Biotransformation Rate Research Articles

Development and intercomparison of single and multicompartment physiologically-based toxicokinetic models: Implications for model selection and tiered modeling frameworks

This study describes the development and intercomparison of generic physiologically-based toxicokinetic (PBTK) models for humans comprised of internally consistent one-compartment (1Co-) and multi-compartment (MCo-) implementations (G-PBTK). The G-PBTK models were parameterized for an adult male (70 kg) using common physiological parameters and in vitro biotransformation rate estimates and subsequently evaluated using independent concentration versus time data (n = 6) and total elimination half-lives (n = 15) for diverse organic chemicals. The model performance is acceptable considering the inherent uncertainty in the biotransformation rate data and the absence of model calibration. The G-PBTK model was then applied using hypothetical neutral organics, acidic ionizable organics and basic ionizable organics (IOCs) to identify combinations of partitioning properties and biotransformation rates leading to substantial discrepancies between 1Co- and MCo-PBTK calculations for whole body concentrations and half-lives. The 1Co- and MCo-PBTK model calculations for key toxicokinetic parameters are broadly consistent unless biotransformation is rapid (e.g., half-life less than five days). When half-lives are relatively short, discrepancies are greatest for the neutral organics and least for the acidic IOCs which follows from the estimated volumes of distribution (e.g., VDSS = 9.6–15.4 L/kg vs 0.3–1.6 L/kg for the neutral and acidic compounds respectively) and the related approach to internal chemical equilibrium. The model intercomparisons demonstrate that 1Co-PBTK models can be applied with confidence to many exposure scenarios, particularly those focused on chronic or repeat exposures and for prioritization and screening-level decision contexts. However, MCo-PBTK models may be necessary in certain contexts, particularly for intermittent, short-term and highly variable exposures. A key recommendation to guide model selection and the development of tiered PBTK modeling frameworks that emerges from this study is the need to harmonize models with respect to parameterization and process descriptions to the greatest extent possible when proceeding from the application of simpler to more complex modeling tools as part of chemical assessment activities.

Relevance of desorption kinetics and permeability for in vitro-based predictions of hepatic clearance in fish.

The impact of desorption kinetics and permeation kinetics on in vitro-based predictions of in vivo hepatic blood clearances is investigated in the present study. Most commonly, possible limitations due to slow desorption of chemicals from albumin or slow permeation of chemicals through cellular membranes are not considered when in vivo clearances are predicted from in vitro biotransformation rate constants. To evaluate whether the most commonly used extrapolation models might thus overlook important kinetic limitations, we compare predictions of in vivo clearance that explicitly consider desorption and permeation kinetics with predictions of in vivo clearance that neglect these aspects. Our results show that strong limitations due to slow permeation kinetics are possible depending on the assumed permeability value. While permeability values estimated with a mechanistic approach are fast enough to avoid significant limitations, other experimentally derived permeability values lead to dramatically decreased in vivo clearance predictions. These latter values lead to unrealistically low in vivo biotransformation estimates. Furthermore, we also evaluated the implications of desorption kinetics using experimentally determined desorption rate constants. These evaluations show that slow desorption kinetics are unlikely to limit in vivo clearance.

Biotransformation of 5,7-Methoxyflavones by Selected Entomopathogenic Filamentous Fungi

5,7-Dimethoxyflavone, a chrysin derivative, occurs in many plants and shows very low toxicity, even at high doses. On the basis of this phenomenon, we biotransformed a series of methoxy-derivatives of chrysin, apigenin, and tricetin obtained by chemical synthesis. We used entomopathogenic fungal strains with the confirmed ability of simultaneous hydroxylation/demethylation and glycosylation of flavonoid compounds. Both the amount and the place of attachment of the methoxy group influenced the biotransformation rate and the product's amount nascent. Based on product and semi-product structures, it can be concluded that they are the result of cascading transformations. Only in the case of 5,7,3',4',5'-pentamethoxyflavone, the strains were able to attach a sugar molecule in place of the methoxy substituent to give 3'-O-β-d-(4″-O-methylglucopyranosyl)-5,7,4',5'-tetramethoxyflavone. However, we observed the tested strains' ability to selectively demethylate/hydroxylate the carbon C-3' and C-4' of ring B of the substrates used. The structures of four hydroxyl-derivatives were determined: 4'-hydroxy-5,7-dimethoxyflavone, 3'-hydroxy-5,7-dimethoxyflavone, 3'-hydroxy-5,7,4',5'-tetramethoxyflavone, and 5,7-dimethoxy-3',4'-dihydroxyflavone (5,7-dimethoxy-luteolin).

