Biokinetic Studies Research Articles

Quantitative biokinetics of titanium dioxide nanoparticles after intravenous injection in rats: Part 1

Submicrometer TiO2 particles, including nanoparticulate fractions, are used in an increasing variety of consumer products, as food additives and also drug delivery applications are envisaged. Beyond exposure of occupational groups, this entails an exposure risk to the public. However, nanoparticle translocation from the organ of intake and potential accumulation in secondary organs are poorly understood and in many investigations excessive doses are applied. The present study investigates the biokinetics and clearance of a low single dose (typically 40–400 μg/kg BW) of 48V-radiolabeled, pure TiO2 anatase nanoparticles ([48V]TiO2NP) with a median aggregate/agglomerate size of 70 nm in aqueous suspension after intravenous (IV) injection into female Wistar rats. Biokinetics and clearance were followed from one-hour to 4-weeks. The use of radiolabeled nanoparticles allowed a quantitative [48V]TiO2NP balancing of all organs, tissues, carcass and excretions of each rat without having to account for chemical background levels possibly caused by dietary or environmental titanium exposure. Highest [48V]TiO2NP accumulations were found in liver (95.5%ID after one day), followed by spleen (2.5%), carcass (1%), skeleton (0.7%) and blood (0.4%). Detectable nanoparticle levels were found in all other organs. The [48V]TiO2NP content in blood decreased rapidly after 24 h while the distribution in other organs and tissues remained rather constant until day-28. The present biokinetics study is part 1 of a series of studies comparing biokinetics after three classical routes of intake (IV injection (part 1), ingestion (part 2), intratracheal instillation (part 3)) under identical laboratory conditions, in order to test the common hypothesis that IV-injection is a suitable predictor for the biokinetics fate of nanoparticles administered by different routes. This hypothesis is disproved by this series of studies.

Molecular and Kinetic Characterization of Planktonic Nitrospira spp. Selectively Enriched from Activated Sludge

Nitrospira spp. are chemolithoautotrophic nitrite-oxidizing bacteria (NOB), which are ubiquitous in natural and engineered environments. However, there exist few independent biokinetic studies on Nitrospira spp., likely because their isolation and selective enrichment from environmental consortia such as activated sludge can be challenging. Herein, planktonic Nitrospira spp. cultures closely related to Candidatus Nitrospira defluvii (Nitrospira lineage I) were successfully enriched from activated sludge in a sequencing batch reactor by maintaining sustained limiting extant nitrite and dissolved oxygen concentrations. Morphologically, the enrichment consisted largely of planktonic cells with an average characteristic diameter of 1.3 ± 0.6 μm. On the basis of respirometric assays, estimated maximum specific growth rate (μmax), nitrite half saturation coefficient (KS), oxygen half saturation coefficient (KO), and biomass yield coefficient (Y) of the enriched cultures were 0.69 ± 0.10 d-1, 0.52 ± 0.14 mg-N/L, 0.33 ± 0.14 mg-O2/L, and 0.14 ± 0.02 mg-COD/mg-N, respectively. These parameters collectively reflect not just higher affinities of this enrichment for nitrite and oxygen, respectively, but also a higher biomass yield and energy transfer efficiency relative to Nitrobacter spp. Used in combination, these kinetic and thermodynamic parameters can help toward the development and application of energy-efficient biological nutrient removal processes through effective Nitrospira out-selection.

Optimization and biokinetic studies on pretreatment of sludge for enhancing biogas production

Excess sludge generation is a major problem in biological effluent treatment processes. Utilization of excess sludge for gas production is an attractive route, which could be enhanced by pretreatment methods. This study involves two sets of experiments. The first set covers mechanical pretreatment of both feed and inoculum. The second set involves alkaline and mechanical treatments of feed and only mechanical treatment of inoculum. Response surface methodology was used for experimental design, analysis and optimization. The optimized mechanical treatment volume of feed was found to be 50%. Diligent mechanical treatment of inoculum resulted in enhanced microbial activity and improved gas production. Reduction in volatile solids, proteins and carbohydrates was observed to a maximum of 63, 84 and 78.5%, respectively. Feed was subjected to alkali treatment in order to reduce mechanical energy input and to improve solubilization. Compared to mechanical treatment alone, enhanced gas production of about 15% was observed at an optimized pH of 11.8 and SRT of 21 days. A biokinetic model was formulated, simulated and validated for the degradation of organics and gas production.

