Geochemistry of Arsenic and Toxic Response

2015 ◽  
pp. 96-129 ◽  
Keyword(s):  
Toxic Response

Use of Toxicokinetics in Risk Assessment Based on In Vitro Data

1993 ◽  
Vol 21 (2) ◽  
pp. 173-180
Author(s):  
Gunnar Johanson
Keyword(s):  
Risk Assessment ◽  
Whole Body ◽  
External Exposure ◽  
Target Dose ◽  
Toxic Response ◽  
Route Of Exposure ◽  
Vitro Data ◽  
In Vitro Data

This presentation addresses some aspects of the methodology, advantages and problems associated with toxicokinetic modelling based on in vitro data. By using toxicokinetic models, particularly physiologically-based ones, it is possible, in principle, to describe whole body toxicokinetics, target doses and toxic effects from in vitro data. Modelling can be divided into three major steps: 1) to relate external exposure (applied dose) of xenobiotic to target dose; 2) to establish the relationship between target dose and effect (in vitro data, e.g. metabolism in microsomes, partitioning in tissue homogenates, and toxicity in cell cultures, are useful in both steps); and 3) to relate external exposure to toxic effect by combining the first two steps. Extrapolations from in vitro to in vivo, between animal and man, and between high and low doses, can easily be carried out by toxicokinetic simulations. In addition, several factors that may affect the toxic response by changing the target dose, such as route of exposure and physical activity, can be studied. New insights concerning the processes involved in toxicity often emerge during the design, refinement and validation of the model. The modelling approach is illustrated by two examples: 1) the carcinogenicity of 1,3-butadiene; and 2) the haematotoxicity of 2-butoxyethanol. Toxicokinetic modelling is an important tool in toxicological risk assessment based on in vitro data. Many factors, some of which can, and should be, studied in vitro, are involved in the expression of toxicity. Successful modelling depends on the identification and quantification of these factors.

Survival and Function of Fibroblasts Stored as Stock Cultures at a Non-freezing Temperature

1993 ◽  
Vol 21 (2) ◽  
pp. 206-209
Author(s):  
Anders H. G. Andrén ◽  
Anders P. Wieslander
Keyword(s):  
Cell Growth ◽  
Cell Line ◽  
Cell Lines ◽  
Fibroblast Cell ◽  
Freezing Temperature ◽  
Mouse Fibroblast ◽  
Toxic Response ◽  
Normal Manner ◽  
And Function

Cytotoxicity, measured as inhibition of cell growth of cultured cell lines, is a widely used method for testing the safety of biomaterials and chemicals. One major technical disadvantage with this method is the continuous routine maintenance of the cell lines. We decided to investigate the possibility of storing stock cultures of fibroblasts (L-929) in an ordinary refrigerator as a means of reducing the routine workload. Stock cultures of the mouse fibroblast cell line L-929 were prepared in plastic vials with Eagle's minimum essential medium. The vials were stored in a refrigerator at 4–10°C for periods of 7–31 days. The condition of the cells after storage was determined as cell viability, cell growth and the toxic response to acrylamide, measured as cell growth inhibition. We found that the L-929 cell line can be stored for 2–3, weeks with a viabilty > 90% and a cell growth of about 95%, compared to L-929 cells grown and subcultured in the normal manner. The results also show that the toxic response to acrylamide, using refrigerator stored L-929 cells, corresponds to that of control L-929 cells. We concluded that it is possible to store L-929 cells in a refrigerator for periods of up to 3 weeks and still use the cells for in vitro cytotoxic assays.

scholarly journals The Role of Polymeric Coatings for a Safe-by-Design Development of Biomedical Gold Nanoparticles Assessed in Zebrafish Embryo

Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1004
Author(s):  
Pamela Floris ◽  
Stefania Garbujo ◽  
Gabriele Rolla ◽  
Marco Giustra ◽  
Lucia Salvioni ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Significant Inhibition ◽  
Zebrafish Embryos ◽  
Design Development ◽  
Embryo Viability ◽  
Fish Embryo ◽  
Toxic Response ◽  
Consequent Reduction ◽  
Vertebrate Model ◽  
Safe By Design