Acritical review and weight of evidence approach for assessing the bioaccumulation of phenanthrene in aquatic environments.

Bioaccumulation (B) assessment is challenging because there are various B‐metrics from laboratory and field studies, multiple criteria and thresholds for classifying bioaccumulative (B), very bioaccumulative (vB), and not bioaccumulative (nB) chemicals, as well as inherent variability and uncertainty in the data. These challenges can be met using a weight of evidence (WoE) approach. The Bioaccumulation Assessment Tool (BAT) provides a transparent WoE assessment framework that follows Organisation for Economic Co‐operation and Development (OECD) principles for performing a WoE analysis. The BAT guides an evaluator through the process of data collection, generation, evaluation, and integration of various lines of evidence (LoE) (i.e., B‐metrics) to inform decision‐making. Phenanthrene (PHE) is a naturally occurring chemical for which extensive B and toxicokinetics data are available. A B assessment for PHE using the BAT is described that includes a critical evaluation of 74 measured in vivo LoE for fish and invertebrate species from laboratory and field studies. The number of LoE are reasonably well balanced across taxa (i.e., fish and invertebrates) and the different B‐metrics. Additionally, in silico and in vitro biotransformation rate estimates and corresponding model‐predicted B‐metrics are included as corroborating evidence. Application of the BAT provides a consistent, coherent, and scientifically defensible WoE evaluation to conclude that PHE is not bioaccumulative (nB) because the overwhelming majority of the bioconcentration, bioaccumulation, and biomagnification metrics for both fish and invertebrates are below regulatory thresholds. An analysis of the relevant data using fugacity ratios is also provided, showing that PHE does not biomagnify in aquatic food webs. The critical review identifies recommendations to increase the consistency of B assessments, such as improved standardization of B testing guidelines, data reporting requirements for invertebrate studies, and consideration of temperature and salinity effects on certain B‐metrics. Integr Environ Assess Manag 2021;17:911–925. © 2021 Concawe. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)

The added value of Bayesian inference for estimating biotransformation rates of organic contaminants in aquatic invertebrates.

Toxicokinetic (TK) models refer to the process of contaminant bioaccumulation as a balance between rate of uptake from different sources (e.g., water or food), and rate of elimination via different processes such as excretion, growth and/or biotransformation. Biotransformation can considerably modify the fate of chemicals in an organism, especially their bioavailability, residence time, and toxicity. Invertebrate models generally neglect this process as they assume a low metabolic activity. However, some species such as Gammarus sp. amphipods are able to metabolize a vast range of organic compounds. Some recent TK models include biotransformation, but they prove limited for estimating related parameters by giving negative values and/or large uncertainties for biotransformation rate(s). Here we propose a generic TK model accounting for biotransformation using a Bayesian framework for simultaneously estimating the parameters. We illustrated the added value of our method by fitting this generic TK model to 22 published datasets of several benthic invertebrate species exposed to different chemicals. All parameters are estimated simultaneously for all datasets and showed narrow estimates. Furthermore, the median model predictions and their 95% credibility intervals showed that the model confidently fitted the data. In most cases the uncertainties around biotransformation rate(s) were reduced in comparison to the original studies. From a methodology standpoint, this paper reflects that Bayesian inference has real added value for simultaneously estimating all TK parameters for parent chemicals and their metabolite(s) based on all available data, while accounting for different types of data and the correlation between parameters. Bayesian inference was able to overcome the limits of previous methods, since no parameters were fixed and no irrelevant negative values were obtained. Moreover, the 95% credibility intervals around model predictions, which are core uncertainties for Environmental Risk Assessment, were easily acquired.

