Incidence of developmental defects at the no observed adverse effect level (NOAEL).
Bioassay data from Teratology, Vol. 1 (1968) through Vol. 40 (1990), were utilized which were sufficient to establish no observed adverse effect levels (NOAEL's) for 120 experiments on 93 developmental toxicants in animals. The observed incidence (risk) at the NOAEL was calculated as the proportion of affected fetuses minus the proportion affected in the control animals. This calculation did not require any dose-response modeling. Data were primarily from experiments on rats and mice with a few studies on rabbits and hamsters. There did not appear to be differences in risks at the NOAEL among these four species. For each experiment, the risk at the NOAEL was tabulated for all of the adverse effects which shared the same NOAEL. Since the observed risk at the NOAEL for either dead/resorbed or abnormal fetuses exceeded 1% in about one-fourth of the cases, this suggests that a benchmark dose with a risk on this order would eliminate the higher risks and serve as a basis for establishing reference doses. If the lower confidence limit on a benchmark dose is used in place of the NOAEL, better experimental designs with more animals would result in tighter confidence limits, giving larger (less stringent) reference doses than poorer experiments.
Gaylor
D W
DW
National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079.
D000014:Abnormalities, Drug-Induced; D000818:Animals; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D051379:Mice; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D012306:Risk