Predicting GHS toxicity using RTCA and discrete-time Fourier transform

In order to promote the acceptance of cell-based toxicity testings, the accuracy of cytotoxicity test must be determined when compared to in vivo results. Traditional methods of cytotoxicity analysis, such as LC[Formula: see text] (concentration where 50% of the cells are killed) can be problematic since they have been found to vary with time. Technological advances in cytotoxicity testing make it easy to record the dynamic data on changes in cell proliferation, morphology, and damage. To effectively and reasonably analyze the dynamic data, we present a new in vitro toxicity assessed method using the discrete-time Fourier transform (DTFT) which maps the measured cell index from the time domain to the frequency domain. The direct current (DC) component of the DTFT is extracted as a feature which reflects the intensity of cytotoxicity. The smaller the value, the higher the cytotoxicity. Then, a novel toxicity index, as expressed in terms of DC[Formula: see text], is calculated. Results generated with selected test chemicals are compared favorably with data obtained from The Interagency Coordinating Committee on the Validation of Alternative Method (ICCVAM) report concerning the prediction of acute systemic toxicity in rodents. The method can be applied with the standard and high throughput to estimate acute rodent oral toxicity which reduces the number of animals required in subsequent pharmacological/toxicological studies.

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A Toxicological Evaluation of Germanium Sesquioxide (Organic Germanium)

Journal of Toxicology ◽

10.1155/2020/6275625 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Robin A. Reddeman ◽

Róbert Glávits ◽

John R. Endres ◽

Timothy S. Murbach ◽

Gábor Hirka ◽

...

Keyword(s):

Micronucleus Test ◽

Germanium Dioxide ◽

Oral Toxicity ◽

Toxicological Evaluation ◽

Toxicological Studies ◽

Adverse Effect Level ◽

Dose Oral ◽

Chromosomal Aberration Test

A battery of OECD- and GLP-compliant toxicological studies was performed to assess the safety of a highly purified germanium sesquioxide, an organic form of the naturally occurring, nonessential trace element germanium. Germanium dioxide and germanium lactate citrate (inorganic germaniums) have been shown to induce renal toxicity, whereas germanium sesquioxide (an organic germanium) has been shown to have a more favorable safety profile. However, past toxicity studies on germanium sesquioxide compounds have not clearly stated the purity of the tested compounds. In the studies reported herein, there was no evidence of mutagenicity in a bacterial reverse mutation test or an in vitro mammalian chromosomal aberration test. There was no genotoxic activity observed in an in vivo mammalian micronucleus test at concentrations up to the limit dose of 2000 mg/kg bw/day. In a 90-day repeated-dose oral toxicity study in Han:WIST rats conducted at doses of 0, 500, 1000, and 2000 mg/kg bw/day by gavage, there were no mortalities, treatment-related adverse effects, or target organs identified. The no-observed-adverse-effect-level (NOAEL) was determined to be 2000 mg/kg bw/day.

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An Evaluation of the Genotoxicity and Subchronic Oral Toxicity of Synthetic Curcumin

Journal of Toxicology ◽

10.1155/2018/6872753 ◽

2018 ◽

Vol 2018 ◽

pp. 1-27 ◽

Cited By ~ 9

Author(s):

Sreenivasa Rao Damarla ◽

Rajesh Komma ◽

Upendra Bhatnagar ◽

Navin Rajesh ◽

Sadik Mohmad Abdulhamid Mulla

Keyword(s):

