Brominated flame retardants (BFRs) are chemicals used in e.g. electronic equipment, textiles and plastics for the prevention of fire. Over recent decades, concern has been raised regarding some heavily used BFRs, since the levels in the environment have been increasing. In the present thesis, persistent, bioaccumulative, and toxic (PBT) properties were studied for a structurally varied set of BFRs selected to represent more than 60 organic BFRs. The studied BFRs include: 2,4,4'-tribromodiphenyl ether (BDE 28), 2,2',3,4,4',5',6-heptabromodiphenyl ether (BDE  183), decabromodiphenyl ether (BDE 209), hexabromocyclododecane (HBCD), tetrabromobisphenol A (TBBPA), tetrabromobisphenol A 2-hydroxyethyl ether (TBBPA OHEE), 2,4,6-tribromophenol (246BrPh), 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH), and hexabromobenzene (HxBrBz). It is likely that soil will act as a sink for BFRs. Therefore, studies of BFRs were performed on persistence in soil, and on bioaccumulation from soil in the earthworm Eisenia fetida. Large variation in the biodegradability in soil among the tested BFRs was observed. The studied brominated diphenyl ethers (BDE 28 and BDE 209) were very persistent under both aerobic and anaerobic conditions, while 246BrPh and TBECH degraded quickly in both aerobic and anaerobic soil. The bioaccumulation in earthworm from soil was high for HxBrBz, TBECH and for tested brominated diphenyl ethers with 4-6 bromine atoms (BDE 47, BDE 99, and BDE 153). Bioaccumulation was also studied in zebrafish after dietary exposure to a mixture of BFRs. It was shown that several metabolites were formed and retained in zebrafish, which highlights the importance of also searching for and identifying persistent degradation products. Maternal transfer was shown for all BFRs present in the female zebrafish. This shows that zebrafish young (fry) are exposed to these BFRs at approximately the same concentrations as female zebrafish during the early-life stages, when fish are usually most sensitive to organic contaminants. Toxicity of individual BFRs and a BFR mixture was studied in Nitocra spinipes using a silica gel-based system. Highest toxicities were observed for BDE 28, TBBPA, and TBBPA OHEE. In the mixture toxicity study, simultaneous exposure to low concentrations (individually causing no significant effect) of six BFRs significantly affected the survival of Nitocra spinipes. The results from the PBT studies presented in the thesis and literature data were compared with the criteria for PBT classification, as set in the European REACH legislation. Further, some BFRs with physico-chemical properties similar to those of identified PBTs were suggested to be prioritized for future PBT testing.

La contribution de l’inhalation et de la voie percutanée à l’exposition totale à des composés organiques volatils (COV) présents dans l’eau potable est une problématique qui suscite un intérêt grandissant en santé publique et au niveau réglementaire. Jusqu’à tout récemment, seule l’ingestion était considérée dans l’évaluation du risque des contaminants de l’eau. L’objectif de ce projet était de caractériser l’impact de l’exposition multivoie sur la pharmacocinétique et la dose interne de trois COV : le toluène (TOL), le n-hexane (HEX) et le cyclohexane (CYCLO). À cette fin, un modèle expérimental animal a été utilisé et un modèle toxicocinétique à base physiologique (TCBP) a été adapté pour le TOL. Des rats Sprague-Dawley ont été exposés par voies uniques (inhalation, orale et percutanée) ou simultanées (multivoie) aux solvants. Pour le TOL, les trois voies ont été expérimentées, alors que la voie percutanée n’a pas été retenue pour le HEX et le CYCLO. Des prélèvements sanguins ont permis de caractériser les cinétiques sanguines. Les niveaux sanguins, obtenus lors des expositions multivoies, étaient généralement plus élevés que la somme des niveaux associés aux expositions par voies uniques, fait illustré par le rapport des surfaces sous la courbe expérimentale versus les prédictions (TOL : 1,30 et 2,19 ; HEX : 1,55 ; CYCLO : 0,98 et 0,99). Le modèle TCBP prédit bien la cinétique du TOL lors d’expositions par voies uniques et par multivoies. Les données expérimentales obtenues suggèrent que la dose interne résultant d’une exposition multivoie ne peut pas toujours être prédite par la somme des doses internes obtenues lors d’expositions par voies uniques. Ce phénomène serait explicable par la saturation du métabolisme. La modélisation TCBP est un outil efficace pour l’estimation du risque relatif à l’exposition multivoie aux COV présents dans l’eau potable. / The contribution of dermal and inhalation routes of exposure to volatile organic chemicals (VOCs) in drinking water is increasingly drawing attention. Until recently, ingestion was the only route considered in risk assessment of drinking water contaminants. The general objective of this study was to characterize multi-route exposures on the pharmacokinetics and internal dose of three VOCs: toluene (TOL), n-hexane (HEX) and cyclohexane (CYCLO). Towards this goal, an experimental animal model was developed and a physiologically-based toxicokinetic (PBTK) model was adapted in order to take account route-specific absorption parameters of TOL. Sprague-Dawley rats were given a single dose of VOCs by oral ingestion, inhalation or dermal route. Additional groups of rat were exposed by the three routes simultaneously. In the case of HEX and CYCLO, dermal route was not considered. Blood samples were collected in order to compare kinetics following simple and multiroute exposures. Blood levels obtained following multiroute exposures were generally higher than predictions (i.e., the sum of the blood levels obtained for single route exposures) (as revealed by area under curve ratio: TOL :1,30 et 2,19; HEX : 1,55; CYCLO : 0,98 et 0,99). The PBTK model described adequately the kinetics of TOL in rats following single and multiroute exposures. The results suggest that internal dose arising from multiple routes is not necessarely comparable to the sum of the blood levels obtained for single route exposures. This phenomenon would be attributable to degree of saturation during aggregate exposures. Furthermore, the present study demonstrated that PBTK model can be used to predict/interpret blood levels associated with multiroute exposures to VOCs in drinking water, using toluene as a model substance.