scholarly journals Safety assessment of β-fructofuranosidase from Aspergillus brunneoviolaceus

2021 ◽  
Vol 5 ◽  
pp. 239784732110553
Author(s):  
Trung Duc Vo ◽  
Jwar Meetro ◽  
Barry Lynch ◽  
Shahrzad Tafazoli ◽  
Akio Ichihara ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Chromosomal Aberration ◽  
Food Industry ◽  
Toxicity Testing ◽  
In Vitro Assays ◽  
Sprague Dawley ◽  
Reverse Mutation ◽  
Chromosomal Aberration Assay

β-Fructofuranosidase (β-D-fructofuranoside fructohydrolase; EC 3.2.1.26) is used in the production of fructo-oligosaccharides that are commonly used by the food industry as prebiotics for their purported health benefits. The β-fructofuranosidase discussed herein is obtained from a novel source organism that is a non-genetically modified strain of Aspergillus brunneoviolaceus, which phylogenetically belongs to the Aspergillus section Nigri. The safety of β-fructofuranosidase was evaluated in a series of toxicology studies as prescribed by Tier 1 toxicity testing by the European Food Safety Authority, including an evaluation of the mutagenicity and genotoxicity potential using the in vitro bacterial reverse mutation and mammalian chromosomal aberration assays, as well as systemic toxicity in a 90-day oral subchronic toxicity study in Sprague-Dawley rats. β-Fructofuranosidase was demonstrated to lack mutagenic or genotoxic potential based on the results of the in vitro assays due to absence of increased revertant colonies in the bacterial reverse mutation test and incidence of chromosome aberrations in the chromosomal aberration assay. Administration of β-fructofuranosidase by gavage at doses up to 1200 mg total organic solids (TOS)/kg body weight/day for 90 days did not elicit any systemic toxic effects in rats based on a lack of adverse effect in any study parameter, and therefore the no-observed-adverse-effect level of β-fructofuranosidase was concluded to be 1200 mg TOS/kg body weight/day, the highest dose tested. The results of the toxicology studies on β-fructofuranosidase from A. brunneoviolaceus demonstrate this species to be a safe and suitable source of enzymes for use by the food industry.

Evaluation of the Toxicity of Intravenous Delivery of Auroshell Particles (Gold–Silica Nanoshells)

2012 ◽  
Vol 31 (6) ◽  
pp. 584-594 ◽  
Author(s):  
Shayne C. Gad ◽  
Kelly L. Sharp ◽  
Charles Montgomery ◽  
J. Donald Payne ◽  
Glenn P. Goodrich
Keyword(s):  
Water Solution ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Gold Nanoshells ◽  
Sprague Dawley ◽  
Ovary Cells ◽  
Good Laboratory ◽  
Chromosomal Aberration Assay

Gold nanoshells (155 nm in diameter with a coating of polyethylene glycol 5000) were evaluated for preclinical biocompatibility, toxicity, and biodistribution as part of a program to develop an injectable device for use in the photothermal ablation of tumors. The evaluation started with a complete good laboratory practice (GLP) compliant International Organization for Standardization (ISO)-10993 biocompatibility program, including cytotoxicity, pyrogenicity (US Pharmacopeia [USP] method in the rabbit), genotoxicity (bacterial mutagenicity, chromosomal aberration assay in Chinese hamster ovary cells, and in vivo mouse micronucleus), in vitro hemolysis, intracutaneous reactivity in the rabbit, sensitization (in the guinea pig maximization assay), and USP/ISO acute systemic toxicity in the mouse. There was no indication of toxicity in any of the studies. Subsequently, nanoshells were evaluated in vivo by intravenous (iv) infusion using a trehalose/water solution in a series of studies in mice, Sprague-Dawley rats, and Beagle dogs to assess toxicity for time durations of up to 404 days. Over the course of 14 GLP studies, the gold nanoshells were well tolerated and, when injected iv, no toxicities or bioincompatibilities were identified.