Micronucleus Test ◽

Repeated Dose ◽

Oral Toxicity ◽

Split Dose ◽

Toxicological Studies ◽

Adverse Effect Level ◽

Dose Oral ◽

Chromosomal Aberration Test

A battery of toxicological studies was conducted in accordance with international guidelines to investigate the genotoxicity and repeated-dose oral toxicity in rats of synthetic curcumin (VEAMIN 99, >99% purity). There was no evidence of mutagenicity in a bacterial reverse mutation test, whereas an in vitro mammalian chromosomal aberration test was positive for induction of chromosomal aberrations which is in line with results reported for natural curcumin. There was no evidence of genotoxicity in an in vivo mammalian micronucleus test. Synthetic curcumin did not cause mortality or toxic effects in a 90-day repeated-dose oral toxicity study at daily doses of 250, 500, or 1000 mg/kg body weight (bw)/day (administered by gavage in a split dose). The no observed adverse effect level (NOAEL) determined from the 90-day study was 1000 mg/kg bw/day for both male and female Wistar rats.

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A Toxicological Assessment of Creatyl-l-Leucine

International Journal of Toxicology ◽

10.1177/1091581817751142 ◽

2018 ◽

Vol 37 (2) ◽

pp. 171-187 ◽

Cited By ~ 4

Author(s):

Robin A. Reddeman ◽

Róbert Glávits ◽

John R. Endres ◽

Timothy S. Murbach ◽

Gábor Hirka ◽

...

Keyword(s):

Micronucleus Test ◽

Female Rats ◽

Repeated Dose ◽

Oral Toxicity ◽

Synthetic Compound ◽

Male And Female Rats ◽

Toxicological Studies ◽

Dose Oral

A battery of toxicological studies was conducted to investigate the genotoxicity and repeated-dose oral toxicity of creatyl-l-leucine, a synthetic compound, in rats in accordance with internationally accepted guidelines. There was no evidence of mutagenicity in a bacterial reverse mutation test and in an in vitro mammalian chromosomal aberration test. There was no genotoxic activity observed in an in vivo mammalian micronucleus test at concentrations up to the limit dose of 2,000 mg/kg bw/d. Creatyl-l-leucine did not cause mortality or toxic effects in Hsd.Han Wistar rats in a 90-day repeated-dose oral (gavage) toxicity study at doses of 1,250, 2,500, and 5,000 mg/kg bw/d. The no observed adverse effect level from the 90-day study was determined to be 5,000 mg/kg bw/d, the highest dose tested, for both male and female rats.

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Toxicological Behavior of Gold Nanoparticles on Various Models: Influence of Physicochemical Properties and Other Factors

International Journal of Toxicology ◽

10.1177/1091581819863130 ◽

2019 ◽

Vol 38 (5) ◽

pp. 357-384 ◽

Cited By ~ 13

Author(s):

Olusola B. Adewale ◽

Hajierah Davids ◽

Lynn Cairncross ◽

Saartjie Roux

Keyword(s):

Gold Nanoparticles ◽

Physicochemical Properties ◽

In Vitro Toxicity ◽

In Ovo ◽

Toxicity Assay ◽

Study Protocols ◽

Toxicological Studies ◽

Potential Applications

Potential applications of gold nanoparticles in biomedicine have increasingly been reported on account of the ease of synthesis, bioinert characteristics, optical properties, chemical stability, high biocompatibility, and specificity. The safety of these particles remains a great concern, as there are differences among toxicity study protocols used. This article focuses on integrating results of research on the toxicological behavior of gold nanoparticles. This can be influenced by the physicochemical properties, including size, shape, surface charge, and other factors, such as methods used in the synthesis of gold nanoparticles, models used, dose, in vivo route of administration, and interference of gold nanoparticles with in vitro toxicity assay systems. Several researchers have reported toxicological studies with regard to gold nanoparticles, using various in vitro, in vivo, and in ovo models. The conflicting results concerning the toxicity of gold nanoparticles should thus be addressed to justify the safe use of gold nanoparticles in biomedicine.

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A Toxicological Evaluation of Mango Leaf Extract (Mangifera indica) Containing 60% Mangiferin

Journal of Toxicology ◽

10.1155/2019/4763015 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 12

Author(s):

Robin A. Reddeman ◽

Róbert Glávits ◽

John R. Endres ◽

Amy E. Clewell ◽

Gábor Hirka ◽

...

