Assessment of the toxic effects of parabens, commonly used preservatives in cosmetics, and their halogenated by-products on human skin and endothelial cells

Parabens, widely used as preservatives in cosmetics, are increasingly concerning due to potential health risks, while their chlorinated and brominated by-products, found in aquatic environments, pose additional toxicity concerns. This study evaluated the toxic effects of parabens, their metabolite, and three halogenated by-products on human skin and endothelial cells using cytotoxicity and wound healing assays. Human epidermal keratinocytes (HEK001) and human dermal microvascular endothelial cells (HMEC-1) were used as models. In keratinocytes, butylparaben (BuP) and benzylparaben (BeP) were the most cytotoxic, with EC50 values of 1.52 ± 0.51 µM and 3.34 ± 0.97 µM, respectively. Halogenated parabens, such as methyl 3‑chloro-4-hydroxybenzoate (CMeP) and methyl 3,5-dibromo-4-hydroxybenzoate (DBMeP), also showed significant cytotoxicity, with EC50 values of 2.20 ± 0.76 µM and 1.49 ± 0.37 µM. Methylparaben (MeP), ethylparaben (EtP), and the metabolite 4-hydroxybenzoic acid (HBA) showed lower toxicity, with EC50 values ranging from 536 ± 178 µM to 1,313 ± 464 µM. In endothelial cells, MeP, EtP, and HBA had reduced toxicity, and halogenated by-products were less toxic, with EC50 values from 788 ± 140 µM to >10 mM. High concentrations (100 µM) of BuP, BeP, and halogenated by-products significantly inhibited wound healing in both cell types, while halogenated parabens inhibited keratinocyte proliferation at just 1 µM. This research enhances understanding of parabens' impact on wound healing, informing safety assessments for cosmetics and personal care products.