Parabens in over-the-counter drugs for pediatric use and their contribution to body burden

• Paraben levels in pediatric liquid drugs and exposure in toddlers were assessed. • Methyl and propyl parabens were highest in drugs from Finland, Malaysia, and Korea. • Drug consumption accounts for high urinary paraben levels shown in Korean toddlers. • High 95th-to-median urinary paraben ratios were observed for Korean toddlers. • Liquid drugs are an important source of episodic but high-level paraben exposure. Parabens are commonly used as antimicrobial preservatives in consumer products, including over-the-counter (OTC) liquid medications. However, limited data are available on their occurrence in pediatric OTC drugs and their contribution to internal exposure in toddlers. 82 pediatric OTC liquid drugs from 13 countries were analyzed for four parabens and benzoic acid (BA). The use patterns and concentrations of parabens varied by country: Korean samples (n=19) contained all four parabens and BA, whereas U.S. samples contained only BA. Methyl paraben (MeP) and propyl paraben (PrP) were found at the highest levels in Finland, Malaysia, and Korea. Estimated daily intakes (EDIs) based on prescribed dosages of pediatric OTC drugs in Korean toddlers were highest for MeP, followed by PrP and BuP. The EDIs of MeP and PrP from OTC drugs in Korean toddlers approximated the 95th percentile of EDIs back-calculated from urinary paraben concentrations in national biomonitoring data (n=578), whereas EtP and BuP did not show such correspondence. Moreover, the 95th percentile-to-median urinary concentration ratios for MeP and PrP in Korean toddlers were several times higher than those in other countries, suggesting specific sources of exposure, such as medication use, among the high-exposure group. Supporting this hypothesis, urinary MeP and PrP levels were positively correlated with medication use in the national biomonitoring data. These findings suggest that liquid medications are an important yet underrecognized source of high-level, albeit transient, paraben exposure in toddlers. As this exposure source is related to formulation choices, the use of alternative preservatives in pediatric medications could be considered to minimize unnecessary exposure.