Application of quantitative structure--activity relationships for assessing the aquatic toxicity of phthalate esters

Phthalate esters (PEs) are an important class of industrial chemicals for which an extensive aquatic toxicity database is available. The objectives of this study were to use these data to develop quantitative structure-activity relationships (QSARs) that describe aquatic toxicity for different freshwater and marine species, gain insights into toxicity mechanisms, and calculate PE water quality criteria using statistical extrapolation procedures. Results for low-molecular-weight PEs with log Kow<6 indicate that toxicity data conform to a simple log Kow-dependent QSAR. Fish were found to be more sensitive than algae while invertebrates spanned a wide range in toxicological response. Freshwater and marine species demonstrated a similar distribution of sensitivities. Comparison of species-dependent QSARs supports the hypothesis that biotransformation plays an important role in explaining toxicity differences observed between species. Estimated critical body residues (CBRs) for parent PE in fish were in the range reported for other polar organic chemicals while CBRs for parent PE plus associated metabolites were in the range reported for nonpolar narcotics (i.e., baseline toxicity) suggesting a possible putative role of PE metabolites. Depending on extrapolation procedure and assumptions, predicted no-effect concentrations (PNECs) for dimethyl, diethyl, dibutyl, and butybenzyl phthalate ranged from 3109 to 4780, 865 to 1173, 43 to 62, and 38 to 60 microg l(-1), respectively. PNECs derived using this approach provide a transparent technical basis to support aquatic risk assessment for low-molecular-weight PEs. Results for high-molecular-weight PEs (log Kow>6) indicate that these chemicals are not acutely or chronically toxic to freshwater or marine organisms due to the combined role of low water solubility and limited bioconcentration potential which precludes attainment of internal concentrations that are required to elicit adverse effects. It is concluded that attempts to establish aquatic PNECs for high-molecular-weight PEs are not scientifically defensible.