Optimizing drug discovery by Investigative Toxicology: Current and future trends.

Investigative Toxicology describes the de-risking and mechanistic elucidation of toxicities, supporting early safety decisions in the pharmaceutical industry. Recently, Investigative Toxicology has contributed to a shift in pharmaceutical toxicology, from a descriptive to an evidence-based, mechanistic discipline. This was triggered by high costs and low throughput of Good Laboratory Practice in vivo studies, and increasing demands for adhering to the 3R (Replacement, Reduction and Refinement) principles of animal welfare. Outside the boundaries of regulatory toxicology, Investigative Toxicology has the flexibility to embrace new technologies, enhancing translational steps from in silico, in vitro to in vivo mechanistic understanding to eventually predict human response. One major goal of Investigative Toxicology is improving preclinical decisions, which coincides with the concept of animal-free safety testing. Currently, compounds under preclinical development are being discarded due to the use of inappropriate animal models. Progress in Investigative Toxicology could lead to humanized in vitro test systems and the development of medicines less reliant on animal tests. To advance this field a group of 14 European-based leaders from the pharmaceutical industry founded the Investigative Toxicology Leaders Forum (ITLF), an open, non-exclusive and pre-competitive group that shares knowledge and experience. The ITLF collaborated with the Centre for Alternatives to Animal Testing Europe (CAAT-Europe) to organize an "Investigative Toxicology Think-Tank", which aimed to enhance the interaction with experts from academia and regulatory bodies in the field. Summarizing the topics and discussion of the workshop, this article highlights Investigative Toxicology's position by identifying key challenges and perspectives.

Poisoning of dogs and cats by drugs intended for human use.

One of the main causes of poisoning of small animals is exposure to drugs intended for human use. Poisoning may result from misuse by pet owners, off-label use of medicines or, more frequently, accidental ingestion of drugs that are improperly stored. This review focuses on classes of drugs intended for human use that are most commonly involved in the poisoning of small animals and provides an overview of poisoning episodes reported in the literature. To perform this review a comprehensive search of public databases (PubMed, Web of Science, Scopus, Google Scholar) using key search terms was conducted. Additionally, relevant textbooks and reference lists of articles pertaining to the topic were reviewed to locate additional related articles. Most published information on small animal poisoning by drugs intended for human use was from animal and human poison control centres or from single case reports. The dog was the species most frequently poisoned. The major drugs involved included analgesics (nonsteroidal anti-inflammatory drugs), antihistamines (H1-antihistamines), cardiovascular drugs (calcium channel blockers), central nervous system drugs (selective serotonin reuptake inhibitors, baclofen, benzodiazepines and zolpidem), gastrointestinal drugs (loperamide), nutritional supplements (vitamin D and iron salts) and respiratory drugs (ß2-adrenergic receptor agonists).

Animal poisoning in Europe. Part 3: Wildlife.

This review article is the third in a series on animal poisoning in Europe and represents a collation of published and non-published wildlife poisoning data from Belgium, France, Greece, Italy and Spain over the last 10 years. Birds, particularly waterfowl and raptors, were more commonly reported as victims of poisoning than wild mammals. In addition to specific but important toxicological disasters, deliberate primary or secondary poisonings are of concern to all countries. Metals (particularly lead arising from sporting/hunting activities) and pesticides (mainly anticholinesterases and anticoagulants) are frequent causes of poisoning, and often have fatal consequences. A more unified and consistent approach throughout European countries to improve the reporting and the analytical confirmation of wildlife poisoning would help to reduce the number of cases of malicious or negligent animal poisoning.