Document VjgK8YeL9JvaaN40r5wkB29kw

HL-14 REV. 5/91 E. I. DU PONT DE NEMOURS AND COMPANY Haskell Laboratory for Toxicology and industrial Medicine P.O. Box 50, Elkton Road Newark, Delaware 19714-0050 DU PONTc e n t r a l r e s e ar c h a n d d e v e l o p me n t June 19, 1992 TECHNICAL FILE cc: M.S.Bogdanffy Timothy S. Bingman, D.A.B.T. Engineering Function, Du Pont 1370 Washington Pike Bridgeville, PA 15017 Dear Tim: Sorry for delay in not getting back to you. Following are my comments on the proposal entitled, "Bioavailability of Lead: Selection of Dosing Methods and"Animal Model from Soil", by J.B. Henegham and N. Misllea. Phase I: Since this is an approach to examine several variables, it is unclear why five different lead concentrations are needed; three would be sufficient. A similar approach should be used for the controlled chemical variable studies. Task 2: In this case, animals would receive the three dose levels. Analysis for lead would take place on the high and low samples, and if a difference occurred then it would be worthwhile to analyze the mid-dose group. Task 3: Animal model variation study: there is a need to provide adequate details in the section including the lead dose(s), number of animals, reason<s) for selecting the time course identified, and how the information in Task 2, controlled chemical variables studies, fit into its design. DUP040011289 June 19, 1992 Another item is the animal species issue. The justification for pigs, if selected, for the species of choice could limit the expansion of these studies since it is unlikely that the same number of experiments could be performed in the same time or economic frame as with rats. In addition, if additional studies would be needed, the limited number of facilities which could handle these animals could impact the efficiency of such a study. With this in mind, consideration of a pig to rat conversion or scaling effort would allow the work to be conducted in rats without loss of data collected on the pigs. Also, costs of use and disposal of contaminated pigs could require funds that could otherwise go to experiments with rats. If you would like to discuss this further, don't hesitate to call me. Yours truly, Neil D, Krivanek Staff Toxicologist NDK: jiiig DUP040011290