How the COVID-19 pandemic highlights the necessity of animal research.

Recently, a petition was offered to the European Commission calling for an immediate ban on animal testing. Although a Europe-wide moratorium on the use of animals in science is not yet possible, there has been a push by the non-scientific community and politicians for a rapid transition to animal-free innovations. Although there are benefits for both animal welfare and researchers, advances on alternative methods have not progressed enough to be able to replace animal research in the foreseeable future. This trend has led first and foremost to a substantial increase in the administrative burden and hurdles required to make timely advances in research and treatments for human and animal diseases. The current COVID-19 pandemic clearly highlights how much we actually rely on animal research. COVID-19 affects several organs and systems, and the various animal-free alternatives currently available do not come close to this complexity. In this Essay, we therefore argue that the use of animals is essential for the advancement of human and veterinary health.

To mate or not to mate: a retrospective analysis of two-generation studies for evaluation of criteria to trigger additional mating in the extended one-generation design.

An extended one-generation study is proposed to replace the standard two-generation study, and would eliminate breeding F1 animals unless triggered by effects on parental reproduction or pup development. Nine two-generation studies in rats were reviewed to determine whether reproductive or developmental toxicity was more pronounced in the F2 generation. Three studies lacked reproductive effects, one had reproductive toxicity only in parental animals, three had mostly equivalent effects between generations, and two showed greater toxicity in the second generation. In each study with relevant effects, criteria proposed by Cooper et al. [Cooper RL, Lamb IV JC, Barlow SM, Bently K, Brady AM, Doerrer NG, et al. A tiered approach to life stages testing for agricultural chemical safety assessment. Crit Rev Toxicol 2006;36:69-98.] were applied to determine whether additional breeding would be triggered in the extended one-generation design. Additional mating was triggered for all but one study with more pronounced F1 reproductive toxicity. Thus, while the extended one-generation design may be a useful substitution for the two-generation study, more stringent criteria must first be developed to determine whether additional mating is actually needed.

Intravenous tolerability of an acid vehicle in Sprague Dawley rats and beagle dogs after daily slow bolus injection and infusion for one hour during 14 days.

To assess the tolerability of an acid vehicle to be used in toxicology studies, a low pH aqueous solution containing 16.4 mg/ml of citric acid, 4.2 mg/ml of disodium phosphate, 25 mg/ml of mannitol, adjusted with phosphoric acid/NaOH 1 M to pH 3 was daily administered intravenously to rats and dogs for 14 consecutive days. The dosing regimen consisted of a slow intravenous bolus injection given over 30 s (0.75 and 0.625 ml/kg, for rats and dogs, respectively) followed by intravenous infusion for one hour (3.75 and 2.75 ml/kg/h, for rats and dogs, respectively). In rats, the dose was administered via the lateral tail vein. In dogs, the intravenous bolus dose was administered via the vena cephalica, vena saphena or vena jugularis, whilst the infusion dose was given into the vena cephalica or vena saphena. In rats, administration of the vehicle was associated with clinical signs (occasional mild vocalization and agitation) which were considered to be due to local irritation during the dosing procedure. Nevertheless, only mild histopathological changes at the injection site were found, while no relevant clinical chemistry changes were found in this species. However, the vehicle caused significant vascular damage with thrombus formation in the dog. It is therefore concluded that this vehicle is suitable for 2-week rat toxicity studies, if carefully applied. The vehicle with its present regimen should not be used in dogs, in view of the prohibitive findings.