DETERMINATION OF POTENTIAL HEALTH-EFFECTS IN THE MOUSE COMPARING INTRANASAL AND PERORAL EXPOSURE TO PSEUDOMONAS-AERUGINOSA AND ESCHERICHIA-COLI

Mouse models were developed and evaluated to determine if potential he alth effects associated with intranasal and peroral exposure to microb ial biotechnology agents could be detected. Mice were challenged with two dissimilar microorganisms: Pseudomonas aeruginosa AC869 and Escher ichia coli BJ19. Intranasal challenge of mice with 1 . 7 x 10(8) CFU o r 1 . 7 x 10(7) CFU of strain AC869 resulted in 100 per cent and 50 pe r cent mortality respectively. Peroral treatment with strain AC869 cau sed 33 per cent and 8 per cent mortality upon treatment with 2 . 2 x 1 0(9) and 2 . 2 x 10(8) CFU respectively. E. coli was not fatal after a dministration by either exposure route. Recovery of AC869 from lungs, small and large intestines and caecum following intranasal- and perora l-treatment was observed. E. coli BJ19 was recovered from the same fou r organs following peroral and intranasal challenge. Intranasal challe nge resulted in a higher concentration and a longer persistence of str ain BJ19 in the intestinal system than direct peroral challenge. In ad dition, increases in lung weights were associated with strains BJ19 an d AC869 treatment. Translocation from the intestinal tract to the mese nteric lymph nodes (MLN), liver, and spleen and negative effects on ti ssue and body weights were detectable for both exposure routes and wer e dependent on the dosed strain. Overall, mice could be used to detect adverse health effects when dosed independently with microbial agents from different genera.