Bruce Solka, PhD
Sr. Principal Scientist, Unilever Corp., Retired
10/22/2018
The following are brief thoughts on the concept of ethylene being an endogenous component of the human body and significance with respect to ethylene oxide in the environment.
Sterigenics has commented that “healthy human bodies internally produces (sic) EO”(www.Sterigenicswillowbrook.com, Review of ATSDR Report) and “the mean normallyproduced level of EO for a non-smoker is 19,000 times greater than the risk level stated in EPA’s Integrated Risk Information System.” (www.Sterigenicswillowbrook.com, FAQs). Overlooking the fact that the latter statement compares a quantity or concentration of a substance to a probability (two different things), Sterigenics may be basing these claims upon weak foundations.
The frequently expressed Sterigenics position that humans produce ethylene (ET) and ethylene oxide (EO) at amounts comparable to, or even exceeding, the amounts resulting from their Willowbrook plant emissions (so-called endogenous equivalent values EE) seems primarily based on a single paper (Kirman, 2017) published of a study funded by the Ethylene Oxide Panel of the American Chemistry Council.
Kirman cites a reaction product of EO with hemoglobin as a biomarker of EO exposure. He then summarizes measured values of that marker from about 20 studies of subjects with little or no exposure to EO (control) and 30 studies of subjects with both occupational and tobacco smokederived EO exposure. He then calculates an “endogenous equivalent value” based on just twostudies with a total of four data points from the 1990s (DFG, 1994, and Angerer, et al, 1998).
These studies correlated exogenous EO exposure to concentrations of the biomarker. Thereis some confusion in Section 2.3 where Fig. 3 is referred to but the numerical values cited in the text do not match the data of Fig. 3. That is, a 500 to 2000 ppb EO range is cited in the text but Fig. 3 shows data points in the 200 to 1400 ppb EO range.
Kirman’s work may be sound but it would be hoped that data used to support regulation levels of a known carcinogen would be of a more robust and extensive nature.
Sterigenics also identifies EO as produced in the human body by Cytochrome P450 oxidation of ethylene “as part of its normal metabolic processes”
(www.Sterigenicswillowbrook.com, FAQs). However, in a recent study (Paardekooper, et al, 2017) have shown results that “signifyethylene as a novel biomarker for infection and oxidative stress with potentially importantclinical implications.” They cite systemic inflammation caused by peroxidation of unsaturated lipids as a source of the ethylene. Systemic inflammation could be described as a disease state and not normal to the human body. Similarly, in another recent study, endogenous production of ethylene by lipid peroxidation was monitored by measuring in real time the exhaled ethylene in the breath of patients undergoing oxidative stress due to cardiac surgery (Cristescu, et al, 2014). Cristescu cites “extensive biochemical evidence linking production of ethylene to lipid peroxidation”. Other examples of ethylene formation in vivo as a product of oxidative damage can be found in references cited in these two papers.
Although both of these papers show a few ppb ethylene background in their subjects before oxidation tests or surgery the authors do not comment on that background. The systemic background may be due to inhalation of the ubiquitous 5 to 20 ppb background ethylene in ambient air. In any case ethylene (and hence ethylene oxide) quantities in the human body seem to be very dependent of various disease or stress conditions. This may suggest that concentrations of such a compound may not be the best means to support establishment of disease risk factors.
References:
Cristescu, S.M., Kiss, R., te Lintel Hekkert, S., Dalby,M., Harren, F.J.M., Risby, T.H., and Marczin, N., “Real-time monitoring of endogenous lipid peroxidation by exhaled ethylene in patientsundergoing cardiac surgery”Am J Physiol Lung Mol Physiol 307:L509-515, 2014
Kirman, C.R., Hays, S.M., “Derivation of endogenous equivalent values to support riskassessment and risk management decisions for an endogenous carcinogen:Ethylene oxide”,Regulatory Toxicology and Pharmacology 91 (2017) 165-172
Paardekooper, L.M., van den Bogaart, G., Kox,M., Dingjan, I., Neerincx, A.H., Bendix, M.B., terBeest, M., Haaren, F.J.M., Risby, T., Pickkers, P., Marczin,M., and Cristescu, S.M., “Ethylene, an early marker of systemic inflammation in humans”, Nature.com/scientificreports,7:6889,DOI:10.1038/s41598-017-05930-9