Aromatic amines sources, environmental impact and remediation

Aromatic amines are widely used industrial chemicals as their major sources in the environment include several chemical industry sectors such as oil refining, synthetic polymers, dyes, adhesives, rubbers, perfume, pharmaceuticals, pesticides and explosives. They result also from diesel exhaust, combustion of wood chips and rubber and tobacco smoke. Some types of aromatic amines are generated during cooking, special grilled meat and fish, as well. The intensive use and production of these compounds explains its occurrence in the environment such as in air, water and soil, thereby creating a potential for human exposure. Since aromatic amines are potential carcinogenic and toxic agents, they constitute an important class of environmental pollutants of enormous concern, which efficient removal is a crucial task for researchers, so several methods have been investigated and applied. In this chapter the types and general properties of aromatic amine compounds are reviewed. As aromatic amines are continuously entering the environment from various sources and have been designated as high priority pollutants, their presence in the environment must be monitored at concentration levels lower than 30 mg L1, compatible with the limits allowed by the regulations. Consequently, most relevant analytical methods to detect the aromatic amines composition in environmental matrices, and for monitoring their degradation, are essential and will be presented. Those include Spectroscopy, namely UV/visible and Fourier Transform Infrared Spectroscopy (FTIR); Chromatography, in particular Thin Layer (TLC), High Performance Liquid (HPLC) and Gas chromatography (GC); Capillary electrophoresis (CE); Mass spectrometry (MS) and combination of different methods including GC-MS, HPLC-MS and CE-MS. Choosing the best methods depend on their availability, costs, detection limit and sample concentration, which sometimes need to be concentrate or pretreated. However, combined methods may give more complete results based on the complementary information. The environmental impact, toxicity and carcinogenicity of many aromatic amines have been reported and are emphasized in this chapter too. Lately, the conventional aromatic amines degradation and the alternative biodegradation processes are highlighted. Parameters affecting biodegradation, role of different electron acceptors in aerobic and anaerobic biodegradation and kinetics are discussed. Conventional processes including extraction, adsorption onto activated carbon, chemical oxidation, advanced oxidation, electrochemical techniques and irradiation suffer from drawbacks including high costs, formation of hazardous by-products and low efficiency. Biological processes, taking advantage of the naturally processes occurring in environment, have been developed and tested, proved as an economic, energy efficient and environmentally feasible alternative. Aerobic biodegradation is one of the most promising techniques for aromatic amines remediation, but has the drawback of aromatic amines autooxidation once they are exposed to oxygen, instead of their degradation. Higher costs, especially due to power consumption for aeration, can also limit its application. Anaerobic degradation technology is the novel path for treatment of a wide variety of aromatic amines, including industrial wastewater, and will be discussed. However, some are difficult to degrade under anaerobic conditions and, thus, other electron acceptors such as nitrate, iron, sulphate, manganese and carbonate have, alternatively, been tested.

TiO2-Photocatalyzed degradation of phenol in saline media in an annular reactor: hydrodynamics, lumped kinetics, intermediates, and acute toxicity

The photocatalytic degradation of phenol in aqueous suspensions of TiO2 under different salt concentrations in an annular reactor has been investigated. In all cases, complete removal of phenol and mineralization degrees above 90% were achieved. The reactor operational parameters were optimized and its hydrodynamics characterized in order to couple mass balance equations with kinetic ones. The photodegradation of the organics followed a Langmuir-Hinshelwood-Hougen-Watson lumped kinetics. From GC/MS analyses, several intermediates formed during oxidation have been identified. The main ones were catechol, hydroquinone, and 3-phenyl-2-propenal, in this order. The formation of negligible concentrations of 4-chlorophenol was observed only in high salinity medium. Acute toxicity was determined by using Artemia sp. as the test organism, which indicated that intermediate products were all less toxic than phenol and a significant abatement of the overall toxicity was accomplished, regardless of the salt concentration.