Biotransformation of lincomycin and fluoroquinolone antibiotics by the ammonia oxidizers AOA, AOB and comammox: A comparison of removal, pathways, and mechanisms

In this study, we evaluated the biotransformation mechanisms of lincomycin (LIN) and three fluoroquinolone antibiotics (FQs), ciprofloxacin (CFX), norfloxacin (NFX), and ofloxacin (OFX), which regularly enter aquatic environments through human activities, by different ammonia-oxidizing microorganisms (AOM). The organisms included a pure culture of the complete ammonia oxidizer (comammox) Nitrospira inopinata, an ammonia oxidizing archaeon (AOA) Nitrososphaera gargensis, and an ammonia-oxidizing bacterium (AOB) Nitrosomonas nitrosa Nm90. The removal of these antibiotics by the pure microbial cultures and the protein-normalized biotransformation rate constants indicated that LIN was significantly co-metabolically biotransformed by AOA and comammox, but not by AOB. CFX and NFX were significantly co-metabolized by AOA and AOB, but not by comammox. None of the tested cultures transformed OFX effectively. Generally, AOA showed the best biotransformation capability for LIN and FQs, followed by comammox and AOB. The transformation products and their related biotransformation mechanisms were also elucidated. i) The AOA performed hydroxylation, S-oxidation, and demethylation of LIN, as well as nitrosation and cleavage of the piperazine moiety of CFX and NFX; ii) the AOB utilized nitrosation to biotransform CFX and NFX; and iii) the comammox carried out hydroxylation, demethylation, and demethylthioation of LIN. Hydroxylamine, an intermediate of ammonia oxidation, chemically reacted with LIN and the selected FQs, with removals exceeding 90%. Collectively, these findings provide important fundamental insights into the roles of different ammonia oxidizers and their intermediates on LIN and FQ biotransformation in nitrifying environments including wastewater treatment systems.

Biotic and abiotic transformation of amino acids in cloud water: experimental studies and atmospheric implications

Abstract. The interest in organic nitrogen and particularly in quantifying and studying the fate of amino acids (AAs) has been growing in the atmospheric-science community. However very little is known about biotic and abiotic transformation mechanisms of amino acids in clouds. In this work, we measured the biotransformation rates of 18 amino acids with four bacterial strains (Pseudomonas graminis PDD-13b-3, Rhodococcus enclensis PDD-23b-28, Sphingomonas sp. PDD-32b-11, and Pseudomonas syringae PDD-32b-74) isolated from cloud water and representative of this environment. At the same time, we also determined the abiotic (chemical, OH radical) transformation rates within the same solutions mimicking the composition of cloud water. We used a new approach by UPLC–HRMS (ultra-performance liquid chromatography–high-resolution mass spectrometry) to quantify free AAs directly in the artificial-cloud-water medium without concentration and derivatization. The experimentally derived transformation rates were used to compare their relative importance under atmospheric conditions with loss rates based on kinetic data of amino acid oxidation in the aqueous phase. This analysis shows that previous estimates overestimated the abiotic degradation rates and thus underestimated the lifetime of amino acids in the atmosphere, as they only considered loss processes but did not take into account the potential transformation of amino acids into each other.

Carbonyl reduction pathway in hepatic in vitro metabolism of anthracyclines: Impact of structure on biotransformation rate

Carbonyl reduction biotransformation pathway of anthracyclines (doxorubicin, daunorubicin) is a significant process, associated with drug metabolism and elimination. However, it also plays a pivotal role in anthracyclines-induced cardiotoxicity and cancer resistance. Herein, carbonyl reduction of eight anthracyclines, at in vivo relevant concentrations (20 μM), was studied in human liver cytosol, to describe the relationship between their structure and metabolism. Significant differences of intrinsic clearance between anthracyclines, ranging from 0,62–74,9 μL/min/mg were found and associated with data from in silico analyses, considering their binding in active sites of the main anthracyclines-reducing enzymes: carbonyl reductase 1 (CBR1) and aldo-keto reductase 1C3 (AKR1C3). Partial atomic charges of carbonyl oxygen atom were also determined and considered as a factor associated with reaction rate. Structural features, including presence or absence of side-chain hydroxy group, a configuration of sugar chain hydroxy group, and tetracyclic rings substitution, affecting anthracyclines susceptibility for carbonyl reduction were identified.

