Elevated Exposure to Pharmaceutical and Personal Care Products Increases Hyperlipidemia Risk: The Mediating Effect of Thyroid Hormones

Epidemiological evidence of the association between pharmaceutical and personal care product (PPCP) exposure and hyperlipidemia risk remains limited. In 2021, a case-control study was conducted in China, involving 103 participants with hyperlipidemia and 419 healthy controls, to investigate the effects of PPCP exposure on hyperlipidemia risk and the mediating roles of thyroid hormones. Among the individual PPCP, 4-hydroxybenzophenone showed the strongest association with hyperlipidemia risk (OR: 1.52; 95% CI: 1.01, 2.28), followed by triclosan (OR: 1.38; 95% CI: 1.01, 1.89). Mixture exposure levels of PPCP above the 50th percentile were associated with an elevated risk of hyperlipidemia, with 2,4-dihydroxybenzophenone (BP-1) contributing most to the risk, followed by ethyl-protocatechuate. Significant mediating effects of free-triiodothyronine were observed in the relationships between triclosan, BP-1, and ΣPPCP exposure, and hyperlipidemia, with the mediated proportions of 12.19, 12.86, and 11.66%, respectively. These findings indicated that thyroid hormones played an important mediating role in the association and deserve more attention. Network toxicology models suggested that inhibiting lipolysis, promoting oxidative stress, and inflammatory responses may be potential biological mechanisms of PPCP-induced hyperlipidemia. For the first time, we identified the mediating effect of thyroid hormones on the association between PPCP exposure and hyperlipidemia risk, providing valuable insights into the mechanism for further toxicology studies.