In the biomedical field, gold nanoparticles (GNPs) have attracted the attention of the scientific community thanks to their high potential in both diagnostic and therapeutic applications. The extensive use of GNPs led researchers to investigate their toxicity, identifying stability, size, shape, and surface charge as key properties determining their impact on biological systems, with possible strategies defined to reduce it according to a Safe-by-Design (SbD) approach. The purpose of the present work was to analyze the toxicity of GNPs of various sizes and with different coating polymers on the developing vertebrate model, zebrafish. In particular, increasing concentrations (from 0.001 to 1 nM) of 6 or 15 nm poly-(isobutylene-alt-maleic anhydride)-graft-dodecyl polymer (PMA)- or polyethylene glycol (PEG)-coated GNPs were tested on zebrafish embryos using the fish embryo test (FET). While GNP@PMA did not exert significant toxicity on zebrafish embryos, GNP@PEG induced a significant inhibition of embryo viability, a delay of hatching (with the smaller size NPs), and a higher incidence of malformations, in terms of tail morphology and eye development. Transmission electron microscope analysis evidenced that the more negatively charged GNP@PMA was sequestered by the positive charges of chorion proteins, with a consequent reduction in the amount of NPs able to reach the developing embryo and exert toxicological activity. The mild toxic response observed on embryos directly exposed to GNP@PMA suggest that these NPs are promising in terms of SbD development of gold-based biomedical nanodevices. On the other hand, the almost neutral GNP@PEG, which did not interact with the chorion surface and was free to cross chorion pores, significantly impacted the developing zebrafish. The present study raises concerns about the safety of PEGylated gold nanoparticles and contributes to the debated issue of the free use of this nanotool in medicine and nano-biotechnologies.

scholarly journals 4518 Metabolomic Identifiers Predictive of Adverse Events due to Acetaminophen Administration

2020 ◽  
Vol 4 (s1) ◽  
pp. 110-110
Author(s):  
Brandon Joseph Sonn ◽  
Kennon Heard ◽  
Andrew Monte
Keyword(s):  
High Performance ◽  
Adverse Reactions ◽  
Demographic Variable ◽  
Liquid Chromatography Mass Spectrometry ◽  
Chi Square ◽  
Toxic Response ◽  
Therapy Initiation ◽  
Study Population ◽  
Therapeutic Doses ◽  
Time Point

OBJECTIVES/GOALS: Acetaminophen (Tylenol, APAP) toxicity has been well documented and well explored over the last 50 years. However, there has been no investigation into identification of specific metabolites that can predict which patients will have adverse reactions to therapeutic doses of APAP. METHODS/STUDY POPULATION: 205 subjects recruited from the Denver, CO community received the highest recommended daily dosing of APAP, 4 grams, for 16 days. Subjects were grouped by 1) alanine aminotransferase (ALT) at any monitored time point above 60units/L (n = 20) vs 2) no increase in ALT at any time point (n = 185). Blood was collected at days 0, 4, 7, 16, and 31. Samples were run on ultra-high performance liquid chromatography mass spectrometry with 27 heavy-labeled standards for metabolites documented to be associated with APAP metabolism. Data will be analyzed to look for significant changes in metabolite and demographic variable expressions using t-tests, chi square and logistic regression, as appropriate. RESULTS/ANTICIPATED RESULTS: It is expected that there will be greater elevations of conjugated non-toxic APAP metabolites (APAP-glucuronide, APAP-sulfate) in subjects whose ALT did not elevate because of successful hepatoprotection. Conjugated APAP metabolites are expected to only be present in samples taken after APAP therapy initiation confirming exposure as compared to being predictive of toxic response. Increases in lactate and cysteine in pre-exposure samples would allow for prediction of APAP toxicity as they are expected to have increased expression in subjects whose ALT became elevated which is indicative of increased hepatic damage due to oxidative damage. DISCUSSION/SIGNIFICANCE OF IMPACT: Identification of metabolites and/or demographic factors associated with toxic response to APAP prior to administration could advise APAP recommendations. Quantification of post-APAP administration metabolites would identify extent of successful hepatoprotective mechanisms.