Role of Ammonia Oxidation in Organic Micropollutant Transformation during Wastewater Treatment: Insights from Molecular, Cellular, and Community Level Observations.

Organic micropollutants (OMPs) are a threat to aquatic environments, and wastewater treatment plants may act as a source or a barrier of OMPs entering the environment. Understanding the fate of OMPs in wastewater treatment processes is needed to establish efficient OMP removal strategies. Enhanced OMP biotransformation has been documented during biological nitrogen removal and has been attributed to the cometabolic activity of ammonia-oxidizing bacteria (AOB) and, specifically, to the ammonia monooxygenase (AMO) enzyme. Yet, the exact mechanisms of OMP biotransformation are often unknown. This critical review aims to fundamentally and quantitatively evaluate the role of ammonia oxidation in OMP biotransformation during wastewater treatment processes. OMPs can be transformed by AOB via direct and indirect enzymatic reactions: AMO directly transforms OMPs primarily via hydroxylation, while biologically produced reactive nitrogen species (hydroxylamine (NH2OH), nitrite (NO2-), and nitric oxide (NO)) can chemically transform OMPs through nitration, hydroxylation, and deamination and can contribute significantly to the observed OMP transformations. OMPs containing alkyl, aliphatic hydroxyl, ether, and sulfide functional groups as well as substituted aromatic rings and aromatic primary amines can be biotransformed by AMO, while OMPs containing alkyl groups, phenols, secondary amines, and aromatic primary amines can undergo abiotic transformations mediated by reactive nitrogen species. Higher OMP biotransformation efficiencies and rates are obtained in AOB-dominant microbial communities, especially in autotrophic reactors performing nitrification or nitritation, than in non-AOB-dominant microbial communities. The biotransformations of OMPs in wastewater treatment systems can often be linked to ammonium (NH4+) removal following two central lines of evidence: (i) Similar transformation products (i.e., hydroxylated, nitrated, and desaminated TPs) are detected in wastewater treatment systems as in AOB pure cultures. (ii) Consistency in OMP biotransformation (rbio, μmol/g VSS/d) to NH4+ removal (rNH4+, mol/g VSS/d) rate ratios (rbio/rNH4+) is observed for individual OMPs across different systems with similar rNH4+ and AOB abundances. In this review, we conclude that AOB are the main drivers of OMP biotransformation during wastewater treatment processes. The importance of biologically driven abiotic OMP transformation is quantitatively assessed, and functional groups susceptible to transformations by AMO and reactive nitrogen species are systematically classified. This critical review will improve the prediction of OMP transformation and facilitate the design of efficient OMP removal strategies during wastewater treatment.

Feeding composition and sludge retention time both affect (co-)metabolic biotransformation of pharmaceutical compounds in activated sludge systems

The role of heterotrophic and nitrifying microorganisms in the (co-)metabolic biotransformation of 10 pharmaceutically active compounds (PhACs) was investigated. To this aim, biotransformation assays were performed with heterotrophic and nitrifying sludge developed separately in a two-stage full-scale activated sludge system. Each stage was operated at different inflow wastewater characteristics and sludge retention times (on average 8 d and 35 d). The biotransformation capacity of each sludge was evaluated in the absence of primary substrate and in the presence of acetate and ammonium, to independently elucidate the co-metabolic role of heterotrophs and nitrifiers present in both sludges. Trimethoprim, diclofenac and carbamazepine were recalcitrant (removal < 5% after 1 d; biotransformation rate < 50 µg/g VSS·d) under all the tested conditions. High concentrations of caffeine, acetaminophen and iopromide were quickly biotransformed (> 80% after 1 d; > 800 µg/g VSS·d) in the absence of primary substrates. The heterotrophic sludge only showed a co-metabolic effect towards erythromycin, which increased its biotransformation rate between 43% and 53% when acetate and ammonium were supplied. In contrast, when stimulated, nitrifiers and slow-growing heterotrophs present in the nitrifying sludge co-metabolically biotransformed acetaminophen, ibuprofen and naproxen to a significant extent. Sulfamethoxazole was recalcitrant, except when the nitrifying sludge was fed with acetate (> 800 µg/g VSS·d), suggesting that slow-growing heterotrophs co-metabolically biotransformed it. This study provides evidence that biotransformation of PhACs depends on several metabolic activities, as the heterotrophic activity of the nitrifying sludge, which are not only determined by the SRT but also by the feeding composition.

