With the available information from genotoxicity studies, and with the pattern of tumor results from the cancer bioassays, what is your overall conclusion on the mutagenic potential of 1,3-D in humans following in vivo exposure (please explain)?

Answer Explanations

• Clearly NOT mutagenic

  Expert 5

  The tumor studies in experimental animals only show tumor induction at very high doses and these doses likely saturated relevant metabolic pathways and led to tumorigenesis by pathways unlikely to occur under exposure levels that humans might encounter. For a carcinogen acting via a genotoxic/mutagenic pathway I would expect a near linear dose response. Furthermore the highest levels of exposure in the inhalation studies in mice, that were below the KMD were nontumorigenic and were several orders of magnitude above the worst case scenarios in humans.

• Clearly NOT mutagenic

  Expert 1

  Clear negative in state-of-art gene mutation assay, amongst other studies

• Most likely NOT mutagenic

  Expert 14

  As a general statement and as also answered previously to question 2.10, genotoxicity must be thoroughly and deeply investigated with the appropriate in vitro and in vivo test batteries for hazard identification, regardless of cancer bioassay information/results, since the implication of mutations are not limited to cancer but involve genetic diseases and other somatic illnesses.
  Based on the available information from genotoxicity studies, my overall conclusion on the mutagenic potential of 1,3-D is that it is "most likely NOT mutagenic" since the mutagenic concern derived from positive findings observed in bacterial and mammalian cell mutagenicity assays is ruled out mainly by the clear negative outcome obtained in the Big Blue rat assay via oral route (Young 2018). Such a result is usually extrapolated to humans independently by the pattern of tumor results obtained from the cancer bioassays.