Phthalate metabolites in urine of CF patients are associated with use of enteric-coated pancreatic enzymes

Abstract

In metabolomic studies using liquid chromatography mass spectrometry of urine from children with cystic fibrosis (CF), high levels of metabolites of low molecular weight phthalates were found. Phthalate metabolite excretion was explained by therapy with enteric-coated pancreatic enzyme replacements. Phthalate metabolite identity was confirmed by tandem mass spectrometry. Pancreatic insufficient CF children taking Cotazym ECS ®, which is formulated with diethyl phthalate (DEP), had urinary metabolites of DEP. Children taking Creon ®, which has dibutyl phthalate (DBP), excreted DBP metabolites. The estimated concentrations of free MEP were 2–3 orders of magnitude higher than reported from environmental phthalate exposure. Enteric-coated pancreatic enzymes can expose individuals with CF to incessant, high oral intakes of phthalates. Although adverse effects have neither been shown to be present nor absent, we raise the need to consider that individuals requiring life-long therapy with some current pancreatic enzyme replacements chronically ingest high amounts of phthalates.