U. S. Environmental Protection Agency, Contracts Management Division (MD-33), Attn: ORDSC, Research Triangle Park, NC 27711

A -- GASTROINTESTINAL ABSORPTION STUDIES OF CHLORPYRIFOS USING A SINGLE-PASS INTESTINAL PERFUSION TECHNIQUE SOL UZG211 DUE 091499 POC Pamela E. Smith (919) 541-0635, Purchasing Agent THIS IS A COMBINED SYNOPSIS/SOLICITATION FOR COMMERCIAL ITEMS PREPARED IN ACCORDANCE WITH THE FORMAT IN SUBPART 12.6, AS SUPPLEMENTED WITH ADDITIONAL INFORMATION INCLUDED IN THIS NOTICE. THIS ANNOUNCEMENT CONSTITUTES THE ONLY SOLICITATION; QUOTES ARE BEING REQUESTED AND A WRITTEN SOLICITATION WILL NOT BE ISSUED. The solicitation number is U2G211 and the solicitation is being issued as a Request for Quote (RFQ). The solicitation document and incorporated provisions and clauses are those in effect through Federal Acquisition Circular 97-13. The Environmental Protection Agency (EPA) anticipates that the contract will be awarded as a result of full and open competition. A firm-fixed-price purchase order is anticipated to result from the award of this solicitation. The associated Standard Industrial Code (SIC) is 8731. This procurement requires the contractor to provide Gastrointestinal absorption studies of chlorpyrifos using a single-pass intestinal perfusion technique. STATEMENT OF WORK: BACKGROUND: One often seeks to evaluate exposure models by comparing predictions with "real-world" field or clinical data, and it is convenient to use urinary or blood-borne biomarkers as a point of comparison. Hence, exposure modelers need to make the connection between an amount of chemical inhaled, ingested, or absorbed through the skin and the corresponding concentration of the chemical or one of its metabolites in urine or blood over time. Making these connections necessitates an understanding of the processes and factors governing the rate of absorption of the chemicals into the body as well as the rates of metabolism and elimination. The available data on the oral rate of absorption of organophosphate insecticides is limited. A commonly cited study fit oral absorption data to a model which assumed that the rate of uptake from the gastrointestinal (GI) tract was proportional to the mass of the chemical in the GI tract. The constant of proportionality was determined to be 1.3 hr-1, which indicates very rapid absorption from the GI tract. However, in this study, chlorpyrifos was dissolved in methylene chloride and deposited on a lactose tablet for administration. The methylene chloride was allowed to evaporate before the tablet was administered. Chlorpyrifos is lipophilic suggesting it might be readily absorbed in the intestine, but it has not been determined whether the rate of absorption is independent of the vehicle and method of administration. What has also not been determined is if there is a primary site of absorption for chlorpyrifos in the GI tract or if it is equally permeable throughout. Understanding where chlorpyrifos is absorbed will aid in the determination of how the consumption of chlorpyrifos with different types of foods might alter its oral bioavailability. It would also be useful to confirm the absorption rate constant for chlorpyrifos as well as the fraction of an administered dose that is absorbed. PURPOSE OF CONTRACT: Single-pass Intestinal Perfusion (SPIP) is an in situ method for determining the permeability of a chemical through the membrane of the intestine where most absorption of nutrients and other materials takes place within the GI tract. The technique involves isolating a small segment of the intestine in a live animal and perfusing the intestinal lumen with a known quantity of the chemical of interest, letting the perfusate flow through the segment. The concentration of material is then measured in the perfusate as it leaves the segment. This technique will be used to determine permeability parameters for chlorpyrifos in the rat intestine. This is a pilot level study on one compound. If the technique works well, it might be extended to other organophosphate insecticides in the future. Specific aims of this project: 1) Perform the SPIP technique using chlorpyrifos to determine the intestinal wall permeability of chlorpyrifos. 2)Perform the SPIP technique in several regions of the small intestine to examine regional differences in permeability. 2) wall of laboratory animals to chlorpyrifos and will determine whether or not there is regional variability in this parameter. Task 1. Develop Quality Assurance Project Plan: Under this task the contractor shall prepare and submit a Quality Assurance Project Plan (QAPP) to EPA for the proposed work. Data Collection shall not begin until the EPA has approved the QAPP. Task 1 Product: The contractor shall perform the work described in Task 1 and submit the draft and final QAPP to the EPA PO in both hard-copy and electronic (either Wordperfect 8 or Microsoft Word 6.0 or later) formats. Task 1 Schedule: Draft QAPP -- 1 month after award of purchased order. EPA will provide comments on the draft to the contractor within 2 weeks after receipt of draft QAPP. The Contractor shall provide the Final QAPP addressing EPA comments on the draft within 2 weeks of receipt of comments. EPA will provide notification of the final QAPP within 1 week of an acceptable final QAPP. Task 1 Successful Completion: The task will be successfully completed with the approval of the QAPP by EPA. Task 2: Complete proposed study and submit experimental data. Under this task, the contractor shall: 1) Perform the experiments as described in the approved study design. Prepare and submit the experimental data along with a concise report. The report shall include any deviations from the study design and QAPP along with justification, tables of experimental results including QA/QC results, and conclusions and recommendations. 