence
of the parent chemical, daminozide also has been classified as a Group B2
carcinogen.
Daminozide produced some maternal toxicity but no developmental
toxicity in rats and rabbits. In a reproduction study using rats, daminozide
caused systemic toxicity at the highest dose levels, but did not cause
reproductive toxicity. Neither daminozide nor UDMH have been shown to
cause mutagenic effects. In metabolism studies, daminozide was rapidly
excreted by minipigs.
Dietary Exposure
There are no longer any registered food or feed uses of daminozide,
and all tolerances have been revoked. Dietary exposure therefore is not
anticipated.
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Occupational and Residential Exposure
EPA performed a detailed analysis of the cancer risk to workers
(mixers, loaders and applicators) from exposure to daminozide and UDMH.
The total risk is a sum of the risk from direct exposure to daminozide
(which is converted to UDMH when it is absorbed through the skin or
lungs), plus the risk from exposure to the UDMH contaminant in
commercial products (which increases in the mixing tank, prior to
application).
EPA estimated risks from dermal and inhalation exposure to
daminozide and UDMH for large greenhouse and small greenhouse uses,
assuming application of fine spray (which would result in the greatest
exposure). The estimated combined cancer risks range from 1.4 in 1
million (for workers in large greenhouses) to 5.8 in 10 million (for workers
in small greenhouses). EPA considers these estimated risks to be
reasonable.
In view of the known toxicological properties of daminozide and
UDMH, however, as well as the likelihood of foliar residues, EPA is
strengthening the current 24 hour Reentry Interval, which allows workers to
reenter treated areas during the 24 hours after application if they wear
protective clothing. The Agency instead is requiring a 24-hour Restricted
Entry Interval, which prohibits reentry to perform hand labor for 24 hours
following treatment except under very narrow circumstances, described in
the Worker Protection Standard (WPS) for Agricultural Pesticides.
EPA also is requiring personal protective equipment (PPE) for early
entry workers, consistent with that required for pesticides classified as
Toxicity Category II for acute dermal toxicity. Post-application exposure to
daminozide is mostly on the hands from handling treated plants. Therefore,
for early entry as allowed by the WPS, level II PPE including chemical-
resistant gloves must be used.
Human Risk Assessment
Daminozide does not pose human dietary risks since food-related uses
are no longer registered and dietary exposure is not anticipated.
Greenhouse workers may be exposed to daminozide dermally or by
inhalation, during or after application of the pesticide to plants. Risks from
this exposure should be mitigated by observing the more stringent 24-hour
Restricted Entry Interval and, in cases where reentry is necessary, by using
the required personal protective equipment including chemical-resistant
gloves. Daminozide is not expected to cause an unreasonable cancer risk to
workers when used in accordance with these requirements, which will be
reflected in product labeling as a result of this RED.
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Environmental
Assessment
Environmental Fate
Daminozide is stable to hydrolysis (it does not decompose readily by
reaction with water); hydrolysis does not contribute significantly to the
dissipation of daminozide in the environment. However, daminozide
degrades rapidly in soil, leaving only volatile compounds and bound
residues, including low levels of the degradate formaldehyde. Thus, its
mobility probably is not a concern. Since registered products are labeled
only for use in confined greenhouse areas, daminozide is not expected to
occur in agricultural runoff or ground water.
Ecological Effects
Since daminozide may be applied only inside greenhouses, eco-toxicity
data were used only to evaluate the hazard to non-target organisms that
could result from misuse or spillage during transport, and to determine
appropriate environmental hazard label statements. Daminozide is
practically non-toxic to mammals, birds and freshwater fish, on an acute
basis. It is slightly toxic to aquatic invertebrates.
Additional Data
Required
Ecological Effects Risk Assessment
Environmental exposure is expected to be minimal when daminozide is
used according to product label directions. Therefore, the ecological risk
from use of daminozide also is expected to be very low.
The generic data base for daminozide is substantially complete.
However, EPA is requiring additional information on a previously
submitted aerobic soil metabolism study as confirmatory data. EPA also is
requiring product-specific data, including product chemistry and acute
toxicity studies, as well as revised Confidential Statements of Formula and
revised labeling for reregistration of pesticide products containing
daminozide.
Product Labeling
Changes Required
All end-use daminozide products must comply with EPA's pesticide
product labeling requirements. In addition:
° Compliance with Worker Protection Standard (WPS) - Any
product whose labeling permits use in the production of an agricultural
plant on any agricultural establishment (farm, forest, nursery or
greenhouse) must comply with the labeling requirements of:
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• PR Notice 93-7, "Labeling Revisions Required by the
Worker Protection Standard (WPS)," and
• PR Notice 93-11, "Supplemental Guidance for PR Notice 93-
7."
Unless specifically directed in the RED, all statements required by
these two PR Notices must appear on product labeling exactly as
instructed in the Notices. Labels must be revised by April 21, 1994,
for products distributed or sold by the primary registrant or
supplementally registered distributors, and by October 23, 1995, for
products distributed or sold by anyone.
° Exclusionary Statement - All end-use product labels must carry
the following statement on the front panel near the product name or
Directions for Use:
"For use only in commercial or research greenhouses or shade
houses."
° Personal Protective Equipment (PPE) Requirements - All end-
use product labeling must carry the following PPE requirements:
"Applicators and other handlers must wear:
—Coveralls over short-sleeved shirt and short pants
—Chemical-resistant or waterproof gloves (*)
—Chemical-resistant footwear plus socks
—Chemical-resistant headgear for overhead exposure
—Chemical-resistant apron when cleaning equipment, mixing, or
loading" (**)
* See Supplement Three of PR Notice 93-7.
** "Mixing" or "loading" may be removed if the product is
formulated as "ready-to-use."
° Entry Restrictions - A 24-hour Restricted Entry Interval (REI) is
required for all uses, for all end-use products. The Personal
Protective Equipment (PPE) for early entry should be that which is
required for applicators of daminozide, except no apron or respirator
is required. These REI and PPE instructions should be inserted into
the standardized statements required by PR Notice 93-7.
• Single active ingredient products - Adopt these entry
restrictions and remove any conflicting ones from labeling.
• Multiple active ingredient products - Compare these entry
restrictions with those on current labeling and retain the more
protective restrictions.
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Regulatory
Conclusion
The use of currently registered pesticide products containing
daminozide in accordance with labeling consistent with the RED and
approved by the Agency will not pose unreasonable risks or adverse effects
to humans or the environment. Therefore, all uses of these products are
eligible for reregistration.
These daminozide products will be reregistered once the product-
specific data, revised Confidential Statements of Formula and revised
labeling are received and accepted by EPA.
For More
Information
EPA is requesting public comments on the Reregistration Eligibility
Decision (RED) document for daminozide during a 60-day time period, as
announced in a Notice of Availability published in the Federal Register. To
obtain a copy of the RED document or to submit written comments, please
contact the Pesticide Docket, Public Response and Program Resources
Branch, Field Operations Division (7506C), Office of Pesticide Programs
(OPP), US EPA, Washington, DC 20460, telephone
703-305-5805.
Following the comment period, the daminozide RED document will be
available from the National Technical Information Service (NTIS), 5285
Port Royal Road, Springfield, VA 22161, telephone 703-487-4650.
For more information about EPA's pesticide reregistration program,
the daminozide RED, or reregistration of individual products containing
daminozide, please contact the Special Review and Reregistration Division
(7508W), OPP, US EPA, Washington, DC 20460, telephone 703-
308-8000.
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 8:00 am and 6:00 pm Central Time, Monday
through Friday.
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