Document ID: EPA-HQ-OPP-2012-0671-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-09-26T04:00Z

OFFICE OF CHEMICAL SAFETY
AND POLLUTION PREVENTION
                 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                            WASHINGTON, D.C.  20460

MEMORANDUM

DATE:		August 22, 2012

SUBJECT:	Preliminary Human Health Assessment for the Registration Review of Cytokinins (as Kinetin) [Chemical Name, 1-H-Purin-6-amine, N-(2-furanylmethyl)-]. 
            
            Registration Review Case Number: 4107
            Chemical Class:	Biochemical
            PC Codes: 116801 and 116802
            CAS Number: 525-79-1
            Active Ingredient Tolerance Exemption: 40 CFR § 180.1157
            Type of Review: Human Health Assessment

FROM:		Colin G. Walsh, M.S., Biologist  /s/  08/22/2012	
            Biochemical Pesticides Branch
            Biopesticides & Pollution Prevention Division (7511P)

TO:			Leonard Cole, Senior Regulatory Action Leader
            Biochemical Pesticides Branch
            Biopesticides & Pollution Prevention Division (7511P) 

ACTION REQUESTED

The following scoping document contains the preliminary human health assessment for the biopesticide, cytokinins (as kinetin), in support of the development of the Registration Review Preliminary Work Plan.  

Executive Summary

Based on the available data and information, the Agency does not foresee the need for new data or for new risk assessments for this active ingredient, cytokinins (as kinetin). Hazard and exposure information as well as Agency risk assessments on cytokinins (as kinetin) were evaluated against current safety standards established by the Agency's scientific policies and regulations and it was determined that there is no need to conduct additional risk assessments. The active ingredient is naturally occurring, has a non-toxic mode of action, is of low toxicity, and has very low use rates. There is reasonable certainty of no harm to the general population from exposure to this chemical in pesticide products when it is used according to label instructions.  
  
I. Background

Cytokinin is comprised of the following four naturally occurring cytokinins derived from aqueous extract of seaweed meal: zeatin, N[6]-methylaminopurine, N[6]-dimethylaminopurine, and N[6]-isopentenylaminopurine (EPA, 1995). Kinetin [chemical name, 1-H-Purin-6-amine, N-(2-furanylmethyl)-] is a synthetic version of cytokinin and acts as a plant growth regulator (PGR) that is used to enhance the growth and development of plants. Cytokinins are used on growing crops, young trees, ornamentals, and golf courses to increase fruit size, yield, blossoms, branching, healthy appearance, and other desirable growth effects (EPA, 1995). Historically, the Agency has classified kinetin as a synthetic cytokinin; however, more recent data indicate that the chemical is naturally occurring in plants and animals (Barciszewski et al., 2000; EPA, 2001). 

The active ingredient was first registered by the Agency in 1978. There are currently 50 registered products containing the active ingredient (PC Codes 118601 and 118602). Three of these products are manufacturing-use products (MPs); the remaining 47 are end-use products (EPs). Of the 47 EPs, 19 contain cytokinins (as kinetin) as the sole active ingredient; the remaining 28 contain the active ingredient along with another active ingredient(s). In general, cytokinins (as kinetin) are found in very low concentrations in EPs with the highest concentration at 1.11% (42 of 47 EPs at an a.i. concentration of less than 0.15%).

The chemical is currently not approved for use as an inert ingredient in pesticide products.  
        
II. Tolerances

Cytokinins (specifically: aqueous extract of seaweed meal and kinetin) are exempt from the requirement of a tolerance under 40 CFR § 180.1157 in or on all food commodities when used as plant regulators on plants, seeds, or cuttings and on all food commodities after harvest in accordance with good agricultural practices. [64 FR 31505, June 11, 1999]  

III. Incidents

According to the Incident Data System, there have been no reported incidents from the use of EPA-registered products that contain the active ingredient, cytokinins, between January 1, 1992 and August 15, 2012. 

IV. Toxicity Profile

Sufficient data have been provided to fulfill the biochemical pesticide data requirements under 40 CFR § 158.2050 for the current use patterns for this active ingredient, cytokinins (as kinetin).  The data available to the Agency are summarized in Table 1 below.

