• Evaluation of the applicability of the Benchmark approach to existing toxicological data. Framework: Chemical compounds in the working place

      Appel MJ; Bouman HGM; Pieters MN; Slob W; CSR (Rijksinstituut voor Volksgezondheid en Milieu RIVMAdviescentrum voor chemische arbeidsomstandigheden (ACCA) TNO, 2001-11-09)
      Five chemicals used in workplace, for which a risk assessment had already been carried out, were selected and the relevant critical studies re-analyzed by the Benchmark approach. The endpoints involved included continuous, and ordinal data. Dose-response modeling could be reasonablyapplied to the dose-response data encountered, and Critical Effect Doses (CEDs) could be derived for almost all of the endpoints considered. The resulting benchmark dose for the study as a whole was close to the NOAEL in two cases, and higher than the LOAEL in two other cases where no NOAEL could be derived. In the fifth case the dose-response data were considered inconclusive after analysis by the Benchmark approach, making the choice of the study involved as the critical study doubtful.It is concluded that the Benchmark approach appears applicable to OECD toxicity studies, if at least two dose groups with (different) effects are observed. In situations where only one dose group shows effects the benchmark approach does not offer much of an improvement over the NOAEL approach. However, the situation that bserved effects are not replicated in other dose groups may give unreliable results whatever approach used, including the NOAEL approach. A single significantly different dose group could be the result of some unknown experimental factor otherthan the applied dose, and therefore replication of effects in different dose groups is a prerequisite, whatever method of analysis is used. The re-analysis of the five compounds selected illustrates that the Benchmark approach helps in getting a more complete view of the toxicity of the compound, if effects at different levels are observed in different dose groups.<br>