Variation in Methylmercury Metabolism and Elimination in Humans: Physiological Pharmacokinetic Modeling Highlights the Role of Gut Biotransformation, Skeletal Muscle, and Hair.

The biological half-life (t1/2) of methylmercury (MeHg) shows considerable individual variability (t1/2 < 30 to > 120 days), highlighting the importance of mechanisms controlling MeHg metabolism and elimination. Building on a prior physiologically based pharmacokinetic (PBPK) model, we elucidate parameters that have the greatest influence on variability of MeHg t1/2 in the human body. Employing a dataset of parameters for mean organ volumes and blood flow rates appropriate for man and woman (25-35 years) and child (4 - 6 years), we demonstrate model fitness by simulating data from our prior controlled study of MeHg elimination in people. Model predictions give MeHg t1/2 of 46.9, 38.9, and 31.5 days and steady-state blood MeHg of 2.6, 2.6, and 2.3 µg/l in man, woman, and child, respectively, subsequent to a weekly dose of 0.7 µg/kg body weight. The major routes of elimination are biotransformation to inorganic Hg in the gut lumen (73% in adults, 61% in child) and loss of MeHg via excretion within growing hair (13% in adults, 24% in child). Local and global sensitivity analyses of model parameters reveal that variation in biotransformation rate in the gut lumen, and rates of transport between gut lumen and gut tissue, have the greatest influence on MeHg t1/2. Volume and partition coefficients for skeletal muscle (SM) and gut tissue also show significant sensitivity affecting model output of MeHg t1/2. Our results emphasize the role of gut microbiota in MeHg biotransformation, transport kinetics at the level of the gut, and SM mass as moderators of MeHg kinetics in the human body.

Magnetically immobilized edible Bacillus natto for the biotransformation of polydatin to resveratrol and its bioactivity assessment

Resveratrol is a natural polyphenolic compound widely present in plants, which has been widely used in in food additives, beverages, cosmetics and other fields. Whereas, the applicability of resveratrol is limited since it mainly exits in glycosylated form namely polydatin. In the present study, a novel biotransformation strategy was created to produce resveratrol from P. cuspidatum by magnetically immobilized Bacillus natto strains. The biotransformation conditions were statistically investigated though Box-Behnken design (BBD) with three-factor based on single-factor experiments. The optimal conditions were obtained as follows: treated temperature 37 ℃, fermented time 46 h and immobilized beads/solid ratio of 1.4 g/g. After biotransformation, the maximum biotransformation rate of polydatin reached 98.60 %, and the resveratrol yield achieved 11.27 mg/g, which was 18.18-fold to untreated one. In addition, the recovered magnetically immobilized Bacillus natto strains was still obtained 15.47-fold resveratrol yield to that of unfermented one after 3 runs. The new method established in this work could be a sustainable and effective biotransformation technology for resveratrol production from plant.

Recent advances in microencapsulation of drugs for veterinary applications.

Microencapsulation is a process where very minute droplets or particles of solid or liquid or gas are trapped with a polymer to isolate the internal core material from external environmental hazards. Microencapsulation is applied mostly for flavor masking, fortification, and sustained and control release. It improves palatability, absorption, and bioavailability of drugs with good conformity. Microencapsulation has been widely studied in numerous drug delivery systems for human health. The application of microcapsules in the veterinary pharmaceutical sciences is increasing day by day. The treatment systems for humans and animals are likely to be similar, but more complex in the veterinary field due to the diversity of the species, breeds, body size, biotransformation rate, and other factors associated with animal physiology. Commercially viable, economically profitable, and therapeutically effective microencapsulated vaccine, anthelmintic, antibacterial, and other therapeutics have a great demand for livestock and poultry production. Nowadays, researchers emphasize the controlled and sustained-release dosage form of drugs in the veterinary field. This paper has highlighted the microencapsulation materials, preparation techniques, characteristics, roles, and the application of microcapsules in veterinary medicine.

