Cabin Pressure

As discussed in Chapter 2, at cruise altitude, the aircraft cabin is typically pressurized to the equivalent of an altitude of 6,000–8,000 ft (1,829–2,438 m), with a corresponding barometric pressure of 609–564 mm Hg and an ambient PO₂ of 128–118 mm Hg (see Table 5–2). As specified in the Federal Aviation Regulation (FAR) 25.841, aircraft “cabin pressure altitude” must not exceed 8,000 ft at the aircraft's highest operating altitude (14 CFR 1986).

TABLE 5–2

Barometric Pressure and PO₂.

The reduced pressure in the cabin environment results in several physiological changes in the passengers and crew. Specifically, the reduced ambient air pressure will cause the gas in body cavities (e.g., middle ear, sinuses, and gastrointestinal tract) to expand in volume by as much as 25%. In the lungs, the lower PO₂ in ambient air will reduce the oxygen (O₂) pressure in the alveoli from the normal value of 105 mm Hg. That decrease will lower systemic arterial PO₂. In healthy people, the arterial PO₂ is usually about 5–10 mm Hg lower than the alveolar PO₂ (see Table 5–2). It is the arterial PO₂ that determines the amount of O₂ that is carried by the hemoglobin in the blood, expressed as the percent hemoglobin saturation.

Table 5–3 shows the arterial O₂ saturation at various altitudes without supplemental O₂. At an altitude of 7,500 ft (2,287 m), the PO₂ begins to approach the steep-slope portion of the O₂-hemoglobin dissociation curve (Figure5–1 ). Further small changes in PO₂ in the cabin can lead to large changes in the O₂ content of the blood.

TABLE 5–3

Hypobaric Pressure and Arterial O₂ Saturation.

FIGURE 5–1

O₂-hemoglobin dissociation curve shows relationship between PO₂ in blood (X-axis) and amount of O₂ held by blood hemoglobin (Y-axis). Important feature of curve is sharp drop in O₂ content of hemoglobin when PO₂ falls below 60 mm Hg.

The relationship between arterial PO₂ and hemoglobin saturation is an Sshaped curve. As shown in Figure 5–1, at an arterial PO₂ greater than 60 mm Hg, hemoglobin is more than 90% saturated with O₂.

For healthy adults at sea level, hemoglobin is 95–97% saturated. Even at an altitude of 8,000 ft (2,439 m), the O₂ saturation of hemoglobin remains at least 90% for healthy adults at rest because their arterial PO₂ is above 60 mm Hg. Below arterial PO₂ of 60 mm Hg, there is a steep decline in the curve, over which a slight change in arterial PO₂ can lead to large changes in hemoglobin saturation. The significance of this curve with respect to the aircraft environment is that at cruise altitudes (reduced air pressure), alveolar and arterial PO₂ are reduced. However, the hemoglobin saturation decreases only slightly unless arterial PO₂ falls below 60 mm Hg. A drop in arterial PO₂ from 100 to 60 mm Hg will result in only a 10% drop in hemoglobin saturation.

In persons with chronic obstructive pulmonary disease (COPD) or asthma, there may be inadequate O₂ exchange between the air in the lungs and the blood. In this case, even at sea level, arterial PO₂ may be considerably lower than alveolar PO₂ (i.e., some affected persons may have less than 90% hemoglobin saturation when at rest; many more will experience this effect on exertion). The situation is worsened at higher altitudes or with exercise; under these conditions, hemoglobin saturation will be substantially lower than in healthy persons at sea level or in sedentary persons, respectively. For these people, lowering alveolar PO₂ by lowering ambient air pressure may also decrease the arterial PO₂ and substantially lower the amount of O₂ carried by the blood

The 1986 NRC report on airliner cabin environment summarized the effects of altitude on PO₂ and recommended that passengers with heart or lung disease be educated about the risks posed by flight. It also recommended that passengers with middle ear problems be told about the effects of cabin pressure in general. However, that committee had few direct data on the hemoglobin saturation that might be expected in passengers and cabin crew under normal flight conditions of commercial aircraft. Some studies have since examined the effects of cabin pressurization on PO₂ in humans. Real-time continuous monitoring of hemoglobin saturation in flight has indicated that considerable changes can occur in a given person and that there are considerable differences among people.

