Profile of toxic response to sediments using whole-animal and in vitro submitochondrial particle (SMP) assays

1996 ◽  
Vol 15 (3) ◽  
pp. 319-324 ◽  
Author(s):  
Alan D. Bettermann ◽  
Jonathan C. Dorofi ◽  
James M. Lazorchak
Keyword(s):  
Toxic Response ◽  
Submitochondrial Particle

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 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 Methylmercury Epigenetics

Toxics ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 56 ◽  
Author(s):  
Megan Culbreth ◽  
Michael Aschner
Keyword(s):  
Dna Methylation ◽  
Mirna Expression ◽  
Epigenetic Modifications ◽  
Nervous System Development ◽  
Gene Promoters ◽  
Toxic Response ◽  
The Impact ◽  
The Brain

Methylmercury (MeHg) has conventionally been investigated for effects on nervous system development. As such, epigenetic modifications have become an attractive mechanistic target, and research on MeHg and epigenetics has rapidly expanded in the past decade. Although, these inquiries are a recent advance in the field, much has been learned in regards to MeHg-induced epigenetic modifications, particularly in the brain. In vitro and in vivo controlled exposure studies illustrate that MeHg effects microRNA (miRNA) expression, histone modifications, and DNA methylation both globally and at individual genes. Moreover, some effects are transgenerationally inherited, as organisms not directly exposed to MeHg exhibited biological and behavioral alterations. miRNA expression generally appears to be downregulated consequent to exposure. Further, global histone acetylation also seems to be reduced, persist at distinct gene promoters, and is contemporaneous with enhanced histone methylation. Moreover, global DNA methylation appears to decrease in brain-derived tissues, but not in the liver; however, selected individual genes in the brain are hypermethylated. Human epidemiological studies have also identified hypo- or hypermethylated individual genes, which correlated with MeHg exposure in distinct populations. Intriguingly, several observed epigenetic modifications can be correlated with known mechanisms of MeHg toxicity. Despite this knowledge, however, the functional consequences of these modifications are not entirely evident. Additional research will be necessary to fully comprehend MeHg-induced epigenetic modifications and the impact on the toxic response.

Comparison of in vitro submitochondrial particle and Microtox® assays for determining the toxicity of organotin compounds

1998 ◽  
Vol 17 (6) ◽  
pp. 1005-1012 ◽  
Author(s):  
Emanuele Argese ◽  
Cinzia Bettiol ◽  
Annamaria Volpi Ghirardini ◽  
Matteo Fasolo ◽  
Gianumberto Giurin ◽  
...  
Keyword(s):  
Organotin Compounds ◽  
Submitochondrial Particle

Trans-resveratrol modulates the catalytic activity and mRNA expression of the procarcinogen-activating human cytochrome P450 1B1

2000 ◽  
Vol 78 (11) ◽  
pp. 874-881 ◽  
Author(s):  
Thomas KH Chang ◽  
Wendy BK Lee ◽  
Hin Hin Ko
Keyword(s):  
Gene Expression ◽  
Cytochrome P450 ◽  
Catalytic Activity ◽  
Pcr Analysis ◽  
Mrna Levels ◽  
Toxic Response ◽  
Cytochrome P450 1B1 ◽  
Cyp1b1 Mrna ◽  
Mcf 7

The present study was performed to determine if trans-resveratrol (3,5,4'-trihydroxy-trans-stilbene) modulates the catalytic activity and gene expression of cytochrome P450 1B1 (CYP1B1). In vitro, trans-resveratrol decreased human recombinant CYP1B1-catalyzed 7-ethoxyresorufin O-dealkylation activity, with an IC50 value of 1.4 ± 0.2 µM (mean ± SEM). Enzyme kinetic analysis indicated that trans-resveratrol inhibited CYP1B1 enzyme activity by a mixed-type inhibition and the apparent Ki was 0.75 ± 0.06 µM. To determine if trans-resveratrol modulates constitutive CYP1B1 gene expression, cultured MCF-7 human breast carcinoma cells were treated with trans-resveratrol. As indicated by RT-PCR analysis, treatment of MCF-7 cells with 10 µM trans-resveratrol decreased relative CYP1B1 mRNA levels after 5 h, but not after 1.5 or 3 h, of exposure. trans-Resveratrol treatment at 5, 7.5, 10, or 20 µM for 5 h produced a concentration-dependent decrease in CYP1B1 mRNA levels. The extent of suppression was ~50% at 20 µM concentration. The suppressive effect was not a consequence of a toxic response to the compound as assessed by a cell proliferation assay. Overall, our novel finding that trans-resveratrol inhibits the catalytic activity and suppresses the constitutive gene expression of CYP1B1 leads to the possibility that this nutraceutical confers protection against toxicity and carcinogenicity induced by compounds that undergo CYP1B1-catalyzed bioactivation.Key words: cytochrome P450, CYP1B1, 7-ethoxyresorufin, nutraceutical, trans-resveratrol.

scholarly journals BIOLOGICAL SAFETY EVALUATION OF 99mTc-DTPA-KETOCONAZOLE FOR DIAGNOSIS OF FUNGAL INFECTION

2016 ◽  
Vol 1 (3) ◽  
pp. 138
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.

