Uncovering the connection: ethylene exposure and endogenous ethylene oxide levels in humans

Ethylene oxide (EtO) is a known carcinogen, with general population exposure primarily from air pollution and smoking. EtO can also form internally via ethylene (ET) oxidation, which originates from both environmental sources and endogenous processes like lipid peroxidation. This has raised questions about ET exposure as a primary source of endogenous EtO, though quantitative evidence remains limited.

To investigate the impact of total ET exposure-external and internal-on endogenous EtO in non-smoking and non-occupational populations ("non-exposed").

Literature and pharmacokinetic analyses were conducted to assess the evidence on ET exposure and associated EtO levels. Since most ET is exhaled unmetabolized, breath analysis provides the best estimate of total ET exposure. Two pharmacokinetic approaches were utilized to link ET exposure and EtO body burden. Circulating EtO was evaluated by its hemoglobin adducts, [N-(2-hydroxyethyl)valine or HEV], a method commonly applied in high-exposure contexts, but its application is less certain for background exposure.

The literature review indicated that exhaled ET concentrations varied among identified studies with a median of 12 ppb (range: 0.2-740 ppb). Across studies of purified air conditions, exhaled ET concentrations were lower (0.2-1.2 ppb), suggesting limited internal ET contribution. In an ET- and EtO-free environment, the pharmacokinetic models predict that <1-2 ppb exhaled ET can arise from internal ET sources in 70-kg adults. With a nominal ambient ET exposure (15 ppb), predicted exhaled ET reaches 16 ppb, aligned with the literature. In the same exposure conditions, less than 3.5 pmol HEV/g globin-under 20% of background HEV (approximately 20 pmol/g globin) observed in non-exposed populations-can be attributed to ET-derived EtO, suggesting unidentified HEV sources.

This analysis shows that endogenous EtO arising from ET exposures appears much lower than previously suggested in "non-exposed" populations. Given EtO's carcinogenic potential, further research, including methodology enhancement, is warranted.

This innovative study is the first to integrate a literature review, pharmacokinetic modeling, and biomarker analysis to examine the relationship between ethylene (ET) exposure and endogenous ethylene oxide (EtO), a known human carcinogen. Our findings contribute valuable insights to improve risk assessment and advance scientific understanding of EtO exposure.