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Consumer health risk assessment for feed additives is based on the estimated human exposure to the additive that may occur in livestock edible tissues compared to its hazard. We present an approach using alternative methods for consumer health risk assessment. The aim was to use the fewest possible number of animals to estimate its hazard and human exposure without jeopardizing the safety upon use. As an example we selected the feed flavoring substance piperine and applied in silico modeling for residue estimation, results from literature surveys, and Read-Across to assess metabolism in different species. Results were compared to experimental in vitro metabolism data in rat and chicken, and to quantitative analysis of residues' levels from the in vivo situation in livestock. In silico residue modeling showed to be a worst case: the modeled residual levels were considerably higher than the measured residual levels. The in vitro evaluation of livestock versus rodent metabolism revealed no major differences in metabolism between the species. We successfully performed a consumer health risk assessment without performing additional animal experiments. As shown, the use and combination of different alternative methods supports animal welfare consideration and provides future perspective to reducing the number of animals.

Precision-cut liver slices are frequently used to study hepatic toxicity and metabolism of xenobiotics in vitro. Successful cryopreservation techniques will enhance an efficient and economic use of scarcely available (human) liver tissue. For primary hepatocytes, slow freezing has been accepted as the best approach towards successful cryopreservation. For slices, however, no agreement exists on the optimal way of cryopreservation and both slow and fast freezing techniques have been reported. The aim of the present study was to determine the applicability of a computer-controlled slow freezing technique for the cryopreservation of (rat) liver slices. Thus far, this technique has not been described in detail. Our studies confirmed that slow freezing was most successful in the cryopreservation of primary rat hepatocytes. Based on this observation, the slow freezing technique was applied to the cryopreservation of rat liver slices. Directly after thawing, slice viability was between 60 and 100% of fresh values, depending on the parameter determined. However, after additional culturing, slice viability was reduced. This decrease in slice viability was more pronounced in comparison to primary hepatocytes. In conclusion, the slow freezing technique was confirmed to be a successful approach for the cryopreservation of primary rat hepatocytes, and was found to be of limited use for the cryopreservation of rat liver slices. Copyright (C) 2000 Elsevier Science Ltd. Chemicals/CAS: Adenosine Triphosphate, 56-65-5; Dinitrochlorobenzene, 97-00-7; Formazans; Glutathione Transferase, EC 2.5.1.18; Glutathione, 70-18-8; Lactate Dehydrogenase, EC 1.1.1.27; MTT formazan, 23305-68-2; Proteins; Testosterone, 57-85-2; Tetrazolium Salts; Urea, 57-13-6

The borehole deformation type of rock stress measuring instrument, which is the subject of this paper measures radial displacements in the direction of one or more diameters of the borehole in which it is installed for the purpose of determining the stresses in the rock in which the borehole is drilled. The stresses are calculated from the changes in borehole diameter using formular derived by means of the theory of elasticity. Not included in the considerations of this paper is the so-called borehole inclusion type of rock stress measuring instrument. In principle, it also measures radial displacements in boreholes, but it is a ‘rigid’ or ‘stiff’ type while the one dealt with in this article is a ‘soft’ type of displacement measuring device. The former offers considerable resistance to the radial displacements of the borehole, the latter, a negligible resistance. A full discussion of the influence of the ‘rigidity’ of rock stress measuring instruments upon the scope of their usefulness was recently published in this journal by Hult et al.[1] Up to the present, many instruments of the soft borehole deformation type have been developed. In this paper an analysis is given of their operating principles in the hope that a clearer picture of their potentialities on the one hand and their limitations on the other may be obtained.