Acute systemic toxicity--prospects for tiered testing strategies.
After many years of controversy and debate, the LD50 test was finally deleted by the end of 2002. Three alternative animal tests, the Fixed Dose Procedure, the Acute Toxic Class Method and the Up and Down Procedure have been developed which give rise to significant improvements in animal welfare. They have recently undergone revision to improve their scientific performance but more importantly to increase their regulatory acceptance. They can now be used within a strategy for acute toxicity testing for all types of test substances and for all regulatory and in-house purposes. In vitro cytotoxicity tests could be used as adjuncts to these alternative animal tests within the next year or so to improve dose level selection and thus give further modest improvements in the numbers of animals used. However, the total replacement of animal tests requires a considerable amount of further test development, followed by validation, and is at least 10 years away.
Botham
P A
PA
Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SK10 4TJ, UK. phil.botham@syngenta.com
D032761:Animal Experimentation; D000826:Animal Testing Alternatives; D000818:Animals; D049673:History, 20th Century; D006801:Humans; D007928:Lethal Dose 50; D015203:Reproducibility of Results; D018675:Toxicity Tests / Q000266:history / Q000379:methods* / Q000592:standards