Systematic review of studies of ethylene in the breath of healthy individuals indicates limited potential for endogenous exposures to its metabolite, ethylene oxide.
Measurement of Et in breath
We conducted a systematic review beginning with a thorough search and screening that identified 25 studies with data on breath Et in healthy individuals without occupational exposure. Five studies used gas chromotography and 20 studies used laser photoacoustic spectroscopy (LPAS). Reported results were diverse (< 0.. Review of these studies focused on rigor of the chemical analysis and potential for recent exposure to Et. For example, reliable LPAS results with the CO2 laser system used for Et analysis depend on fully addressing interference effects of CO2 in normal breath and accounting for potential interference from lower concentration compounds (e.g., acetone and ammonia). Information on Et concentrations on inhaled air and on subjects smoking behavior (a source of Et) is needed for interpretation of breath findings. We assigned ratings of high, medium, and low to each study for each evaluation factor. One or more "low" ratings led to an overall rating of a study as "low".
Among studies rated high quality, mean breath Et was on the order of 0.5 ppb. Some additional studies were judged sound except for lacking data on room air Et and smoking. In our database these studies also reported ~1 ppb breath Et. Other studies, including those reporting higher levels of breath Et generally had both analytical deficiencies and lacked data on Et in room air. These concerns would generally bias measured Et concentrations high, and these studies were not judged informative as to typical levels of breath Et.
PBPK results for Et and EtO
Additionally, two studies with medium and high ratings applied measurements of Et in breathing chambers to estimate a mass rate of endogenous production of Et. Both simplified PK and PBPK analyses predicted that steady state breath levels of Et resulting from endogenous production are ~ 1ppb. The PBPK models also predicted the metabolism of Et to EtO and the resulting formation of HEV adducts from the binding of EtO. When we input breath-based estimates of endogenous Et production into the most recent PBPK model (Filser, 2018), estimated HEV levels (e.g., 1.6 pmol/g Hb) were an order of magnitude lower than typically measured background HEV levels.