Systematic review and Integrated Approaches to Testing and Assessment (IATA) of PFOA and PFOS for endocrine disrupting effects based on the AOP framework

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been extensively used as surfactants, surface protectors, food packaging materials, and fire-retardants. Due to serious adverse effects on human and environment, they are now considered as legacy compounds. In this study, the effects of PFOA and PFOS on endocrine disruption were assessed using the Integrated Approaches to Testing and Assessment (IATA) methodology based on the adverse outcome pathway (AOP). PFOA/PFOS in vitro data for enzyme activities for steroidogenesis, hormone levels of 17β-estradiol and testosterone, receptor binding capacity, receptor transcriptional activation, cell proliferation and differentiation were collated and assessed to elucidate the association between the data with the human adverse outcomes. Multiple studies indicate that PFOA/PFOS alter enzyme activities, hormone levels, receptor transcription, and cell proliferation. Moreover, associations were found between in vitro data and human outcomes including semen quality, menarche, menopause, menstrual cycle, infertility, miscarriage, cancer, and birth weight. This study effectively links toxic mechanisms to human adverse outcomes of PFOA and PFOS. However, in vitro data based on the molecular initial events (MIEs) and key events (KEs) in AOP frame works are not enough and often inconsistent for integrated assessment, which suggest that more data for endocrine disruption are required for clear and complete IATA of PFOA and PFOS.