Bone marrow micronucleus assay in Brown-Norway rats exposed to diphenyl-methane-4,4 '-diisocyanate

Four groups of young adult male Brown-Norway rats (strain: BN/RijHsd) were either exposed whole-body (WB) to filtered air (negative control) or to res pirable aerosols of monomeric diphenylmethane-4,4 ' -diisocyanate (MDI) at actual breathing zone concentrations of 9.2 +/-1.5 and 118 +/-E 8.6 mg/m(3) . One additional group was exposed to 11,0 +/- 14.4 mg/m(3) MDI using a nos e-only (NO) mode. Exposure was I h/day, one exposure per week on 3 consecut ive weeks. MDI aerosols were generated using either a condensation (WB) or a dispersion-condensation (NO) principle with resultant MMADs of 2.4-3.1 mu m and 1.2 mum (GSD approximate to1.5), respectively. Humidity ranged from a pproximate to 40% (WB) to approximate to5% (NO). Positive controls received cyclophosphamide and colcemid. Micronuclei in polychromatic erythrocytes ( MN-PCE) were counted in bone marrow smears prepared after the final exposur e on post-exposure days 1, 2 and 7 and stained with acridine orange or Wrig ht-Giemsa. Both the WB-exposure regimen and the 7-day sampling time point w ere based upon a previous study in which a significant increase in MN-PCE w as reported to occur. Rats exposed to 118 (WB) and 110 mg/m(3) MDI (NO) exh ibited signs of respiratory distress, including hypothermia, and increased lung weights when compared to WB-exposed rats. The intensity of changes app eared to be slightly more pronounced in NO-exposed rats. At no time point d id this study provide any evidence of an MDI-induced effect on the frequenc y of MN-PCE. No differences in outcome existed following staining with acri dine orange or Wright-Giemsa. There was an absence of any effect on the fre quency of mast cells and their frequency was low enough not to interfere wi th the outcome of study. Positive control groups exhibited significant incr eases in MN-PCE. In summary, monomeric MDI aerosol did not induce cytogenet ic damage in Brown-Norway rats when investigated according to current testi ng guidelines.