Toxic response of graphene nanoplatelets in vivo and in vitro

2014 ◽  
Vol 89 (9) ◽  
pp. 1557-1568 ◽  
Author(s):  
Eun-Jung Park ◽  
Gwang-Hee Lee ◽  
Beom Seok Han ◽  
Byoung-Seok Lee ◽  
Somin Lee ◽  
...  
Keyword(s):  
Graphene Nanoplatelets ◽  
Toxic Response

scholarly journals Unbiased Approach for the Identification of Molecular Mechanisms Sensitive to Chemical Exposures

2020 ◽  
Author(s):  
Alexander Suvorov ◽  
Victoria Salemme ◽  
Joseph McGaunn ◽  
Anthony Poluyanoff ◽  
Menna Teffera ◽  
...  
Keyword(s):  
Public Health ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Future Research ◽  
Gene Interactions ◽  
Molecular Pathways ◽  
Toxic Response ◽  
Mechanisms Of Toxicity ◽  
Chemical Exposures

Background: Targeted methods that dominated toxicological research until recently did not allow for screening of all molecular changes involved in toxic response. Therefore, it is difficult to infer if all major mechanisms of toxicity have already been discovered, or if some of them are still overlooked. Objectives: To identify molecular mechanisms sensitive to chemical exposures in an unbiased manner. Methods: We used data on 641,516 unique chemical-gene interactions from the Comparative Toxicogenomic Database. Only data from high-throughput gene expression experiments with human, rat or mouse cells/tissues were extracted. The total number of chemical-gene interactions was calculated for every gene, and used as a measure of gene sensitivity to chemical exposures. These values were further used in enrichment analyses to identify molecular mechanisms sensitive to chemical exposures. Results: Remarkably, use of different input subsets with non-overlapping lists of chemical compounds identified largely the same genes and molecular pathways as most sensitive to chemical exposures, indicative of an unbiased nature of our analysis. One of the most important findings of this study is that almost every known molecular mechanism may be affected by chemical exposures. Predictably, xenobiotic metabolism pathways and mechanisms of cellular response to stress and damage were among the most sensitive. Additionally, our analysis identified a range of highly sensitive molecular pathways, which are not widely recognized by modern toxicology as major targets of toxicants, including lipid metabolism pathways, longevity regulation cascade and cytokine mediated signaling. Discussion: Molecular mechanisms identified as the most sensitive to chemical exposures are relevant for significant public health problems, such as aging, cancer, metabolic and autoimmune disease. Thus, public health system will likely benefit from future research focus on these sensitive molecular mechanisms. Additionally, approach used in this study may guide identification of priority adverse outcome pathways (AOP) for in-vitro and in-silico toxicity testing methods.

scholarly journals Mycorrhizal Colonization Increases Herbicide Toxicity in Apple

1994 ◽  
Vol 119 (6) ◽  
pp. 1255-1260 ◽  
Author(s):  
C. Hamel ◽  
F. Morin ◽  
A. Fortin ◽  
R.L. Granger ◽  
D.L. Smith
Keyword(s):  
Relative Elongation ◽  
Dry Mass ◽  
Mycorrhizal Colonization ◽  
Mass Reduction ◽  
Apple Rootstocks ◽  
Apple Trees ◽  
Toxic Response ◽  
Herbicide Treatments ◽  
Mycorrhizal Plants

Herbicides are increasingly used in orchards. Since apple trees strongly depend on mycorrhizae, the effects of three commonly used herbicides on the host plant and endophyte were examined. Symbiosis between tissue-cultured P16 apple rootstocks and Glomus versiforme (Karsten) Berch was established under greenhouse conditions. Simazine (1, 2, 10, and 20 μg a.i./g), dichlobenil (1, 5, 10, and 25 μg a.i./g), paraquat (0.5, 1, 10, and 100 μg a.i./g), or water was applied to mycorrhizal and nonmycorrhizal plants as a soil drench. The response of mycorrhizal plants to herbicide was greater, and the relative elongation rate was more sharply reduced in mycorrhizal (76%) than in nonmycorrhizal plants (33%). Six weeks after herbicide application, dry mass reduction due to herbicides was similar (39% and 36%) for mycorrhizal and nonmycorrhizal plant shoots, respectively, while root dry mass reduction was larger for mycorrhizal (63%) than nonmycorrhizal plants (46%). None of the herbicide treatments affected root colonization. However, an in vitro hyphal elongation test with G. intraradices Schenck & Smith and herbicide-amended (0, 1, 10, 100, and 1000 μg a.i./g) gellan gum solidified water showed that either dichlobenil or paraquat, even at the lowest concentrations, could significantly reduce hyphal elongation. Simazine did not affect hyphal elongation in vitro, a result suggesting that improved absorption capacity of mycorrhizae explains, at least in part, the increased phytotoxicity of some herbicides. It was found that plant mortality was higher among mycorrhizal than nonmycorrhizal apple trees for all herbicide treatments. The increased CO2 assimilation rates of dichlobenil-treated mycorrhizal plants contrasted with the decreased rates of control plants measured 1 week after dichlobenil treatment. This indicates a physiological interaction between mycorrhizal colonization and dichlobenil in the toxic response of apple plants. Chemical names used: 2-chloro-4,6-bis-ethylamino-s-triazine (simazine), 2,6-dichlorobenzonitrile (dichlobenil), 1,1'-dimethyl-4,4'bipyridinium (paraquat).

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