TA-102 / Sun Pharma - LARVOL DELTA

An Open-Label Study to Assess Safety (clinicaltrials.gov) - P1 | N=88 | Completed | Sponsor: Taro Pharmaceuticals USA | Phase classification: P2 ➔ P1

Phase classification • Dermatology • Immunology • Psoriasis

An Open-Label Study to Assess Safety (clinicaltrials.gov) - P2 | N=88 | Completed | Sponsor: Taro Pharmaceuticals USA | Unknown status ➔ Completed

Trial completion • Dermatology • Immunology • Psoriasis

Synacinn™: Bacterial reverse mutation test data in five histidine-requiring strains of Salmonella Typhimurium. (PubMed, Data Brief) - "The present data described the analysis of mutagenicity in Synacinn by assessing the point mutations occurring due to Synacinn™ exposure to five tester strains of Salmonella typhimurium (TA1537, TA1535, TA98, TA100 and TA102), in the presence or absence of an exogenous mammalian metabolic activation system (S9)...Genetic integrity of all the tester strains used was confirmed by performing genotyping before their use. All the data acceptability criteria were fulfilled confirming the validity of the test."

Journal

Genotoxic effect induced by dried nicotiana tabacum leaves from tobacco barns (kiln-houses) in chinese hamster lung fibroblast cells (V79). (PubMed, J Toxicol Environ Health A) - "Mutagenicity was not found using the Salmonella/Microsome test (TA98, TA100, and TA102 strains) with and without metabolic activation...Using CG/MS nicotine amounts present were 1.56 mg/g dry tobacco leaf powder. Due to the observed genotoxicity in V79 cells, more investigations are needed to protect the health of tobacco workers exposed daily to this complex mixture of toxic substances present in dry tobacco leaves."

Journal

Plinia cauliflora (Mart.) Kausel (Jaboticaba) leaf extract: in vitro anti-Trypanosoma cruzi activity, toxicity assessment and phenolic-targeted UPLC-MS metabolomic analysis. (PubMed, J Ethnopharmacol) - "The present study demonstrated that P. cauliflora leaf extract is a potential source of antiparasitic bioactive compounds, however it presents cytotoxic effects in liver cell lines."

Journal • Preclinical • Inflammation • Metabolic Disorders

Evaluation of soils under the influence of coal mining and a thermoelectric plant in the city of Candiota and vicinity, Brazil. (PubMed, Mutat Res) - "Results of Salmonella/microsome assays were negative, only Candiota and Pinheiro Machado samples showed a statistical increase of his + colonies in TA102. Our work describes biological data on these cells exposed to coal-contaminated soil, confirming the sensitivity of the Comet Assay in V79 cells and Salmonella/microsome assay for the evaluation of the effects of complex mixtures. These findings help to understand the spatial distribution of contaminants in the local soil related to a power plant, which is important for planning public safety actions."

Journal

In vitro genotoxicity assessment of functional ingredients: DHA, rutin and α-tocopherol. (PubMed, Food Chem Toxicol) - "A miniaturized version of the Ames test in Salmonella typhimurium TA97a, TA98, TA100, TA102, and TA1535 strains (following the principles of OECD 471), and the in vitro micronucleus test in TK6 cells (OECD 487) were performed...This article complements the evidence already available about the genotoxicity of these compounds. However, more studies are needed in order to elucidate the consequences of their use as functional ingredients in human health."

Journal • Preclinical

Assessment of the mutagenicity of two common indoor air pollutants, formaldehyde and toluene. (PubMed, Indoor Air) - "In this study, we developed and improved a bacterial reverse mutation assay (Ames test) by using a direct gas exposure module to directly determine the mutagenicity of indoor air quality using five tester bacterial strains (TA98, TA100, TA102, TA1535, and TA1537)...The weak, direct-acting, indirect-acting, and time-dependent mutagen of 50 ppm toluene was also confirmed. Moreover, our improved Ames module and the exposure conditions provided in this study can be further applied to evaluate the mutagenicity of indoor air quality."

