Use of New Approach Methodologies to Study the Developmental Toxicity of Polycyclic Aromatic Hydrocarbons

Summary

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been linked to developmental toxicity in human and many animal species. To date, there is limited knowledge on the developmental toxicity of PAHs, especially alkylated PAHs

In this thesis, the influence of the presence and of the position of a methyl-substituent on PAHs on their in vitro developmental toxicity and the possible mode(s) of action underlying this toxicity was investigated. Moreover, the usefulness of a battery of in vitro assays to evaluate the developmental toxicity of petroleum substances with varying level of PAHs was assessed. Finally, the in vivo developmental toxicity of 8-methyl-benzo[a]pyrene was predicted using physiologically-based kinetic (PBK) modeling facilitated quantitative in vitro to in vivo extrapolation and read-across from benzo[a]pyrene.

Overall, the thesis demonstrates that the use of new approach methodologies provides insight in the developmental toxicity of unsubstituted (parent) and methylated PAHs and complex materials containing these constituents, thereby ultimately contributing to reduce the number of experimental animals required to assess the developmental toxicity of these substances.