Dose and litter allocations in the design of teratological studies for detecting hormesis

BACKGROUND: Hormesis is being recognized in the field of toxicology due to the stimulating effects of some toxic compounds at low exposure levels. Therefore, it is desirable that experimental designs for toxicological studies be flexible enough to aid in the detection of hormetic effects. Current designs may still not have enough power to do this. METHODS: A simulation study was conducted to determine teratological study designs that would yield more power over standard designs in detecting hormesis. Developmental toxicity endpoints of interest are the number of dead/resorbed or malformed fetuses in a litter. The simulation designs mimic teratological experiments in terms of sample size and number of dose levels. Modified designs with even dose spacing at low levels and reallocated litters are investigated to determine the power of hormetic detection. RESULTS: Designs with reallocated litters (with more litters at low exposure levels than at high levels) and even dose spacing have more power than those with equal litters per group and uneven dose spacing. CONCLUSIONS: Through appropriate modifications of current experimental designs, such as reallocation of litters and even dose spacing, we can better detect hormetic effects.