[Stem-cell engraftment as delayed therapy to repair organophosphate-induced brain damage]. / Utilisation potentielle des greffes de cellules souches pour le traitement différé des lésions cérébrales induites par les neurotoxiques organophosphorés.

Amongst organophosphate compounds, both pesticides and warfare neurotoxics are probably the most representative. These compounds are irreversible acetylcholinesterase inhibitors. Usual clinical signs observed after acute poisoning are mainly respiratory distress, convulsions and seizures. Following acute poisoning, an emergency treatment must be provided as soon as possible (maximum delay of 1 hour post-poisoning), to prevent irreversible brain damage and patient death. At the present time, there is no efficient delayed treatment which could be provided if this 1 hour latency is overpassed. However, neurogenesis by stem cell engraftment, eventually complemented by gene therapy strategy, could be a potential therapeutic approach to repair organophosphate-induced brain damage. Main stem cell engraftement strategies successfully used for brain damage of various origins are reviewed in this Article.

[Are acute toxicity testing and the three Rs rule reconcilable? Example of the lethal dose 50 determination]. / Les études de toxicité aiguë chez l'animal et la règle des trois R sont-elles conciliables? Exemple de la détermination des doses létales 50%

Toxicity assessment and demonstration of innocuousness of chemical compounds have been part of the research studies conducted in the fields of pharmacy, agriculture and chemical industry for years. Acute systemic toxicity studies are an important element of the safety evaluation. They remain compulsory for regulatory purposes and important for the public opinion that does not accept the risk anymore. Evolutions of the ethics in animal experiments foster a necessary reduction of the number of animals involved in this type of experiments, following the well-known principle of the three Rs rule of Russell and Burch (1959) (Reduction, refinement and replacement). These two views seem in contradiction. Using the example of acute toxicity testing and focusing on the now very criticized parameter lethal dose 50, we will present approaches, including statistical ones, that a toxicologist can use, when free to choose, to keep on conducting the indispensable in vivo studies while abiding by ethical recommendations.