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Vinyl chloride (VC) is both a known carcinogen and a regulated chemical, and its production capacity has almost doubled over the last 20 years, currently 27 million tons/year worldwide. According to recent reports it is still a cause for concern. VC has been found as a degradation product of chloroethylene solvents (perchloroethylene and trichloroethylene) and in landfill gas and groundwater at concentrations up to 200 mg/m(3) and 10 mg/L, respectively. Worldwide occupational exposure to VC still seems to be high in some countries (e.g., averages of approximately 1,300 mg/m(3) until 1987 in one factory), and exposure may also be high in others where VC is not regulated. By combining the most relevant epidemiologic studies from several countries, we observed a 5-fold excess of liver cancer, primarily because of a 45-fold excess risk from angiosarcoma of the liver (ASL). The number of ASL cases reported up to the end of 1998 was 197 worldwide. The average latency for ASL is 22 years. Some studies show a small excess risk for hepatocellular carcinoma, and others suggest a possible risk of brain tumors among highly exposed workers. Lung cancer, lymphomas, or leukemia do not seem to be related to VC exposure according to recent results. The mutation spectra observed in rat and human liver tumors (ASL and/or hepatocellular carcinoma) that are associated with exposure to VC are clearly distinct from those observed in sporadic liver tumors or hepatic tumors that are associated with other exposures. In rats, the substitution mutations found at A:T base pairs in the ras and p53 genes are consistent with the promutagenic properties of the DNA adduct 1,N(6)-ethenoadenine formed from VC metabolites. Risk assessments derived from animal studies seem to overestimate the actual risk of cancer when comparing estimated and reported cases of ASL. Images Figure 1 Figure 2

The thresholds of toxicological concern (TTCs) define limit values for substances of unknown toxicity below which dietary intake is considered to be of no concern to human health. The TTC concept has already been used for risk assessment of e.g. food contaminants or flavoring substances and is in discussion to be applied to other classes of compounds such as cosmetic ingredients, household products, non-relevant metabolites in drinking water, and impurities in pharmaceuticals. The present publication aimed to evaluate whether the current TTC concept can also be applied to define limit values for inhalation exposure, using a data set of 203 industrial chemicals from the database RepDose.It has been shown, that the NOEC values in classes 1, 2, and 3 are distributed over six orders of magnitude resulting in a considerable overlap between the distribution curves for the three classes. Inhalation thresholds for Cramer classes 1 (compounds likely to be of low-toxicity), 2 (compounds likely to be of moderate toxicity), and 3 (compounds suspect for high toxicity) were analyzed close to the approach described by Munro for oral TTCs. The 5th percentiles NOEC of Cramer classes 1-3 result in thresholds of 1.5×10-3ppm for Cramer class 1 and 2.2×10-5ppm for Cramer class 3. A threshold could not be derived for class 2 because of the small number of compounds available. If calculated as body doses, the inhalation thresholds for classes 1 and 3 (71 and 4μg/person/d, respectively) are considerably lower than the oral thresholds derived by Munro (1800 and 90μg/person/d). It has been shown that one reason for this difference is the high sensitivity of the respiratory tract to local effects.In a next step, the values obtained were further refined. If organophosphates or compounds with structural alerts for genotoxicity are excluded, the TTC in Cramer class 1 increases, whereas the TTC in Cramer class 3 remains the same. Based on these analyses two inhalation TTCs for non-genotoxic compounds are proposed: 3.6×10-3ppm (180μg/person/d) for Cramer class 1 and 2.4×10-5ppm (4μg/person/d) for Cramer class 3. © 2010 Elsevier Inc.

A database for repeated dose toxicity data has been developed. Studies were selected by data quality. Review documents or risk assessments were used to get a pre-screened selection of available valid data. The structure of the chemicals should be rather simple for well defined chemical categories. The database consists of three core data sets for each chemical: (1) structural features and physico–chemical data, (2) data on study design, (3) study results. To allow consistent queries, a high degree of standardization categories and glossaries were developed for relevant parameters. At present, the database consists of 364 chemicals investigated in 1018 studies which resulted in a total of 6002 specific effects. Standard queries have been developed, which allow analyzing the influence of structural features or PC data on LOELs, target organs and effects. Furthermore, it can be used as an expert system. First queries have shown that the database is a very valuable tool.

Summary Palladium is a metal the output and use of which has more than doubled in the past ten years. It is used in dental appliances, chemical catalysts, electrical appliances and jewellery, but the greatest increase in Pd demand has been in automotive emission control catalysts. Studies on Pd concentrations in ancient ice and recent snow samples reflect the increase in mining, smelting and use of palladium in the last decades. Increases of palladium in the environment have been shown in air and dust samples. There is no data as yet available to assess the effect of this exposure A major source of health concern is the sensitization risk of Pd as very low doses are sufficient to cause allergic reactions in susceptible individuals. Persons with known nickel allergy may be especially susceptible. Workers occupationally exposed to Pd include miners, dental technicians and chemical workers. The latter are exposed mainly to Pd salts several of which may cause primary skin and eye irritations. It is advised that persons with known Pd allergy should not work with Pd compounds. The general population may come into contact with palladium mainly through mucosal contact with dental restorations and jewellery containing palladium and possibly via emissions from Pd catalysts. Protection of the public from related adverse effects may be achieved by the use of alloys with high corrosion stability and thus minimal release of palladium. In general, in dental patients who are sensitive to Pd, restorations using Pd-containing materials should not be used although Pd has been used without allergic effects in some of these individuals. Further, those patients who have an allergy to nickel should be informed that use of Pd-containing dental materials may cause Pd allergy, though this risk appears to be low.