Transformation kinetics of cyclophosphamide and ifosfamide by ozone and hydroxyl radicals using continuous oxidant addition reactors.

The detection of pharmaceuticals in water and wastewater has triggered human and ecological health concerns. As highly toxic compounds, chemotherapy agents (CAs), such as the cyclophosphamide (CYP) and ifosfamide (IFO) structural isomers, represent a unique threat. This research elucidated the fate of CYP and IFO during ozonation and advanced oxidation by hydroxyl radicals (HO•). Novel semi-batch reactors were used to determine the second-order rate constants for CYP and IFO with O3 and HO•. These reactors provided independent control of the oxidant exposure through continuous and constant aqueous ozone and peroxone (O3-H2O2) addition. The rate constants for transformation of CYP and IFO by ozone were 2.58 ± 0.40 M-1s-1 and 6.95 ± 0.21 M-1s-1, respectively, indicating that ozone alone is not suitable for treating CAs. Transformation of CYP and IFO by hydroxyl radicals was fast, with rate constants of 2.69(±0.17)×109 M-1s-1 and 2.73(±0.16)×109 M-1s-1, respectively. The major transformation products formed by O3 and HO attack consisted of the 4-hydroxy-, 4-keto-, dechloroethyl-, and imino- derivatives of CYP and IFO. Low yields of the active metabolites of the CAs, namely phosphoramide mustard and isophosphoramide mustard, were detected. These findings suggest that treated water may retain the ability to alkylate DNA and confer toxicity.

Importance of doping, dopant distribution, and defects on electronic band structure alteration of metal oxide nanoparticles: Implications for reactive oxygen species.

Metal oxide nanoparticles (MONPs) are considered to have the potency to generate reactive oxygen species (ROS), one of the key mechanisms underlying nanotoxicity. However, the nanotoxicology literature demonstrates a lack of consensus on the dominant toxicity mechanism(s) for a particular MONP. Moreover, recent literature has studied the correlation between band structure of pristine MONPs to their ability to introduce ROS and thus has downplayed the ROS-mediated toxicological relevance of a number of such materials. On the other hand, material science can control the band structure of these materials to engineer their electronic and optical properties and thereby is constantly modulating the pristine electronic structure. Since band structure is the fundamental material property that controls ROS-producing ability, band tuning via introduction of dopants and defects needs careful consideration in toxicity assessments. This commentary critically evaluates the existing material science and nanotoxicity literature and identifies the gap in our understanding of the role of important crystal structure features (i.e., dopants and defects) on MONPs' electronic structure alteration as well as their ROS-generation capability. Furthermore, this commentary provides suggestions on characterization techniques to evaluate dopants and defects on the crystal structure and identifies research needs for advanced theoretical predictions of their electronic band structures and ROS-generation abilities. Correlation of electronic band structure and ROS will not only aid in better mechanistic assessment of nanotoxicity but will be impactful in designing and developing ROS-based applications ranging from water disinfection to next-generation antibiotics and even cancer therapeutics.

Bioavailability of Fullerene under Environmentally Relevant Conditions: Effects of Humic Acid and Fetal Bovine Serum on Accumulation in Lipid Bilayers and Cellular Uptake.

Carbon fullerene (C60) has emerged at the forefront of nanoscale research and application due to its unique properties. As the production of this nanoparticle rapidly increases, it can be released into natural aquatic environments and can accumulate in biological systems. This research examined the effects of humic acid and fetal bovine serum (FBS), which are ubiquitous in aquatic environments and representative of blood plasma in living organisms, respectively, on bioavailability of fullerene. Bioavailability was investigated using in vitro methods for lipid membrane accumulation and cellular uptake studies. Humic acid and FBS significantly changed the characteristics of fullerene including its particle size and surface charge. The effects of humic acid on lipid accumulation of fullerene depended on the lipid head charge. FBS also significantly decreased the lipid accumulation when positively charged and zwitterionic head groups were present on the lipids, possibly due to the higher steric repulsion of the protein coated nanoparticles. In addition, both humic acid and FBS protein effectively lowered the amounts of fullerene taken up by Caco-2 cells, which are derived from a human colorectal adenocarcinoma and have similar functions to the small intestinal epithelium. Results of this study suggest that surface modification of fullerene by environmentally relevant matrices can significantly affect the biological transport, as well as the possible toxicity of this nanomaterial.

A coupled sensor-spectrophotometric device for continuous measurement of formaldehyde in indoor environments.