Lung and stomach cancer associations with groundwater radon in North Carolina, USA.

The risk of indoor air radon for lung cancer is well studied, but the risks of groundwater radon for both lung and stomach cancer are much less studied, and with mixed results. Geomasked and geocoded stomach and lung cancer cases in North Carolina from 1999 to 2009 were obtained from the North Carolina Central Cancer Registry. Models for the association with groundwater radon and multiple confounders were implemented at two scales: (i) an ecological model estimating cancer incidence rates at the census tract level; and (ii) a case-only logistic model estimating the odds that individual cancer cases are members of local cancer clusters. For the lung cancer incidence rate model, groundwater radon is associated with an incidence rate ratio of 1.03 [95% confidence interval (CI) = 1.01, 1.06] for every 100 Bq/l increase in census tract averaged concentration. For the cluster membership models, groundwater radon exposure results in an odds ratio for lung cancer of 1.13 (95% CI = 1.04, 1.23) and for stomach cancer of 1.24 (95% CI = 1.03, 1.49), which means groundwater radon, after controlling for multiple confounders and spatial auto-correlation, increases the odds that lung and stomach cancer cases are members of their respective cancer clusters. Our study provides epidemiological evidence of a positive association between groundwater radon exposure and lung cancer incidence rates. The cluster membership model results find groundwater radon increases the odds that both lung and stomach cancer cases occur within their respective cancer clusters. The results corroborate previous biokinetic and mortality studies that groundwater radon is associated with increased risk for lung and stomach cancer.

Pulmonary distribution of nanoceria: comparison of intratracheal, microspray instillation and dry powder insufflation

Particles can be delivered to the respiratory tract of animals using various techniques. Inhalation mimics environmental exposure but requires large amounts of aerosolized NPs over a prolonged dosing time, varies in deposited dose among individual animals, and results in nasopharyngeal and fur particle deposition. Although less physiological, intratracheal (IT) instillation allows quick and precise dosing. Insufflation delivers particles in their dry form as an aerosol. We compared the distribution of neutron-activated 141CeO2 nanoparticles (5 mg/kg) in rats after (1) IT instillation, (2) left intrabronchial instillation, (3) microspraying of nanoceria suspension and (4) insufflation of nanoceria dry powder. Blood, tracheobronchial lymph nodes, liver, gastrointestinal tract, feces and urine were collected at 5 min and 24 h post-dosing. Excised lungs from each rat were dried at room temperature while inflated at a constant 30 cm water pressure. Dried lungs were then sliced into 50 pieces. The radioactivity of each lung piece and other organs was measured. The evenness index (EI) of each lung piece was calculated [EI = (μCi/mgpiece)/(μCi/mglung)]. The degree of EI value departure from 1.0 is a measure of deposition heterogeneity. We showed that the pulmonary distribution of nanoceria differs among modes of administration. Dosing by IT or microspraying resulted in similar spatial distribution. Insufflation resulted in significant deposition in the trachea and in more heterogeneous lung distribution. Our left intrabronchial instillation technique yielded a concentrated deposition into the left lung. We conclude that animal dosing techniques and devices result in varying patterns of particle deposition that will impact biokinetic and toxicity studies.

Biokinetic datasets of PEI F25-LMW complexed and non-complexed 32P-siRNA within different lung compartments.

Biokinetics data of lung-administered PEI F25-LMW/siRNA polyplexes within different lung compartments are presented. Thereby, at three different timepoints (1 h, 3 h, 8 h), the data was determined by calculations to the 32P-radioactivity in the whole mouse body. Additionally, data was optimized to the available PEI F25-LMW/siRNA polyplexes in the target organ and therefore normalized to the sum of all lung compartments. Methods, other biokinetics data and the discussion of the results are published in “Biokinetic studies of non-complexed siRNA versus nano-sized PEI F25-LMW/siRNA polyplexes following intratracheal instillation into mice” (Lipka et al., 2016 [1]).

