The determination of two emerging perfluoroalkyl substances and related halogenated sulfonic acids and their significance for the drinking water supply chain.

In the present study analytical methodologies were developed for two newly emerging polar perfluorinated alkyl substances (PFAS), namely F3-MSA, and HFPO-DA, in order to assess the occurrence and levels of these PFAS in Dutch and Belgian waters. Two separate methods were needed for analysing F3-MSA and HFPO-DA. A mixed-mode and a reversed phase C18 method were developed for F3-MSA and HFPO-DA, respectively, using a high resolution Orbitrap Fusion mass spectrometer for detection, yielding satisfactory LOD and LOQ results for both analytes. A sample campaign was performed collecting single grab samples from various locations and different stages of the drinking water production chain. Whereas both PFAS were absent in groundwaters, they were found to be present in surface waters, river bank and dune infiltrates, process water, and drinking water, demonstrating the persistence and mobility of both compounds. Based on provisional health-based guideline values (0.15 µg L-1 for HFPO-DA, 11.9 mg L-1 for F3-MSA), the current levels in drinking water from the suppliers involved in this study do not pose a health risk for the human population. Common removal processes used in drinking water production appeared to remove these polar compounds at most partially. At locations close to potential sources of these chemicals (e.g. fluoropolymer production sites), the quality of surface water or river bank filtrate abstracted for production of drinking water must therefore be monitored.

Application of effect-directed analysis to identify mutagenic nitrogenous disinfection by-products of advanced oxidation drinking water treatment.

Advanced oxidation processes are important barriers for organic micropollutants in (drinking) water treatment. It is however known that medium pressure UV/H2O2 treatment may lead to mutagenicity in the Ames test, which is no longer present after granulated activated carbon (GAC) filtration. Many nitrogen-containing disinfection by-products (N-DBPs) result from the reaction of photolysis products of nitrate with (photolysis products of) natural organic material (NOM) during medium pressure UV treatment of water. Identification of the N-DBPs and the application of effect-directed analysis to combine chemical screening results with biological activity would provide more insight into the relation of specific N-DBPs with the observed mutagenicity and was the subject of this study. To this end, fractions of medium pressure UV-treated and untreated water extracts were prepared using preparative HPLC and tested using the Ames fluctuation test. In addition, high-resolution mass spectrometry was performed on all fractions to assess the presence of N-DBPs. Based on toxicity data and read across analysis, we could identify five N-DBPs that are potentially genotoxic and were present in relatively high concentrations in the fractions in which mutagenicity was observed. The results of this study offer opportunities to further evaluate the identity and potential health concern of N-DBPs formed during advanced oxidation UV drinking water treatment.

In vitro testing for direct immunotoxicity: state of the art.

Immunotoxicity is defined as the toxicological effects of xenobiotics including pharmaceuticals on the functioning of the immune system and can be induced in either direct or indirect ways. Direct immunotoxicity is caused by the effects of chemicals on the immune system, leading to immunosuppression and subsequently to reduced resistance to infectious diseases or certain forms of nongenotoxic carcinogenicity.In vitro testing has several advantages over in vivo testing, such as detailed mechanistic understanding, species extrapolation (parallelogram approach), and reduction, refinement, and replacement of animal experiments. In vitro testing for direct immunotoxicity can be done in a two-tiered approach, the first tier measuring myelotoxicity. If this type of toxicity is apparent, the compound can be designated immunotoxic. If not, the compound is tested for lymphotoxicity (second tier). Several in vitro assays for lymphotoxicity exist, each comprising specific functions of the immune system (cytokine production, cell proliferation, cytotoxic T-cell activity, natural killer cell activity, antibody production, and dendritic cell maturation). A brief description of each assay is provided. Only one assay, the human whole blood cytokine release assay, has undergone formal prevalidation, while another one, the lymphocyte proliferation assay, is progressing towards that phase.Progress in in vitro testing for direct immunotoxicity includes prevalidation of existing assays and selection of the assay (or combination of assays) that performs best. To avoid inter-species extrapolation, assays should preferably use human cells. Furthermore, the use of whole blood has the advantage of comprising multiple cell types in their natural proportion and environment. The so-called "omics" techniques provide additional mechanistic understanding and hold promise for the characterization of classes of compounds and prediction of specific toxic effects. Technical innovations such as high-content screening and high-throughput analysis will greatly expand the opportunities for in vitro testing.