A Comparison of Blood Collection Techniques in Mice and their Effects on Welfare.

Multiple methods are used to collect blood from mice; these methods have different effects on animal welfare. This study compared blood collection from facial, chin, and saphenous locations with regard to various parameters, including the time needed to collect blood, the number of attempts needed, success at completing the blood collection, volume of blood loss, weight changes in the mouse, presence of external lesions after blood collection and gross lesions at necropsy, physical signs during blood collection (vocalization, urination, and defecation), fecal corticosterone after blood collection, and blood chemistry values. While no one technique was clearly better for animal welfare, each technique had benefits and drawbacks.

Room Decontamination Using Ionized Hydrogen Peroxide Fog and Mist Reduces Hatching Rates of Syphacia obvelata Ova.

This study evaluated the efficacy of ionized hydrogen peroxide (iHP) fog and mist for environmental and surface decontaminationof Syphacia obvelata ova in rodent rooms. Ova were collected by perianal tape impression from S. obvelata infectedmice. In experiment 1, ova were exposed to iHP using a whole-room fogging decontamination system with a 15 min initialfog application cycle in unoccupied rodent rooms. Ova were removed from the fogged environment after a 15 min, 30 min, 90min, or 240 min iHP exposure time. In experiment 2, a second cohort of ova were exposed to iHP using the whole-room foggingdecontamination system. Ova were removed after 3, 4 or 6 continuous fog application cycles with 45 min dwelling timebetween each cycle and 15 h dwelling time for the last time point. In experiment 3, a third set of ova was exposed to an iHPsurface misting unit with 1, 2, or 3 iHP mist applications. A 7 min contact time followed each application. After exposure, ovawere incubated in a hatching medium for 6 h. Control ova were maintained at room temperature without iHP exposure beforeincubation in the hatching medium. After incubation, the number of ova hatched was assessed by microscopic examination.For experiment 1, results ranged from 46% to 57% of exposed ova hatched. For experiment 2, results ranged from 43% to 49%of ova hatched. For experiment 3, 37% to 46% of exposed ova hatched. Conversely, for the control groups above 80% of ovahatched for all 3 experiments. These data suggest that exposure to iHP fog and mist has variable effectiveness in reducingviability of S. obvelata ova at the time points tracked. Further studies are needed to identify iHP exposures that will furtherreduce or eliminate the hatching of rodent pinworm ova.

Evaluation of cynomolgus monkey pregnane X receptor, primary hepatocyte, and in vivo pharmacokinetic changes in predicting human CYP3A4 induction.

Monkeys have been proposed as an animal model to predict the magnitude of human clinical drug-drug interactions caused by CYP3A4 enzyme induction. To evaluate whether the cynomolgus monkey can be an effective in vivo model, human CYP3A4 inducers were evaluated both in vitro and in vivo. First, a full-length pregnane X receptor (PXR) was cloned from the cynomolgus monkey, and the sequence was compared with those of rhesus monkey and human PXR. Cynomolgus and rhesus monkey PXR differed by only one amino acid (A68V), and both were highly homologous to human PXR (approximately 96%). When the transactivation profiles of 30 compounds, including known inducers of CYP3A4, were compared between cynomolgus and human PXR, a high degree of correlation with EC(50) values was observed. These results suggest that cynomolgus and human PXR respond in a similar fashion to these ligands. Second, two known human CYP3A4 inducers, rifampicin and hyperforin, were tested in monkey and human primary hepatocytes for induction of CYP3A enzymes. Both monkey and human hepatocytes responded similarly to the inducers and resulted in increased RNA and enzyme activity changes of CYP3A8 and CYP3A4, respectively. Lastly, in vivo induction of CYP3A8 by rifampicin and hyperforin was shown by significant reductions of midazolam exposure that were comparable with those in humans. These results show that the cynomolgus monkey can be a predictive in vivo animal model of PXR-mediated induction of human CYP3A4 and can provide a useful assessment of the resulting pharmacokinetic changes of affected drugs.

Clinical pathology laboratory values of rats housed in wire-bottom cages compared with those of rats housed in solid-bottom cages.

Rats are used routinely for the discovery of new pharmaceuticals and for toxicology testing to fulfill regulatory requirements. In 1999, a survey showed that 80% of all rodents housed in toxicology studies were housed in wire-bottom cages. However, both the National Research Council and Association for the Assessment and Accreditation of Laboratory Animal Care, International, recommend housing rats in solid-bottom cages with bedding. In this study 2 groups of male Sprague Dawley rats were housed in the same room for 4 wk and provided the same food and water by the same husbandry staff person. The only variable in the study was the type of housing. One group was housed in solid-bottom polycarbonate cages with bedding and the other group in standard wire-bottom caging. Clinical pathology laboratory evaluations of complete blood count, serum chemistries, urinalysis, urine creatinine, urine corticosterone, blood coagulation, and hepatic cytochrome P450 isoenzyme mRNA levels were performed. No clinically relevant differences were found between the 2 groups for any of the laboratory data.