During the past several years, concern has risen over potential pollution of waterways with estrogenic compounds, including steroidal hormones from human and animal sources. One potential source of steroid hormone contamination is through the incomplete removal of these compounds in wastewater treatment systems (WTS). To address this issue, laboratory mineralization assays using 14C-labeled estrogens and testosterone were performed with biosolids from four municipal treatment plants and one industrial system. The importance of adapted microbial populations in the removal of estrogen was shown by the dramatic differences in mineralization of 14C-17β-estradiol by biosolids from a municipal plant compared to that from the industrial plant, 84% versus 4%, respectively. Indeed, biosolids from all of the municipal plants mineralized 70−80% of added 14C-17β-estradiol to 14CO2 in 24 h. Removal of 14C-17β-estradiol from the aqueous phase by biodegradation and/or biosorption to cell matter was greater than 90%. A recombinant yeast estrogen assay (YES assay) also confirmed that biological estrogenic activity was removed from the biosolid samples to below the detection limit (1.56 nM). 14C-Testosterone was mineralized to 14CO2 in all four municipal biosolids in amounts ranging from 55% to 65%; moreover, total removal of 14C-testosterone from the aqueous phase was 95%. First-order rate constants k were obtained for the mineralization and removal from the aqueous phase of natural and a synthetic steroid hormone in biosolids from one WTP. In these biosolids, 14C-17β-estradiol and 14C-testosterone were rapidly mineralized to 14C-CO2 (k = 0.0042 ±0.0002 min-1 and 0.0152 ± 0.0021 min-1, respectively), whereas the mineralization of the synthetic estrogen 14C-17α-ethinylestradiol was 25−75-fold less (k = 0.0002 ± 0.0000 min-1). In addition, mineralization of 14C-ethinylestradiol did not reach completion in 24 h with only 40% mineralized to 14C-CO2. Approximately 20% of the 14C-ethinylestradiol remained in the aqueous phase and was biologically active as determined by the YES assay. Changes in temperature of approximately 15 °C had a statistically significant effect on the rate of mineralization and removal of 14C-17β-estradiol from the aqueous phase but not for 14C-testosterone or 14C-17α-ethinylestradiol. These results suggest that biosolids in municipal plants in this region have the capability to remove natural steroid hormones in their influents over a range of temperatures but may be less effective at removing the synthetic estrogen 17α-ethinylestradiol.
The aim of this study was to determine which descriptor best parametrized the electrophilicity of aromatic compounds with regard to their acute toxicity. To achieve this, toxicity data for 203 substituted aromatic compounds containing a nitro- or cyano group were evaluated in the 40-h Tetrahymena pyriformis population growth impairment assay. Quantitative structure-activity relationships (QSARs) were developed relating toxic potency [log(IGC(50)(-1))] with hydrophobicity quantified by the 1-octanol/water partition coefficient (log P) and electrophilic reactivity quantified by the molecular orbital parameters, either the energy of the lowest unoccupied molecular orbital (E(LUMO)) or maximum acceptor superdelocalizability (A(max)) was developed. For the full data set, E(LUMO) and A(max) were collinear (r = 0.87). A comparison of the QSARs [log(IGC(50)(-1)) = 0.40 log P - 0.94E(LUMO) - 1.27; n = 203, r(2) = 0.60, s = 0.49, F = 151] and [log(IGC(50)(-1)) = 0.37 log P + 13.1A(max) - 4.30; n = 203, r(2) = 0.70, s = 0.42, F = 237] reveals A(max) to be the better electrophilic parameter for modeling these data. Analysis of outliers indicates a preponderance of 4-subsituted nitrophenols and nitroanilines. Smaller datasets (51 and 102 compounds) selected in order to reduce the collinearity between A(max) and E(LUMO) were also evaluated. Results indicate A(max) to be the superior descriptor of electrophilicity for the purpose of toxicological QSARs for aromatic compounds. Development of QSARs using partial least-squares yielded similar results.
Abstract-In a previous study, structure-based rules were formulated to predict estrogenicity of phenolic molecules. The determination of estrogenic activity (EC50) and acute toxicity (LC50) of benzophenones was undertaken, and experimental and predicted estrogenic potency values were compared. The Saccharomyces cerevisiae-based lac-Z reporter assay was used to generate experimental data. Estrogenicity was measured colormetrically as -galactosidase activity. On the basis of the series of rules, -galactosidase activity was predicted correctly for 14 of the 18 benzophenones tested. As predicted, benzophenone, as well as derivatives with a methyl-, chloro-, or nitro-substituent, exhibited no -galactosidase activity. As anticipated, 4-hydroxybenzophenone exhibited weak -galactosidase activity (EC50 value of e-06 M). The 3-hydroxybenzophenone exhibited almost the same activity as the 4-hydroxy derivative, whereas the 2-hydroxy derivative was nonactive. It was observed while replacing the para-hydroxyl group with an amino moiety decreased -galactosidase activity by a half order of magnitude, replacement of the para-hydroxy moiety with a methoxy group negated activity. The nonsymmetrical trihydroxylated benzophenone exhibited activity near to the monohydroxyl derivative. Near symmetrical tri-and symmetrical tetrahydroxylated benzophenones were determined to have greater estrogenic activity (EC50 values of e-07 M) than nonsymmetrical molecules. A comparison of estrogenicity (EC50) with acute toxicity (LC50) reveals a less than a 10-fold difference in activities for weaker estrogenic compounds. However, the more hydrophilic, stronger estrogenic compounds typically exhibit a difference of two to three orders of magnitude between EC50 and LC50 values.
Carboxylic acids have been conspicuously absent from the quantitative structure activity relationship (QSAR) literature. This study investigated the aquatic toxicity (log(IGC50(-1)) of selected mono- and di-carboxylic acids and their sodium, or disodium salts, tested in the Tetrahymena population growth assay. The relationship between log(IGC50(-1)) and hydrophobicity as described by the 1-octanol/water partition coefficient (log Kow) revealed a distinct sub-class. The relationship [log(IGC50(-1)) = 0.27(log Kow) - 0.68; n = 16, r2 = 0.943, s = 0.07, F = 233, Pr > F = 0.0001] was derived for mono-carboxylic acids. The QSAR [log(IGC50(-1)) = 0.19(log Kow) - 0.66; n = 9, r2 = 0.951, s = 0.08, F = 135, Pr > F = 0.0001] was generated for the di-carboxylic acids. Regression analysis of data for the monosodium carboxylic acid salts yielded the model, log(IGC50(-1)) = 0.60 (log Kow) + 0.58; n = 4, r2 = 0.932, s = 0.19, F = 41.2, Pr > F = 0.008. Values for the ionization constant (pKa) and the energy of the lowest unoccupied molecular orbital (ELUMO) do not vary within the sub-class for saturated acids. Moreover, pKa and ELUMO did not describe differences in toxicity between sub-classes of saturated aliphatic carboxylic acids and salts. However, these descriptors did vary for unsaturated acids. Inclusion of unsaturated acids afforded the derivation of a global response-surface for all aliphatic carboxylic acids, log(IGC50(-1)) = 0.25(log Kow) - 0.13(ELUMO) - 0.54; n = 34, r2 = 0.850, s = 0.138, F = 87.9, Pr > F = 0.0001. Outliers to the response-surface included small molecules that provided 2-positions in which the molecule could potentially undergo electrophilic attacked and other more large, hydrophobic molecules.
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