Radioimmunotherapy of prostate cancer targeting human kallikrein-related peptidase 2.

BackgroundProstate cancer ranks as the second most lethal malignancy in the Western world. Previous targeting of prostate-specific antigen and human kallikrein-related peptidase 2, two related enzymes abundantly expressed in prostatic malignancies, with radioimmunoconjugates intended for diagnostic purposes, have proven successful in rodent prostate cancer (PCa) models. In this study, we investigated the uptake and therapeutic efficacy of 177Lu-m11B6, a human kallikrein-related peptidase 2 (hK2)-targeting radioimmunoconjugate in a pre-clinical setting.MethodsThe murine 11B6 antibody, m11B6, with high affinity for hK2, was labeled with 177Lu. Therapy planning was done from a biokinetic study in LNCaP xenografts, and therapeutic activities of 177Lu-m11B6 were administered to groups of mice. Body weight and general conditions of the mice were followed over a period of 120 days.ResultsThe tumor uptake in LNCaP xenografts was 30 ± 8.2 % injected activity per gram 1 week post-injection. In vivo targeting was hK2-specific as verified by a 2.5-fold decrease in tumor uptake in pre-dosed xenografts or by a fourfold lower tumor accumulation in hK2-negative DU 145 xenografts. Therapy showed a dose-dependent efficacy in LNCaP xenografts treated with 177Lu-m11B6. No therapeutic effect was seen in the control groups. The median survival for the lowest given activity of 177Lu-m11B6 was 88 days compared to that of 38 days in mice given labeled non-specific IgG. For the higher administrated activities, total tumor regression was seen with minimal normal organ toxicity.ConclusionsWe have proven the possibility of radioimmunotherapy targeting hK2 in subcutaneous prostate cancer xenografts. 177Lu-m11B6 exhibited high therapeutic efficacy, with low observed toxicity. Additionally, an evaluation of the concept of pre-therapy planning using a dosimetry model was included in this radioimmunotherapy study.

Biokinetic studies of non-complexed siRNA versus nano-sized PEI F25-LMW/siRNA polyplexes following intratracheal instillation into mice

Successful gene therapy requires stability and sufficient bioavailability of the applied drug at the site of action. In the case of RNA interference (RNAi), non-viral vectors play a promising role for delivering intact siRNA molecules. We selected a low molecular weight polyethyleneimine (PEI F25-LMW) and investigated the biokinetics of PEI F25-LMW/siRNA polyplexes in comparison to non-complexed siRNA molecules upon intratracheal application into mice. Additionally, a bronchoalveolar lavage was performed to locate the siRNA within the different lung compartments and to analyse possible inflammatory reactions. Liquid scintillation counting of a 32P-label was used to follow the siRNA within the whole body. During the complete observation time more than 75% of the applied dose was found at the target site. The complexation with PEI F25- LMW prevented the siRNA from being degraded and cleared and prolonged its retention time. A low inflammatory reaction was observed on the basis of cell differentiation. Taken together, PEI F25-LMW meets fundamental requirements on non-viral vectors for local pulmonary siRNA delivery.

Cytotoxicity, Uptake Behaviors, and Oral Absorption of Food Grade Calcium Carbonate Nanomaterials.

