A--Amendment 1: "Method of Analysis to Perform a Tissue-Based Cumulative Risk Assessment for Mixtures of Chemicals"

NAICS Code: 541620 The following is added to the synopsis dated February 14, 2003: F. Milestones and Deliverables: Submit QA Project Plan (March, 2003) Submit the draft approach (April, 2003) Submit the final approach (July, 2003) Submit the draft information on chemical mixtures and available information (June, 2003) Submit the draft final report (July, 2003) Submit the final report and hard copies of all literature cited in the report (September, 2003) Deliver a professional quality seminar on the approach to the EPA in Cincinnati (September, 2003) G. Quality Assurance: This project requires no calculation of existing data, regardless of its origin in the peer reviewed literature. The contractor shall evaluate procedures previously published in the peer-reviewed literature (see references) and develop a comprehensive method comprised of the various individual procedures previously developed, reviewed and published. The contractor shall develop a justification for the application of the developed approach to the chemical mixtures (one specified), based on information publically available from EPA sources, and from the peer reviewed literature. All critical steps in the developed approach and information contained in the identification and justification for the chemical mixtures shall be clearly identified as to source, with the Contractor to place an emphasis on information available in the peer-reviewed literature. The description of the chemical mixtures shall include information on the metabolism, partition coefficients and pharmacokinetic information on components from the peer-reviewed literature. Because information not from EPA public sources or the peer-reviewed literature will be the exception, rather than the usual, any information not found from publically available EPA sources or from the peer-reviewed literature shall be additionally and uniquely identified (as simple as an asterisk and footnote) as having its origin not in the peer-reviewed literature. All information shall be accurately referenced. H. Acceptance Criteria: The contractor shall provide by electronic submission: one copy of up to two separate files containing text and figures for the final report. The report shall be titled, "Method of Analysis to Perform a Tissue-Based Cumulative Risk Assessment for Mixtures of Chemicals" and shall be formatted in the manner usual for publication in the peer reviewed literature in accordance with the NCEA Instruction Manual for Contractors, March 2002 (attached). The report shall present 1) a brief synopsis of guidance in US EPA (2000) and US EPA (2002), 2) the approach organized in a step-wise manner and described in a straightforward fashion and with sufficient detail as to allow a reader only casually acquainted with the field of risk assessment but well-versed in toxicology and pharmacokinetics to understand the principles set forth in the report, but not necessarily successfully implement the approach, and 3) descriptions of two chemical mixtures, containing specific information on metabolism and pharmacokinetics of each component, available in the peer-reviewed literature. I. Conflict of Interest The Contractor warrants that, to the best of the Contractor's knowledge and belief, that there are no relevant facts or circumstances which could give rise to a conflict of interest, as defined in FAR subpart 9.5, or that the Contractor has disclosed all such relevant information. The Contractor agrees to notify the Contracting Officer immediately, that to the best of its knowledge and belief, no actual or potential conflict of interest exists or to identify to the Contracting Officer any actual or potential conflict of interest the Contractor may have. The Contractor agrees that if an actual or potential conflict of interest is identified during the performance, the Contractor will immediately make a full disclosure in writing to the Contracting Officer. This disclosure shall include a description of actions which the Contractor has taken or proposes to take, after consulting with the Contracting Officer, to avoid, mitigate, or neutralize the actual or potential conflict of interest. The Contractor shall continue performance until notified by the Contracting Officer of any contrary action to be taken. J. Contract Publication Review Procedures (EPAAR 1552.237-70) (ARP 1984) The Contractor may not publish, present briefings or release any material resulting directly or indirectly from work performed under this contract in any conference, presentation, forum, publication or other discussions without the prior approval of the EPA Project Officer. K. References: Clewell, HJ, Andersen, ME and Barton HA. (2002). A consistent approach for the application of pharmacokinetic modeling in cancer and noncancer risk assessment. Environ. Health Perspect.110:85-93. Dobrev, ID, Andersen, ME and Yang, RSH. (2002). Assessing interaction thresholds for trichloroethylene in combination with tetrachloroethylene and 1,1,1-trichloroethane using gas uptake studies and PBPK modeling. Arch Toxicol 75:134-144. Haddad, S, Beliveau M, Tardif, R, Krishnan K. (2002). A PBPK modeling-based approach to account for mixtures interactions in the health risk assessment of chemical mixtures. Toxicol Sci 63:125-131. Kedderis, GL. (1997). Extrapolation of in vitro enzyme induction data to humans in vivo. Chem Biol Interact. 