Organophosphate esters in milk across thirteen countries from 2020 to 2023: Concentrations, sources, temporal trends and ToxPi priority to humans

Abstract

Recent increases in organophosphate ester (OPE) application have led to their widespread presence, yet little is known about their temporal trends in food. This study collected milk samples from 13 countries across three continents during 2020-2023, finding detectable OPEs in all samples (range: 2.25-19.7; median: 7.06ng/g ww). Although no statistical temporal differences were found for the total OPEs during the 4-year sampling campaign, it was interesting to observe significant variations in the decreasing trend for Cl-OPEs and concentration variations for aryl-OPEs and alkyl-OPEs (p < 0.05), indicating changing OPE use patterns. Packaged milk exhibited significant higher OPE levels than those found in directly collected raw unpackaged milk, and milk with longer shelf-life showed higher OPE levels, revealing packaging material as a contamination source. No significant geographical differences were observed in milk across countries (p > 0.05), but Shandong Province, a major production site in China, showed relatively higher OPE concentrations. The Monte Carlo simulation of estimated daily intakes indicated no exposure risk from OPEs through milk consumption. The molecular docking method was used to assess human hormone binding affinity with OPEs, amongst which aryl-OPEs had the highest binding energies. The Toxicological-Priority-Index method which integrated chemical property, detection frequency, risk quotients, hazardous quotients and endocrine-disrupting effects was employed to prioritize OPEs. Aryl-OPEs showed the highest scores, deserving attention in the future. Environmental ImplicationsEven though the recent applications of OPEs were substantial, little is known about their temporal trends in food. This gap in knowledge constrains our ability to identify the most concerning OPEs and evaluate the effect of regulatory measures. Over four years of milk sampling, we observed a distinct shift in OPE types attributable to regulatory actions. We further examined factors influencing OPE levels such as packaging migration, cow excretion, and geographical distribution. By utilizing the ToxPi method, we assessed and ranked the risks of OPEs in milk by integrating various factors and confirmed their endocrine-disrupting effects through molecular docking methods.