Table 1: Human Health Assessment Data Requirements for Cytokinins (40 CFR § 158.2050)
                           Study/OCSPP Guideline No.
                                    Results
                         Toxicity Category/Description
                                     MRID
Acute oral toxicity (rat)
(870.1100)
           LD50 > 5,000 mg/kg body weight in male and female rats
                             Toxicity Category IV
                                   45453301
Acute dermal toxicity (rat)	
(870.1200)
           LD50 > 5,000 mg/kg body weight in male and female rats
                             Toxicity Category IV
                                   45453302
Acute inhalation toxicity	 (rat)
(870.1300)
                  LC50 > 2.09 mg/L in male and female rats
                             Toxicity Category IV
                                   45453303
Primary eye irritation (rabbit)	
(870.2400)
One hour after test substance instillation, all three treated eyes exhibited conjunctivitis and at 24 hours two eyes exhibited corneal opacity. The overall incidence and severity of irritation decreased with time. All animals were free of ocular irritation by 72 hours. Test substance is classified as mildly irritating to the eye.
                             Toxicity Category III
                                   45453304
Primary dermal irritation (rabbit)
(870.2500)
Animals did not exhibit any dermal irritation at any test site during the study. Test substance is classified as non-irritating to the skin. 
                             Toxicity Category IV 
                                   45453305
Dermal sensitization  (guinea pig)
(870.2600)
                  Test substance is not a dermal sensitizer. 
                                       -
                                   45453306
90-Day oral toxicity 
(870.3100)
The data requirement has been historically waived because of low acute mammalian toxicity and very low use rates which would not significantly increase dietary intake over natural consumption in foods. The historical information to support the data requirement is adequate.
                                       -
                                EPA RED (1995)
90-Day dermal toxicity 
(870.3250)
The Agency has historically concluded that these occupational exposures and subsequent risks will be negligible because of the low acute mammalian toxicity and very low use rates. In addition, any unlikely dermal exposure will be mitigated on the label by precautionary statements and PPE requirements. The historical information to support the data requirement is adequate.
                                       -
                                EPA RED (1995)
90-Day inhalation toxicity 
(870.3465)
The Agency has historically concluded that these occupational exposures and subsequent risks will be negligible because of the low acute mammalian toxicity and very low use rates. In addition, any unlikely inhalation exposure will be mitigated on the label by precautionary statements and PPE requirements. The historical information to support the data requirement is adequate.
                                       -
                                EPA RED (1995)
Developmental toxicity
 (870.3700)
The data requirement has been historically waived because of low acute mammalian toxicity and very low use rates which would not significantly increase dietary intake over natural consumption in foods. The historical information to support the data requirement is adequate.
                                       -
                                EPA RED (1995)
Mutagenicity
(870.5100, 5300 and 5375)
The data requirement has been historically waived because of low acute mammalian toxicity and very low use rates which would not significantly increase dietary intake over natural consumption in foods. The historical information to support the data requirement is adequate.
                                       -
                                EPA RED (1995)

V. References

Barciszewski, J, G. Siboska, SIS. Rattan. 2000. Occurrence, biosynthesis and properties of kinetin (N-6-furfuryladenine). Plant Growth Regulation. Vol. 32(2-3): 257-265.

EPA. 1995. Reregistration Eligibility Document (RED) for Cytokinin and R.E.D. Fact Sheet for Cytokinin, Kinetin, and N[6]-Benzyladenine. U.S. Environmental Protection Agency Office of Prevention, Pesticides and Toxic Substances. December 1995.
	http://www.epa.gov/oppsrrd1/REDs/4107.pdf
	http://www.epa.gov/pesticides/biopesticides/ingredients/factsheets/factsheet_116801.htm

EPA. 2001. Biopesticides Fact Sheet for Cytokinin. U.S. Environmental Protection Agency Office of Prevention, Pesticides and Toxic Substances. December 2001.
	http://www.epa.gov/opp00001/chem_search/reg_actions/registration/fs_G-29_01-Dec-01.pdf

cc: Colin G. Walsh, Leonard Cole, BPPD Science Review File, IHAD/ARS, Colin G. Walsh, FT, PY-S, August 22, 2012