The role of nanoparticles in bleed air in the etiology of Aerotoxic Syndrome: A review of cabin air-quality studies of 2003-2023.

Aerotoxic Syndrome may develop as a result of chronic, low-level exposure to organophosphates (OPs) and volatile organic compounds in the airplane cabin air, caused by engine oil leaking past wet seals. Additionally, acute high-level exposures, so-called "fume events," may occur. However, air quality monitoring studies concluded that levels of inhaled chemicals might be too low to cause adverse effects. The presence of aerosols of nanoparticles (NPs) in bleed air has often been described. The specific hypothesis is a relation between NPs acting as a vector for toxic compounds in the etiology of the Aerotoxic Syndrome. These NPs function as carriers for toxic engine oil compounds leaking into the cabin air. Inhaled by aircrew NPs carrying soluble and insoluble components deposit in the alveolar region, where they are absorbed into the bloodstream. Subsequently, they may cross the blood-brain barrier and release their toxic compounds in the central nervous system. Olfactory absorption is another route for NPs with access to the brain. To study the hypothesis, all published in-flight measurement studies (2003-2023) of airborne volatile (and low-volatile) organic pollutants in cabin air were reviewed, including NPs (10-100 nm). Twelve studies providing data for a total of 387 flights in 16 different large-passenger jet aircraft types were selected. Maximum particle number concentrations (PNC) varied from 104 to 2.8 × 106 #/cm3 and maximum mass concentrations from 9 to 29 µg/m3. NP-peaks occurred after full-power take-off, in tailwind condition, after auxiliary power unit (APU) bleed air introduction, and after air conditioning pack failure. Chemical characterization of the NPs showed aliphatic hydrocarbons, black carbon, and metallic core particles. An aerosol mass-spectrometry pattern was consistent with aircraft engine oil. It is concluded that chronic exposure of aircrew to NP-aerosols, carrying oil derivatives, maybe a significant feature in the etiology of Aerotoxic Syndrome. Mobile NP measuring equipment should be made available in the cockpit for long-term monitoring of bleed air. Consequently, risk assessment of bleed air should include monitoring and analysis of NPs, studied in a prospective cohort design.

The role of carbon monoxide in aerotoxic syndrome.

Chronic low-level exposure to toxic compounds in airplane cabin air may result in Aerotoxic Syndrome (AS). Aetiologic agents are organophosphates and numerous volatile organic hydrocarbons originating from leaks of engine oil and hydraulic fluids. Despite a documented history spanning decades, the role of carbon monoxide remains controversial. What evidence exists that carbon monoxide (CO), present in the cocktail of toxic compounds in bleed air, contributes to the AS? We selected 22 publications encompassing 888 flights with 18 different aircraft types. In one study of 100 flights, fume events were confirmed in 38. Four studies were initialized after air quality incidents. The cabin CO concentrations could be categorized in three levels, 1) low (<5 ppm), without health implications, 2) moderate (5-10 ppm) with probably health implications in case of chronic exposure, and 3) high > 10 ppm, with health effects in case of acute and chronic exposure. These levels were recorded in 12, 6 and 4 studies respectively. In the six studies in category 2, max CO concentrations ranged from 5.8-9.4 ppm. The four studies with CO > 10 ppm comprised 376 of the 888 flights (42%) with six aircraft types. Toxic CO levels ranging between 13-60 ppm were identified in at least 129 of 888 (14.5%) flights. In one study with high CO levels four flight attendants were diagnosed with CO poisoning with elevated HbCO levels. Max CO levels in aviation are either the same or higher than current occupational exposure limits (OEL) for ground-based workplace exposures or levels for urban street transport environments. Specific aspects of aviation should be taken into consideration: the effect of low(er) air pressure at high altitudes increasing the toxicity of CO, and the binding of CO to CYP enzymes, leading to impaired organophosphate detoxification. We conclude that CO must be considered an important factor in the lubrication derived cocktail of airborne toxic compounds causing AS. In line with the WHO advice, a reduction of the OEL to 5 ppm over 8 hr time weighted average (TWA) for aircrew is strongly recommended. And we advocate continuous monitoring during all phases of flight and installation of CO detectors in the air supply ducts to the aircraft cabin.