Calcium is the most abundant mineral in human body and essential for the formation and maintenance of bones and teeth as well as diverse cellular functions. Calcium carbonate (CaCO3) is widely used as a dietary supplement; however, oral absorption efficiency of CaCO3 is extremely low, which may be overcome by applying nano-sized materials. In this study, we evaluated the efficacy of food grade nano CaCO3 in comparison with that of bulk- or reagent grade nano CaCO3 in terms of cytotoxicity, cellular uptake, intestinal transport, and oral absorption. Cytotoxicity results demonstrated that nano-sized CaCO3 particles were slightly more toxic than bulk materials in terms of oxidative stress and membrane damage. Cellular uptake behaviors of CaCO3 nanoparticles were different from bulk CaCO3 or Ca2+ ions in human intestinal epithelial cells, showing efficient cellular internalization and elevated intracellular Ca2+ levels. Meanwhile, CaCO3 nanoparticles were efficiently transported by microfold (M) cells in vitro model of human intestinal follicle-associated epithelium, in a similar manner as Ca2+ ions did. Biokinetic study revealed that the biological fate of CaCO3 particles was different from Ca2+ ions; however, in vivo, its oral absorption was not significantly affected by particle size. These findings provide crucial information to understand and predict potential toxicity and oral absorption efficiency of food grade nanoparticles.

How meaningful are risk determinations in the absence of a complete dataset? Making the case for publishing standardized test guideline and ‘no effect’ studies for evaluating the safety of nanoparticulates versus spurious ‘high effect’ results from single investigative studies

A recent review article critically assessed the effectiveness of published research articles in nanotoxicology to meaningfully address health and safety issues for workers and consumers. The main conclusions were that, based on a number of flaws in study designs, the potential risk from exposures to nanomaterials is highly exaggerated, and that no ‘nano-specific’ adverse effects, different from exposures to bulk particles, have been convincingly demonstrated. In this brief editorial we focus on a related tangential issue which potentially compromises the integrity of basic risk science. We note that some single investigation studies report specious toxicity findings, which make the conclusions more alarming and attractive and publication worthy. In contrast, the standardized, carefully conducted, ‘guideline study results’ are often ignored because they can frequently report no adverse effects; and as a consequence are not considered as novel findings for publication purposes, and therefore they are never considered as newsworthy in the popular press. Yet it is the Organization for Economic Cooperation and Development (OECD) type test guideline studies that are the most reliable for conducting risk assessments. To contrast these styles and approaches, we present the results of a single study which reports high toxicological effects in rats following low-dose, short-term oral exposures to nanoscale titanium dioxide particles concomitant with selective investigative analyses. Alternatively, the findings of OECD test guideline 408, standardized guideline oral toxicity studies conducted for 90 days at much higher doses (1000 mg kg−1) in male and female rats demonstrated no adverse effects following a very thorough and complete clinical chemical, as well as histopathological evaluation of all of the relevant organs in the body. This discrepancy in study findings is not reconciled by the fact that several biokinetic studies in rats and humans demonstrate little or no uptake of nanoscale or pigment-grade TiO2 particles following oral exposures. We conclude that to develop a competent risk assessment profile, results derived from standardized, guideline-type studies, and even ‘no effect’ study findings provide critically useful input for assessing safe levels of exposure; and should, in principle, be readily acceptable for publication in peer-reviewed toxicology journals. This is a necessary prerequisite for developing a complete dataset for risk assessment determinations.

Toxicity and Biokinetics of Colloidal Gold Nanoparticles.

Gold nanoparticles (Au-NPs) have promising potential for diverse biological application, but it has not been completely determined whether Au-NP has potential toxicity in vitro and in vivo. In the present study, toxicity of Au-NP was evaluated in human intestinal cells as well as in rats after 14-day repeated oral administration. Biokinetic study was also performed to assess oral absorption and tissue distribution. The results demonstrated that Au-NP did not cause cytotoxic effects on cells after 24 h exposure in terms of inhibition of cell proliferation, membrane damage, and oxidative stress. However, when a small number of cells were exposed to Au-NP for seven days, colony forming ability remarkably decreased by Au-NP treatment, suggesting its potential toxicity after long-term exposure at high concentration. Biokinetic study revealed that Au-NP slowly entered the blood stream and slightly accumulated only in kidney after oral administration to rats. Whereas, orally administered Au ions were rapidly absorbed, and then distributed in kidney, liver, lung, and spleen at high levels, suggesting that the biological fate of Au-NP is primarily in nanoparticulate form, not in ionic Au. Fourteen-day repeated oral toxicity evaluation showed that Au-NP did not cause severe toxicity in rats based on histopathological, hematological, and serum biochemical analysis.

