SEDL / STP / STP737-EB / STP34169S

Statistical Inconsistencies in the Use of No-Observed-Effect Levels in Toxicity Testing

Skalski, JR
Research scientist, Battelle, Pacific Northwest Laboratory, Richland, Wash.

Pages: 11    Published: Jan 1981

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Abstract

Use of the no-observed-effect level (NOEL) as an experimental end point violates the principle of negative inference, the logical basis of statistical hypothesis testing. The NOEL is based on the nonrejection of the hypothesis of no toxic effect, whereas scientific methods stress conclusions based on the rejection of a hypothesis. Failure to reject this hypothesis may result either because the concentration is “safe” or because the experimental protocol to detect a toxic response is insensitive, but the cause is indeterminant and the error rate unknown. The lowest rejected concentration tested (LRCT) is recommended as an experimental end point. By the use of LRCT the rate of misclassification is known and is equal to α. Experimental designs that emphasize both the biological and the statistical significance of LRCT end points are recommended.