United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7501W)
EPA-738-F-95-025
December 1995
R.E.D. FACTS
Pesticide
Reregistration
Cytokinin
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 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 a
complete set of studies from pesticide producers, describing the human
health and environmental effects of each pesticide. The Agency develops
any mitigation measures or regulatory controls needed to effectively reduce
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 reregi strati on, EPA explains the basis
for its decision in a Reregistration Eligibility Decision (RED) document.
This fact sheet summarizes the information in the RED document for
reregi strati on case number 4107, Cytokinin.
Use Profile
Cytokinin is a group of plant regulators that promote cell division, leaf
expansion and retard leaf aging. Cytokinin is applied to growing crops (field
crops, vegetable crops, small fruits, vines and tree fruit), young trees,
ornamentals, and golf courses to increase fruit size, yield, blossoms,
branching, healthy appearance, and other desirable growth effects.
Cytokinin is comprised of four naturally occurring cytokinins derived from
aqueous extract of seaweed meal — zeatin [6-(4-hydroxy-3-methylbut-trans-
2-enylamino)-purine], N6-methylaminopurine, N6-dimethylaminopurine, and
N6-isopentenylaminopurine — and synthetic cytokinin — kinetin [6-
(furfurylamino)purine]. Cytokinins (i.e. naturally occurring) in aqueous
extracts of seaweed meal, are derived from the following algae: Laminaria
digitata, Laminaria hyperborea, Fucus serratus and Ascophyllum nodosum.
Several, if not all of these species of algal species are consumed by man
and/or livestock. The extracts from these plant species (e. g. the naturally
occurring Cytokinins) are exempt from the requirements of tolerances when
used as plant regulators in or on many raw agricultural commodities (40
CFR 180.1042).
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Formulation Types Registered:
Formulations include a soluble concentrate/liquid (manufacturing use
product), and flowable concentrate, soluble concentrate/liquid, ready-to-use
liquid (end use products).
Methods and Rates of Application:
Cytokinin may be applied by aircraft, irrigation system, ground spray
equipment, seed treatment, or soil incorporation.
Use Practice Limitations:
Preharvest Intervals of 14 or 21 days may be required, depending on
the crop.
The Use Practice Limitations listed below do not apply to all uses on all
products:
"Do not allow rinse water to contaminate streams, ponds and lakes, as
water life may be endangered."
"Do not apply through any type of irrigation system."
"Do not apply to any body of water."
"For terrestrial uses, do not apply directly to water or to areas where
surface water is present or to intertidal areas below the mean high
water mark."
"Do not connect an irrigation system (including greenhouse systems)
used for pesticide application to public water system unless the
pesticide label-prescribed safety devices for public water systems are
in place."
Regulatory
History
The plant growth regulator, Cytokinin, was initially registered in the
United States in 1978 as CYTEX®(EPA Reg. No. 35980-1) for applications
to certain citrus, fruit and vegetable crops. Cytokinin acts as a plant
regulator by promoting cell division; minimizing effects of stress;
stimulating roots; increasing yield; increasing vegetative growth; and
increasing tuber firmness.
During Phase 4 of the accelerated pesticide reregi strati on process, the
data base for Cytokinin was evaluated and determined to be inadequate in
satisfying certain requirements for biochemical pesticides which include
plant regulators. A DCI was issued in August 1993 to fill the outstanding
data gaps.
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Human Health
Assessment
Since the DCI, the Agency's initial position regarding these data gaps
was re-evaluated. All of these data requirements, except a Non-target insects
study, were waived because available information indicates that Cytokinin
does not cause unreasonable adverse effects: (1) The principal constituents
of Cytokinin, algae and seaweed, are natural components of fish diets, (2)
Cytokinin has a very low acute mammalian toxicity, (3) Cytokinin is used as
a dietary supplement in animal feeds, and (4) Cytokinin pesticide products
are expected to have no adverse effects to fish and wildlife.
Toxicity
In studies using laboratory animals, Cytokinin generally has been
shown to be of low acute toxicity. The acute dermal toxicity
(LD50> 2g/kg), eye irritation (slight irritation), and dermal irritation
(slightly irritating) place Cytokinin in Toxicity Category III (the second
lowest of four toxicity categories). Cytokinin's oral toxicity (LD50> 5g/kg)
places it in Toxicity Category IV (the lowest of four toxicity categories).
[NOTE: For acute oral, dietary, mammalian/avian/aquatic toxicity:
Category I = very highly or highly toxic
Category II = moderately toxic
Category III = slightly toxic
Category IV = practically non-toxic]
Dietary Exposure
Only the four naturally occurring Cytokinins, derived from certain
algal species, are exempt from the requirement of a tolerance when used as
a plant growth regulator (40 CFR 180.1042). At this time, synthetic
Cytokinin is not included in this tolerance exemption.