Utilization of rat lymphocytes for the in vitro chromosomal aberration assay

Mutagenesis ◽  
1989 ◽  
Vol 4 (2) ◽  
pp. 147-153 ◽  
Author(s):  
Anil K. Sinha ◽  
B.Bhaskar Gollapudi ◽  
V.Ann Linscombe ◽  
Mary L. McClintock
Keyword(s):  
Chromosomal Aberration ◽  
Rat Lymphocytes ◽  
Chromosomal Aberration Assay

Subchronic Hepatotoxicity Evaluation of 1,2,4-Tribromobenzene in Sprague-Dawley Rats

2012 ◽  
Vol 31 (3) ◽  
pp. 250-256 ◽  
Author(s):  
Darol E. Dodd ◽  
Linda J. Pluta ◽  
Mark A. Sochaski ◽  
Kathleen A. Funk ◽  
Russell S. Thomas
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Exposure Time ◽  
Clinical Signs ◽  
Liver Weight ◽  
Sprague Dawley ◽  
Significant Incidence ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level

Male Sprague-Dawley rats were exposed to 1,2,4-tribromobenzene (TBB) by gavage for 5 days, 2, 4, and 13 weeks at 0, 2.5, 5, 10, 25, or 75 mg/kg per d. There were no TBB exposure-related clinical signs of toxicity or changes in body weight. Liver weight increases were dose and exposure time related and statistically significant at ≥10 mg/kg per d. Incidence and severity of centrilobular cytoplasmic alteration and hepatocyte hypertrophy were dose and time related. The 75 mg/kg per d group had minimally increased mitoses within hepatocytes (5 days only). Hepatocyte vacuolation was observed (13 weeks) and was considered TBB exposure related at ≥25 mg/kg per d. Concentrations of blood TBB increased linearly with dose and at 13 weeks, ranged from 0.5 to 17 µg/mL (2.5-75 mg/kg per d). In conclusion, rats administered TBB doses of 10-75 mg/kg per d for 13 weeks had mild liver effects. A no observed adverse effect level of 5 mg/kg per d was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses ≥10 mg/kg per d.

scholarly journals Safety assessment of purine nucleosidase from Aspergillus luchuensis

2021 ◽  
Vol 5 ◽  
pp. 239784732110614
Author(s):  
Trung D Vo ◽  
Jwar Meetro ◽  
Seth Floyd ◽  
Barry Lynch ◽  
Shahrzad Tafazoli ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Production ◽  
Clinical Chemistry ◽  
Alcoholic Beverages ◽  
Sprague Dawley ◽  
Purine Base ◽  
Toxicological Studies ◽  
Adverse Effect Level ◽  
Aspergillus Luchuensis

Purine nucleosidase (EC 3.2.2.1) catalyzes the N-riboside hydrolysis of purine nucleosides to D-ribose and a purine base. This enzyme may be used in the production of beer and other alcoholic beverages to reduce the purine content of these products. Purine nucleosidase was obtained from Aspergillus luchuensis naturally occurring in grain sources. The safety profile of purine nucleosidase is not well documented in the scientific literature, and a series of toxicological studies were undertaken to investigate the safety of its use in food production. Purine nucleosidase from A. luchuensis was non-mutagenic and non-clastogenic in a standard Ames test and in vitro mammalian chromosome aberration assay. Administration of purine nucleosidase in a 90-day subchronic toxicity study in Sprague-Dawley rats did not elicit adverse findings on any hematology, clinical chemistry, urinalysis, organ weight, or histopathological parameter at doses up to 1700 mg total organic solids (TOS)/kg body weight/day, the highest dose tested. The results suggest purine nucleosidase to lack systemic toxic effect. The no-observed-adverse-effect level was concluded to be 1700 mg TOS/kg body weight/day. The results of the toxicology studies support the safety of purine nucleosidase from a non-genetically modified strain of A. luchuensis when used in food production.

scholarly journals Kidney-based in vitro models for drug-induced toxicity testing

