Author
John A. Timbrell
Bio: John A. Timbrell is an academic researcher from King's College London. The author has contributed to research in topics: Cadmium chloride & Glutathione. The author has an hindex of 15, co-authored 24 publications receiving 2926 citations.
Topics: Cadmium chloride, Glutathione, Toxicity, Biomarker discovery, Taurine
Papers
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TL;DR: Different sensitivity was observed for each assay with the neutral red and the MTT assay being the most sensitive in detecting cytotoxic events compared to the LDH leakage and the protein assay.
1,305 citations
TL;DR: The metabolic fate of a xenobiotic can have an important bearing on its toxic potential, the disposition of the compound in the body and the excretion of the compounds.
Abstract: Xenobiotics, which are absorbed into biological systems by passive diffusion across membranes are usually lipid soluble and not ideally suited for excretion. Indeed very lipophilic substances may remain in the mammalian body for many years. After a xenobiotic has been absorbed, it may undergo biotransformation to products which are rapidly excreted and therefore elimination of the compound from the animal is facilitated. However, biotransformation may also change the biological activity of the substance. Hence, the metabolic fate of the compound can have an important bearing on its toxic potential, the disposition of the compound in the body and the excretion of the compound. The metabolic reactions involved are usually divided into phase 1 and phase 2 reactions, the latter being conjugation reactions. The products of metabolism are usually more water soluble than the original compound. Although usually detoxifying, these reactions, especially phase 1 ones, sometimes increase toxicity.
Keywords:
biotransformation;
metabolism;
Phase 1;
Phase 2;
conjugation;
cytochrome;
hydroxylation;
oxidation;
dealkylation
502 citations
Book•
30 Oct 1991TL;DR: Dose-response relationship factors affecting toxic response - disposition, metabolism factors affecting metabolism and disposition toxic responses to foreign compounds biochemical mechanisms of toxicity - specific examples.
Abstract: Dose-response relationship factors affecting toxic response - disposition, metabolism factors affecting metabolism and disposition toxic responses to foreign compounds biochemical mechanisms of toxicity - specific examples.
489 citations
TL;DR: The use of biomarkers in toxicology is becoming increasingly important and some of the new developments, particularly in relation to biomarkers of exposure and response, are mentioned.
222 citations
Book•
26 Feb 1989TL;DR: In this article, the authors present a methodology for toxicity testing and risk assessment of household products, including industrial chemicals, food additives, and contaminants, using Toxicity Testing and Risk Assessment (TRAIA).
Abstract: Disposition of Toxic Compunds Types of Exposure and Response Drugs as Toxic Substances Industrial Chemicals Food Additives and Contaminants Pesticides Environmental Pollutants Natural Products Household Products Toxicity Testing and Risk Assessment.
120 citations
Cited by
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TL;DR: There is little doubt that measurements of bioaccumulation and biomarker responses in fish from contaminated sites offer great promises for providing information that can contribute to environmental monitoring programs designed for various aspects of ERA.
4,397 citations
TL;DR: Different sensitivity was observed for each assay with the neutral red and the MTT assay being the most sensitive in detecting cytotoxic events compared to the LDH leakage and the protein assay.
1,305 citations
TL;DR: An extensive review of existing data in the form of tables, encompassing many therapeutic classes is presented and the different contamination sources as well as fate and both acute and chronic effects on non-target organisms are reviewed.
1,281 citations
TL;DR: The suitability of a mouse spermatogonial stem cell line as a model to assess nanotoxicity in the male germline in vitro is assessed and it is suggested that this cell line provides a valuable model with which to assess the cytotoxicity of nanoparticles in the germ line in vitro.
1,196 citations
TL;DR: The most comprehensive exploration of genetic loci influencing human metabolism thus far, comprising 7,824 adult individuals from 2 European population studies, is reported, reporting genome-wide significant associations at 145 metabolic loci and their biochemical connectivity with more than 400 metabolites in human blood.
Abstract: Genome-wide association scans with high-throughput metabolic profiling provide unprecedented insights into how genetic variation influences metabolism and complex disease. Here we report the most comprehensive exploration of genetic loci influencing human metabolism thus far, comprising 7,824 adult individuals from 2 European population studies. We report genome-wide significant associations at 145 metabolic loci and their biochemical connectivity with more than 400 metabolites in human blood. We extensively characterize the resulting in vivo blueprint of metabolism in human blood by integrating it with information on gene expression, heritability and overlap with known loci for complex disorders, inborn errors of metabolism and pharmacological targets. We further developed a database and web-based resources for data mining and results visualization. Our findings provide new insights into the role of inherited variation in blood metabolic diversity and identify potential new opportunities for drug development and for understanding disease.
985 citations