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.

Health consequences of exposure to aircraft contaminated air and fume events: a narrative review and medical protocol for the investigation of exposed aircrew and passengers.

Thermally degraded engine oil and hydraulic fluid fumes contaminating aircraft cabin air conditioning systems have been well documented since the 1950s. Whilst organophosphates have been the main subject of interest, oil and hydraulic fumes in the air supply also contain ultrafine particles, numerous volatile organic hydrocarbons and thermally degraded products. We review the literature on the effects of fume events on aircrew health. Inhalation of these potentially toxic fumes is increasingly recognised to cause acute and long-term neurological, respiratory, cardiological and other symptoms. Cumulative exposure to regular small doses of toxic fumes is potentially damaging to health and may be exacerbated by a single higher-level exposure. Assessment is complex because of the limitations of considering the toxicity of individual substances in complex heated mixtures.There is a need for a systematic and consistent approach to diagnosis and treatment of persons who have been exposed to toxic fumes in aircraft cabins. The medical protocol presented in this paper has been written by internationally recognised experts and presents a consensus approach to the recognition, investigation and management of persons suffering from the toxic effects of inhaling thermally degraded engine oil and other fluids contaminating the air conditioning systems in aircraft, and includes actions and investigations for in-flight, immediately post-flight and late subsequent follow up.

Ultrafine particle levels measured on board short-haul commercial passenger jet aircraft.

BACKGROUND: Airline crew members report adverse health effects during and after inhalation exposure to engine oil fumes sourced to the air supply system onboard commercial and military aircraft. Most investigations into the causal factors of their reported symptoms focus on specific chemical contaminants in the fumes. The adverse health effects reported in aircrew exposed to the aircraft air supply, bled unfiltered off the engine or Auxiliary Power Unit (APU) may be related to particulate exposures, which are widely known to effect health. While oil contaminates the aircraft air supply, some suggest that this will only occur when there is a bearing seal failure, others document that there is low level oil contamination of the air supply during normal engine operation. This brief pilot study explores whether particulate exposure may be associated with the normal engine/APU and air supply operation and to therefore increase the understanding that UFP exposures may have on crew and passengers. METHODS: An ultrafine particle counter was utilised by an experienced airline captain in the passenger cabin of four short-haul commercial passenger aircraft. All flights were under 90 min on aircraft from two different carriers ranging from 7 months to 14 years old. RESULTS: UFP concentrations showed maximum concentrations ranging from 31,300 to 97,800 particles/cm3 when APU was selected on as a source of air on the ground and with engine bleed air and the air conditioning packs selected on during the climb. In 2 of the 4 flights the peaks were associated with an engine oil smell. Increases in UFP particle concentrations occurred with changes in engine/APU power and air supply configuration changes. CONCLUSIONS: This study identified increases in UFP concentrations associated with engine and APU power changes and changes in air supply configuration. These results correlated with times when engine and APU oil seals are known to be less effective, enabling oil leakage to occur. The concentrations reached in the passenger cabins exceeded those taken in other ground-based environments. UFP exposures in aircraft cabins during normal flight indicates there will be health consequences for long serving aircrew and some passengers.

Characterization of the frequency and nature of bleed air contamination events in commercial aircraft.

Contamination of the bleed air used to pressurize and ventilate aircraft cabins is of concern due to the potential health and safety hazards for passengers and crew. Databases from the Federal Aviation Administration, NASA, and other sources were examined in detail to determine the frequency of bleed air contamination incidents. The frequency was examined on an aircraft model basis with the intent of identifying aircraft make and models with elevated frequencies of contamination events. The reported results herein may help investigators to focus future studies of bleed air contamination incidents on smaller number of aircrafts. Incident frequency was normalized by the number of aircraft, number of flights, and flight hours for each model to account for the large variations in the number of aircraft of different models. The focus of the study was on aircraft models that are currently in service and are used by major airlines in the United States. Incidents examined in this study include those related to smoke, oil odors, fumes, and any symptom that might be related to exposure to such contamination, reported by crew members, between 2007 and 2012, for US-based carriers for domestic flights and all international flights that either originated or terminated in the US. In addition to the reported frequency of incidents for different aircraft models, the analysis attempted to identify propulsion engines and auxiliary power units associated with aircrafts that had higher frequencies of incidents. While substantial variations were found in frequency of incidents, it was found that the contamination events were widely distributed across nearly all common models of aircraft.

Tricresyl phosphate and the aerotoxic syndrome of flight crew members--current gaps in knowledge.

Tricresyl phosphate (TCP), and in particular its tri-ortho substituted isomer (o,o,o-TCP), has been frequently used in aircraft engine oil. Bleed air, provided to the flight deck and cabin can contain traces of TCP. TCP can cause neurotoxic effects in humans. Regularly, airline pilots complain about loss of memory, headaches, dizziness, tunnel vision and other neurotoxic effects. The concentrations of TCP reported in flight deck air (max. ca. 50-100 ng m(-3) total TCP) do not exceed provisional toxicity thresholds. These thresholds, however, contain a very high uncertainty and need further underpinning. The many non-detects and relatively low TCP concentrations reported suggest that TCP on its own is not likely to be responsible for the reported health problems of pilots. Specific conditions in air planes and other toxic compounds present in bleed air, whether or not in combination with TCP, may be responsible for the reported neurotoxic syndromes. Sensitivity of individuals seems to be an important factor as well. The clinical signs observed with a selected group of pilots are serious enough to call for further elucidation of this issue.