Inhibition of Mycobacterium tuberculosis tyrosine phosphatase PtpA by synthetic chalcones: Kinetics, molecular modeling, toxicity and effect on growth

Tuberculosis (TB) is a major cause of morbidity and mortality throughout the world, and it is estimated that one-third of the world`s population is infected with Mycobacterium tuberculosis. Among a series of tested compounds, we have recently identified five synthetic chalcones which inhibit the activity of M. tuberculosis protein tyrosine phosphatase A (PtpA), an enzyme associated with M. tuberculosis infectivity. Kinetic studies demonstrated that these compounds are reversible competitive inhibitors. In this work we also carried out the analysis of the molecular recognition of these inhibitors on their macromolecular target, PtpA, through molecular modeling. We observed that the predominant determinants responsible for the inhibitory activity of the chalcones are the positions of the two methoxyl groups at the A-ring, that establish hydrogen bonds with the amino acid residues Arg17, His49, and Thr12 in the active site of PtpA, and the substitution of the phenyl ring for a 2-naphthyl group as B-ring, that undergoes p stacking hydrophobic interaction with the Trp48 residue from PtpA. Interestingly, reduction of mycobacterial survival in human macrophages upon inhibitor treatment suggests their potential use as novel therapeutics. The biological activity, synthetic versatility, and low cost are clear advantages of this new class of potential tuberculostatic agents. (C) 2010 Elsevier Ltd. All rights reserved.

Heterogeneous photocatalytic degradation of acid dyes in aqueous TiO2 suspensions: Kinetics and toxicity

This work assesses the photocatalytic (TiO2/UV) degradation of a simulated acid dye bath (Yellow 3, Red 51, Blue 74, and auxiliary chemicals). Color and phytotoxicity removal were monitored by spectrophotometry and lettuce (Lactuca sativa) seeds as the test organism, respectively. Mineralization was determined by DOC analyses. Photocatalytic, photolytic, and adsorption experiments were performed, showing that adsorption was negligible. After 240 minutes of irradiation, it was achieved 96% and 78% of color removal with photocatalysis and photolysis, respectively. 37% of mineralization occurred with photocatalysis only. The dye bath was rendered completely non-toxic after 60 minutes of photocatalytic treatment; the same result was only achieved with photolysis after 90 minutes. A kinetic model composed of two first-order in series reactions was used. The first photocatalytic decolorization rate constant was k(1) = 0.062 min(-1) and the second k(2) = 0.0043 min(-1), approximately two times greater than the photolytic ones.

TiO(2)-PHOTOCATALYZED DEGRADATION OF PHENOL IN SALINE MEDIA IN AN ANNULAR REACTOR: HYDRODYNAMICS, LUMPED KINETICS, INTERMEDIATES, AND ACUTE TOXICITY

The photocatalytic degradation of phenol in aqueous suspensions of TiO(2) under different salt concentrations in an annular reactor has been investigated. In all cases, complete removal of phenol and mineralization degrees above 90% were achieved. The reactor operational parameters were optimized and its hydrodynamics characterized in order to couple mass balance equations with kinetic ones. The photodegradation of the organics followed a Langmuir-Hinshelwood-Hougen- Watson lumped kinetics. From GC/MS analyses, several intermediates formed during oxidation have been identified. The main ones were catechol, hydroquinone, and 3-phenyl-2-propenal, in this order. The formation of negligible concentrations of 4-chlorophenol was observed only in high salinity medium. Acute toxicity was determined by using Artemia sp. as the test organism, which indicated that intermediate products were all less toxic than phenol and a significant abatement of the overall toxicity was accomplished, regardless of the salt concentration.

Poloxamer-based binary hydrogels for delivering tramadol hydrochloride: sol-gel transition studies, dissolution-release kinetics, in vitro toxicity, and pharmacological evaluation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

SYSTEMIC TOXICITY IN RODENTS FOLLOWING ACUTE AND SUBCHRONIC INHALATION OF FORMALDEHYDE (FLOW CYTOMETRY, CELL CYCLE KINETICS, ALKALINE ELUTION)

