Influencing Trend and Extent of Combined Exposure Levels of Total Arsenic and Inorganic Arsenic on Arsenic Methylation Capacity Among University Students: Findings from Bayesian Analysis Using Kernel Machine Regression

Abstract The arsenic (As) methylation capacity is an important determinant of the susceptibility to arsenic-related diseases. Total As (TAs) or inorganic As (iAs) was reported to associate with As methylation capacity individually, however, influencing trend and extent of their combined exposure levels on methylation capacity remains poorly understood. We measured urinary concentrations of iAs, monomethylarsonic (MMA), and dimethylarsinic (DMA) acids using HPLC-HG-AFS, and calculated the primary (PMI: (MMA+DMA)/TAs) and secondary (SMI: DMA/(MMA+DMA)) methylation capacity indexes in 209 university students in Hefei, China, a non-As endemic area. Subjects were given with a standardized questionnaire to inquire their sociodemographic characteristics. Bayesian kernal machine regression (BKMR) analysis was used to estimate the association of lnTAs and lniAs levels with methylation indices (ln%MMA, ln%DMA, lnPMI, lnSMI). The median concentration of iAs, MMA and DMA was 1.22, 0.92 and 12.17 μg/L, respectively; the proportions of iAs, MMA and DMA were 8.76%, 6.13% and 84.84%, respectively. Females had higher %DMA and lower %MMA, while males had lower %DMA and higher %MMA. The combined levels of lnTAs and lniAs showed monotonic decrease in change of ln%DMA and lnSMI other than ln%MMA, additionally, change in ln%PMI was decreased only when levels of lnTAs and lniAs were larger than their 60th percentiles compared to they were at 50th percentile. With regard to single exposure level, the lnTAs showed positive correlation with ln%DMA, lnPMI, lnSMI when lniAs was set at a specific level; while lniAs showed negative correlation with ln%DMA, lnPMI, lnSMI when lnTAs was set at a specific level; and all the dose-response relationships were nonlinear. Our results suggested that combined levels of TAs and iAs played an important role in reducing As methylation capacity, expecially iAs; and the reduction only occured when TAs and iAs were up to a certain combined level.