Phospholipid derivatives of cladribine and fludarabine: Synthesis and biological properties

Phospholipid derivatives of anticancer nucleosides cladribine and fludarabine (F-ara-A) bearing 1,2- and 1,3-diacylglycerol moieties have been prepared by the H-phosphonate approach using 1,1,3,3-tetraisopropyldisiloxane-1,3-diyl protecting group for cladribine and a combination of tert-butyldimethylsilyl and levulinyl protecting groups for 2-fluoroadenine nucleosides. The synthesized conjugates exhibited lower in vitro antiproliferative activity against human tumor cell lines in comparison with the same concentrations of the parent cladribine and fludarabine phosphate. In the course of biokinetic study, it was found that intragastric administration of phospholipid F-ara-A derivatives to Wistar rats and ICR outbred male mice led to a slow release of F-ara-A into the bloodstream, a smooth increase in nucleoside concentration, and prolonged serum circulation of liberated nucleoside. The oral bioavailability of F-ara-A from 1,2-dimyristoylglycerophosphate derivative 29 was similar to its oral bioavailability from fludarabine phosphate.

Modeling interorgan distribution and bioaccumulation of engineered nanoparticles (using the example of silver nanoparticles)

In this paper we demonstrate the validity of a mathematical chamber model to describe the absorption, distribution, and bioaccumulation of nonmetabolizable nanoparticles (NPs) using the example of silver NPs in the organism of laboratory rat. The model is constructed using experimental data on the bioaccumulation and biodistribution of silver NPs of average diameter of 35 ± 15 nm (M ± SD) radiolabeled with 110mAg. In the minimally acceptable form, the model includes all “chambers” in which NP level in the course of the experiment was no lower than 20–25% of its blood content, namely, the gastrointestinal tract (GIT), blood itself, osteomuscular carcass, liver, and spleen. NP bioaccumulation and biodistribution in these chambers is described by five independent linear differential equations of the 1st order. A numerical solution of this system of equations, with account for the data on timing of NP excretion from the GIT in the content of feces, makes it possible to determine the biokinetic rate constants for the interorgan transfer of NPs. These rate constants are used to establish the dose-dependence of the peak (maximum) and quasi-stationary NP content in critical target organs, respectively, in the case of acute (single) and subchronic (repeated) administration of NP in the gastrointestinal tract. The results justify the value of the method of mathematically modeling the interstitial transport and distribution of NPs to assess their potential toxic effects on a system level using previously obtained in vitro data and results from biokinetic studies.

The fate of calcium carbonate nanoparticles administered by oral route: absorption and their interaction with biological matrices.

BackgroundOrally administered particles rapidly interact with biological fluids containing proteins, enzymes, electrolytes, and other biomolecules to eventually form particles covered by a corona, and this corona potentially affects particle uptake, fate, absorption, distribution, and elimination in vivo. This study explored relationships between the biological interactions of calcium carbonate particles and their biokinetics.MethodsWe examined the effects of food grade calcium carbonates of different particle size (nano [N-Cal] and bulk [B-Cal]: specific surface areas of 15.8 and 0.83 m2/g, respectively) on biological interactions in in vitro simulated physiological fluids, ex vivo biofluids, and in vivo in gastrointestinal fluid. Moreover, absorption and tissue distribution of calcium carbonates were evaluated following a single dose oral administration to rats.ResultsN-Cal interacted more with biomatrices than bulk materials in vitro and ex vivo, as evidenced by high fluorescence quenching ratios, but it did not interact more actively with biomatrices in vivo. Analysis of coronas revealed that immunoglobulin, apolipoprotein, thrombin, and fibrinogen, were the major corona proteins, regardless of particle size. A biokinetic study revealed that orally delivered N-Cal was more rapidly absorbed into the blood stream than B-Cal, but no significant differences were observed between the two in terms of absorption efficiencies or tissue distributions. Both calcium carbonates were primarily present as particulate forms in gastrointestinal fluids but enter the circulatory system in dissolved Ca2+, although both types showed partial phase transformation to dicalcium phosphate dihydrate. Relatively low dissolution (about 4%), no remarkable protein–particle interaction, and the major particulate fate of calcium carbonate in vivo gastrointestinal fluids can explain its low oral absorption (about 4%) regardless of particle size.ConclusionWe conclude that calcium carbonate nanoparticles can act more actively with biological matrices in vitro and ex vivo, but that in vivo, their biological interactions and biokinetics are not affected by particle size.

