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6-benzyladenine Registration of the Major Change in Labeling for 6-benzyladenine, Contained in the Pesticide Product MaxCel Plant Growth Regulator 3/05

New York State Department of Environmental Conservation
Division of Solid & Hazardous Materials

Bureau of Pesticides Management
Pesticide Product Registration Section
625 Broadway, Albany, New York 12233-7257
Phone 518-402-8768     FAX 518-402-9024
Website: http://www.dec.state.ny.us/website/dshm/pesticid/pesticid.htm
E-Mail: ppr@gw.dec.state.ny.us

March 29, 2005

CERTIFIED MAIL
RETURN RECEIPT REQUESTED


Mr. Joseph L. Powell
State Project Manager, R&RA
Valent BioSciences Corporation
1600 Rivera Avenue, Suite 200
Walnut Creek, California 94596

Dear Mr. Powell:

Re: Registration of the Major Change in Labeling for 6-benzyladenine, Contained in the Pesticide Product MaxCel Plant Growth Regulator (EPA Reg. No. 73049-407)

The New York State Department of Environmental Conservation (Department) has reviewed the application and additional data, received May 18, 2004, from Valent BioSciences Corporation, to register the above-mentioned product in New York State. The product contains an increased application rate for the active ingredient (ai) 6-benzyladenine (chemical code 116901).

The application was deemed complete for purposes of review on December 20, 2004 and a registration decision is due by May 19, 2005. MaxCel Plant Growth Regulator is currently registered in New York State and is labeled for fruit thinning and enhancement of fruit size when applied to apples in the post-bloom period. The proposed increase in application rate of 6-benzyladenine to apples (from 30 to 182 grams per acre per year) represents a major change in labeled use pattern for this active ingredient in New York State.

Maxel Plant Growth Regulator contains 1.9% 6-benzyladenine, or 0.166 lb ai/gallon. The inerts do not appear to be solvent carriers.

The need for environmental fate and groundwater data (Tier II (40 CFR 158.690(d)(2)(vii through xv)) was not triggered because of the practically nontoxic results indicated in the Tier I studies. Since environmental fate data were waived, there is no impact to the groundwater to be assessed.

The United States Environmental Protection Agency (USEPA) classified the active ingredient 6-benzyladenine as a biochemical pesticide because it resembles natural plant growth regulators and it acts through a nontoxic mode of action. Accordingly, the USEPA required limited data for federal registration of the Maxcel product. Data from acute toxicity studies indicate that neither 6-benzyladenine nor the Maxcel product was very toxic to laboratory animals via the oral, dermal or inhalation routes of exposure. Also, neither the active ingredient nor the formulated product was very irritating to the skin (tested on rabbits) nor were they skin sensitizers (tested on guinea pigs). However, both were moderately irritating to the eyes (tested on rabbits). In a rat subchronic feeding study, 6-benzyladenine caused a decrease in body weight gain, and some kidney effects characterized by minimal histological changes and an increase in blood urea nitrogen levels at a dose of 304 milligrams per kilogram body weight per day (mg/kg/day); the no-observed-effect level (NOEL) was 111 mg/kg/day. 6-Benzyladenine was negative in several genotoxicity studies. In a rat developmental toxicity study, this chemical caused decreased fetal body weights and an increased incidence of unossified and asymmetrical sternebrae and hydrocephalus in offspring at a maternal dose of 175 mg/kg/day; the NOEL was 50 mg/kg/day. The skeletal effects and hydrocephalus were believed related to the decreased body weights. Maternal toxicity characterized by a decrease in body weight, body weight gain and food consumption, was reported at 175 mg/kg/day with a NOEL of 50 mg/kg/day.

The USEPA waived the requirement for all chronic/carcinogenicity studies as well as any additional subchronic, developmental/reproductive toxicity and genotoxicity studies for federal registration of Maxcel Plant Growth Regulator Solution. A search of the toxicological literature did not find any significant new information on the toxicity of 6-benzyladenine.

The USEPA issued an exemption from the requirement of a tolerance for 6-benzyladenine in or on apples when this active ingredient is used at the maximum labeled application rate on apples (up to 182 grams per acre per year). The USEPA Office of Pesticide Programs calculated a chronic population adjusted dose (cPAD) for 6-benzyladenine of 0.05 mg/kg/day based on the NOEL of 50 mg/kg/day from the rat developmental toxicity study and an uncertainty factor of 1,000. The USEPA estimated that chronic dietary exposure to 6-benzyladenine would be 0.03% of the cPAD for the general U.S. population and 0.2% for non-nursing infants. This chronic exposure analysis is based primarily on the conservative assumptions that 100% of the apple crops are treated and contain a residue level of 0.01 parts per million (about twice the average residue levels measured in apples during field trials).

A quantitative risk assessment was not required by the USEPA for occupational exposure to 6-benzyladenine in the Maxcel product. Risks from occupational exposure were considered negligible by USEPA because of the active ingredient's relatively low acute toxicity and lack of any other toxicity concerns, as well as the product label requirement for the use of personal protective equipment (long-sleeved shirt, long pants, shoes plus socks).

There are no chemical-specific State or federal drinking water/groundwater standards for 6-benzyladenine. Based on its chemical structure, 6-benzyladenine falls under the 50 microgram per liter general New York State drinking water standard for an "unspecified organic contaminant" (10 NYCRR Part 5, Public Water Systems).

The available toxicity data required to support the registration of Maxcel Plant Growth Regulator Solution indicate that neither this formulated product nor its active ingredient 6-benzyladenine is very toxic following acute exposures. The subchronic and developmental studies indicate some toxicological potential, but effects were only seen at relatively high doses. Significant risks to the general public are not expected given the agricultural use pattern and the low residues of 6-benzyladenine in apples. Worker risks are also expected to be minimal given the relatively low application rate and the product label requirement to use personal protective equipment. While the product can cause some eye irritation, the label contains the precautionary statement "Causes moderate eye irritation. Avoid contact with eyes or clothing." which is compatible with the USEPA Label Review Manual guidance. Given the above, the Department does not object to the registration of Maxcel Plant Growth Regulator Solution in New York State.

An analytical methods review was completed and found to be technically acceptable and complete for the analysis of 6-benzyladenine in the technical grade material.

The Department concludes that MaxCel Plant Growth Regulator should not have an adverse effect on the health of workers or the general public, or the ground and surface water of New York State when used as labeled.

Therefore, the Department hereby accepts for general use registration in New York State MaxCel Plant Growth Regulator (EPA Reg. No. 73049-407), which contains the Major Change in Labeling for the active ingredient 6-benzyladenine.

Enclosed is your Certificate of Pesticide Registration and New York State stamped "ACCEPTED" label.

Valent BioSciences Corporation is reminded that if New York State registration is requested for this product or for any other product which contains 6-benzyladenine with an increased application rate and/or expanded use sites, the product will be considered a Major Change in Labeling and the Department will require an extensive review.

If you have any questions, please contact Samuel Jackling, Chief of our Pesticide Product Registration Section, at (518) 402-8768.

Sincerely,

Maureen P. Serafini
Director
Bureau of Pesticides Management

Enclosures
cc: w/enc. - N. Kim/D. Luttinger - NYS Dept. of Health
R. Zimmerman/R. Mungari - NYS Dept. of Ag. & Markets