Associations of a mixture of urinary phthalate metabolites with blood lipid traits: A repeated-measures pilot study

Evidence is available about the associations of phthalates or their metabolites with blood lipids, however, the mixture effects of multiple phthalate metabolites on blood lipid traits remain largely unknown. In this pilot study, 106 individuals at three age groups of <18, 18- and ≥60 years were recruited from the residents (n = 1240) who were randomly selected from two communities in Wuhan city, China. The participants completed the questionnaire survey and physical examination as well as provided urine samples in the winter of 2014 and the summer of 2015. We measured urinary levels of nine phthalate metabolites using a high-performance liquid chromatography-tandem mass spectrometry. We estimated the associations of individual phthalate metabolite with blood lipid traits by linear mixed effect (LME) models, and assessed the overall association of the mixture of nine phthalate metabolites with blood lipid traits using Bayesian kernel machine regression (BKMR) models. LME models revealed the negative association of urinary mono-2-ethylhexyl phthalate (MEHP) with total cholesterol (TC) as well as of urinary mono-benzyl phthalate or urinary MEHP with low density lipoprotein cholesterol (LDL-C). BKMR models revealed the negative overall association of the mixture of nine phthalate metabolites with TC or LDL-C, and DEHP metabolites (especially MEHP) had a greater contribution to TC or LDL-C levels than non-DEHP metabolites. The findings indicated the negative overall association of the mixture of nine phthalate metabolites with TC or LDL-C. Among nine phthalate metabolites, MEHP was the most important component for the changes of TC or LDL-C levels, implying that phthalates exposure may disrupt lipid metabolism in the body. Exposure to multiple phthalates was negatively related to blood TC or LDL-C values.