HPLC Analysis and Bio-kinetics Study of Pyrazinamide in Healthy Volunteers After Oral Administration

Pyrazinamide is use for the treatment of tuberculosis in all over the world. Bio kinetics deals with the mathematical description of drug changes in the body with time function. This study was designed to investigate the bio kinetics of Pyrazinamide after oral administration of Pyrazinamide (25mg) tablet in 10 healthy volunteers. The blood samples of each volunteer were collected from 0.5 to 12 hours at different time intervals after the medication. The concentration of Pyrazinamide in plasma samples were determined by high performance liquid chromatography (HPLC). Quantitative observations were recorded that include the mean ± SD value of absorption rate constant (Ka), time to peak (Tmax) and peak concentration (Cmax) were 0.38 ± 0.25/h, 2.248 ± 0.64 h and 4.165 ± 2.13µg/mL, respectively. The mean ± SD values of absorption half-life (t1/2a) and elimination half-life (t1/2b) were 2.078 ± 1.678h and 0.2908 ± 1.721 hours. The mean ± SD values of volume of distribution and total body clearance were 40 ± 27.4L and 3.351 ± 1.27 h, respectively. Mean residue time (MRT) showed mean ± SD and area under curve (AUC) were 17.23 ± 12.78 h and 90.4 ± 76.2 h.mg/L, respectively.

Biokinetics of zinc oxide nanoparticles: toxicokinetics, biological fates, and protein interaction

Biokinetic studies of zinc oxide (ZnO) nanoparticles involve systematic and quantitative analyses of absorption, distribution, metabolism, and excretion in plasma and tissues of whole animals after exposure. A full understanding of the biokinetics provides basic information about nanoparticle entry into systemic circulation, target organs of accumulation and toxicity, and elimination time, which is important for predicting the long-term toxic potential of nanoparticles. Biokinetic behaviors can be dependent on physicochemical properties, dissolution property in biological fluids, and nanoparticle–protein interaction. Moreover, the determination of biological fates of ZnO nanoparticles in the systemic circulation and tissues is critical in interpreting biokinetic behaviors and predicting toxicity potential as well as mechanism. This review focuses on physicochemical factors affecting the biokinetics of ZnO nanoparticles, in concert with understanding bioavailable fates and their interaction with proteins.

In vitro and in vivo interactions of selected nanoparticles with rodent serum proteins and their consequences in biokinetics.

When particles incorporated within a mammalian organism come into contact with body fluids they will bind to soluble proteins or those within cellular membranes forming what is called a protein corona. This binding process is very complex and highly dynamic due to the plethora of proteins with different affinities and fractions in different body fluids and the large variation of compounds and structures of the particle surface. Interestingly, in the case of nanoparticles (NP) this protein corona is well suited to provide a guiding vehicle of translocation within body fluids and across membranes. This NP translocation may subsequently lead to accumulation in various organs and tissues and their respective cell types that are not expected to accumulate such tiny foreign bodies. Because of this unprecedented NP accumulation, potentially adverse biological responses in tissues and cells cannot be neglected a priori but require thorough investigations. Therefore, we studied the interactions and protein binding kinetics of blood serum proteins with a number of engineered NP as a function of their physicochemical properties. Here we show by in vitro incubation tests that the binding capacity of different engineered NP (polystyrene, elemental carbon) for selected serum proteins depends strongly on the NP size and the properties of engineered surface modifications. In the following attempt, we studied systematically the effect of the size (5, 15, 80 nm) of gold spheres (AuNP), surface-modified with the same ionic ligand; as well as 5 nm AuNP with five different surface modifications on the binding to serum proteins by using proteomics analyses. We found that the binding of numerous serum proteins depended strongly on the physicochemical properties of the AuNP. These in vitro results helped us substantially in the interpretation of our numerous in vivo biokinetics studies performed in rodents using the same NP. These had shown that not only the physicochemical properties determined the AuNP translocation from the organ of intake towards blood circulation and subsequent accumulation in secondary organs and tissues but also the the transport across organ membranes depended on the route of AuNP application. Our in vitro protein binding studies support the notion that the observed differences in in vivo biokinetics are mediated by the NP protein corona and its dynamical change during AuNP translocation in fluids and across membranes within the organism.