Keyword(s):

Leaf Extract ◽

Micronucleus Test ◽

Mangifera Indica ◽

Female Rats ◽

Oral Toxicity ◽

Toxicological Evaluation ◽

Male And Female Rats ◽

Toxicological Studies

A battery of OECD- and GLP-compliant toxicological studies was performed on mango leaf extract (Mangifera indica) containing 60% mangiferin (MLE). No evidence of genotoxicity was found in a bacterial reverse mutation test (Ames). While evidence of clastogenic activity was noted in an in vitro chromosomal aberration test, an in vivo mammalian micronucleus test showed no findings up to the limit dose (2000 mg/kg bw). A 90-day repeated dose oral toxicity study was conducted in rats using doses of 0 (vehicle control), 500, 1000, and 2000 mg/kg bw/day. Based on the lack of mortality or toxic effects in the 90-day study, the NOAEL for MLE in Han:Wist male and female rats was determined to be 2000 mg/kg bw/day, the highest dose tested.

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Antitumor Potential of Annona muricata Linn. An Edible and Medicinal Plant in Mexico: In Vitro, In Vivo, and Toxicological Studies

Molecules ◽

10.3390/molecules26247675 ◽

2021 ◽

Vol 26 (24) ◽

pp. 7675

Author(s):

Verenice Merlín-Lucas ◽

Rosa María Ordoñez-Razo ◽

Fernando Calzada ◽

Aida Solís ◽

Normand García-Hernández ◽

...

Keyword(s):

Cytotoxic Activity ◽

Flavonoid Glycosides ◽

Annona Muricata ◽

Oral Toxicity ◽

Brine Shrimp Lethality Assay ◽

Toxicological Studies ◽

4T1 Cells ◽

Ethanol Extracts

Annona muricata (Am) is a plant used in traditional Mexican medicine to treat cancer. In this study, ethanol extracts of Am collected in Acapulco and Tecpan from Guerrero state were evaluated orally on Balb/c mice inoculated with 4T1 cells, for cytotoxic activity (CA) on 4T1 cells, in brine shrimp lethality assay (BSLA), and for acute oral toxicity in mice. In addition, ethanol extracts were subjected to high-performance liquid chromatography (HPLC) with diode array detection. Results showed that the extracts collected in December in Acapulco (AcDe) and Tecpan (TeDe) exhibited the most significant antitumor and cytotoxic activity. In the BSLA, the most important effect was observed in the extracts from Acapulco and Tecpan collected in June (AcJu) and August (TeAg), respectively. The samples from Acapulco (AcJu, and AcAg) and Tecpan (TeJu and TeAg) showed the highest toxicity. The analysis of the extracts, AcDe and TeDe, by HPLC revealed that flavonoids, rutin, narcissin, and nicotinflorin were the major components. These findings suggest that extracts from Am collected in Acapulco and Tecpan in the month of December may be an important source to obtain flavonoid glycosides with anticancer potential specifically against breast cancer. This also supports the use of Am to treat cancer in Mexican traditional medicine.

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Phytochemical, Analytical and Medicinal Studies of Holoptelea integrifolia Roxb. Planch - A Review

Current Traditional Medicine ◽

10.2174/2215083805666190521103308 ◽

2019 ◽

Vol 5 (4) ◽

pp. 270-277 ◽

Cited By ~ 2

Author(s):

Vijay Kumar ◽

Simranjeet Singh ◽

Ragini Bhadouria ◽

Ravindra Singh ◽

Om Prakash

Keyword(s):

