In Vivo Mutagenicity at the Hprt Locus in B6C3F1 Mice following 16-Week Exposure to Ozone Alone or in Combination with 4-(N-Methyl-N-Nitrosamino)-1-(3-Pyridyl)-1-Butanone and/or Dibutyl Phthalate

We investigated the potential toxicological interactions between 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and/or dibutyl phthalate (DBP) and ozone using the hprt mutation assay following a 16-week exposure period. Male and female B6C3F1 mice were exposed for 6 h/day over 16 weeks to ozone (0.5 ppm), NNK (1.0 mg/kg), DBP (5000 ppm), or two- or three-way combinations of these agents. Across both sexes, every treatment group exhibited an elevated frequency of TGr lymphocytes relative to controls, and the two combination groups showed additive interactions with ozone in both sexes over the 16-week period. Taken together, these findings demonstrate the potential additive genotoxic effects of NNK, DBP, ozone, and their combinations; specifically, under the conditions tested, co-exposure to ozone, NNK, and DBP produced additive genotoxicity relative to ozone exposure alone.