Despite long-standing awareness of adverse health effects associated with chronic human exposure to formaldehyde, this hazardous air pollutant remains a challenge to measure in indoor environments. Traditional analytical techniques evaluate formaldehyde concentrations over several hours to several days in a single location in a residence, making it difficult to characterize daily temporal and spatial variation in human exposure to formaldehyde. There is a need for portable, easy-to-use devices that are specific and sensitive to gas-phase formaldehyde over short sampling periods so that dynamic processes governing formaldehyde fate, transport, and potential remediation in indoor environments may be studied more effectively. A recently developed device couples a chemical sensor element with spectrophotometric analysis for detection and quantification of part per billion (ppbv) gas-phase formaldehyde concentrations. This study established the ability of the coupled sensor-spectrophotometric device (CSSD) to report formaldehyde concentrations accurately and continuously on a 30-min sampling cycle at low ppbv concentrations previously untested for this device in a laboratory setting. Determination of the method detection limit (MDL), based on 40 samples each at test concentrations of 5 and 10 ppbv, was found to be 1.9 and 2.0 ppbv, respectively. Performance of the CSSD was compared with the dinitrophenylhydrazine (DNPH) derivatization method for formaldehyde concentrations ranging from 5-50 ppbv, and a linear relationship with a coefficient of determination of 0.983 was found between these two analytical techniques. The CSSD was also used to monitor indoor formaldehyde concentrations in two manufactured homes. During this time, formaldehyde concentrations varied from below detection limit to 65 ppbv and were above the US National Institute for Occupational Safety and Health (NIOSH) recommended exposure limit (REL) of 16 ppbv, which is also the exposure limit value now adopted by the US Federal Emergency Management Agency (FEMA) to procure manufactured housing, 80% and 100% of the time, respectively.

Gas-phase formaldehyde adsorption isotherm studies on activated carbon: correlations of adsorption capacity to surface functional group density.

Formaldehyde (HCHO) adsorption isotherms were developed for the first time on three activated carbons representing one activated carbon fiber (ACF) cloth, one all-purpose granular activated carbon (GAC), and one GAC commercially promoted for gas-phase HCHO removal. The three activated carbons were evaluated for HCHO removal in the low-ppm(v) range and for water vapor adsorption from relative pressures of 0.1-0.9 at 26 °C where, according to the IUPAC isotherm classification system, the adsorption isotherms observed exhibited Type V behavior. A Type V adsorption isotherm model recently proposed by Qi and LeVan (Q-L) was selected to model the observed adsorption behavior because it reduces to a finite, nonzero limit at low partial pressures and it describes the entire range of adsorption considered in this study. The Q-L model was applied to a polar organic adsorbate to fit HCHO adsorption isotherms for the three activated carbons. The physical and chemical characteristics of the activated carbon surfaces were characterized using nitrogen adsorption isotherms, X-ray photoelectron spectroscopy (XPS), and Boehm titrations. At low concentrations, HCHO adsorption capacity was most strongly related to the density of basic surface functional groups (SFGs), while water vapor adsorption was most strongly influenced by the density of acidic SFGs.

Modeling binding equilibrium in a competitive estrogen receptor binding assay.

Although the free concentration is more significant in the environmental chemistry and toxicology of receptor-mediated toxicants, few studies have been conducted to use it as a dose-metric. The relative binding affinity of three model endocrine disrupting compounds, diethylstilbestrol (DES), ethynylestradiol (EE2), and bisphenol A (BPA), were evaluated using a competitive ELISA with human estrogen receptor alpha. After measuring the available receptors and the dissociation constant for 17beta-estradiol, binding inhibition curves using the free concentration as the dose-metric were obtained by assuming species equilibrium in the ELISA system and compared with apparent inhibition curves generated using the nominal concentration as the dose-metric. Because ligand binding to estrogen receptors may reduce its free concentration in the assay system, the differences between the two curves for free and nominal concentrations are more significant for more strongly binding ligands. The ratio of a compound's nominal concentration causing 50% inhibition (IC50) to the IC50 of DES, the positive control, was strongly affected by specific assay conditions, while that estimated by modeling free concentration is independent of receptor concentration, indicating that the free concentration is a better dose-metric for a competitive binding assay.

Partitioning of moderately hydrophobic endocrine disruptors between water and synthetic membrane vesicles.

The partition coefficient between water and lipid membrane vesicles (Klipw) has been used as an alternative to the 1-octanol-water partition coefficient (Kow) between water and organic solvent, because it more closely represents actual biological membranes. Despite theoretical differences, log Klipw correlates well with log Kow for conventional nonpolar organic pollutants. In the present study, Klipw values of 11 structurally diverse endocrine-disrupting chemicals (EDCs) were measured for three different types of lipid membrane vesicles from dipalmitoylphosphatidylcholine (DPPC), DPPC/cholesterol, and palmitoyloleoylphosphatidylcholine. Correlation analyses were conducted to evaluate the effects of hydrophobicity, molar liquid volume (MLV), and polar surface area (PSA) for 20 EDCs, including nine from a previous study. Correlations that include MLV and PSA reduce the predicted value of log Klipw, suggesting that lipid membranes are less favorable than 1-octanol for a hydrophobic solute because of the higher molar volume and higher hydrogen-bonding potential. These results suggested that Kow alone has limited potential for estimating Klipw and that additional descriptors are required. In addition, Klipw values vary by as much as two orders of magnitude because of the changes in membrane fluidity and the amount of cholesterol in the lipid bilayer. Therefore, lipid components should be chosen carefully to evaluate the bioconcentration of these compounds.