Research needs to improve risk assessment of fiber toxicity

Risk characterization of exposure to toxic compounds requires information on the intrinsic toxic properties, including toxic mechanism and toxicokinetics, on dose response at the most critical targets for identification of the NOEL or for extrapolation from high to low dose, and on human exposure. Abundant information is available on the intrinsic properties of MMMF, on the three D's (dose, dimension, durability) and on the toxic mechanisms. However, only a few of these studies provide information on the dose response of the effects or of the mechanisms investigated. Moreover, in many cases single high doses exceeding the MTD have been applied and are difficult to interpret for lower exposure scenarios. Risk characterization is further hampered by the still open question whether MMMF are directly genotoxic or induce secondary genotoxicity via inflammation. Finally, there is disagreement about the relevance of animal studies on MMMF for humans and thus about the most rational extrapolation of the dose response of toxic effects observed in animals to man. These deficits are briefly described and discussed from a toxicological point of view.