Commentary on: de Ree H, et al. "Health risk assessment of exposure to tricresyl phosphates (TCPs) in aircraft: a commentary" [Neurotoxicology (2014), http://dx.doi.org/10.1016/j.neuro.2014.08.011].

The paper by de Ree et al. mischaracterizes some key components of the reported association between exposure to aviation engine oil fumes and delayed, chronic neurological illness reported by exposed crewmembers. The authors are correct that airline crewmembers inhale oil fumes when the ventilation air that is supplied to the cabin and flight deck is contaminated with pyrolyzed oil. It is longrecognized that engine oil fumes can contaminate the ventilation supply air on aircraft (SAE, 2011; Reddall, 1955), and all aviation engine oils used on the global commercial fleet contain tricresyl phosphates (TCPs), approximately 2–6%, by weight (OHRCA-ACER, 2014). However, the authors do not mention that the oil fumes contain a mixture of neurotoxic compounds that does include, but is not limited to, TCPs. For example, one of the two TCP blends marketed for engine oils also contains trixylenyl phosphates (ICLIP, 2011) which are recognized as neurotoxic (NLM, 2013). Further, there is some evidence that the TCP additives in an oil can react with other chemical constituents upon heating to form additional organophosphates, such as neurotoxic trimethylolpropane phosphate (TMPP) (Wright, 1996). In addition to the reported hazardous ingredients in most engine oils, chemical analyses of engine oil fumes have identified a long list of unreported compounds, such as acrolein, amines, carboxylic acids, carbon monoxide, formaldehyde, toluene, and xylene (ASHRAE, 2012; ACARM, 2007; DERA, 2001; van Netten and Leung, 2000; Paciorek et al., 1978). Some of these compounds may be present in the bulk oil sample, and others are generated upon heating the oil to temperatures within the range of an operating aircraft engine or auxiliary power unit. Individually, these compounds may not be recognized first and foremost as neurotoxins, but the impact on the central nervous system of inhalation exposure to the complex chemical mixture in oil fumes has received little attention. The authors reference the potential for transient exposures to low-levels of oil-based contaminants in the ventilation air, and attempt to measure those potential exposures on a small number of flights. Certainly, there is some evidence that aircraft ventilation supply may contain low levels of oil-based contaminants on a relatively routine basis (Cranfield, 2011; Murawski and Michaelis, 2011), and on aircraft without recognized mechanical failures sourced, at least in part, to imperfect or delayed closure of the engine seals during engine power setting changes (SAE, 2011). However, most cases of chronic neurological illness documented by airline crewmembers follow documented exposure to oil fumes in the flight deck, cabin, or both, that is significant enough to necessitate a change in flight plan (i.e., canceled or diverted) and emergency medical care to address acute symptoms (Murawski, 2011). The authors’ claim that crews consider exposure to ToCP responsible for the delayed neurological symptoms that can follow an exposure to oil fumes is also misstated. The TCP blends marketed for aviation engine oils must contain a minimum of 99.8% meta/para isomers; thus, no more than 0.2% of the TCPs in aviation engine oils will contain some combination of as many as six ortho isomers, one of which may be ToCP (SAE, 2005). This means that the ToCP content in the oil will range from 0 to 0.006%, assuming an average 3% total TCPs. If the combined ortho isomer content of the TCPs is as low as the authors suggest (0.03–0.06%), then the likelihood of finding ToCP is even lower, since it means that an oil with a 3% TCP content would contain 0 to 0.0018% ToCP. Given these facts, it makes no sense to rely on ToCP, either as a metric of exposure to oil fumes on aircraft or as a stand-alone metric of neurotoxic hazard, when there is little, if any, ToCP in the fumes, and even if ToCP is present, it is not the only neurotoxic compound in the fumes. Also on the subject of TCPs, the authors characterize the meta and para TCPs that dominate commercial engine oil formulations, NeuroToxicology 46 (2015) 165–166