
EPA BIOPESTICIDES AND POLLUTION PREVENTION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

EPA Biopesticides and Pollution Prevention Division contact: Linda Hollis, 703-308-8733

SUBMISSION: Email the completed template to: hollis.linda@epa.gov.

TEMPLATE:

Plant Health Care Inc.

[1F8901]

	EPA has received a pesticide petition (1F8901) from Plant Health Care Inc., 2626 Glenwood Avenue, Suite 350, Raleigh, NC 27608 requesting, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180

   

	2. to establish an exemption from the requirement of a tolerance for
	
   
	2. biochemical pesticide PDHP 25279

	
Pursuant to section 408(d)(2)(A)(i) of FFDCA, as amended, Plant Health Care Inc. has submitted the following summary of information, data, and arguments in support of their pesticide petition. This summary was prepared by Plant Health Care Inc. and EPA has not fully evaluated the merits of the pesticide petition. The summary may have been edited by EPA if the terminology used was unclear, the summary contained extraneous material, or the summary unintentionally made the reader conclude that the findings reflected EPA's position and not the position of the petitioner.


I. Plant Health Care Inc. Petition Summary
   
   	[1F8901]

A. Product Name and Proposed Use Practices

	PDHP 25279 when used as an active ingredient in biochemical pesticide formulations to be applied to growing crops or seeds.

B. Product Identity/Chemistry

	1. Identity of the pesticide and corresponding residues. PDHP 25279 is a Peptide Derived from Harpin Protein (PDHP) (specifically, harpin or harpinαβ) that is produced by fermentation and identified by the following criteria: (1) consists of a peptide less than 5 kD in size, less than 40 amino acids in length, that is acidic (pI<7.0) and contains no cysteine residues; (2) the source(s) of genetic material encoding the protein are bacterial plant pathogens not known to be mammalian pathogens or any structurally, functionally similar peptide produced synthetically; (3) elicits the Natural Defense Mechanism (NDM), which is characterized as rapid, localized cell death in plant tissue after infiltration of the peptide into the intercellular spaces of plant leaves or roots; (4) is heat stable (retains NDM activity when heated to 65 °C for 20 minutes); (5) is readily degraded by a proteinase representative of environmental conditions as well as degradation by environmental factors such as oxidation and hydrolysis; (6) exhibits a rat acute oral toxicity (LD50) of greater than 5,000 mg product/kg body weight.


	2. Magnitude of residues at the time of harvest and method used to determine the residue. NA-Remove

	3. A statement of why an analytical method of detecting and measuring the levels of the pesticide residue are not needed. An analytical method for detecting and measuring the levels of the pesticide residue for PDHP 25279 is not applicable.  Considering the lack of toxicity observed in toxicology studies, it is expected that, when used as proposed, PDHP 25279 would not result in residues that are of toxicological concern.

C. Mammalian Toxicological Profile

	Studies to evaluate the safety to mammals were conducted on PDHP 25279 (acute oral toxicity and acute inhalation toxicity) or another PDHP (PDHP 91398) that has an almost identical amino acid sequence. The PDHPs have low acute toxicity by the oral, dermal and inhalation routes. For PDHP 25279, the acute oral LD50 was >5000 mg/kg bw and the acute inhalation LC50 was >2.11 mg/L, which corresponds to EPA Toxicity Category IV by both routes. The substantially similar PDHP 91398 peptide also demonstrated acute oral and dermal LD50 values >5,000 mg/kg bw and was minimally irritating to the skin and eyes of rabbits, resulting in an EPA Toxicity Category IV for these routes of exposure. PDHP 91398 was not a dermal sensitizer. 

D. Aggregate Exposure

	1. Dietary exposure. Dietary exposure from use of PDHP 25279 as proposed is minimal based on the very low proposed pre-harvest application rates and rate of degradation. 

	i. Food.  The results of toxicity testing following acute oral exposure, the route most relevant to assessment of risks to health from exposure to food, indicate there is no risk to human health from PDHP 25279. There are no reports of human health hazards related to oral exposure to other PDHPs or to the parent harpin or harpinαβ proteins, which have been registered for years. The absence of acute toxicity in laboratory animals following oral and inhalation exposures to high doses of the product demonstrates the benign nature of PDHP 25279. Finally, PDHPs degrade rapidly in the field and so residues on crops are not expected.

	ii. Drinking water. Exposure of humans to residues of PDHP 25279 in drinking water would be minimal based on the proposed product application rates and rate of degradation of the active ingredient.  Results of the acute oral toxicity testing have shown that PDHP 25279 is non-toxic at the highest test dose (LD50 >5000 mg/kg bw). Additionally, results of the acute inhalation toxicity testing have also shown low toxicity (LC50 >2.11 mg/L).  There are no reports of human health hazards related to oral exposure to the parent proteins, harpin or harpinαβ. The absence of acute toxicity in laboratory animals following oral and inhalation exposure to high doses of the product demonstrates the nontoxic nature of PDHP 25279.


	2. Non-dietary exposure. The potential for non-dietary exposure to the general population, including infants and children, is unlikely as the proposed use sites are application to growing plants or crops or seeds. The results of toxicity testing discussed above indicate there is no risk to human health or the environment from PDHP 25279. There are no reports of ecological or human health hazards related to oral exposure to harpin or harpinαβ proteins. The absence of acute toxicity in laboratory animals following oral, dermal, or inhalation exposure to high doses of PDHP 25279 demonstrates the benign nature of the product.

E. Cumulative Effects

	Section 408(b)(2)(D) (9v) of the FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider "available information" concerning the cumulative effects of a particular pesticide's residues and "other substances that have a common mechanism of toxicity." There is no indication that PDHP 25279 acts by a common mechanism of action with other compounds to result in any cumulative effects. 


F. Safety Determination

	1. U.S. population. Acute toxicity studies have shown that PDHPs are non-toxic to mammals when exposure is through oral, dermal, and inhalation routes and also lack irritation potential in mammals. There are no reports of human health hazards caused by the proteins from which PDHP 25279 is derived, harpin and harpinαβ. The lack of acute toxicity indicates that the hazard associated with the use of PDHP 25279 is low. There is a reasonable certainty of no harm to the general United States population from exposure to this active ingredient.

	2. Infants and children. It is not expected that, when used as proposed, PDHP25279 would result in residues that are of toxicological concern. There is a reasonable certainty of no harm for infants and children from exposure to PDHP 25279 from the proposed uses.


G. Effects on the Immune and Endocrine Systems

	To date, there is no evidence to suggest that PDHP 25279 functions in a manner toxic to the immune system, similar to any known hormone, or that it can act as an endocrine disrupter.


H. Existing Tolerances

	There are no current tolerances or tolerance exemptions in place for PDHP 25279.

I. International Tolerances

	There are no current tolerances or tolerance exemptions in place for PDHP 25279.