Journal

Characterization of the Novel Mitochondrial Genome Segregation Factor TAP110 in Trypanosoma brucei. (PubMed, J Cell Sci) - "The assembly of TAP110 into the TAC region seems to require the TAC but not the kDNA itself, however once TAP110 has been assembled it also interacts with the kDNA. Finally, for the first time we use ultrastructure expansion microscopy in trypanosomes to reveal the precise position of TAP110 between TAC102 and the kDNA, showcasing the potential of this approach."

Journal

In Vitro Genotoxicity Assessment of Functional Ingredients: Betaine, Choline, and Taurine. (PubMed, Foods) - "The European Food Safety Authority (EFSA) tiered approach for food additives in concordance with the safety assessment of chemicals in food developed by Food and Agriculture Organization/World Health Organization (FAO/WHO) was followed; the miniaturized Ames test in Salmonella typhimurium TA97a, TA98, TA100, TA102, and TA1535 strains (following the principles of Organization for Economic Co-operation and Development (OECD) 471), and the micronucleus test (OECD 487) in TK6 cells were performed...None of the compounds produced any signs of genotoxicity in any of the conditions tested. This article increases the limited evidence available and complements the EFSA recommendations for the in vitro genotoxicity testing of nutrients."

Journal • Preclinical • MPG • OGG1

Genotoxicity and mutagenicity assessment of a standardized extract (P2Et) obtained from Caesalpinia spinosa. (PubMed, Toxicol Rep) - "Similarly, P2Et did not induce gene mutations by base pair changes or frameshifts in the genome of Salmonella Typhimurium strains TA98, TA100, TA102, TA1535 and TA1537 at the tested range of concentrations up to 5000 μg/plate in the absence and presence of metabolic activation. Therefore, the P2Et was considered as non- mutagenic and non-genotoxic at the conditions of the tests."

Journal • Melanoma • Oncology • Solid Tumor

Safety of eight nucleic acid dyeson (PubMed, Wei Sheng Yan Jiu) - "This research shows that, except EB, the other dyes show no mutagenicity under working concentration, but show varying mutagenicity under high concentration. SYBRSafe and SYBRGreenI are highly toxic, and the operators must have high precautions when making diluted solution of them."

Clinical • Journal

Structure-Activity Relationship (SAR) and in vitro Predictions of Mutagenic and Carcinogenic Activities of Ixodicidal Ethyl-Carbamates. (PubMed, Biomed Res Int) - "Endpoint of mutagenicity with and without metabolic activation showed that the ethyl-carbamates were negative (p <0.05) for mutagenicity induction in strains TA97, TA98, TA102, TA1535, TA1537 and TA1538 of Salmonella typhimurium...The endpoint of carcinogenicity in rats were negative for LQM 919 (p <0.05,) and LQM 996 (p <0.001). The results of the present study strongly suggest that ethyl-carbamates do not represent a risk for cancer in mammals."

Journal • Preclinical • Oncology • ER

A promissing Ames battery for mutagenicity characterization of new dyes. (PubMed, Environ Mol Mutagen) - "The most sensitive was YG1041, followed by TA97a > TA98 > TA100 =TA1538 >TA102...We propose that dyes should be tested in a tiered approach using YG1041 followed by TA97a, TA98 and TA100 in concentration-response experiments. This work provides additional information on the dye mutagenicity database available in the literature."

Journal

Evaluation of the Acute Toxicity and Genotoxicity of the Rice Biofortified with β-Glucan (PubMed, Sichuan Da Xue Xue Bao Yi Xue Ban) - "Whether with S activation or not, no genotoxicity was found to the tested strains TA97a, TA98, TA100, TA102 and TA1535. All results of the three genotoxicity tests were negative. Under the current experimental conditions, β-glucan biofortified rice showed no obvious acute toxicity and genotoxicity."

