From screening to risk assessment: a comparative study on product usage, human burden, and potential neurotoxicity of novel paraben analogues

Parabens are extensively used preservatives with endocrine disrupting effects and neurotoxicity. Their restricted usage may drive the development of alternatives for producing preservative-free products. Nevertheless, the prevalence and health risks of paraben analogues remain poorly understood. Herein, we screened potential paraben analogues using high-resolution mass spectrometry and assessed their prevalence in personal care products (PCPs) and population exposure trends. We first identified p-hydroxyacetophenone (PhAc), a structural analogue of parabens, in children's urine based on the common fragmentation characteristics of parabens. Quantitative analysis revealed that the average content of PhAc in PCPs was 2-38 times higher than that of typical parabens. Furthermore, the longitudinal biomonitoring study conducted from 2016 to 2023 revealed that the geometric mean levels of PhAc in the urine of children aged 5-13 years in South China increase from 35.20 μg/L to 102.68 μg/L, which is 1-3 orders of magnitude greater than parabens. Nevertheless, PhAc is not a permitted preservative in PCPs and its health risk is unclear. To investigate the potential neurotoxicity of extensively present PhAc, neuronal cells were exposed to different concentrations of PhAc and typical parabens for 24 h, respectively. The results indicated that PhAc exhibited greater potential neurotoxicity than methylparaben, the most widely used paraben. Even exposure to doses comparable to urinary PhAc concentrations (100 nM-1 μM) could significantly disrupt metabolism homeostasis, damage cell membranes and morphology, and increase apoptosis rate in neuronal cells. Therefore, PhAc, a new paraben analogue with wider product applications, higher human exposure, and greater potential neurotoxicity, may pose considerable ecological and human health risks.