Tolerance exemptions are often based on the results of 90-Day (or
longer) feeding and developmental toxicity studies submitted to support
reregi strati on. However, it is the Agency's opinion that these studies can be
waived for naturally occurring and synthetic Cytokinin because of low acute
mammalian toxicity and very low use rates, which would not significantly
increase dietary intake over natural consumption in foods. The Agency, will
be proposing an exemption from the requirement of a tolerance for certain
Cytokinins (zeatin [6-(4-hydroxy-3-methylbut-trans-2-enylamino)-purine],
N6-methylaminopurine, N6-dimethylaminopurine, N6-
isopentenylaminopurine), and synthetic cytokinin — kinetin [6-
(furfurylamino)purine] for all raw agricultural commodities (RACs). The
exemption will apply only when application rates do not exceed 250 grams
of active ingredient/acre/year. The Agency believes this action does not
present any unreasonable risk. It is based on Cytokinin's low acute
mammalian toxicity, its low use rates, exposure in the diet from numerous
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natural plant food sources, and minimal exposure in the diet derived from
consumption of treated commodities under the proposed maximum label use
rates.
The Agency has concluded that dietary exposure risks from consuming
commodities treated with Cytokinin, either naturally occurring or synthetic,
are not expected.
Occupational and Residential Exposure
Based on the application methods listed on Cytokinin product labels,
the potential for eye, dermal and inhalation exposure to agricultural workers
does exist. However, since Cytokinin is in Toxicity Categories III and IV
for acute oral, dermal, eye irritation and dermal irritation, to reduce worker
exposure. The Agency has concluded that these occupational exposures and
subsequent risks will be negligible because of Cytokinin's low acute
mammalian toxicity and low use rates. Also, the precautionary product
labeling stipulated in the RED document will sufficiently mitigate exposures
and any subsequent risks to agricultural workers.
Human Risk Assessment
Since exposures and subsequent risks from Cytokinin applications are not
expected, any potential risks from exposure to treated plants will be mitigated by
the use of personal protective equipment required by the Worker Protection
Standard, supplemented by specific precautionary labeling required by this RED.
Post-application reentry workers are required to observe a 12 hour Restricted
Entry Interval. Because of Cytokinin's ubiquitous nature and low toxicity,
however, it is a candidate for a reduced reentry interval: from 12 hours to 4
fours.
Environmental
Assessment
Based on a review of all available ecological data, exposure information,
and Cytokinin's non-toxic mode of action, the Agency expects that applications of
Cytokinin will pose minimal risk to nontarget wildlife and fish.
Environmental fate studies for biochemicals are not imposed unless adverse
effects are observed in ecological effects data. Since no adverse effects are
anticipated, the Agency will not, at this time, impose any environmental fate data
requirements for the currently registered uses of Cytokinin.
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Additional Data
Required
Product Labeling
Changes
Required
EPA is requiring a revised Confidential Statements of Formula (CSFs)
and revised product labeling for reregi strati on.
The Agency has reexamined the toxicological data base for Cytokinin
and concluded that the current precautionary labeling (i.e. Signal Word,
Statement of Practical Treatment, WPS required labeling, and other label
statements associated with mitigating risks) adequately mitigate any risks
associated with the use of this plant growth regulator.
Regulatory
Conclusion
Based on the reviews of the generic data for Cytokinin, the Agency
has sufficient information on health effects and the potential for causing
adverse effects in fish and wildlife. The Agency has determined that
products containing Cytokinin, when labeled and used as specified in this
RED, will not pose unreasonable risks or adverse effects to humans or the
environment. Therefore, the Agency concludes that products containing
Cytokinin for certain uses that have a tolerance exemption (i.e. food
uses/commodities listed in 40 CFR 180.1042) are eligible for reregi strati on.
Other food uses of Cytokinin which do not have an exemption from
tolerance requirements (i.e., those food uses/commodities not listed in 40
CFR 180.1042) will become eligible for reregi strati on only when a
tolerance exemption is issued and becomes a final rule. The Agency plans to
propose such an exemption and pending public comment, issue a final rule
in early 1996.
For More
Information
EPA is requesting public comments on the Reregi strati on Eligibility
Decision (RED) document for Cytokinin 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.
Electronic copies of the RED and this fact sheet can be downloaded
from the Pesticide Special Review and Reregi strati on Information System at
703-308-7224. They also are available on the Internet on EPA's gopher
server, GOPHER. EPA. GOV, or using ftp onFTP.EPA.GOV, or using
WWW (World Wide Web) on WWW. EPA. GOV.
Printed copies of the RED and fact sheet can be obtained from EPA's
National Center for Environmental Publications and Information
(EPA/NCEPI), PO Box 42419, Cincinnati, OH 45242-0419, telephone
513-489-8190, fax 513-489-8695.
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Following the comment period, the Cytokinin RED document also
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 reregi strati on program,
the Cytokinin RED, or reregi strati on of individual products containing
Cytokinin, please contact the Biopesticides and Pollution Prevention
Division (7501W), OPP, US EPA, Washington, DC 20460, telephone 703-
308-8712.
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, Monday through Friday.
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