3 - decen - 2 - one DP Number: 373085

PC Code: 068403 EPA File Symbol No.: 5481 - LAI Ty pe of Review: Human Health Toxicity

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION **UNITED ST AT**  **ES ENVIRONMENT AL**  **PROTECTION A GENCY** 

WA SHINGTON, D.C. 20460

**MEMORANDUM DATE:**  August 22 , 201 2 **SUBJECT** : Preliminary Human Health Assessment for the Registration Review of Cy tokinins (as Kinetin) [Chemical Name, 1 - H - Purin - 6 - amine, N - (2 - furanylmethyl) - ] . **Registration Review Case Number:** 4107 **Chemical Class:** Biochemical **PC Code s**  **:** 11680 1 and 116802 **CAS Number:** 525 - 79 - 1 **Active Ingredient Tolerance Exe mption:**  40 CFR § 180.115 7 **Type of Review:** Human Health Assessment **FROM:** Colin G. Walsh, M.S. , Biologi st /s/ 0 8 /22 /201 2

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, c ytokinins (as kinetin) , in support of the development of the Registration Review Preliminary Work Plan.

**Executive Summary**Cy

tokinins (as Kinetin) P C Code s : 116801 and 116802 Ty pe of Review: Human Health Assessment (Registration Review)

2 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 , cy tokinins (as kinetin) . Hazard and exposure information as well as Agency risk assessments on cy tokinins (as kinetin) were evaluated against current safety standards established by the Agency’s scientific policies and regulatio ns 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** Cy tokinin is comprised of the following four naturally occurring cy

tokinins 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 sy

nthetic version of cy

tokinin and act s as a plant growth regulator (PGR) that is used to enhance the growth and development of plants. Cy tokinins 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 s ynthetic cytokinin; however, more recent data indicate that the chemical is naturally

occurring in plant s and animals (Barciszewski et al., 2000 ; EPA, 2001 ). The active ingredient was first registered b y the Agency in 19 78 . There are currentl y 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 cy tokinins (as kinetin) as the sole active ingredient; the remaining 28 contain the active ingredient along with another active ingredient (s) . In general, cy tokinins (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 currentl y not approved for use as an inert ingredient in pesticide products. **II. Tolerances** Cy tokinins (specifically : aqueous extract of seawee d meal and kinetin) are exempt from the requirement of a tolerance under 40 CFR § 180.115 7 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** Cy

tokinins (as Kinetin) P C Code s : 116801 and 116802 Ty pe of Review: Human Health Assessment (Registration Review)

3 According to the Incident Data System, there have been no reported incidents from the use of EPA - registered products that contain the active ingredient, cy tokinins , between January 1, 1992 and August 15 , 201 2 . **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, cy tokinins (as kinetin) . The data available to the Agency are summarized in Table 1 below.Cy

tokinins (as Kinetin) P C Code s : 116801 and 116802 Ty pe of Review: Human Health Assessment (Registration Review)

4 **Table 1**  **: Human Health Assessment Data Requirements**  **for Cytok**  **inins (40**  **CFR § 158.2050) Study/** **OCSPP Guideline No.**  **Results Toxicity**  **Category/Description MRID**  Acute oral toxicity (rat) (870.1100) LD 50 > 5,000 mg/kg body weight in male and female rats Toxicity Category IV 45453301 Acute dermal toxicity (rat) (870.1200) LD 50 > 5,000 mg/kg body weight in male and female rats Toxicity Category IV 45453302 Acute inhalation toxicity (rat) (870.1300) LC 50 > 2.0 9 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 c onjunctivitis 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 Catego ry II I 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 (870.325 0) 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 The data requirement has been historically - EPA REDCy

tokinins (as Kinetin) P C Code s : 116801 and 116802 Ty pe of Review: Human Health Assessment (Registration Review)

5 **Table 1**  **: Human Health Assessment Data Requirements**  **for Cytok**  **inins (40**  **CFR § 158.2050) Study/** **OCSPP Guideline No.**  **Results Toxicity**  **Category/Description MRID**  (870.5100, 5300 and 5375) 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. (1995)

**V. References** Barciszewski, J, G. Siboska, SI S. Rattan. 2000. Occurrence, bios ynthesis and properties of kinetin (N - 6 - furfuryladenine). Plant Growth Regulation. Vol. 32(2 - 3): 257 - 265. EPA. 199 5 . Reregistration Eligibility Document (RED) for C ytokinin and R.E.D. Fact Sheet for Cy tokinin, 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/f actsheets/factsheet_116801.htm EPA. 2001. Biopesticides Fact Sheet for C ytokinin. 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 , 201 2