An overview of the complications of acute and chronic mercury exposures. Past, present and future

Mercury is a chemical element that has been known since prehistoric times and has been used over time as a component of paints, in the treatment of various diseases, and later in various industrial compounds. Mercury enters the body transcutaneously, by inhaling or by ingesting food contaminated with mercury. The most common cause of mercury poisoning is eating seafood, but people can get mercury poisoning from industrial processing, thermometers, dental work, and old paints. The most vulnerable are people at occupational risk due to chronic exposure, as well as fetuses in the intrauterine period. Mercury poisoning produces extremely serious effects on the nervous, renal, and gastrointestinal systems. The nature and extent of mercury poisoning depend on factors such as the route of exposure, the rate of exposure, the distribution and biotransformation of mercury in the body, the chemical form of mercury or the mercury compound. Both mercury in the blood and the urine should not exceed 10 μg/L. The critical values of mercury in the blood are &gt;150 μg/L and the lethal ones exceed 800 μg/L. New diagnostic methods allow the rapid and accurate identification of the concentration of mercury in biological products. Treatment is based on the use of chelating agents. However, the prognosis of mercury poisoning is extremely variable, due to the potentially irreversible nature of the lesions.

Ciprofloxacin-degrading Paraclostridium sp. isolated from sulfate-reducing bacteria-enriched sludge: Optimization and mechanism

Ciprofloxacin (CIP), one of the most widely used fluoroquinolone antibiotics, is frequently detected in the effluents of wastewater treatment plants and aquatic environments. In this study, a CIP-degrading bacterial strain was isolated from the sulfate reducing bacteria (SRB)-enriched sludge, identified as Paraclostridium sp. (i.e., strain S2). The effects of critical operational parameters on CIP removal by the strain S2 were systematically studied and these parameters were optimized via response surface methodology to maximize CIP removal. Furthermore, the pathway and kinetics of CIP removal were investigated by varying the initial CIP concentrations (from 0.1 to 20 mg/L). The CIP removal was characterized by rapid sorption followed by biotransformation with a specific biotransformation rate of 1975.7 ± 109.1 µg/g-cell dry weight/h at an initial CIP concentration of 20 mg/L. Based on the main transformation products, several biotransformation pathways have been proposed including piperazine ring cleavage, OH/F substitution, decarboxylation, and hydroxylation as the major transformation reactions catalyzed by cytochrome P450 and dehydrogenases. Acute toxicity assessment apparently shows that CIP biotransformation by strain S2 resulted in the formation of less toxic intermediates. To the best of our knowledge, this is the very first study in which a key functional microbe, Paraclostridium sp., highly effective in CIP biotransformation, was isolated from SRB-enriched sludge. The findings of this study could facilitate in developing appropriate bioaugmentation strategy, and in designing and operating an SRB-based engineered process for treating CIP-laden wastewater.

During the winter, the performance of a temperate-zone channel catfish biofloc technology production system

In an outdoor biofloc technology production system, channel catfish (Ictalurus punctuates) have been successfully produced. In the tropics, outdoor biofloc production systems are used all year, while channel catfish research was limited to the growth season and biofloc production tanks. Harvested and put to rest for the winter. If a biofloc production system is to be used outside, Farmers in temperate latitudes, then, throughout the winter, data gaps related to system and fish performance. This issue must be addressed. The purpose of this research was to fill up these data gaps for channel catfish culture. Low (153.3 mg/L) water from a recently finished biofloc production experiment for this research; high total suspended solids (790.0 mg/L) were maintained. Per water source, there are three 15.7-m3 tanks. For a 152-day period, each type was supplied (8 kg/m3) with market-size channel catfish from the same research. From November through April, you will be studying. During the experiment, mean chlorophyll a concentrations were comparable in both treatments. Treatments diverged after 55 days, and chlorophyll a concentration grew linearly. (P 0.001, R2 = 0.721) in the low solids treatment to a mean final concentration of 2251.7 mg/m3. Ammonia Spikes of ammonium chloride (1.25–1.5 mg TAN) were added three times throughout the experiment. Completely biotransformed, presumably via algal absorption and nitrification. Biotransformation rate of ammonia. In the high solids (P 0.001, R2 = 0.920) and low solids (P 0.001, R2 = 0.920), was directly linked to mean water temperature. Treatments with (P = 0.002, R2 = 0.761). In biofloc tanks, catfish survival was excellent (99.75%) throughout the winter. There were no significant differences between the treatments. There was no significant difference in net fish output between the two groups. Treatments. Net fish yields, on the other hand, were 1–4% lower than starting fish biomasses. In the biofloc, there is water. Regardless of the weather, production tanks seemed to maintain their capacity to biotransform ammonia throughout the winter. Regardless of whether phytoplankton or suspended solids predominate, and despite ongoing ammonia nitrogen addition, having a functioning biofloc in the spring eliminates the need for a lengthy start-up period when establishing a new biofloc. Biofloc is completely functioning, as are the TAN and nitrite spikes.

