United States
                   Environmental Protection
                        Prevention, Pesticides
                        And Toxic Substances
December 1995
                   R.E.D.   FACTS
     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).

                      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
                      "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."
      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.

Human Health
      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.

      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

                     natural plant food sources, and minimal exposure in the diet derived from
                     consumption of treated commodities under the proposed maximum label use
                           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

                           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.

   Additional Data
 Product Labeling
     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.
     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
     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.

     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-
     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.