CHAPTER 6: Acute Systemic Toxicity: Oral, Dermal and Inhalation Exposures Check Access

Contemporary regulatory test guidelines offer reduction and refinement approaches to the in vivo testing of acute oral, dermal and inhalation toxicity. It is also clear that further reduction in the numbers of animals used in acute toxicity studies may be obtained through the use of more intelligent testing strategies, fully utilising the available data or by questioning the absolute requirement for a study. Assays of basal cytotoxicity have also been shown to have good predictivity for acute systemic toxicity for the majority of chemicals and may therefore be incorporated into a tiered testing strategy, enabling further reduction of animal numbers by informing the choice of starting dose level in studies in vivo. The future total replacement of in vivo studies requires the continuing development of a testing battery incorporating in vitro assays of basal cytotoxicity, cell-specific cytotoxicity and assays of cell-specific function in common targets of toxicity together with assessment of structural alerts and the role of toxicokinetic parameters including metabolism in the expression of toxicity. Such a test battery may eventually prove sufficiently predictive of acute systemic toxicity to replace animal studies entirely.