Systemic toxicity was evaluated in Sprague-Dawley (SD) rats and A-strain mice exposed to HCHO inhalation at 0, 0.5, 3, or 15 ppm for six hours/day, five days/week for up to 24 weeks. Toxicity was measured by flow cytometry to detect changes in cell cycle RNA and DNA content and by alkaline elution to detect DNA protein cross-link (DPC) formation.^ A G(,2)M block was detected in SD rat marrow following one week of exposure to 0.5, 3, or 15 ppm HCHO, but this block did not persist. No effect was noticed in mouse marrow. Only a minimal increase in RNA content was detected in rat or mouse marrow while exfoliated lung cells showed a significant increase in RNA activity after one week of exposure.^ Acute exposure in SD rats for four hours/day for one or three days at 150 ppm showed an increase in RNA activity in exfoliated lung cells but not in the marrow after one day. On the third day, dead cells were detected in exfoliated lung cells.^ In alkaline elution studies, no DPC were detected in marrow of SD rats after 24 weeks exposure up to 15 ppm. During acute exposures, a dose response relationship was detected in SD rat exfoliated lung cells which yielded cross-linking factors of 0.954, 1.237, and 1.417 following a four hour exposure to 15, 50, or 150 ppm, respectively. No DPC were detected in the marrow at 150 ppm. In vitro exposures to HCHO of CHO and SHE cells and rat marrow cells revealed the production of DPC and DNA-DNA cross-links.^ Cytoxan treatment of SD rats was used to provide positive controls for flow cytometry and alkaline elution. A drastic reduction in RNA content and cycling cells occurred one day following treatment. After four days, RNA content was greatly increased; and on day eleven the marrow had regenerated. DPCs were detected in both the marrow and the exfoliated lung cells.^ The lack of significant responses in SD rats and A-strain mice below 15 ppm HCHO is explainable by host defense mechanisms. Apparently, the mucociliary apparatus and enzymatic detoxification are sufficient to reduce systemic toxicity to low level concentrations of formaldehyde. ^

Delivery of daunorubicin to cancer cells with decreased toxicity by association with a lipidic nanoemulsion that binds to LDL receptors

A lipidic nanoemulsion termed LDE concentrates in neoplastic cells after injection into the bloodstream and thus can be used as a drug carrier to tumour sites. The chemotherapeutic agent daunorubicin associates poorly with LDE; the aim of this study was to clarify whether the derivatization of daunorubicin by the attachment of an oleyl group increases the association with LDE, and to test the cytotoxicity and animal toxicity of the new preparation. The association of oleyl-daunorubicin (oDNR) to LDE showed high yield (93 +/- 2% and 84 +/- 4% at 1:10 and 1:5 drug:lipid mass, respectively) and was stable for at least 20 days. Association with oDNR increased the LDE particle diameter from 42 +/- 4 nm to 75 +/- 6 nm. Cytotoxicity of LDE-oDNR was reduced two-fold in HL-60 and K-562 cell lines, fourteen-fold in B16 cells and nine-fold in L1210 cells when compared with commercial daunorubicin. When tested in mice, LDE-oDNR showed remarkable reduced toxicity (maximum tolerated dose > 253 mu mol kg(-1), compared with <3 mu mol kg(-1) for commercial daunorubicin). At high doses, the cardiac tissue of LDE-oDNR-treated animals had much smaller structural lesions than with commercial daunorubicin. LDE-oDNR is therefore a promising new preparation that may offer superior tolerability compared with commercial daunorubicin.

Sorption kinetics and intrapaticulate diffusivity of As(III) bioremediation from aqueous solution, using modified and unmodified coconut fiber

The pollution and toxicity problems posed by arsenic in the environment have long been established. Hence, the removal and recovery remedies have been sought, bearing in mind the efficiency, cost effectiveness and environmental friendliness of the methods employed. The sorption kinetics and intraparticulate diffusivity of As (III) bioremediation from aqueous solution using modified and unmodified coconut fiber was investigated. The amount adsorbed increased as time increased, reaching equilibrium at about 60 minutes. The kinetic studies showed that the sorption rates could be described by both pseudo-first order and pseudo-second order process with the later showing a better fit with a value of rate constant of 1.16 x 10-4 min-1 for the three adsorbent types. The mechanism of sorption was found to be particle diffusion controlled. The diffusion and boundary layer effects were also investigation. Therefore, the results show that coconut fiber, both modified and unmodified is an efficient sorbent for the removal of As (III) from industrial effluents with particle diffusion as the predominant mechanism.

Polarographic study and electrode kinetics of [Zn(II) - antibiotics - cephaloglycin] system vis a vis kinetics of electrode reactions

Electrode kinetics and complex formation of Zn(II) using doxycycline, chlortetracycline, oxytetracycline, tetracycline, minocycline, amoxicillin, chloramphenicol and cephaloglycin were reported at pH = 7.30 ± 0.01 in = 1.0 molL-1 NaClO4 used as supporting electrolyte at 25.0°C. Kinetic parameters viz. transfer coefficient (α), degree of irreversibility (λ) and rate constant (k) were determined. The study showed that 'Transition state' behaves between reactant (O) and product (R) response to applied potential. The stability constants varied from 2.14 to 10.31 showing that these drugs or their complexes could be used against Zn toxicity.