Journal • Hematological Malignancies • Lymphoma • Oncology

Mutagenicity and genotoxicity assessment of a new biopreservative product rich in Enterocin AS-48. (PubMed, Food Chem Toxicol) - "To assess its potential as food additive, the mutagenicicity and genotoxicity has been assayed by means of the bacterial reverse-mutation assay in Salmonella typhimurium TA97A, TA98, TA100, TA102, TA1535 strains (Ames test, OECD 471) and the micronucleus test (MN) (OECD 487) in L5178Y/ Tk+/- cells. Negative results in the mutagenicity and genotoxicity assays point out the good safety profile of the byproduct and support its use as additive. Further toxicological studies are required before its approval and commercial application."

Journal

A comparison of three approaches for the discovery of novel tripartite attachment complex proteins in Trypanosoma brucei. (PubMed, PLoS Negl Trop Dis) - "Here we apply and compare three different approaches (proximity labelling, immunoprecipitation and yeast two-hybrid) to identify novel interactors of TAC102 and subsequently verify their localisation. Furthermore, we establish the direct interaction of TAC102 and p166 in the unilateral filaments of the TAC."

Journal

Cytochrome P450 inhibition potential and initial genotoxic evaluation of 14-O-[(4,6-diaminopyrimidine-2-yl)thioacetyl] mutilin. (PubMed, Sci Rep) - "In the Ames test, Salmonella strains TA97, TA98, TA100, TA102 and TA1535 were treated with or without the metabolic activation (S9). Analysis showed the average number of revertant colonies per plate was less in double in the groups treated with DPTM than that in the negative control plate and showed no dose-related increase."

Journal • CYP1A2 • CYP2E1 • CYP3A4

Comparative Toxigenicity and Associated Mutagenicity of Aspergillus fumigatus and Aspergillus flavus Group Isolates Collected from the Agricultural Environment. (PubMed, Toxins (Basel)) - "The Ames test was performed on Salmonella typhimurium strains TA98, TA100 and TA102, without and with S9mix (exogenous metabolic activation system). On the other hand, AFB and AFM modulate negatively the mutagenicity of AFB when mixed in binary or tertiary mixtures. Thus, the evaluation of the mutagenicity of "natural" mixtures is an integrated parameter that better reflects the potential impact of exposure to toxigenic Aspergilli."

Journal

Etomidate is devoid of genotoxicty and mutagenicity in human lymphocytes and in the Salmonella typhimurium/microsomal activation test. (PubMed, Toxicol In Vitro) - "Finally, etomidate (2046.8 and 4093.5 μM) was not mutagenic in the Salmonella/microsome mutagenicity assay, which used four Salmonella typhimurium strains (TA97a, TA98, TA100, and TA102) to detect frameshift and base-substitution mutations. In summary, etomidate is a weak oxidative DNA damaging anesthetic and is devoid of mutagenic properties in eukaryotic and prokaryotic models."

Journal • Anesthesia • Oncology

Evaluation of Genotoxicity and Mutagenicity of Ketamine on Human Peripheral Blood Leukocytes and in Salmonella typhimurium. (PubMed, Toxicol In Vitro) - "Thus, in the present work, we decided to evaluate the genotoxic and mutagenic effects of ketamine on human peripheral blood leukocytes (PBLs) and Salmonella typhimurium (TA98, TA97a, TA100, and TA102) through several well-established experimental protocols based on different parameters in the presence or not of exogenous metabolizing S9 fraction. However, the oxidative DNA lesions were almost completely repaired which reflects in the lack of mutagenesis (micronuclei and chromosomal aberrations) on human PBLs and no increases in revertants numbers on S. typhimurium/microsome test (500 to 5000 μg/plate). In summary, ketamine is a weak oxidative DNA damaging agent and is devoid of mutagenic properties on eukaryotic and prokaryotic models."

Journal • Pain • Psychiatry