REPORT OF THE BTS UKEMS WORKING GROUP ON DOSE SETTING IN INVIVO MUTAGENICITY ASSAYS
Authors/Editors
Research Areas
Publication Details
Output type: Journal article abstract
Author list: FIELDER RJ, ALLEN JA, BOOBIS AR, BOTHAM PA, DOE J, ESDAILE DJ, GATEHOUSE DG, HODSONWALKER G, MORTON DB, KIRKLAND DJ, RICHOLD M
Publisher: SAGE Publications
Publication year: 1993
Volume number: 12
Issue number: 3
Start page: 189
End page: 198
Number of pages: 10
ISSN: 0960-3271
eISSN: 1477-0903
Languages: English-Great Britain (EN-GB)
Unpaywall Data
Open access status: closed
Abstract
Furthermore, it was important to put the bone marrow study in context. In the UK, Regulatory Authorities would not accept negative data from one tissue as providing adequate reassurance regarding the absence of in-vivo activity. Data from at least one other assay using a different tissue would be needed. It would not therefore be necessary to use 'heroic' and unrealistically high doses in the bone marrow assay in a misguided attempt to obtain absolute assurance from the one study. It is believed that Regulatory Authorities in most other countries would seek data from more than one in-vivo assay before discounting positive data from in-vitro studies. The group also considered in quantitative terms, the actual difference in MTD in the mouse if based on 'evident toxicity' or on lethality (an estimate of a dose equivalent to 50-80% the LD50 value). There was relatively little difference between the two levels, due to the steep dose response for toxicity seen in the mouse with most compounds.
Keywords
6-mercaptopurine
