An analysis of cumulative risks based on biomonitoring data for six phthalates using the Maximum Cumulative Ratio

The Maximum Cumulative Ratio (MCR) quantifies the degree to which a single chemical drives the cumulative risk of an individual exposed to multiple chemicals. Phthalates are a class of chemicals with ubiquitous exposures in the general population that have the potential to cause adverse health effects in humans. This work used the MCR to evaluate coexposures to six phthalates as measured in biomonitoring data from the most recent cycle (2013-2014) of the National Health and Nutrition Examination Survey (NHANES). The values of MCR, Hazard Index (HI), and phthalate-specific Hazard Quotients (HQs) were determined for 2663 NHANES participants aged six years and older by using reverse dosimetry techniques to calculate steady-state doses consistent with concentrations of metabolites of six phthalates in urine and using Tolerable Daily Intake values. There were 21 participants (0.8% of the NHANES sample) with HI>1. Of those, 43% (9/21) would have been missed by chemical-by-chemical assessments (i.e. all HQs were less than one). The mean MCR value in the 21 participants was 2.1. HI and MCR values were negatively correlated (p<0.001) indicating that most participants, especially those with elevated HI values, had their cumulative risks driven by relatively large doses of a single phthalate rather than doses of multiple phthalates. The dominate phthalate varied across participants. Children (aged 6-17years) had a higher HI values (p<0.01) than adults (18+ years). However, the probability of having HI>1 was not driven by age, gender, or ethnicity. The cumulative exposures of concern largely originated from a subset of three of the fifteen possible pairs of the six phthalates. These findings suggest that cumulative exposures were a potential concern for a small portion of the surveyed participants involving a subset of the phthalates explored. The largest risks tended to occur in individuals whose exposures were dominated by a single phthalate.