Generation of hazard indices for cumulative exposure to phthalates for use in cumulative risk assessment

Exposures to multiple chemicals may contribute to increased risk of similar adverse effects. Cumulative risk may be estimated using a hazard index (HI), the sum of individual hazard quotients (HQ, ratio of exposure to the reference value). We demonstrate the HI approach for five phthalates: di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP), diisobutyl phthalate (DiBP), diisononyl phthalate (DiNP), and butyl benzyl phthalate (BBP). Phthalate exposure for the US general population is estimated using urine metabolite levels from NHANES, extrapolating to ingested 'dose' using the creatinine correction approach. We used two sets of reference values: European Union Tolerable Daily Intakes and Denmark Environmental Protection Agency Derived No Effect Levels. We also investigated the use of an alternate reference value for DEHP, derived from a recent study on male reproductive system development. HQs and HIs were calculated for the total population ages 6 years and older, as well as for men and women of approximate reproductive age (18-39 years), and children (6-11 years). Median HQs ranged from <0.01 for BBP, to ∼0.1 (using established values) or ∼2 (using an alternate value) for DEHP. Median HIs were <0.30 (95th percentiles just >1.0), and were driven by DEHP and DBP exposures.