Publications by authors named "J van Benthem"
Article Synopsis
- In human health risk assessment, genotoxicity hazards of chemicals typically start with a set of in vitro tests, but these tests don't capture all potential genotoxic endpoints, leading to sometimes contradictory results.
- Mathematical modeling can improve the interpretation of these tests by accounting for each test's strengths and weaknesses, providing objective predictions with associated uncertainties.
- A study found that combining a mammalian in vitro clastogenicity test and a gene mutation test offers strong evidence for genotoxic hazard assessment, but the bacterial reverse mutation (Ames) test alone can still provide useful evidence when no other data is available.
Regulatory genetic toxicology focuses on DNA damage and subsequent gene mutations. However, genotoxic agents can also affect epigenetic marks, and incorporation of epigenetic data into the regulatory framework may thus enhance the accuracy of risk assessment. Additionally, epigenetic alterations may identify non-genotoxic carcinogens that are not captured with the current battery of tests.
View Article and Find Full Text PDFToxTracker is a mammalian cell reporter assay that predicts the genotoxic properties of compounds with high accuracy. By evaluating induction of various reporter genes that play a key role in relevant cellular pathways, it provides insight into chemical mode-of-action (MoA), thereby supporting discrimination of direct-acting genotoxicants and cytotoxic chemicals. A comprehensive interlaboratory validation trial was conducted, in which the principles outlined in OECD Guidance Document 34 were followed, with the primary objectives of establishing transferability and reproducibility of the assay and confirming the ability of ToxTracker to correctly classify genotoxic and non-genotoxic compounds.
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- The study aimed to evaluate the effectiveness and safety of givinostat, a treatment for Becker muscular dystrophy (BMD), in adult males, comparing it to a placebo over 12 months.
- Out of 51 enrolled patients, the treatment did not show a statistically significant improvement in total fibrosis or other primary endpoints after 12 months, although secondary MRI assessments hinted that givinostat might slow disease progression.
- Most adverse events reported were mild to moderate, with 88.2% of patients on givinostat and 52.9% on placebo experiencing side effects.
Quantitative relationships between carcinogenic potency and mutagenic potency have been previously examined using a benchmark dose (BMD)-based approach. We extended those analyses by using human exposure data for 48 compounds to calculate carcinogenicity-derived and genotoxicity-derived margin of exposure values (MOEs) that can be used to prioritize substances for risk management. MOEs for 16 of the 48 compounds were below 10,000, and consequently highlighted for regulatory concern.
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