Interlaboratory cholinesterase determinations and the effect on the results of statistical evaluation of cholinesterase inhibition

Abstract

Cholinesterase activity is often a key parameter in the regulatory assessment of cholinesterase-inhibiting agents such as organophosphorous and carbamate pesticides. Thus, the nature and characteristics of the methodology involved in the measurement of plasma (PChe), erythrocyte (RChe), and brain (BChe) cholinesterase activity takes on a heightened degree of importance. In this study an interlaboratory comparison of cholinesterase activity as determined by various laboratories was conducted in order to assess the influence that different methodologies may have on the results of statistical evaluation of cholinesterase inhibition. RChe, PChe, and BChe from animals exposed to fenthion, a known cholinesterase inhibitor, were determined at 8 different laboratories with experience in cholinesterase determination. Seven different instruments and 5 different assay procedures were employed. Marked differences in both the magnitude of inhibition measured and its designation as a statistically significant difference often occurred between laboratories using both the same as well as different methods of cholinesterase analysis. These findings illustrate the importance of considering not only the sensitivity of a given method of analysis, but also the influence of inter- and intralaboratory variation on statistically responsive aspects of the data profile itself (i.e., precision, sample size, etc.) when establishing regulatory levels (i.e., Reference Doses (RfDs), Health Advisory Levels (HALs), etc.) on the basis of a cholinesterase no-observed- or lowest-observed-effect level (NOEL, LOEL).