Liquid Chromatography ◽

Thin Layer ◽

Thin Layer Chromatography ◽

High Performance ◽

Biologically Active ◽

Toxicological Studies ◽

Wide Range ◽

Layer Chromatography

Holoptelea integrifolia Roxb. Planch (HI) has been used to treat various ailments including obesity, osteoarthritis, arthritis, inflammation, anemia, diabetes etc. To review the major phytochemicals and medicinal properties of HI, exhaustive bibliographic research was designed by means of various scientific search engines and databases. Only 12 phytochemicals have been reported including biologically active compounds like betulin, betulinic acid, epifriedlin, octacosanol, Friedlin, Holoptelin-A and Holoptelin-B. Analytical methods including the Thin Layer Chromatography (TLC), High-Performance Thin Layer Chromatography (HPTLC), High-Performance Liquid Chromatography (HPLC) and Liquid Chromatography With Mass Spectral (LC-MS) analysis have been used to analyze the HI. From medicinal potency point of view, these phytochemicals have a wide range of pharmacological activities such as antioxidant, antibacterial, anti-inflammatory, and anti-tumor. In the current review, it has been noticed that the mechanism of action of HI with biomolecules has not been fully explored. Pharmacology and toxicological studies are very few. This seems a huge literature gap to be fulfilled through the detailed in-vivo and in-vitro studies.

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Mathematical model for the thermal enhancement of radiation response: thermodynamic approach

Scientific Reports ◽

10.1038/s41598-021-84620-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Adriana M. De Mendoza ◽

Soňa Michlíková ◽

Johann Berger ◽

Jens Karschau ◽

Leoni A. Kunz-Schughart ◽

...

Keyword(s):

Protein Denaturation ◽

Collateral Damage ◽

Hyperthermia Treatment ◽

Reversible Process ◽

Technological Advances ◽

Thermal Enhancement ◽

Main Driver ◽

Definition Of

AbstractRadiotherapy can effectively kill malignant cells, but the doses required to cure cancer patients may inflict severe collateral damage to adjacent healthy tissues. Recent technological advances in the clinical application has revitalized hyperthermia treatment (HT) as an option to improve radiotherapy (RT) outcomes. Understanding the synergistic effect of simultaneous thermoradiotherapy via mathematical modelling is essential for treatment planning. We here propose a theoretical model in which the thermal enhancement ratio (TER) relates to the cell fraction being radiosensitised by the infliction of sublethal damage through HT. Further damage finally kills the cell or abrogates its proliferative capacity in a non-reversible process. We suggest the TER to be proportional to the energy invested in the sensitisation, which is modelled as a simple rate process. Assuming protein denaturation as the main driver of HT-induced sublethal damage and considering the temperature dependence of the heat capacity of cellular proteins, the sensitisation rates were found to depend exponentially on temperature; in agreement with previous empirical observations. Our findings point towards an improved definition of thermal dose in concordance with the thermodynamics of protein denaturation. Our predictions well reproduce experimental in vitro and in vivo data, explaining the thermal modulation of cellular radioresponse for simultaneous thermoradiotherapy.

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In Vitro Culture of Human Thyroid Cells: Preliminary Findings on the Role of the Pathological Condition of the Donors

Alternatives to Laboratory Animals ◽

10.1177/026119299702500208 ◽

1997 ◽

Vol 25 (2) ◽

pp. 153-160

Author(s):

Francesca Mattioli ◽

Marianna Angiola ◽

Laura Fazzuoli ◽

Francesco Razzetta ◽

Antonietta Martelli

Keyword(s):

Pathological Condition ◽

Primary Cultures ◽

S Phase ◽

Human Thyroid ◽

Thyroid Cells ◽

Toxicological Studies ◽

Predictive Indicator

Although primary cultures of human thyroid cells are used for endocrinological and toxicological studies, until now no attention has been paid toward verifying whether the hormonal conditions to which the gland was exposed in vivo prior to surgery could influence in vitro responses. Our findings suggest that the hormonal situation in vivo cannot be used as a predictive indicator of triiodothyronine and thyroxine release and/or S-phase frequency in vitro, either with or without the addition of bovine thyrotropin.

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