A probabilistic effect assessment model for hazardous substances at the workplace.

A major problem in risk assessment is the quantification of uncertainties. A probabilistic model was developed to consider uncertainties in the effect assessment of hazardous substances at the workplace. Distributions for extrapolation factors (time extrapolation, inter- and intraspecies extrapolation) were determined on the basis of appropriate empirical data. Together with the distribution for the benchmark dose obtained from substance-specific dose-response modelling for the exemplary substances 2,4,4-trimethylpentene (TMP) and aniline, they represent the input distributions for probabilistic modelling. These distributions were combined by Monte Carlo simulation. The resulting target distribution describes the probability that an aspired protection level for workers is achieved at a certain dose and the uncertainty associated with the assessment. In the case of aniline, substance-specific data on differences in susceptibility (between species; among humans due to genetic polymorphisms of N-acetyltransferase) were integrated in the model. Medians of the obtained target distributions of the basic models for TMP and aniline, but not of the specific aniline model are similar to deterministically derived reference values. Differences of more than one order of magnitude between the medians and the 5th percentile of the target distributions indicate substantial uncertainty associated with the effect assessment of these substances. The probabilistic effect assessment model proves to be a practical tool to integrate quantitative information on uncertainty and variability in hazard characterisation.

A toolkit for dermal risk assessment: toxicological approach for hazard characterization.

The toxicological background for hazard assessment using a simple to use toolkit for assessment and management of health risks from occupational dermal exposure is presented. Hazard assessment is intended to answer the following questions: (i) is the substance under consideration capable of damaging the skin; (ii) is the substance under consideration capable of leading to systemic health effects after having penetrated the skin; (iii) to what extent may the substance become systemically available; (iv) is the hazard influenced by the concentration? Local effects (like irritation or corrosion) and systemic effects (like drowsiness or liver damage) are treated separately, taking into account their possible interrelations. Hazard assessment is performed on the basis of easily available risk phrases, which give a short characterization of the inherent toxicity of a pure chemical or preparation. The information provided by risk phrases and possibly additional data is transformed into a one-dimensional ranking system of intrinsic toxicity (IT) scores. IT scores are expressed in broad categories like low, moderate, high or extreme. This ranking provides plausible information on the relevance of potential skin contact to health effects.

Cancer risk assessment for oral exposure to PAH mixtures.

Cancer risk estimates for oral uptake of polycyclic aromatic hydrocarbons (PAHs) currently are based on risk estimates for benzo[a]pyrene (BAP). The potency of PAH mixtures often is calculated using relative potency values (BAP equivalency factors). We used recent oral carcinogenicity studies with BAP and coal tar mixtures, as well as older studies for a critical reappraisal of the current practice. A literature survey identified several carcinogenicity studies with oral and dermal exposure and lung implantation that allow a direct comparison of the carcinogenic potency of pure BAP and PAH mixtures. Moreover, when the PAH composition of the mixture has been analysed, prediction of the potency of PAH mixtures by BAP equivalency factors could be compared with the observed PAH potency. The analysis indicates that BAP equivalency factors do not describe adequately the potency of PAH mixtures and lead to underestimations of carcinogenic potency in most cases. Evaluation of several studies with various PAH mixtures revealed that the potency ratio between pure BAP and the PAH mixture in the same assay is highly dependent on the exposure pathway and the target organ, therefore potency estimates for PAH mixtures should be derived separately for oral, dermal and inhalative exposure using data from studies with the relevant pathway. A cancer slope factor for oral PAH exposure was derived based on data from a recent feeding study with coal tar mixtures. By using incidence data for all exposure-related tumours, a slope factor for humans of 11.5 (human excess risk per oral lifetime exposure with 1 mg BAP kg(-1)day(-1) in a PAH mixture) was obtained. Our analysis led to the conclusion that the contribution of BAP to the carcinogenic potency of the mixture depends on the exposure pathway and type of cancer observed but is relatively constant for various PAH mixtures from industrial sources. Thus, the derived oral slope factor is recommended to be used for the risk assessment of PAH-contaminated soils.