Semisynthetic aminoglycoside antibiotics : toward biomimetic synthesis, evasion of bacterial resistance and reduced toxicity

Les antibiotiques aminoglycosidiques sont des agents bactéricides de grande valeur et d’efficacité à large spectre contre les pathogènes Gram-positifs et Gram-négatifs, dont plusieurs membres naturels et semisynthétiques sont importants dans l’histoire clinique depuis 1950. Des travaux crystallographiques sur le ribosome, récompensés par le prix Nobel, ont démontré comment leurs diverses structures polyaminées sont adaptées pour cibler une hélice d’ARN dans le centre de codage de la sous-unité 30S du ribosome bactérien. Leur interférence avec l’affinité et la cinétique des étapes de sélection et vérification des tARN induit la synthèse de protéines à basse fidélité, et l’inhibition de la translocation, établissant un cercle vicieux d’accumulation d’antibiotique et de stress sur la membrane. En réponse à ces pressions, les pathogènes bactériens ont évolué et disséminé une panoplie de mécanismes de résistance enzymatiques et d’expulsion : tels que les N acétyltransférases, les O phosphotransférases et les O nucleotidyltransférases qui ciblent les groupements hydroxyle et amino sur le coeur des aminoglycosides; des méthyl-transférases, qui ciblent le site de liaison ribosomale; et des pompes d’expulsion actives pour l’élimination sélective des aminoglycosides, qui sont utilisés par les souches Gram-négatives. Les pathogènes les plus problématiques, qui présentent aujourd’hui une forte résilience envers la majorité des classes d’antibiotiques sur le bord de la pan-résistance ont été nommés des bactéries ESKAPE, une mnémonique pour Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa et Enterobacteriaceae. La distribution globale des souches avec des mécanismes de résistance envers les standards cliniques aminoglycosides, tels que la tobramycine, l’amikacine et la gentamicine, est comprise entre 20 et 60% des isolées cliniques. Ainsi, les aminoglycosides du type 4,6-disubstitués-2-deoxystreptamine sont inadéquats comme thérapies anti-infectieuses à large spectre. Cependant, la famille des aminoglycosides 4,5-disubstitués, incluant la butirosine, la neomycine et la paromomycine, dont la structure plus complexe, pourrait constituter une alternative. Des collègues dans le groupe Hanessian et collaborateurs d’Achaogen Inc. ont démontré que certains analogues de la paraomomycine et neomycine, modifiés par désoxygénation sur les positions 3’ et 4’, et par substitution avec la chaîne N1-α-hydroxy-γ-aminobutyramide (HABA) provenant de la butirosine, pourrait produire des antibiotiques très prometteurs. Le Chapitre 4 de cette dissertation présente la conception et le développement d’une stratégie semi-synthétique pour produire des nouveaux aminoglycosides améliorés du type 4,5 disubstitués, inspiré par des modifications biosynthétiques de la sisomicine, qui frustrent les mécanismes de résistance bactérienne distribuées globalement. Cette voie de synthèse dépend d’une réaction d’hydrogénolyse de type Tsuji catalysée par palladium, d’abord développée sur des modèles monosaccharides puis subséquemment appliquée pour générer un ensemble d’aminoglycosides hybrides entre la neomycine et la sisomicine. Les études structure-activité des divers analogues de cette nouvelle classe ont été évaluées sur une gamme de 26 souches bactériennes exprimant des mécanismes de résistance enzymatique et d’expulsion qui englobe l’ensemble des pathogènes ESKAPE. Deux des antibiotiques hybrides ont une couverture antibacterienne excellente, et cette étude a mis en évidence des candidats prometteurs pour le développement préclinique. La thérapie avec les antibiotiques aminoglycosidiques est toujours associée à une probabilité de complications néphrotoxiques. Le potentiel de toxicité de chaque aminoglycoside peut être largement corrélé avec le nombre de groupements amino et de désoxygénations. Une hypothèse de longue date dans le domaine indique que les interactions principales sont effectuées par des sels des groupements ammonium, donc l’ajustement des paramètres de pKa pourrait provoquer une dissociation plus rapide avec leurs cibles, une clairance plus efficace et globalement des analogues moins néphrotoxiques. Le Chapitre 5 de cette dissertation présente la conception et la synthèse asymétrique de chaînes N1 HABA β substitutées par mono- et bis-fluoration. Des chaînes qui possèdent des γ-N pKa dans l’intervalle entre 10 et 7.5 ont été appliquées sur une neomycine tétra-désoxygénée pour produire des antibiotiques avancés. Malgré la réduction considérable du γ N pKa, le large spectre bactéricide n’a pas été significativement affecté pour les analogues fluorés isosteriques. De plus, des études structure-toxicité évaluées avec une analyse d’apoptose propriétaire d’Achaogen ont démontré que la nouvelle chaîne β,β difluoro-N1-HABA est moins nocive sur un modèle de cellules de rein humain HK2 et elle est prometteuse pour le développement d’antibiotiques du type neomycine avec des propriétés thérapeutiques améliorées. Le chapitre final de cette dissertation présente la proposition et validation d’une synthèse biomimétique par assemblage spontané du aminoglycoside 66-40C, un dimère C2 symétrique bis-imine macrocyclique à 16 membres. La structure proposée du macrocycle a été affinée par spectroscopie nucléaire à un système trans,trans-bis-azadiène anti-parallèle. Des calculs indiquent que l’effet anomérique de la liaison α glycosidique entre les anneaux A et B fournit la pré-organisation pour le monomère 6’ aldéhydo sisomicine et favorise le produit macrocyclique observé. L’assemblage spontané dans l’eau a été étudié par la dimérisation de trois divers analogues et par des expériences d’entre croisement qui ont démontré la généralité et la stabilité du motif macrocyclique de l'aminoglycoside 66-40C.