Removal of pharmaceuticals from human urine during storage, aerobic biological treatment, and activated carbon adsorption to produce a safe fertilizer

Urine has great potential to be an effective fertilizer due to its high nutrient content, however, it can contain potentially worrying pharmaceuticals. Our objective was to study whether urine storage and aerobic biological treatment, i.e. nitrification, was sufficient to remove pharmaceuticals or an additional treatment with activated carbon was necessary to produce a fertilizer from urine. We investigated the abatement of twelve pharmaceuticals, including antibiotics and antivirals, in laboratory experiments representing the treatment steps of anaerobic storage of source-separated human urine, stabilization using partial and full nitrification under acclimatized and non-acclimatized conditions, and treatment of nitrified urine using powdered activated carbon (PAC). Two-month-long-term storage of urine was insufficient to substantially degrade the pharmaceuticals, except for hydrochlorothiazide (>90%). In the partial and full nitrification fed-batch reactors, atazanavir, ritonavir, and clarithromycin were rapidly removed, with biotransformation rate constants greater than 10 L gSS−1d−1. Darunavir, emtricitabine, trimethoprim, N4-acetylsulfamethoxazole, sulfamethoxazole, atenolol, diclofenac, and hydrochlorothiazide were degraded slowly, with biotransformation rate constants of < 1 L gSS−1d−1. With 200 mg PAC L−1, at least 90% of each investigated pharmaceutical was removed. Yeast estrogen screen tests and bioluminescence inhibition tests revealed efficient removal of estrogenicity (99%) and toxicity (56%) using nitrification, and a reduction of 89% and 64%, respectively, using 200 mg PAC L−1. With our study, we provide biotransformation rate constants of compounds never previously investigated. We also show that a combination of nitrification and PAC adsorption enables the production of a safe fertilizer with sufficiently low pharmaceutical concentrations and no removal of beneficial nutrients.

A Reduced Model for Bioconcentration and Biotransformation of Neutral Organic Compounds in Midge.

A bioconcentration factor (BCF) database and a toxicokinetic model considering only biota-water partitioning and biotransformation were constructed for neutral organic chemicals in midge. The database contained quality-reviewed BCF and toxicokinetic data with variability constrained to within 0.5 to 1 log unit. Diverse conditions in exposure duration, flow set-up, substrate presence, temperature, and taxonomic classification did not translate into substantial variability in BCF, uptake rate constant (k1 ), or depuration rate constant (kT ), and no systematic bias was observed in BCFs derived in unlabeled versus radiolabeled studies. Substance-specific biotransformation rate constants kM were derived by difference between the calculated biota-water partitioning coefficient (KBW ) and experimental BCF for developing a midge biotransformation model. Experimental midge BCF was modeled as BCF = KBW /(1 + kM/ k2 ) with log kM (kM in h-1 ) = -0.37 log KOW - 0.06T (in K) + 18.87 (root mean square error [RMSE] = 0.60), log k1 (k1 in L kgwet.wt-1 h-1 ) = -0.0747 W (body weight in mgwet.wt ) + 2.35 (RMSE = 0.48). The KBW value was estimated using midge biochemical composition and established polyparameter linear free energy relationships, and the diffusive elimination rate constant (k2 ) was computed as k2 = k1 /KBW. The BCF model predicted >85% of BCFs that associated with neutral organic compounds (log KOW = 1.46 - 7.75) to within 1 log-unit error margin and had comparable accuracy similar to amphipod or fish models. A number of outliers and critical limitations of the kM model were identified and examined, and they largely reflected the inherent limitation of difference-derived kM , the lack of chemical diversity, and inadequate temperature variation in existing data. Future modeling efforts can benefit from more BCF and toxicokinetic observations of BCF on structurally diverse chemicals for model training, validation, and diagnosis. Environ Toxicol Chem 2021;40:57-71. © 2020 SETAC.