2019 ◽  
Vol 93 (12) ◽  
pp. 3397-3418 ◽  
Author(s):  
João Faria ◽  
Sabbir Ahmed ◽  
Karin G. F. Gerritsen ◽  
Silvia M. Mihaila ◽  
Rosalinde Masereeuw
Keyword(s):  
Adverse Effects ◽  
Drug Disposition ◽  
Drug Effects ◽  
Toxicity Testing ◽  
Cell Types ◽  
In Vitro Assays ◽  
Vascular Effects ◽  
Drug Induced

Abstract The kidney is frequently involved in adverse effects caused by exposure to foreign compounds, including drugs. An early prediction of those effects is crucial for allowing novel, safe drugs entering the market. Yet, in current pharmacotherapy, drug-induced nephrotoxicity accounts for up to 25% of the reported serious adverse effects, of which one-third is attributed to antimicrobials use. Adverse drug effects can be due to direct toxicity, for instance as a result of kidney-specific determinants, or indirectly by, e.g., vascular effects or crystals deposition. Currently used in vitro assays do not adequately predict in vivo observed effects, predominantly due to an inadequate preservation of the organs’ microenvironment in the models applied. The kidney is highly complex, composed of a filter unit and a tubular segment, together containing over 20 different cell types. The tubular epithelium is highly polarized, and the maintenance of this polarity is critical for optimal functioning and response to environmental signals. Cell polarity is dependent on communication between cells, which includes paracrine and autocrine signals, as well as biomechanic and chemotactic processes. These processes all influence kidney cell proliferation, migration, and differentiation. For drug disposition studies, this microenvironment is essential for prediction of toxic responses. This review provides an overview of drug-induced injuries to the kidney, details on relevant and translational biomarkers, and advances in 3D cultures of human renal cells, including organoids and kidney-on-a-chip platforms.

scholarly journals Afferent renal innervation in anti-Thy1.1 nephritis in rats

2020 ◽  
Vol 319 (5) ◽  
pp. F822-F832
Author(s):  
Kristina Rodionova ◽  
Roland Veelken ◽  
Karl F. Hilgers ◽  
Eva-Maria Paulus ◽  
Peter Linz ◽  
...  
Keyword(s):  
Renal Tissue ◽  
In Vitro Assays ◽  
Renal Nerves ◽  
Dual Function ◽  
Sprague Dawley ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Cgrp Release ◽  
Renal Nerve Activity

Afferent renal nerves exhibit a dual function controlling central sympathetic outflow via afferent electrical activity and influencing intrarenal immunological processes by releasing peptides such as calcitonin gene-related peptide (CGRP). We tested the hypothesis that increased afferent and efferent renal nerve activity occur with augmented release of CGRP in anti-Thy1.1 nephritis, in which enhanced CGRP release exacerbates inflammation. Nephritis was induced in Sprague-Dawley rats by intravenous injection of OX-7 antibody (1.75 mg/kg), and animals were investigated neurophysiologically, electrophysiologically, and pathomorphologically 6 days later. Nephritic rats exhibited proteinuria (169.3 ± 10.2 mg/24 h) with increased efferent renal nerve activity (14.7 ± 0.9 bursts/s vs. control 11.5 ± 0.9 bursts/s, n = 11, P < 0.05). However, afferent renal nerve activity (in spikes/s) decreased in nephritis (8.0 ± 1.8 Hz vs. control 27.4 ± 4.1 Hz, n = 11, P < 0.05). In patch-clamp recordings, neurons with renal afferents from nephritic rats showed a lower frequency of high activity following electrical stimulation (43.4% vs. 66.4% in controls, P < 0.05). In vitro assays showed that renal tissue from nephritic rats exhibited increased CGRP release via spontaneous (14 ± 3 pg/mL vs. 6.8 ± 2.8 pg/ml in controls, n = 7, P < 0.05) and stimulated mechanisms. In nephritic animals, marked infiltration of macrophages in the interstitium (26 ± 4 cells/mm2) and glomeruli (3.7 ± 0.6 cells/glomerular cross-section) occurred. Pretreatment with the CGRP receptor antagonist CGRP8–37 reduced proteinuria, infiltration, and proliferation. In nephritic rats, it can be speculated that afferent renal nerves lose their ability to properly control efferent sympathetic nerve activity while influencing renal inflammation through increased CGRP release.