Controlled release system for ametryn using polymer microspheres: Preparation, characterization and release kinetics in water

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The impact of different nanoparticle surface chemistry and size on uptake and toxicity in a murine macrophage cell line

This study investigated the uptake, kinetics and cellular distribution of different surface coated quantum dots (QDs) before relating this to their toxicity. J774.A1 cells were treated with organic, COOH and NH2 (PEG) surface coated QDs (40 nM). Model 20 nm and 200 nm COOH-modified coated polystyrene beads (PBs) were also examined (50 microg ml(-1)). The potential for uptake of QDs was examined by both fixed and live cell confocal microscopy as well as by flow cytometry over 2 h. Both the COOH 20 nm and 200 nm PBs were clearly and rapidly taken up by the J774.A1 cells, with uptake of 20 nm PBs being relatively quicker and more extensive. Similarly, COOH QDs were clearly taken up by the macrophages. Uptake of NH2 (PEG) QDs was not detectable by live cell imaging however, was observed following 3D reconstruction of fixed cells, as well as by flow cytometry. Cells treated with organic QDs, monitored by live cell imaging, showed only a small amount of uptake in a relatively small number of cells. This uptake was insufficient to be detected by flow cytometry. Imaging of fixed cells was not possible due to a loss in cell integrity related to cytotoxicity. A significant reduction (p<0.05) in the fluorescent intensity in a cell-free environment was found with organic QDs, NH2 (PEG) QDs, 20 nm and 200 nm PBs at pH 4.0 (indicative of an endosome) after 2 h, suggesting reduced stability. No evidence of exocytosis was found over 2 h. These findings confirm that surface coating has a significant influence on the mode of NP interaction with cells, as well as the subsequent consequences of that interaction.

Effects of Natural Organic Matter on the Dissolution Kinetics and Bioavailability of Metal Oxide Nanoparticles

The rapid development of nanotechnology and wider applications of engineered nanomaterials (ENMs) in the last few decades have generated concerns regarding their environmental and health risks. After release into the environment, ENMs undergo aggregation, transformation, and, for metal-based nanomaterials, dissolution processes, which together determine their fate, bioavailability and toxicity to living organisms in the ecosystems. The rates of these processes are dependent on nanomaterial characteristics as well as complex environmental factors, including natural organic matter (NOM). As a ubiquitous component of aquatic systems, NOM plays a key role in the aggregation, dissolution and transformation of metal-based nanomaterials and colloids in aquatic environments.

The goal of this dissertation work is to investigate how NOM fractions with different chemical and molecular properties affect the dissolution kinetics of metal oxide ENMs, such as zinc oxide (ZnO) and copper oxide (CuO) nanoparticles (NPs), and consequently their bioavailability to aquatic vertebrate, with Gulf killifish (Fundulus grandis) embryos as model organisms.

