A water-sediment screening tool for measuring biodegradation of organic chemicals.

A water-sediment screening tool (WSST) was developed based on OECD guideline 301 C (MITI I; Ministry of International Trade and Industry, Japan) to generate biodegradation data. The WSST and experimental procedures were tested and validated using aniline (CAS No. 62-53-3) and benzoic acid (CAS No. 65-85-0) as reference substances. In the presence of sediment components a higher endogenous respiration rate in the control vessels without test substance was measured compared to the water-only MITI test system, particularly due to organic constituents. However, it could be demonstrated that a distinct biodegradation in the presence of sediment can be determined and that there is no influence of the sediment pre-treatment on the biological oxygen demand in the WSST. Experiments resulted in biodegradation rates >60% after approximately six days for both compounds. However, degradation of benzoic acid resulted in a shorter lag-phase and a higher degree of degradation compared to aniline. Differences in results between the MITI test system and the WSST observed for aniline can be explained by adsorption to constituents of the sediment and assimilation by activated sludge. In comparison with literature data the results obtained for aniline in the MITI test system and the WSST showed reproducibility and were within the expected range. In conclusion, the WSST is a suitable screening tool to determine kinetic biodegradation data required to predict the biodegradation behaviour of organic chemicals in water-sediment systems and the data might be used to improve quantitative structure-property relationships (QSPRs).

In vitro predictions of skin absorption of caffeine, testosterone, and benzoic acid: a multi-centre comparison study.

To obtain better insight into the robustness of in vitro percutaneous absorption methodology, the intra- and inter-laboratory variation in this type of study was investigated in 10 European laboratories. To this purpose, the in vitro absorption of three compounds through human skin (9 laboratories) and rat skin (1 laboratory) was determined. The test materials were benzoic acid, caffeine, and testosterone, representing a range of different physico-chemical properties. All laboratories performed their studies according to a detailed protocol in which all experimental details were described and each laboratory performed at least three independent experiments for each test chemical. All laboratories assigned the absorption of benzoic acid through human skin, the highest ranking of the three compounds (overall mean flux of 16.54+/-11.87 microg/cm(2)/h). The absorption of caffeine and testosterone through human skin was similar, having overall mean maximum absorption rates of 2.24+/-1.43 microg/cm(2)/h and 1.63+/-1.94 microg/cm(2)/h, respectively. In 7 out of 9 laboratories, the maximum absorption rates of caffeine were ranked higher than testosterone. No differences were observed between the mean absorption through human skin and the one rat study for benzoic acid and testosterone. For caffeine the maximum absorption rate and the total penetration through rat skin were clearly higher than the mean value for human skin. When evaluating all data, it appeared that no consistent relation existed between the diffusion cell type and the absorption of the test compounds. Skin thickness only slightly influenced the absorption of benzoic acid and caffeine. In contrast, the maximum absorption rate of testosterone was clearly higher in the laboratories using thin, dermatomed skin membranes. Testosterone is the most lipophilic compound and showed also a higher presence in the skin membrane after 24 h than the two other compounds. The results of this study indicate that the in vitro methodology for assessing skin absorption is relatively robust. A major effort was made to standardize the study performance, but, unlike in a formal validation study, not all variables were controlled. The variation observed may be largely attributed to human variability in dermal absorption and the skin source. For the most lipophilic compound, testosterone, skin thickness proved to be a critical variable.