Associations between urinary phthalate metabolite concentrations and markers of liver injury in the US adult population

Background: Phthalates have been largely used for years in varieties of products worldwide. However, research on the joint toxic effect of various phthalates exposure on the liver is lacking. Objectives: We aimed to assess exposure to phthalates on liver function tests (LFTs). Methods: This analysis included data on 6046 adults (>= 20 years old) who participated in a National Health and Nutrition Examination Survey (NHANES) in 2007-2016. We employed linear regression and Bayesian kernel machine regression (BKMR), to explore the associations of urinary phthalate metabolites with 8 indicators of LFTs. Results: Di(2-ethylhexyl) phthalate (Sigma DEHP) was found to be positively associated with serum alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) (all P FDR < 0.05). We found significant positive associations of n-ary sumation DEHP, mono-ethyl phthalate (MEP) and mono-(carboxyisononyl) phthalate (MCNP) with total bilirubin (TBIL) (all P FDR < 0.05). Sigma DEHP, mono-n-butyl phthalate (MBP), mono(3-carboxypropyl) phthalate (MCPP) and mono-benzyl phthalate (MBzP) were negatively associated with serum ALB (all P FDR < 0.05). The BKMR analyses showed a significantly positive overall effect on ALT, AST, ALP and TBIL levels with high concentrations of phthalate metabolites and a significantly negative overall effect on ALB and TP, when all the chemicals at low concentrations. Conclusions: Our results add novel evidence that exposures to phthalates might be adversely associated with the indicators of LTFs, indicating the potential toxic effect of phthalate exposures on the human liver.