Student Research: Mona R. Kimbell

Comparisons of Methods for Determining Potency of Developmental Toxicants
1991
Faculty Advisor: 

Abstract

In developmental toxicology the standard method of potency calculation has been based on the concept of a no observed adverse effect level, of the NOAEL. An acceptable daily intake level is determined by dividing the NOAEL by uncertainty factors.

Alternatives to this approach are investigated; The Benchmark dose, which involves using the lower 95% confidence limit for a fixed level of response above background, divided bby uncertainty factors (just as with the NOAEL), and the Human Exposure Rodent Potency Index (HERP), which is used to rank the relative potency of compounds based on the daily human exposure level, divided by the rodent developmental toxicity ED50. Comparisons of the rank order of toxicity are made between HERP, the Benchmark RfD and the NOAEL RfD. The reference dose is a daily dose below which there is believed to be no adverse developmental effect in humans.

Five compounds were selected on the basis of data availability, diversity of exposure and toxicity values. The compounds selected include ethylene glycol, TCDD, diethyl hexyl phthalate, ethylene thiourea, and theophyllin. Each compound has met the study criteria for Segment II teratology tests and exposure data requirements.

The relative potencies of the five compounds as derived by the traditional NOAEL method, Benchmark Dose method, and the ED50 do not differ significantly. The incorporation of human exposure data in the HERP changes the relative order of toxicity risk significantly, indicating the importance of exposure assessment. The benchmark dose method consistently predicted lower values for the toxic dose than did the NOAEL method.