Nationwide hospitalization costs of skin melanoma and non-melanoma skin cancer in Germany.

INTRODUCTION: Non-melanoma skin cancer (NMSC), in contrast to skin melanoma (MEL), is considered a negligible health problem because mortality of NMSC is low. The aim of this study was to provide insights into the burden of NMSC and MEL by analysing nationwide skin cancer hospitalization data and data from a dermatologist panel of Germany. We wanted to estimate hospitalization costs due to skin cancer in Germany. MATERIAL AND METHODS: We analysed the most recent nationwide hospitalization data from 2003 and estimated hospitalization costs due to MEL and NMSC. We estimated the annual number of private dermatologist practice visits in Germany due to skin cancer. RESULTS: In 2003, 20 455 melanoma-related and 41 929 NMSC-related hospitalizations occurred in Germany. Age-standardized hospitalization rates for NMSC were 2.5-fold and 1.8-fold higher among men and women than the rates for MEL, respectively. The age-specific proportions of hospitalizations for NMSC in relation to all cancer-related hospitalizations increased within the age range of 65 years and more. Among people aged 90 years and more, 14% of all cancer-related hospitalizations were due to NMSC. Estimated annual hospitalization costs for MEL were euro50 to 60 million, and those for NMSC were euro105 to 130 million. The estimated number of private dermatologist practice visits in Germany 2003 is considerably higher for NMSC than MEL CONCLUSIONS: Analyses of hospitalizations data and data from private dermatologists give NMSC higher public health relevance than can be obtained from consideration of death statistics.

Joint algal toxicity of 16 dissimilarly acting chemicals is predictable by the concept of independent action.

For a predictive assessment of the aquatic toxicity of chemical mixtures, two competing concepts are available: concentration addition and independent action. Concentration addition is generally regarded as a reasonable expectation for the joint toxicity of similarly acting substances. In the opposite case of dissimilarly acting toxicants the choice of the most appropriate concept is a controversial issue. In tests with freshwater algae we therefore studied the extreme situation of multiple exposure to chemicals with strictly different specific mechanisms of action. Concentration response analyses were performed for 16 different biocides, and for mixtures containing all 16 substances in two different concentration ratios. Observed mixture toxicity was compared with predictions, calculated from the concentration response functions of individual toxicants by alternatively applying both concepts. The assumption of independent action yielded accurate predictions, irrespective of the mixture ratio or the effect level under consideration. Moreover, results even demonstrate that dissimilarly acting chemicals can show significant joint effects, predictable by independent action, when combined in concentrations below individual NOEC values, statistically estimated to elicit insignificant individual effects of only 1%. The alternative hypothesis of concentration addition resulted in overestimation of mixture toxicity, but differences between observed and predicted effect concentrations did not exceed a factor of 3.2. This finding complies with previous studies, which indicated near concentration-additive action of mixtures of dissimilarly acting substances. Nevertheless, with the scientific objective to predict multi-component mixture toxicity with the highest possible accuracy, concentration addition obviously is no universal solution. Independent action proves to be superior where components are well known to interact specifically with different molecular target sites, and provided that reliable statistical estimates of low toxic effects of individual mixture constituents can be given. With a regulatory perspective, however, fulfilment of both conditions may be regarded as an extraordinary situation, and hence concentration addition may be defendable as a pragmatic and precautionary default assumption.

Predicting the joint algal toxicity of multi-component s-triazine mixtures at low-effect concentrations of individual toxicants.

Herbicidal s-triazines are widespread contaminants of surface waters. They are highly toxic to algae and other primary producers in aquatic systems. This results from their specific interference with photosynthetic electron transport. Risk assessment for aquatic biota has to consider situations of simultaneous exposure to various of these toxicants. In tests with freshwater algae we predicted and determined the toxicity of multiple mixtures of 18 different s-triazines. The toxicity parameter was the inhibition of reproduction of Scenedesmus vacuolatus. Concentration-response analyses were performed for single toxicants and for mixtures containing all 18 s-triazines in two different concentration ratios. Experiments were designed to allow a valid statistical description of the entire concentration-response relationships, including the low concentration range down to EC1. Observed effects and effect concentrations of mixtures were compared to predictions of mixture toxicity. Predictions were calculated from the concentration-response functions of individual s-triazines by applying the concepts of concentration addition and independent action (response addition) alternatively. Predictions based on independent action tend to underestimate the overall toxicity of s-triazine mixtures. In contrast, the concept of concentration addition provides highly accurate predictions of s-triazine mixture toxicity, irrespective of the effect level under consideration and the concentration ratio of the mixture components. This also holds true when the mixture components are present in concentrations below their individual NOEC values. Concentrations statistically estimated to elicit non-significant effects of only 1% still contribute to the overall toxicity. When present in a multi-component mixture they can co-operate to give a severe joint effect. Applicability of the findings obtained with s-triazines to mixtures of other contaminants in aquatic systems and consequences for risk assessment procedures are discussed.

A general best-fit method for concentration-response curves and the estimation of low-effect concentrations.

Risk assessments of toxic chemicals currently rely heavily on the use of no-observed-effect concentrations (NOECs). Due to several crucial flaws in this concept, however, discussion of replacing NOECs with statistically estimated low-effect concentrations continues. This paper describes a general best-fit method for the estimation of effects and effect concentrations by the use of a pool of 10 different sigmoidal regression functions for continuous toxicity data. Due to heterogeneous variabilities in replicated data (i.e., heteroscedasticity), the concept of generalized least squares is used for the estimation of the model parameters, whereas a nonparametric variance model based on smoothing spline functions is used to describe the heteroscedasticity. To protect the estimates against outliers, the generalized least-squares method is improved by winsorization. On the basis of statistical selection criteria, the best-fit model is chosen individually for each set of data. Furthermore, the bootstrap methodology is applied for constructing confidence intervals for the estimated effect concentrations. The best-fit method for the estimation of low-effect concentrations is validated by a simulation study, and its applicability is demonstrated with toxicity data for 64 chemicals tested in an algal and a bacterial bioassay. In comparison with common methods of concentration-response analysis, a clear improvement is achieved.

Associations between workload and diseases rarely occurring in sickness absence data.

This study provides rate ratios for sickness absence in relation to workload, which was accessed by means of a job exposure matrix. Emphasis is given to diseases that are seldom studied by sickness absence data either because the incidence is low or because medical treatment is not supplemented by rest from work. A total of 42,508 employees from the metal processing and retail trade were followed for 3 years. Sick leave related to hypertension, ischemic heart diseases, ulcer, neurotic disorders, or work accidents was most frequent in employees exposed to physical demands and low control. In contrast, an inverse relation was observed for psychological demands, for which rate ratios decreased with increasing exposure. This finding might be an expression of work commitment or pressure to attend rather than of coping behavior, because both hard and soft diagnoses were considered.

Regulations for combined effects of pollutants: consequences from risk assessment in aquatic toxicology.

In the analysis of combined effects two reference concepts are currently considered as equally valid for the assessment of mixture toxicities: these are LOEWE additivity (concentration addition) and BLISS independence (response addition) (Greco et al., 1995). The aim of this study of 137 binary mixtures of pesticides and surfactants using an algal biotest was to find rational procedures for the assessment of mixture toxicities in the aquatic environment. By introducing an index on prediction quality the quantitative relationships between predicted and observed effects are evaluated for each concept. It is shown that LOEWE additivity leads to good predictions of mixture toxicities for most combinations, whereas BLISS independence tends to underestimate mixture toxicities. By this it is reaffirmed that there is a solid basis for forthcoming regulatory activities on mixtures of chemicals.