Biokinetic and molecular studies of methanogens in phased anaerobic digestion systems

The influence of differing operational conditions of two-stage digesters on biokinetic characteristics and communities of methanogenic archaea was evaluated. Operating temperature of each phase influenced the archaeal communities significantly. Also, a strong correlation was observed between community composition and temperature and pH. The maximum specific substrate utilization rates (k max) of acetoclastic methanogens in the mesophilic and thermophilic 1st phases were 11.4 and 22.0 mgCOD mgCOD(-1)d(-1), respectively, whereas significantly lower k max values were estimated for the mesophilic and thermophilic 2nd-phase digesters which were 7.6 and 16.6 mgCOD mgCOD(-1)d(-1), respectively. It appeared that the biokinetic characteristics of the acetoclastic methanogen communities were reliant on digester loading rates. Also, higher temperature dependency coefficients (θ) were observed for the long retention time digesters when compared to the values computed for the 1st-phase digesters. Accordingly, the implementation of two sets of biokinetic parameters for acetoclastic methanogen will improve modeling of phased anaerobic digesters.

Biokinetic Studies in the Treatment of Tannery Effluent

The present investigation deals with the anaerobic treatment of composite tan liquor with varying organic loads. BOD of the influent and effluent and MLSS of reactor were determined at various detention times to generate data for kinetic coefficients. The kinetic coefficients k (maximum substrate utilization rate), Ks (half velocity constant), Y (cell yield coefficient) and Kd (decay coefficient) were found to be 1.66 day-1, 1132 mg/L, 0.05 and 0.22 day-1, respectively. Overall BOD removal rate constant ‘K’ was found to be 1.46 day-1. The studies showed that an optimum BOD influent load of 0.8 Kg BOD/m3/day with 3 days retention time could be adopted to yield about 97 percent BOD reduc¬tion. The Bio-kinetic coefficients were evaluated using modified Monod’s equations to study the metabolic performance of the digestion process.

Gold nanoparticle aerosols for rodent inhalation and translocation studies

The intensive use of nano-sized particles in many different applications necessitates studies on their risk assessment as there are still open questions on their safe handling and utilization. For reliable risk assessment, the interaction of nanoparticles (NP) with biological systems after various routes of exposure needs to be investigated using well-characterized NP. We report here on the generation of gold-NP (Au-NP) aerosols for inhalation studies with the spark ignition technique, and their characterization in terms of chemical composition, physical structure, morphology, and specific surface area, and on interaction with lung tissues and lung cells after 1 h inhalation by mice. The originally generated agglomerated Au-NP were converted into compact spherical Au-NP by thermal annealing at 600 °C, providing particles of similar mass, but different size and specific surface area. Since there are currently no translocation data available on inhaled Au-NP in the 10–50 nm diameter range, the emphasis was to generate NP as small as 20 nm for inhalation in rodents. For anticipated in vivo systemic translocation and dosimetry analyses, radiolabeled Au-NP were created by proton irradiating the gold electrodes of the spark generator, thus forming gamma ray emitting 195Au with 186 days half-life, allowing long-term biokinetic studies. The dissolution rate of 195Au from the NP was below detection limits. The highly concentrated, polydisperse Au-NP aerosol (1–2 × 107 NP/cm3) proved to be constant over several hours in terms of its count median mobility diameter, its geometric standard deviation and number concentration. After collection on filters particles can be re-suspended and used for instillation or ingestion studies.