107:109-121. Kedderis, GL and Held, SD (1996). Prediction of furan pharmacokinetics from hepatocyte studies: Comparison of bioactivation and hepatic dosimetry in rats, mice and humans. Toxicol Appl Pharmacol 140:124-130. Lipscomb, J.C., Fisher, J.W., Confer, P.D. and Byczkowski, J.Z. 1998. In Vitro to in Vivo Extrapolation for Trichloroethylene Metabolism in Humans. Toxicol Appl Pharmacol 152:376-387. Snawder, J.E. and Lipscomb, J.C. 2000. Interindividual Variance of Cytochrome P450 Forms in Human Hepatic Microsomes: Correlation of Individual Forms with Xenobiotic Metabolism and Implications in Risk Assessment. Regul. Toxicol. Pharmacol. 32:200-209. Yang, RSH, el-Masri, HA, Thomas, RS, Constan, AA. (1995). The use of physiologically-based pharmacokinetic/pharmacodynamic dosimetry models for chemical mixtures. Tox Lett 82/83:497-504. US EPA 2000. Supplementary Guidance for Conducting Health Risk Assessment of Chemical Mixtures. Risk Assessment Forum, US Environmental Protection Agency, Washington, DC. EPA/600/R-00/002. Online at http://cfpub.epa.gov/ncea/raf/chem_mix.cfm US EPA. 2002. Guidance on Cumulative Risk Assessment of Pesticide Chemicals that Have a Common Mechanism of Toxicity. Office of Pesticide Programs, US Environmental Protection Agency, Washington, DC. Online at www.epa.gov/oppfead1/trac/science/cumulative_guidance.pdf The provision at FAR 52.213-4, Terms and Conditions - Simplified Acquisitions (Other than commercial Items), applies to this to this acquisition. FAR 52.232-34, Payment by Electronic Funds Transfer - Other than Central Contractor Registration also applies. The specific evaluation criteria are as follows: EVALUATION FACTORS/INSTRUCTIONS TO QUOTERS 1. The government intends to issue a single purchase order to the responsible offeror whose quote represents the best overall value to the government based on evaluation of technical factors and price. For the purposes of this best-value evaluation, technical merit relative to the factors listed in paragraph 2 is of greater importance than price. 2. Quotes shall include a narrative describing the proposed approach for accomplishing the requirements set forth in the Statement of Work. The technical approach shall not exceed 15 pages in length. Curriculum Vitae submitted with the proposal are not included in the length restriction, but should be limited to critical information addressing the technical evaluation criteria. At a minimum, this narrative shall identify: Education and Experience (50 points) Individuals who are proficient in PBPK modeling of chemical mixtures, toxicology, enzyme kinetics and mixtures toxicity approaches. Staff education should be verified by signed statements listing degrees, subject, department or college, granting institution, and year obtained. Evidence of experience should be presented. Relevance to other ongoing work (15 points) Scope of work must fall within the experience and practice of ongoing work. Projects currently underway by the contractor which are within the scientific area of this work should be identified and their relevance to the proposed work should be made clear. Staffing Plan (20 points) Balance of appropriate professional levels for conducting the work to assure cost-effective high-quality work, as evidenced by professional level labor hour distribution by task. Past Performance (10 points) Demonstrated performance during the last three years on contracts and/or subcontractors which are similar in scope, magnitude, and complexity to that which is anticipated in this solicitation. Factors for consideration, include (1) quality of products, (2) timeliness of performance, (3) compliance with cost estimate, (4) initiative in meeting requirements, and (5) customer satisfaction. Offerors shall submit 2 copies of their proposals/quotations referencing RFQ-OH-03-00035 no later than March 3, 2003 to Mr. Josh Bowers as follows: via regular mail: U.S. EPA, Contracts Management Division, 26 West Martin Luther King Drive, Cincinnati, OH 45268, or via Express Mail/Hand Carry: U.S. EPA, 4411 Montgomery Road, Suite 300, Norwood, OH 45212. Faxed quotations are acceptable and may be sent to (513)487-2109. Quotations may sent electronically via e-mail to [email protected]. Questions or comments may be directed to Mr. Josh Bowers at 513-487-2104 or via e-mail at [email protected].