Preclinical Toxicology and Anticholangiocarcinoma Activity of Oral Formulation of Standardized Extract of Zingiber Officinale

Planta Medica ◽  
2019 ◽  
Vol 86 (02) ◽  
pp. 104-112 ◽  
Author(s):  
Tullayakorn Plengsuriyakarn ◽  
Kesara Na-Bangchang
Keyword(s):  
Body Weight ◽  
Chronic Toxicity ◽  
Toxicity Testing ◽  
Public Health Problem ◽  
Zingiber Officinale ◽  
Oral Formulation ◽  
Maximum Tolerated Dose ◽  
Toxicity Tests ◽  
Tumor Growth Inhibition ◽  
Sprague Dawley

AbstractCholangiocarcinoma (CCA) remains a significant public health problem in Thailand. New effective and safe drugs are urgently needed. Zingiber officinale Roscoe (ZO) is a widely used medicinal plant for the treatment of several ailments, and the animal study suggests a potential anti-CCA activity. The present study aimed to develop the oral formulation of standardized extract of ZO and investigate toxicological profiles (acute, repeated dose, and chronic toxicity), including anti-CCA activity of the ZO formulation. The oral pharmaceutical formulation of the standardized ZO extract was successfully developed with an acceptable level of contamination and physicochemical and pharmaceutical properties. Acute, subacute, and chronic toxicity tests were conducted in healthy Sprague Dawley rats according to the OECD guidelines. The results showed no evidence of toxicity and death in the acute and subacute toxicity testing with the maximum tolerated dose (MTD) of 5000 and 2000 mg/kg body weight, respectively. Chronic toxicity revealed MTD and No-Observed-Adverse-Effect level (NOAEL) of 1000 mg/kg body weight. The anti-CCA activity was evaluated in CCA-xenografted mouse model. The formulated ZO powder was fed to animals daily for 30 days. Significant anti-CCA activity on tumor growth inhibition and prolongation of survival time were demonstrated at the high (2000 mg/kg body weight) and moderate (1000 mg/kg body weight) dose levels. Further investigation to elucidate molecular targets of action of ZO against CCA cells is encouraged.

2018 Lush Science Prize

2020 ◽  
Vol 48 (1_suppl) ◽  
pp. 18S-25S
Author(s):  
Jenny McCann ◽  
Terry McCann
Keyword(s):  
Public Awareness ◽  
Relevant Literature ◽  
Toxicity Testing ◽  
In Vitro Assays ◽  
Adverse Outcome Pathway ◽  
Annual Conference ◽  
Animal Testing ◽  
Safety Testing ◽  
Animal Replacement

The Lush Prize supports animal-free testing by awarding money prizes of up to £350,000 per year to the most effective projects and individuals who have been working towards the goal of replacing animals in product or ingredient safety testing. Since its inception in 2012, the Lush Prize has distributed almost £2 million. Prizes are awarded for developments in five strategic areas: Science; Lobbying; Training; Public Awareness; and Young Researchers. In 2015, the judges also awarded a Black Box prize for the development of the skin sensitisation Adverse Outcome Pathway and its associated in vitro assays. The Science Prize is awarded to researchers whose work the judging panel believe to have made the most significant contribution, in the preceding year, to the replacement of animal testing. This 2018 Science Background paper outlines the research projects that were presented to the Prize judges as potential candidates for the 2018 Lush Science Prize award. To obtain an overview of developments in the field of animal replacement in toxicity research, recent work by the relevant scientific institutions and projects in this area, including the OECD, CAAT, ECVAM, UK NC3Rs, US Tox21 Programme, the ToxCast programme and EU-ToxRisk, was reviewed. Recent developments in toxicity testing research were investigated by searching the relevant literature. Abstracts from conferences focusing on animal replacement in toxicity testing that were held in the preceding 12 months, were also analysed, including those from the 2017 10th World Congress on Alternatives and Animals in the Life Sciences and the 2018 Society of Toxicology annual conference.

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