Neonatal exposure to phthalate and alternative plasticizers via parenteral nutrition

Int J Pharm. 2023 Jan 25:631:122472. doi: 10.1016/j.ijpharm.2022.122472. Epub 2022 Dec 13.

Abstract

Di-(2-ethylhexyl) phthalate (DEHP), a plasticizer used to soften plastic medical devices (PMDs), was restricted in PMDs due to adverse health effects, being gradually replaced by alternative plasticizers (APs). Parenteral nutrition (PN), essential in the care for premature neonates in the neonatal intensive care unit, is stored in plastic storage bags and administered intravenously through plastic infusion circuits. We investigated to which extent PN contributes to current phthalate and AP exposure in premature neonates. First, we showed that DEHP and several APs are present in relevant amounts in PMDs used for neonatal PN administration. Secondly, ex vivo experiments mimicking clinical PN administration showed that lipid emulsions contained significant concentrations of DEHP and several APs (ATBC, TOTM, DEHT & DEHA), while hardly any plasticizers were detected in non-lipid solutions. ATBC leached from infusion circuits, while lipid emulsions were the major source for DEHP, TOTM, DEHT, and DEHA. PN administration resulted in estimated daily exposures of 13.9 µg/kg/d DEHP and 95.7 µg/kg/d ATBC in premature neonates, below their respective reference doses. Our data indicate that premature neonates requiring PN are still exposed to DEHP, as well as to a range of APs, making it a target for reduction of harmful plasticizer exposure.

Keywords: DEHP; Harmful plastic additives; Neonatal Intensive Care Unit; Parenteral Nutrition; Plastic Medical Devices; Risk assessment.

MeSH terms

  • Diethylhexyl Phthalate*
  • Humans
  • Infant, Newborn
  • Parenteral Nutrition
  • Plasticizers*
  • Plastics
  • Polyvinyl Chloride

Substances

  • Plasticizers
  • phthalic acid
  • trioctyl trimellitate
  • Diethylhexyl Phthalate
  • dioctyl adipate
  • Plastics
  • Polyvinyl Chloride