Bladder cancer as occupational disease and quantitative dose limits for compensation

In the German Ordinance on occupational diseases dose-limit values of carcinogenic substances that serve as decision criteria for compensation have been exclusively authorised by the legislator. These values were established only in exceptional cases as conventions, and the action itself was limited to well-defined preconditions. These preconditions were in accord with defined principles of occupational and social medicine, and were fulfilled only by special, particularly carcinogenic, noxae. However, recently it was attempted to deduce strict dose-limit values for compensation of occupationally caused cancer of the bladder (Weiss et al., 2010). Once more this attempt illustrates the questionable general tendency of experts in the field of the Statutory Accident Insurance (Berufsgenossenschaften) to bypass legislation and to establish further dose limits thus lowering responsibility for the outcome of occupationally relevant carcinogens. Such attempts ignore the above-mentioned preconditions that were fixed earlier with good reasons. For their recently published concept Weiss et al. (2010) are using data obtained from experiments with a few dogs, on the one hand, and a deduction of dose limits for carcinogenic arylamines using observations on smokers, on the other hand. In doing so, Weiss et al. violate fundamental rules of toxicology, such as: the animal experiments are not comparable; the experiments using o-toluidine are based on only one animal with a malignant and a second animal with a premalignant tumour (papilloma) of the bladder out of five animals; cancer susceptibilities in humans and animals are set equal without checking; the steepness of the dose-response curves of the three arylamines are simply assumed to be identical; the prerequisites for the application of the Druckrey/Kuepfmueller formula are missing. Thus, the authors are relying on data that are unsuited for deduction of dose-limit values, which represent decision criteria for the acceptance of occupationally caused cancer of the bladder. Worth mentioning, in particular, is the authors’ assumption that single arylamines, when inhaled together with thousands of xenobiotics, would not act differently in the human organism as if they were inhaled as single substances. Furthermore, the authors neglected the fact that in smokers a special metabolism is operative that is subjected to variations in enzyme induction, catalytic activity, enzyme polymorphisms, and others. Deficits in the evaluation of statistical data used for risk assessment are also obvious. Striking differences in the dose-effect functions of individual arylamines were ignored. Likewise ignored were the differences in dose effect functions (determining the occurrence of cancer of the bladder) that exist between occupationally exposed persons and smokers. Warnings, as expressed in the international scientific literature, not to underestimate occupational risk by using observations made on smokers were unheeded. Furthermore the long-standing observation made by occupational physicians that arylamines are incorporated dermally was not considered. Taken together, the publication of Weiss et al. not only fails to dispel doubts about the feasibility to establish doselimit-values for compensating occupational cancer of the bladder, it is suitable to support those doubts.

Authors: Henschler, Dietrich; Norpoth, Klaus; Thielmann, Heinz Walter; Woitowitz, Hans-Joachim ;Full Source: Zentralblatt fuer Arbeitsmedizin, Arbeitsschutz und Ergonomie 2012, 62(2), 64-75 (German) ;