Effects of parabens on placental development and birth outcomes: Evidence based on targeted risk assessment environmental chemicals strategy.

Parabens (PBs) are widely used preservatives in consumer products and suspected endocrine disruptors associated with adverse pregnancy outcomes. However, a structured framework for quantifying these risks is currently lacking. Employing the Targeted Risk Assessment of Environmental Chemicals (TRAEC) scheme, this study synthesized evidence from 16 epidemiological, 11 in vivo, and 5 in vitro studies, alongside our experimental data. PBs posed a moderate overall risk (score: 6.07), displaying compound-specific profiles. Regarding placental toxicity, methylparaben (MePB) scored highest (6.83), outranking ethylparaben (EtPB: 5.94), propylparaben (PrPB: 5.05), and butylparaben (BuPB: 3.17), whereas MePB (6.67) and BuPB (6.60) dominated birth outcome risks. Literature associated PBs with shortened gestation, restricted fetal growth, thyroid disruption, and metabolic alterations. Mechanistically, our in vitro human trophoblast models demonstrated that MePB and PrPB suppressed cellular proliferation, migration, and tube formation, driving placental insufficiency. These insights underscore the critical need to mitigate maternal PBs exposure to protect fetal-placental health.