Report of the IWGT working group on strategy/interpretation for regulatory in vivo tests

Abstract

A survey conducted as part of an International Workshop on Genotoxicity Testing (IWGT) has identified a number of compounds that appear to be more readily detected in vivo than in vitro. The reasons for this property varies from compound to compound and includes metabolic differences; the influence of gut flora; higher exposures in vivo compared to in vitro; effects on pharmacology, in particular folate depletion or receptor kinase inhibition. It is possible that at least some of these compounds are detectable in vitro if a specific in vitro test is chosen as part of the test battery, but the 'correct' choice of test may not always be obvious when testing a compound of unknown genotoxicity. It is noted that many of the compounds identified in this study interfere with cell cycle kinetics and this can result in either aneugenicity or chromosome breakage. A decision tree is outlined as a guide for the evaluation of compounds that appear to be genotoxic agents in vivo but not in vitro. The regulatory implications of these findings are discussed.

A Review on Mutagenicity Testing for Hazard Classification of Chemicals at Work: Focusing on in vivo Micronucleus Test for Allyl Chloride

“…In the second step, specific in vivo tests are performed to determine the relevance of the in vitro results for the in vivo situation. These in vivo mutagenicity studies are also included because some genotoxicants can only be detected in vivo after metabolic activation [17] . Compared to regulatory carcinogenicity testing, mutagenicity testing is relatively cheap and fast.…”

“…1 ). The reviewers agreed on 31 articles (i.e., references [13] , [14] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] ) and three books (i.e. [15] , [34] , [35] ) that met the inclusion criteria for detailed analysis.…”

Evaluation of the genotoxicity and mutagenicity of Ca3SiO5-based cement

“…An in vivo test can assess the metabolic and pharmacodynamic effects of a product and can help evaluate the influence of gut microbiota on the substance 23, 24 . Therefore, we decided to conduct an in vivo evaluation of the genotoxic and mutagenic properties of Ca 3 SiO 5 .…”

Genotoxicity of Anesthetics EvaluatedIn Vivo(Animals)

“…Literature shows that morphine was nonmutagenic in the Drosophila melanogaster sex-linked recessive lethal mutation assay. However, it increased MN frequency in both red blood and bone marrow cells in the mouse [ 70 ]. Some hypothesis of the in vivo clastogenic effects reported with morphine in mice may be directly related to increase in glucocorticoid levels produced by morphine in this species [ 71 ] or a consequence of hypothermia [ 72 ], which is caused in rodents by this drug, but this is worthy of further study.…”