Parvovirus H1 (H1PV) can be an autonomous parvovirus that is transmitted in rodent populations. last injection. Hematology, blood chemistry, and coagulation analyses did not reveal significant toxicologic changes due to H1PV. Virus injection stimulated the production of IgG antibodies but did not alter mononuclear cell function or induce cytokine release. PCR analysis showed dose-dependent levels of viral genomes in all organs tested. The virus was excreted primarily through feces. These data provide important information regarding H1PV infection in its natural host. Due to the confirmation of the favorable safety profile of H1PV in a permissive animal model, a phase I/IIa clinical trial of H1PV in brain tumor patients could be initiated. = 17), rats received single injections (3 dose levels) of 1 1 108 (high dose), 1 107 (intermediate dose), and LY 2874455 1 106 (low dose) pfu. Animal experiments. For all tests, female, nonpregnant, nulliparous and male SPF Wistar rats (Crl: WI[Han]) were from a managed full-barrier breeding program (Charles River, Sulzfeld, Germany) and examined against infections, including H1 LY 2874455 parvovirus, bacterias and parasites (full list: http://www.criver.com/HealthData/de/H64W090R.pdf). At the start from the scholarly research, rats had been 8 to 12 wk older. All rats had been bred for experimental reasons according to Content 9.2, #7 7 from the German Work on Pet Welfare.6 The research were carried out by BSL Bioservice (Munich, Germany). All tests complied using the German Works on Pet Welfare (Tierschutzgesetz, July 2009), Great Laboratory Methods, and Infection Safety (Infektionsschutzgesetz, January 2001).5,6,9 BSL Bioservice licenses to take care of H1PV and carry out acute and repeated-dose toxicity research had been granted by the federal government of Top Bavaria, Munich, Germany. Pets were held under full-barrier circumstances within an air-conditioned space (10 air modification hourly) at 22 3 C, comparative moisture of 55% 10%, and a 12:12-h lightCdark routine. All rats had been kept in separately ventilated cages (type III H, polysulfone cages with wood-fiber bed linen and tunnels as enrichment) in LY 2874455 order to avoid cross-infection between pets. Cages were changed weekly. An adequate acclimation period (at LY 2874455 least 5 d) was allowed prior to initiating animal experiments. LY 2874455 Animals had free access to a maintenance diet for rats and mice (no. 1324, Altromin, Bielefeld, Eastern Westphalia, Germany) and to tap water, which was sulfur-acidified to a pH of approximately 2.8. Number, sex, and allocation of rats. Acute toxicity study. Thirty rats (15 of each sex) were divided in 3 groups of 10 (5 of each sex). The control group received a single intravenous injection of vehicle only (48% iodixanol in Ringer solution), dose group 1 received a single injection of 8.6 107 pfu H1PV per animal, and dose group 2 received a single injection of 8.6 108 pfu H1PV per animal. The injection volume was 750 L in all rats. Repeated toxicity study. The 223 rats (112 female, 111 male) were allocated into 5 groups of different sizes. All animals received a total of 17 injections. Control group 1 received vehicle only (10% iodixanol in Ringer solution), control group 2 received Ringer solution. Two control groups were included because injection with Ringer solution was unlikely to cause toxic effects, whereas repeated injections of iodixanol could result in toxicity. Rats in groups 3, 4, and 5 each received 17 injections, each of which contained 106 pfu H1PV (low dose, group 3), 107 pfu H1PV (intermediate dose, group 4), or 108 pfu H1PV (high dose, group 5). The allocation of rats and the respective examinations are shown in Table 1. The animals were euthanized either on day 29 Rabbit polyclonal to HMGN3. (24 h after the last administration) or after a recovery period of 14 d (day 43) after the last administration. Table 1. Group definition and allocation of rats Clinical examinations. The observation period was 14 d.