The effects of hypoxia have been studied in a number of situations, including combat flights and passenger transport (Ernsting 1978). Studies conducted during the 1940s suggested that the maximal acceptable degree of hypoxia in passenger aircraft corresponded to a cabin altitude of 8,000 ft, but it was recommended that under routine operating conditions cabin pressure altitude should not exceed 5,000–6,000 ft. The altitude of 8,000 ft was a compromise between the aircraft design and operation requirements and the human performance impairments. Studies by McFarland and Evans (1939), McFarland (1946), and others (Ernsting et al. 1962; Denison et al. 1966; Ledwith 1970) showed that mild hypoxia, as is found in subjects at 8,000 ft, might impair the learning of new tasks and the performance of complex tasks. Most of the studies were conducted on young, healthy men, primarily in the military, who were engaged in vigilance tasks. McFarland and Evans (1939) found an increase in the absolute brightness threshold of the dark-adapted eye at hypoxia equivalent to 7,400 ft but concluded that the change was so small that it was of no practical significance. Ernsting (1978) noted that a “reduction of the cabin altitude from 8,000 to 6,000 ft is associated with a lower incidence of otiotic barotrauma and disturbances in passengers with cardiorespiratory disease.” Studies on performance deficit under hypoxic conditions—86% arterial oxyhemoglobin equivalent to 8,900 ft—showed no effect on performance, including night vision; the threshold for effects appeared to be 82% oxyhemoglobin (9,750 ft) (Fowler et al. 1987).

Cottrell et al. (1995) used continuously reading pulse oximeters to measure O₂ saturation in 38 pilots on 21 flights of about 4 h each. Pressure altitudes in the aircraft cockpits during the cruise portion of the flight were 6,000–9,000 ft (average, 7,610 ft). Maximal and minimal O₂ saturations were 95–99% (mean, 97%±1.1%) and 80–93% (mean, 88.6%±2.9%), respectively. Of the 38 subjects, 20 (53%) developed an O₂ saturation of less than 90% at some time during the flight (duration of time below 90% not given). Baseline O₂ saturation was 95–99%; at 6,000–7,000 ft, saturation was 87–92%; and at 8,000 ft or more, it was 80–91%. No symptoms were reported, and no attempt was made to measure performance decrement. There was no correlation between the minimal oxyhemoglobin saturation and age, height, weight, length of flight, maximal saturation, smoking history, peak cabin altitude, or whether the flight was during the day or night.

In a study of the effects of hypoxia on healthy infants, 34 babies (1–6 mo old; average 3.1 mo) were exposed to 15% O₂ in nitrogen for a mean duration of 6.3 h±2.9 h (Parkins et al. 1998). During exposure, there was a significant increase in the infants' heart rate and time spent in periodic apnea and a decrease in the amount of time spent in regular breathing; respiratory rates did not change significantly. Baseline O₂ saturation decreased from a median of 97.6% (range, 94–100%) in ambient air to 92.8% (range, 84.7–100%) in 15% O₂. Four of the infants had to be removed from the hypoxic conditions early because their O₂ saturation fell below 80% for more than 1 min. The authors suggest that exposure to reduced PO₂, like that encountered on high-altitude flights can result in hypoxia in some infants.

A newborn infant's red blood cells contain up to 77% fetal hemoglobin (Delivoria-Papadopoulos and Wagerle 1990). At 6 mo, the red cells still contain up to 4.7% fetal hemoglobin. Fetal hemoglobin binds O₂ with greater affinity than does adult hemoglobin (see Figure 5–2). That results in greater saturation for any given partial pressure, but it also means that at any given partial pressure fetal hemoglobin holds O₂ more than adult hemoglobin. The net effect is that less O₂ is available for tissue metabolic needs. Thus, infants who experience substantial falls in arterial O₂ saturation may be at greater risk for tissue hypoxia than adults at the same O₂ saturation.

FIGURE 5–2

Oxyhemoglobin equilibrium curves of blood from infants and adults. Source: Adapted from Delivoria-Papadopoulos and Wagerle (1990).

With decreasing cabin pressure, air in the middle ear and sinuses expands and escapes via nostrils and ostia to the outside via the nasopharynx. On descent, increasing ambient pressure requires gas to re-enter the middle ear and sinuses through the same pathways. Both movements can happen only if air can move freely in either direction. If there is blockage due, for example, to an upper respiratory infection, allergy, or tumor, the free flow of air may be impeded, and earache, a feeling of sinus fullness, or dizziness can ensue, particularly on descent. In severe cases, the pressure differential can cause extreme pain, bleeding, or rupture of a tympanic membrane. Likewise, gas in the respiratory tract and gastrointestinal tract expands and contracts with decreasing and increasing cabin pressure. Although gas readily escapes from those parts of the body, minor stomach cramping or bloating might still occur.

