The Hydra attenuata system for detection of teratogenic hazards.

Abstract

By a uniformly applied protocol, adult hydra are exposed to a test substance over a broad range of concentrations, and the minimal toxic concentration is determined to within one-tenth log. In a second experiment, dissociated hydra cells are manipulated into a configuration wherein, if undisturbed, they will achieve the developmental events characteristic of any embryo and undergo total whole-body regeneration. During its 4-day ontogenesis this artificial "embryo" is exposed to the test substance by the same protocol as the adult and the minimal developmentally toxic concentration is determined to within one-tenth log. The ratio of the adult (A) to the developmentally (D) toxic concentration is calculated. A small A/D ratio indicates that the substance disrupts development only at or near the concentration also toxic to the adult (a developmentally nonhazardous substance or coeffective teratogen). A large A/D ratio indicates that a substance disrupts developmental events at a small fraction of the exposure toxic to adults (a developmental hazard). The system is directly predictable of a putative teratogen's hazard potential (A/D ratio) in standard laboratory animals and man. It provides an objective and reliable means to prioritize otherwise untested substances according to the need for further study of their developmental toxicity.