Transformation of Trace Organic Contaminants from Reverse Osmosis Concentrate by Open-Water Unit-Process Wetlands with and without Ozone Pretreatment.

Reverse osmosis (RO) treatment of municipal wastewater effluent is becoming more common as water reuse is implemented in water-stressed regions. Where RO concentrate is discharged with limited dilution, concentrations of trace organic contaminants could pose risks to aquatic ecosystems. To provide a low-cost option for removing trace organic compounds from RO concentrate, a pilot-scale treatment system comprising open-water unit-process wetlands with and without ozone pretreatment was studied over a 2-year period. A suite of ecotoxicologically relevant organic contaminants was partially removed via photo- and bio-transformations, including β-adrenergic blockers, antivirals, antibiotics, and pesticides. Biotransformation rates were as fast as or up to approximately 50% faster than model predictions based upon data from open-water wetlands that treated municipal wastewater effluent. Phototransformation rates were comparable to or as much as 60% slower than those predicted by models that accounted for light penetration and scavenging of reactive oxygen species. Several compounds were transformed during ozone pretreatment that were poorly removed in the open-water wetland. The combined treatment system resulted in a decrease in the risk quotients of trace organic contaminants in the RO concentrate, but still dilution may be required to protect sensitive species from urban-use pesticides with low environmental effect concentrations.

Formation of perfluorocarboxylic acids (PFCAs) during the exposure of earthworms to 6:2 fluorotelomer sulfonic acid (6:2 FTSA)

6:2 fluorotelomer sulfonic acid (6:2 FTSA) is a novel perfluorooctane sulfonate (PFOS) alternative used globally in aqueous film forming foams (AFFFs). Although 6:2 FTSA has been recently detected in the environment, its fate in terrestrial invertebrates remains unclear. The uptake, elimination and biotransformation of 6:2 FTSA in earthworms (Eisenia fetida) were investigated after in vivo and in vitro exposure. 6:2 FTSA could be biodegraded by microorganisms in soil to trifluoroacetic acid (TFA), perfluoropropionic acid (PFPrA), perfluorobutanoic acid (PFBA), perfluoropentanoic acid (PFPeA) and perfluorohexanoic acid (PFHxA). The uptake rate constant (ku) and biota-to-soil accumulation factor (BSAF) of 6:2 FTSA in earthworms were 0.185 goc/gww/d and 0.685 goc/gww, respectively, indicating high bioaccumulative ability in earthworms. Five terminal perfluorocarboxylic acids (PFCAs) metabolites, including TFA, PFPrA, PFBA, PFPeA and PFHxA were observed in both in vivo and in vitro exposure tests, with TFA as the predominant metabolite. However, no perfluoroheptanoic acid (PFHpA) was observed in the present study. The elimination rate constants (ke) increased in the order: 6:2 FTSA (0.057/d) < TFA (0.058/d) < PFPrA (0.071/d) < PFBA (0.084/d) < PFHxA (0.182/d) < PFPeA (0.193/d). Biodegradation of 6:2 FTSA in the earthworm homogenates, cytolchrome P450 (CYP450) enzyme solutions and glutathione-s-transferase (GST) enzyme solutions fitted well with the first order kinetics. The biotransformation rate constants (k) were in the following order: homogenates (0.012/h) > CYP450 (0.009/h) > GST (0.007/h), implying that CYP450 and GST were involved in biotransformation of 6:2 FTSA in earthworms. This study provides important theoretical evidence for the fate of 6:2 FTSA in earthworms.