The laboratory mouse in routine safety testing for marine algal biotoxins and harmful algal bloom toxin research: past, present and future

Mouse bioassays have been a mainstay for detecting harmful concentrations of marine algal toxins in shellfish for over 70 years. Routine monitoring involves intraperitoneal injection of shellfish extracts into mice; shellfish contaminated with algal toxins are thus identified by mortality in exposed mice. With the advent of alternative test methods to detect and quantify specific algal toxins has come increasing criticism of enduring use of mouse bioassays for shellfish safety testing. However, the complete replacement of shellfish safety mouse bioassays by chemical, antibody-based, and functional assays has been and will continue to be a gradual process for various reasons, including skills availability and instrument costs for chromatography-based toxin monitoring. Mouse bioassays for shellfish safety testing do not comply with modern standards for laboratory animal welfare, specifically the requirement in published official methods for death as a test outcome. Mouse bioassays for algal biotoxins in shellfish, as well as fundamental algal toxin research endeavors using in vivo models, are amenable to revision and refinement from a humane endpoints perspective. Regulated hypothermia may be a useful and easily acquired nonlethal toxicological endpoint; objective determination of neuromuscular blockade may allow algal neurotoxin testing and research to enter the domain of humane endpoints evaluation. Relinquishing reliance on subjective test endpoints, including death, will likely also deliver collateral improvements in assay variability and sensitivity