ZnO NPs are known to dissolve at relatively fast rates, and the rate of dissolution is influenced by water chemistry, including the presence of Zn-chelating ligands. A challenge, however, remains in quantifying the dissolution of ZnO NPs, particularly for time scales that are short enough to determine rates. This dissertation assessed the application of anodic stripping voltammetry (ASV) with a hanging mercury drop electrode to directly measure the concentration of dissolved Zn in ZnO NP suspensions, without separation of the ZnO NPs from the aqueous phase. Dissolved zinc concentration measured by ASV ([Zn]ASV) was compared with that measured by inductively coupled plasma mass spectrometry (ICP-MS) after ultracentrifugation ([Zn]ICP-MS), for four types of ZnO NPs with different coatings and primary particle diameters. For small ZnO NPs (4-5 nm), [Zn]ASV was 20% higher than [Zn]ICP-MS, suggesting that these small NPs contributed to the voltammetric measurement. For larger ZnO NPs (approximately 20 nm), [Zn]ASV was (79±19)% of [Zn]ICP-MS, despite the high concentrations of ZnO NPs in suspension, suggesting that ASV can be used to accurately measure the dissolution kinetics of ZnO NPs of this primary particle size.

Using the ASV technique to directly measure dissolved zinc concentration, we examined the effects of 16 different NOM isolates on the dissolution kinetics of ZnO NPs in buffered potassium chloride solution. The observed dissolution rate constants (kobs) and dissolved zinc concentrations at equilibrium increased linearly with NOM concentration (from 0 to 40 mg-C L-1) for Suwannee River humic acid (SRHA), Suwannee River fulvic acid and Pony Lake fulvic acid. When dissolution rates were compared for the 16 NOM isolates, kobs was positively correlated with certain properties of NOM, including specific ultraviolet absorbance (SUVA), aromatic and carbonyl carbon contents, and molecular weight. Dissolution rate constants were negatively correlated to hydrogen/carbon ratio and aliphatic carbon content. The observed correlations indicate that aromatic carbon content is a key factor in determining the rate of NOM-promoted dissolution of ZnO NPs. NOM isolates with higher SUVA were also more effective at enhancing the colloidal stability of the NPs; however, the NOM-promoted dissolution was likely due to enhanced interactions between surface metal ions and NOM rather than smaller aggregate size.

Based on the above results, we designed experiments to quantitatively link the dissolution kinetics and bioavailability of CuO NPs to Gulf killifish embryos under the influence of NOM. The CuO NPs dissolved to varying degrees and at different rates in diluted 5‰ artificial seawater buffered to different pH (6.3-7.5), with or without selected NOM isolates at various concentrations (0.1-10 mg-C L-1). NOM isolates with higher SUVA and aromatic carbon content (such as SRHA) were more effective at promoting the dissolution of CuO NPs, as with ZnO NPs, especially at higher NOM concentrations. On the other hand, the presence of NOM decreased the bioavailability of dissolved Cu ions, with the uptake rate constant negatively correlated to dissolved organic carbon concentration ([DOC]) multiplied by SUVA, a combined parameter indicative of aromatic carbon concentration in the media. When the embryos were exposed to CuO NP suspension, changes in their Cu content were due to the uptake of both dissolved Cu ions and nanoparticulate CuO. The uptake rate constant of nanoparticulate CuO was also negatively correlated to [DOC]×SUVA, in a fashion roughly proportional to changes in dissolved Cu uptake rate constant. Thus, the ratio of uptake rate constants from dissolved Cu and nanoparticulate CuO (ranging from 12 to 22, on average 17±4) were insensitive to NOM type or concentration. Instead, the relative contributions of these two Cu forms were largely determined by the percentage of CuO NP that was dissolved.

Overall, this dissertation elucidated the important role that dissolved NOM plays in affecting the environmental fate and bioavailability of soluble metal-based nanomaterials. This dissertation work identified aromatic carbon content and its indicator SUVA as key NOM properties that influence the dissolution, aggregation and biouptake kinetics of metal oxide NPs and highlighted dissolution rate as a useful functional assay for assessing the relative contributions of dissolved and nanoparticulate forms to metal bioavailability. Findings of this dissertation work will be helpful for predicting the environmental risks of engineered nanomaterials.