3. During the data collection phase of the study, the Contractor shall coordinate with the EPA to have an EPA representative observe the experimental methods being used to perform the study. Task 2 Product: The product consists of draft and final copies of the report in hard-copy and/or electronic format (Wordperfect 8.0 or Microsoft Word 6.0 or later). Experimental data must be submitted in electronic format. The data format must be approved by EPA. Task 2 Schedule: Draft -- No later than 9 months after purchase order award. EPA will provide comments on the draft to the contractor within 2 weeks after receipt of draft. The Contractor shall provide the Final Report addressing EPA comments on the draft within 2 weeks of receipt of comments. The EPA will notify the contractor of approval status within 2 weeks after submission of final. Task 2 Successful Completion: The task will be successfully completed when the report and data have been approved by EPA. Task 3 Develop peer-reviewed journal article: The contractor shall author a peer-reviewed technical article on the determination of the intestinal permeability of chlorpyrifos using the single-pass intestinal perfusion technique. In the manuscript, the contractor shall outline the experimental methods and results of these studies. Task 3 Product: Manuscript submitted to journal for peer-review. Task 3 Schedule: The contractor shall perform this task no later than 4 months following the completion of Task 2. Task 3 Successful Completion: The task will be completed when the manuscript has been submitted to the journal for review. Selection Criteria: 1). Documented prior experience in developing oil phase compositional data sets. 2). Proposed sources of raw data. 3). Proposed numbers of compounds characterized per oil sample and fraction of total oil composition to be determined.PROPOSAL REQUIREMENTS:Technical Proposal shall include a Proposed Study Design for this effort. The proposed study design shall address the following: The applicant shall identify the appropriate laboratory animals for this study and determine the number of animals to use to achieve statistical power. The Design shall document that the permeability of chlorpyrifos in the test species is an adequate surrogate for humans. The proposal shall also outline the analytical method to be used to detect chlorpyrifos in the intestinal perfusate. Methods may include identification by radiolabel or chemical spectrographic analysis. If the method has been used before, the contractor must provide evidence from the literature that this method is suitable for detecting chlorpyrifos. If it is novel, the contractor must provide laboratory evidence that it is suitable. The study design Shall include a list of the data that will be submitted as part of the final report under Task 2. This data should include at a minimum: permeability coefficient for the intestinal wall, some measure of inter-animal variability in permeability, and data indicating the presence or absence of regional variability in intestinal permeability. In addition, the proposed study design shall indicate how the following parameters will be controlled and documented: the concentration of chlorpyrifos measured in the intestinal perfusate as it enters and exits the intestinal segment during each experimental trial, perfusate flow rate, and intestinal segment length. Cost Proposal: The contractor shall provide a price breakdown of performing the tasks outlined in the SOW. Along with supporting documentation to substantiate the proposed price. TECHNICAL EVALUATION CRITERIA: The following criteria shall be used to evaluate potential bidders. 1. Demonstrated credentials and experience in performing research to assess the oral absorption of pharmaceuticals or environmental agents and demonstrated knowledge of the scientific literature in this area. 2. Demonstrated experience in performing single-pass intestinal perfusion studies, specifically applied to environmental agents. 3. Equipment and facilities required to support this research. 4. Past performance -- provide 3 references. 5. Cost shall be secondary to above technical criteria. The following FAR provisions apply to this solicitation: 52.212-1, Evaluation-Instructions to Offerors-Commercial; 52.212-2, Evaluation-Commercial Item. Evaluation criteria to be included in paragraph (a) of provision 52.212-2 are as follows:(I) technical capability to meet the Government requirements; (ii) past performance;(iii) price, in decreasing order of importance. Technical and past performance, when combined, are significantly more important than price. All offerors are to include with their offers a completed copy of provision 52.212-3, Offeror Representations and Certifications-Commercial Items. The following FAR clause applies to this acquisition: 52.212-4, Contract Terms and Conditions-Commercial Items. The following additional FAR clauses which are cited in clauses 52.212-5 are applicable to the acquisition: 52.203-6, Restrictions on Subcontractor Sales to the Government, with Alternate I; 52.203-10, Price or Fee Adjustment for Illegal or Improper Activity; 52.219-14, Limitation on Subcontracting; 52.222-26, Equal Opportunity, 52.222-35, Affirmative Action for Special Disabled and Vietnam Era Veterans; 52.222-36 Affirmative Action for Handicapped Workers; 52.222-37, Employment Reports on Special Disabled Veterans and Veterans of the Vietnam Era; 52.222-41, Service Contract Act of 1965, As Amended. Cost and technical information should be submitted in separate proposals.Please submit two copies of the technical proposal and two copies of the cost proposal to Pamela E. Smith, Purchasing Agent, U.S. Environmental Protection Agency, MD-33, Research Triangle Park, NC 27711. Courier Delivery Address is: U.S. Environmental Protection Agency, Receptionist-Administration Bldg. Lobby, Attn: Pamela E. Smith, 79 Alexander Drive, Research Triangle Park, NC 27709. All offers are due by September 14, 1999, 4:00 p.m. ET. No telephonic or faxed requests will be honored. References can be found at http://www.epa.gov/oam/rtp_cmd. Posted 08/27/99 (W-SN373632). (0239)

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