A semiquantitative method for selection of safety factors in establishing OELs for pharmaceutical compounds

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Abstract
For the purposes of establishing Occupational Exposure Limits (OELs), a conservative methodology similar to those widely used within the pharmaceutical industry for establishing such airborne limits has been developed. This methodology includes selection of the most sensitive, relevant toxicological endpoint(s), scaling for morphologic and physiologic considerations and pharmacokinetic/ pharmacodynamic parameters, and incorporation of an appropriate safety factor. This safety factor is selected to address the uncertainty and variability in extrapolating experimental data obtained in animal experimentation or clinical trials to a “healthy”; worker population. Key to this OEL‐setting methodology is a set of semiquantitative rules for selection of log‐normally distributed safety “sub‐factors.”; This rule set was designed to reward a robust dataset while accounting for the prevalence of response in the pivotal study or studies, species differences, study length, dose response considerations, and the significance of the pivotal effect driving the OEL. The overall, composite safety factor may then be generated as the mathematical product of these discrete, equally‐weighted subfactors, and is used in calculating the final OEL.