Toxic response in human adrenocortical cells exposed to zirconium dioxide nanoparticles

2021 ◽  
Vol 350 ◽  
pp. S94-S95
Author(s):  
L. Zapor ◽  
L. Chojnacka-Puchta ◽  
D. Sawicka ◽  
K. Miranowicz-Dzierżawska ◽  
J. Skowroń
Keyword(s):  
Zirconium Dioxide ◽  
Adrenocortical Cells ◽  
Toxic Response ◽  
Zirconium Dioxide Nanoparticles

Biological Evaluation of a Novel Tissue Engineering Scaffold of Layered Double Hydroxides (LDHs)

2011 ◽  
Vol 493-494 ◽  
pp. 902-908 ◽  
Author(s):  
Fateme Fayyazbakhsh ◽  
Mehran Solati-Hashjin ◽  
M.A. Shokrgozar ◽  
S. Bonakdar ◽  
Y. Ganji ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Layered Double Hydroxides ◽  
Cellular Response ◽  
Calcium Nitrate ◽  
Biological Evaluation ◽  
Osteosarcoma Cell ◽  
Toxic Response ◽  
Double Hydroxides

Bone Tissue Engineering (BTE) composed of three main parts: scaffold, cells and signaling factors. Several materials and composites are suggested as a scaffold for BTE. Biocompatibility is one of the most important property of a BTE scaffold. In this work synthesis of a novel nanocomposite including layered double hydroxides (LDH) and gelatin is carried out and its biological properties were studied. The co-precipitation (pH=11) method was used to prepare the LDH powder, using calcium nitrate, Magesium nitrate and aluminum nitrate salts as starting materials. The resulted precipitates were dried. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) analyses were used to characterize the synthesized powders. The results demonstrated the presence of nanocrystals of Ca-LDH and Mg-LDH as Hexagonal and Layered Morphology. The obtained powders were composed to gelatin via solvent casting method then freez dried. The scaffold was prepared via membrane lamination method from the resulted layers that linked together with gelatin as binder. In order to investigate the scaffold cytotoxicity MTT assay was done with a osteosarcoma cell line. No toxic response was observed in specimens. As a major result, it was demonstrated that the specimen showed a significant cellular response. Then osteosarcoma cells were cultured for 7-day and 14-day extract of powders. The composites osteoconductivity was investigate with cells alkaline phosphatase extraction. The results demonstrated that the Ca-LDH/gelatin composite scaffold has a good potential for bone tissue engineering applications and Mg-LDH specimen has a better osteconductivity.

scholarly journals Recent Developments in Plasmonic Sensors of Phenol and Its Derivatives

2021 ◽  
Vol 11 (22) ◽  
pp. 10519
Author(s):  
Nguyễn Hoàng Ly ◽  
Sang Jun Son ◽  
Ho Hyun Kim ◽  
Sang-Woo Joo
Keyword(s):  
Phenolic Compounds ◽  
Optical Sensors ◽  
Noble Metals ◽  
Raw Material ◽  
Detection Methods ◽  
Localized Surface Plasmon ◽  
Trace Detection ◽  
Toxic Response ◽  
Recent Developments ◽  
Analytical Tools

Many scientists are increasingly interested in on-site detection methods of phenol and its derivatives because these substances have been universally used as a significant raw material in the industrial manufacturing of various chemicals of antimicrobials, anti-inflammatory drugs, antioxidants, and so on. The contamination of phenolic compounds in the natural environment is a toxic response that induces harsh impacts on plants, animals, and human health. This mini-review updates recent developments and trends of novel plasmonic resonance nanomaterials, which are assisted by various optical sensors, including colorimetric, fluorescence, localized surface plasmon resonance (LSPR), and plasmon-enhanced Raman spectroscopy. These advanced and powerful analytical tools exhibit potential application for ultrahigh sensitivity, selectivity, and rapid detection of phenol and its derivatives. In this report, we mainly emphasize the recent progress and novel trends in the optical sensors of phenolic compounds. The applications of Raman technologies based on pure noble metals, hybrid nanomaterials, and metal–organic frameworks (MOFs) are presented, in which the remaining establishments and challenges are discussed and summarized to inspire the future improvement of scientific optical sensors into easy-to-operate effective platforms for the rapid and trace detection of phenol and its derivatives.

scholarly journals Biological Safety Evaluation of 99mTc-DTPA-Ketoconazole for Diagnosis of Fungal Infection

