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Harpin Protein - Registration of a Major Change in Labeled Use Pattern for Messenger® (EPA Reg. No. 69834-2) 10/03

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

Bureau of Pesticides Management, 9th Floor
625 Broadway, Albany, New York 12233-7254
Phone: (518) 402-8788     FAX: (518) 402-9024
Website: www.dec.state.ny.us

October 27, 2003

CERTIFIED MAIL
RETURN RECEIPT REOUESTED


Mr. Frederick S. Betz
Director of Regulatory & Environmental Affairs
EDEN Bioscience Corporation
121 Cathedral Street
Annapolis, Maryland 21401-2703

Dear Mr. Betz:

Re: Registration of a Major Change in Labeled Use Pattern (MCL) for the Active Ingredient Harpin Protein Contained in the Pesticide Product Messenger® (EPA Reg. No. 69834-2)

The New York State Department of Environmental Conservation (Department) has completed review of the application, received June 6, 2003, to register additional uses for the referenced product in New York State. Messenger' (EPA Reg. No. 69834-2) contains the active ingredient harpin protein.

The Department previously reviewed harpin protein as a new active ingredient and Messenger' was registered (reference correspondence from M. Serafini to F. Betz/EDEN Bioscience Corporation, dated April 23, 2001) for agricultural use in greenhouses, shadehouses, nurseries, and field production of a broad spectrum of crops. The proposal to register a pesticide product labeled for nonagricultural (domestic indoor/outdoor) use represents a MCL for harpin protein. Messenger® (3.0% harpin protein) is a biochemical pesticide labeled for plant disease management, insect suppression and growth enhancement on plants grown indoors and outdoors, including roses and other flowers, fruiting trees, berries, vines, herbs, root crops and all ornamental plants such as trees shrubs, and turf. Product may be applied (0.25 ounces in one to three gallons of water) as foliar spray or drench every two to three weeks while plants are actively growing. A maximum annual use rate is not specified.

The registration package was deemed complete for purposes of technical review on July 29, 2003. Pursuant to the review time frame specified in Environmental Conservation Law (ECL) §33-0704.2, a registration decision date of December 26, 2003 was established. The Department conducted toxicological, ecological and environmental fate risk assessments for harpin protein and the Messenger' alternate formulation.

TOXICOLOGICAL RISK ASSESSMENT:
The previous review of Messenger' noted that this pesticide product was neither very acutely toxic by the oral, dermal or inhalation routes of exposure nor was it very irritating to eyes or skin. Although no laboratory dermal sensitization study was conducted, the registrant indicated that there have been no reported incidents of Messenger®-induced hypersensitivity in individuals exposed to this pesticide product during its research, production or field-testing. Based on the low acute toxicity of the Messenger® product, the United States Environmental Protection Agency (USEPA) waived any further toxicity studies and granted an exemption from the requirement of a tolerance for residues of this biochemical pesticide when used in or on all food commodities. An updated search of the toxicological literature did not find any information on adverse reactions from exposure to the active ingredient harpin protein.

Due to submission of an alternate formulation for the Messenger' product, the USEPA required an acute oral toxicity study on the new inert ingredient alone. Also required, was an acute eye irritation study in rabbits using the reformulated Messenger' product. The results of the first study showed that the new inert ingredient was not very acutely toxic by the oral route of exposure. The eye irritation study on the altered Messenger® product demonstrated a slight eye irritation, only minimally more irritating than the original formulation.

Because harpin protein is commercially produced from E. coli, of which some strains can be pathogenic and produce endotoxin, the Department expressed concerns in their previous review for the survival potential of these pathogenic bacteria and the presence of residual plasmids in the Messenger' product. These concerns were satisfactorily addressed when the registrant submitted data demonstrating that the Messenger' product was neither contaminated with detectable human pathogens nor contained significant levels of residual plasmids. The available information indicates that the addition of nonagricultural (domestic indoor/outdoor) uses to the Messenger' label should not pose significant health risks to those who may use the product. Also, the Messenger' alternate formulation should not significantly increase the risk of adverse health effects.

ECOLOGICAL RISK ASSESSMENT:
Harpin protein is an extract from a bacterial pathogen that causes fire blight in apples and pears. When applied to plants, the protein does not harm either the plant or any other organism. Instead, it triggers a target plant's natural defenses, so if the plant should be attacked by pathogenic bacteria or fungi, the plant is better able to ward off the attack. Messenger' is applied at an extremely low concentration, seven to 11 grams per acre, and the natural harpin protein degrades in four to ten days.

The original agricultural label allowed the use of Messenger' on plants in greenhouses, shadehouses, nurseries, and field production of a broad spectrum of crops. The MCL proposes to allow Messenger' to be used for domestic indoor/outdoor (nonagricultural) use. In addition, the formulation of Messenger' product was revised.

The previous ecological review of Messenger' concluded that the active ingredient is benign; it is applied at an extremely low concentration; and it degrades too rapidly in the environment to present any significant level of risk to fish or wildlife. The Messenger' nonagricultural label expands its proposed usage. However, this potential increase in exposure does not result any significant increase in risk to fish and/or wildlife. The new inert ingredient is similarly a chemical that has low toxicity and degrades rapidly. Its integration into the Messenger® formulation does not increase the risks associated with this product. The nonagricultural (domestic indoor/outdoor) uses of Messenger' do not pose any threat of harm to the fish and wildlife resources of New York State.

ENVIRONMENTAL FATE RISK ASSESSMENT:
Messenger' was registered in 2001 for agricultural use. EDEN Bioscience Corporation is now applying for registration for domestic indoor and outdoor use. Harpin protein works by stimulating the plant's pest suppression systems as well as enhancing plant growth. The product contains three percent active ingredient and is applied as a drench or to the foliage at the rate of 0.25 ounces of product to one to three gallons of water. The label recommends applying at two to three week intervals to assure effectiveness. No maximum annual application rate was indicated on the label. The inerts do not appear to be solvent carriers.

Harpin protein is produced in nature by a bacterium which causes fire blight in apples and pears. Environmental fate data were not required by the USEPA due to the low toxicity of this active ingredient. An exemption from the requirement of a tolerance is established for residues of the biochemical pesticide harpin protein on all food commodities. Products that have been exempted from tolerance requirements are not required to perform environmental fate studies. Since environmental fate data were not required, there is no impact to groundwater to assess.

REGISTRATION ACTION:
The proposed Messenger' labeling bearing nonagricultural (domestic indoor/outdoor) uses should not cause unreasonable adverse effects to humans or the environment. The Department hereby accepts Messenger' (EPA Reg. No. 69834-2) for registration in New York State. Messenger' agricultural and nonagricultural labels are registered as separate products in New York State. Enclosed for your files are the Certificate of Pesticide Registration and New York State stamped "ACCEPTED" labeling.

Please note that a proposal by EDEN Bioscience Corporation, or any other registrant, to register a product containing harpin protein, whose labeled uses are likely to increase the potential for significant exposure to humans or impact to the environment, would constitute a MCL use pattern. Such an application must be accompanied by a new application fee and meet the requirements specified in 6 NYCRR Part 326.17.

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

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
G. Good/W. Smith, Cornell University, PMEP