Exclusion of mouse hepatitis virus from a filtered, plastic rodent shipping container during an in transit field challenge.

Although leading suppliers of laboratory mice and rats continue to use filtered shipping boxes to protect their animals from contamination during transport to the end user, no information had been available in the literature to demonstrate that any of these boxes actually accomplish this task. To test this hypothesis, 12 plastic shipping boxes with filters and tight-fitting lids and six cardboard shipping boxes without filters (controls) were each stocked with adult, adventitious disease-free mice. All 18 shipping boxes were transported to a facility housing a breeding colony of mice enzootically infected with four murine viruses, including mouse hepatitis virus (MHV), and were placed inside the colony for 15 h. The boxes were then transported to a commercial testing laboratory, at which the animals were aseptically removed and were held in microisolation cages for 28 days, after which their sera tested for antibody to all four murine viruses. All serum samples from mice held in the control boxes were positive for antibody to MHV, whereas sera from all mice held in filtered boxes were negative for antibody to any of the four viruses. This study demonstrates that at least one type of filtered shipping container protects mice from a field challenge of MHV. To the best of our knowledge, this is the first documentation of any microbial efficacy testing conducted on filtered shipping containers for laboratory animals.

Methyl-CCNU: preclinical toxicologic evaluation of a single iv infusion in dogs and monkeys.

Methyl-CCNU, a compound with marked antitumor activity against the solid Lewis lung tumor in mice, was submitted to a preclinical pharmacologic evaluation. The toxicity of a single iv infusion was tested in 37 beagle dogs and 21 rhesus monkeys. The minimum lethal dose (LD) in dogs was 14 mg/kg and five of six dogs died within 7-10 days after treatment from hematopoietic toxicity with neutropenia, lymphopenia, anemia, and concomitant sepsis. Metaplasia of the intestinal epithelium also occurred. Thrombocytopenia was not observed. Dogs treated with 9.27-1.56 mg/kg exhibited reversible neutropenia and lymphopenia but survived without severe morbidity or histopathologic lesions. In monkeys, interstitial nephritis was the treatment-limiting toxicity and three of six monkeys treated with 45 or 30 mg/kg died, became moribund, or exhibited severe renal histopathologic lesions. One monkey treated with 45 mg/kg had degeneration of the testes. Survivors exhibited reversible toxicity and no histopathologic lesions. Treatment with doses as low as 7.5 mg/kg caused reversible neutropenia, lymphopenia, and anemia. The largest nontoxic dose for a single iv infusion was 3.12 mg/kg (62.40 mg/m2) for the dog and 3.75 mg/kg (45 mg/m2) for the monkey. These and earlier observations showed that methyl-CCNU had approximately one third the toxicity of CCNU. Methyl-CCNU also did not cause the delayed hepatic toxicity which is characteristic of CCNU treatment in the dog.