National Institute for Occupational Safety and Health, PO Box 6495, Cincinnati, OH 45206

B -- DEVELOP A BIOLOGICALLY-BASED MATHEMATICAL MODEL SOL RFQ 00-06 DUE 082800 POC Phyllis Schweickart, 513/533-8185 The National Institute for Occupational Safety and Health, Cincinnati, Ohio has a requirement for a biologically-based mathematical model describing the clearance and retention of chrysotile asbestos fibers in rodent lungs, and to determine the dose-metric(s) that predict disease response. The results of this kinetic modeling will provide a basis for evaluating concordance with human exposure, dose, and response data for chrysotile asbestos (in a separate NIOSH project; not included in this contract). This information will be used in risk assessment of occupational exposure to fibers. The tasks to be accomplished include: (1) a study protocol, including a complete description of the proposed methodology for: (a) quantifying the exposure-dose and the dose-response relationships, (b) calibrating and validating the biomathematical exposure-dose model, (c) assessing the uncertainty in model structure and parameter values, (d) determining sensitivity of the model output to alternative assumptions; (e) extrapolating the rodent dosimetry model to predict fiber lung burdens in humans with occupational exposures, and (f) predicting malignant and nonmalignant disease risk in humans from the rodent data; and (2) development of a biologically-based dosimetry model, including (a) a structure that reflects the major biological compartments influencing disposition of fibers in the lungs, insofar as reasonable, (b) an evaluation of variability, uncertainty, and sensitivity of the model and parameter values, and (c) extrapolation of model to predict fiber lung burdens in humans with occupational exposures to chrysotile; (3) quantification of the dose-response relationship in rats for chrysotile fiber burdens and malignant and nonmalignant diseases and risk predictions in humans, including (a) using existing statistical or biological models in the literature (e.g., logistic, probit, multistage, 2-stage clonal expansion model, or time-to-tumor models) to model the rat data, and (b) predicting malignant and nonmalignant lung diseases in humans with fiber burdens predicted in preceding task; and (4) final report, including abstract, introduction, methods, results, discussion, references, and appendixes (including final programs and data files used for the models). The successful awardee must have personnel with education, work experience, and publications in the areas of biologically-based mathematical modeling and statistical modeling. The successful awardee must also provide documentation on the availability of, or access to, adequate data for the successful completion of this procurement. These data may consist of existing published or unpublished experimental data in laboratory rats or hamsters exposed by chronic inhalation to respirable chrysotile asbestos. A more detailed description of the scope of work and minimum qualifications for personnel and data are provided in the RFQ. Requests for the Request for Quotation must be in writing only. You may FAX your request to the following number: (513) 533-8283, Attn: Phyllis Schweickart. All responsible businesses may submit a written quotation which, if received timely, will be considered by the agency. Simplified Acquisition Procedures will be utilized for this purchase. The anticipated issuance date of this RFQ is August 7, 2000. Posted 07/21/00 (W-SN477594). (0203)

Loren Data Corp. http://www.ld.com (SYN# 0015 20000725\B-0005.SOL)

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