Biomonitoring tri-(2-ethylhexyl) trimellitate (TOTM) exposure in the Neonatal Intensive Care Unit: Investigating potential sources and exposure levels

Plasticizers are chemicals added to plastic polymers, such as polyvinyl chloride, to enhance their flexibility and durability. Di-(2-ethylhexyl) phthalate (DEHP) was the most used plasticizer due to its low cost and enhanced physical stability. However, adverse health effects have been attributed to phthalates and their metabolites. As a result, alternative plasticizers such as tri-(2-ethylhexyl) trimellitate (TOTM), have been developed to replace DEHP, mainly based on physicochemical properties and toxicity studies. In this study, the exposure to TOTM in the Neonatal Intensive Care Unit (NICU) was studied by analysing 8 TOTM urinary metabolites in 190 urine samples from 83 NICU patients and 8 term maternity ward patients. Overall, TOTM metabolites had a higher detection frequency and median concentration in NICU neonates compared to term patients confirming the exposure to TOTM leaching from medical devices. Highest concentrations were found for 5Cx-1-MEPTM, 5OH-2-MEHTM and 2-MEHTM for NICU patients receiving parenteral nutrition and respiratory support, reaching maximum concentrations of 1055 ng/mL, 285 ng/mL and 2931 ng/mL, respectively. These findings are even more remarkable considering the low leaching potential of TOTM from plastic medical devices and the low urinary excretion factors of TOTM metabolites obtained from pharmacokinetic studies. The estimated daily intake for thirteen premature patients exceeded the adult-based DNEL proposed by ECHA, indicating potential TOTM exposure above safe levels for this fragile NICU population, with possible negative health effects that are still insufficiently studied. Since this reference value does not account for the reduced metabolic and renal capacities of premature neonates, the actual risk for these patients may be underestimated.