2017 ◽  
Vol 2 (1) ◽  
pp. 1
Author(s):  
Maula Eka Sriyani ◽  
Hendris Wongso ◽  
Eva Maria Widyasari ◽  
Rizky Juwita Sugiharti ◽  
Iim Halimah ◽  
...  
Keyword(s):  
Single Dose ◽  
Fungal Infection ◽  
Radiochemical Purity ◽  
Safety Evaluation ◽  
Fungal Growth ◽  
In Vitro Assays ◽  
Toxic Response ◽  
Biological Safety ◽  
Safety Parameters

Infectious diseases have become one of the leading cause of mortality around the world, including in the Southeast Asia. One of the microbial that cause infection is fungi. Occasionally, deep-seated fungal infection is difficult to detect using conventional diagnosis methods and therefore leads to inaccurate detection. Our previous research was conducted in order to obtain the labeled compound of <sup>99m</sup>Tc-DTPA-Ketoconazole with a high radiochemical purity (98.40 ± 0.86%). Moreover, the in-vitro assays showed that <sup>99m</sup>Tc-DTPA-Ketoconazole can potentially bind to Candida albicans. On the other hand, in clinical routine use, diagnostic kit should be safe for the patients. Consequently, this research was conducted to determine the biological safety parameters of <sup>99m</sup>Tc-DTPA-Ketoconazole on the animal study, including single dose and acute toxicity test, sterility, and apirogenicity test. The results showed that both the single dose at 34.6 μCi and dose until 149 times of the single dose did not stimulate the toxic response to the animals. In addition, the sterility data revealed that there was no microbial growth after 7 days of incubation at 37°C as well as fungal growth after 14 days of incubation at 25°C. Furthermore, the apirogenicity test using rabbits revealed that there was no increase in temperature more than 0.6°C for each animal and not more than 1.5°C of total increase of temperature for all the animals. It is concluded that the <sup>99m</sup>Tc-DTPA-Ketoconazole is satisfy the requirements of biological safety of a radiopharmaceutical and therefore was acceptable for fungal detection in nuclear medicine.

scholarly journals Incorporating biomarkers in ecological risk assessment of chemical contaminants of soils

2007 ◽  
Vol 26 (2) ◽  
pp. 120-137
Author(s):  
A. J. Reinecke ◽  
S. A. Reinecke ◽  
M. S. Maboeta ◽  
J. P. Odendaal ◽  
R. Snyman
Keyword(s):  
Risk Assessment ◽  
South African ◽  
Field Experiments ◽  
Early Stage ◽  
Population Level ◽  
Diagnostic Tools ◽  
Future Research ◽  
Chemical Contaminants ◽  
Toxic Response ◽  
Future Research Directions

Soil is an important but complex natural resource which is increasingly used as sink for chemicals. The monitoring of soil quality and the assessment of risks posed by contaminants have become crucial. This study deals with the potential use of biomarkers in the monitoring of soils and the assessment of risk resulting from contamination. Apart from an overview of the existing literature on biomarkers, the results of various of our field experiments in South African soils are discussed. Biomarkers may have potential in the assessment of risk because they can indicate at an early stage that exposure has taken place and that a toxic response has been initiated. It is therefore expected that early biomarkers will play an increasing role as diagnostic tools for determining exposure to chemicals and the resulting effects. They may have predictive value that can assist in the prevention or minimising of risks. The aim of this study was to investigate the possibilities of using our results on biomarker responses of soil dwelling organisms to predict changes at higher organisational levels (which may have ecological implications). Our recent experimental results on the evaluation of various biomarkers in both the laboratory and the field are interpreted and placed in perspective within the broader framework of response biology. The aim was further to contribute to the development and application of biomarkers in regulatory risk assessment schemes of soils. This critical review of our own and recent literature on biomarkers in ecotoxicology leads to the conclusion that biomarkers can, under certain conditions, be useful tools in risk assessment. Clear relationships between contamination loads in soil organisms and certain biomarker responses were determined in woodlice, earthworms and terrestrial snails. Clear correlations were also established in field experiments between biomarker responses and changes at the population level. This indicated that, in spite of the fact that direct mechanistic links are still not clarified, biomarkers may have the potential to provide early indications of forthcoming changes at higher organisational levels. Ways are proposed in which biomarkers could be used in the future in risk assessment schemes of soils and future research directions are suggested. 

Sign in / Sign up

Export Citation Format

Share Document