At cabin altitudes during cruise, all crew and passengers are in a decreased-O₂ environment. It is clear that under ordinary conditions of commercial flight, PO₂ can be reduced substantially during rest or in situations of minimal exertion. As stated above, this relatively small decrement usually causes no symptoms in healthy people because hemoglobin remains well saturated with O₂ at altitude. Nevertheless, some people might be sensitive to a lowering of PO₂ and experience various symptoms, including headache, dizziness, fatigue, numbness, and tingling (Sheffield and Heimbach 1996). The array of possible symptoms varies from person to person or even in the same person on different days. The PO₂ values are such that substantial reductions in arterial O₂ content occur and could pose a definite health risk for persons with underlying pulmonary or cardiac disease or untreated or partially treated anemia.

Relative Humidity

As noted in Chapters 1 and 2, the relative humidity in most aircraft cabins is low, typically from 10 to 20% (see Table 1–2) with an average of 15–19%, depending on the aircraft (Nagda et al. 2000). Although, low relative humidity is not an air contaminant, it can affect passenger and crew comfort and health (Rayman 1997). Low relative humidity may cause drying of the skin, mucous membranes, and conjunctivae in the latter case adding a risk for conjunctivitis with its symptoms of tearing and pain, especially in those wearing contact lenses (Eng 1979). Studies have indicated that passengers and cabin crews find the air in the aircraft cabin to be too dry and to lead to such symptoms as dry, itchy, or irritated eyes; dry or stuffy noses; and skin dryness or irritation (Lee et al. 2000). Stuffy, dry nose was the primary complaint in another study of 3,630 passengers in all cabin classes on standard and wide-body aircraft. Although symptoms could not be correlated with aircraft type (comfort rating, 5.34 of 7 for first-class versus 4.46 for coach and no difference in passenger comfort ratings for relative humidity between standard-body and wide-body aircraft), they did reflect flight length: longer flights resulted in more symptoms (Rankin et al. 2000). Low relative humidity has also been associated with fatigue, headaches, and nosebleeds (Space et al. 2000). Low humidity can have a greater effect on passengers who have respiratory infections, asthma, or tracheotomy (Rayman 1997). It has been found that in dry environments, mucus can concentrate; this can reduce ciliary clearance and phagocytic activities in the respiratory tract (Berglund 1998).

In a study of the effects of low humidity on the human eye, Laviana et al. (1988, as cited in Nagda and Hodgson 2001) found that at a relative humidity of either 10% or 30%, eye pain (described as scratchiness, pain, or burning) increased over time up to the fourth hour of exposure (total exposure duration of 10 h) for both a naked eye and an eye covered with a soft contact lens. However, there was no difference in the severity of responses at either 10% or 30% relative humidity and the humidity level did not significantly affect acuity, refractive error or cornea curvature in either eye. In aircraft cabins, symptoms of low humidity, such as eye and nasal irritation, seem to occur within 2 h after exposure begins (Eng 1979); skin symptoms may require at least 4 h to occur (Carleton and Welch 1971, as cited in Nagda and Hodgson 2001). Furthermore, all symptoms increase in severity with time, and an adaptive response to low-humidity environments is not evident (Nagda and Hodgson 2001). At reduced barometric pressures (259–700 mm Hg), symptoms associated with low humidity develop more quickly and are more severe (Carleton and Welch 1971, as cited in Nagda and Hodgson 2001). In a review of the studies that examined potential health effects of exposure to low relative humidity, Nagda and Hodgson (2001) indicated that the study subjects in general were relatively young and that an older study population might have been more likely to perceive changes in relative humidity and also might be more susceptible to health effects of such exposures. They concluded that a modest increase in the relative humidity in an aircraft cabin (e.g., from the current average of 14–19% to about 22–24%) might have beneficial effects similar to those seen in building studies in which a 10% increase in humidity alleviated many of the symptoms of “sick-building syndrome.” Such humidities are below the values that may affect the safety of an aircraft—that is, that might cause condensation in and corrosion of the aircraft shell—or that would result in increased microbial growth.

Although cabin relative humidity is well below the preferred values of 30– 60% suggested in American Society of Heating, Refrigerating and Air-Conditioning Engineers Standard 62–1999, it is questionable whether low humidity has substantial short- or long-term health effects. One investigator reported that in a room with 0% humidity, the degree of dehydration in undressed subjects was insignificant over a period of 7 h (Nicholson 1996). It might be expected that the adverse effects of low relative humidity experienced by crew and passengers will be temporary and will be alleviated when they leave the aircraft. The time required for rehydration will depend on individual physiology and the ambient environment.

Humidity influences the perception of air quality. In one study, as relative humidity increased from 24% to 79%, the air was considered to be less fresh (Berglund 1998). Acceptability of air-quality decreases with increasing temperature and relative humidity (Fang et al. 1998a,b).

Ozone

Although ground-level O₃ is a major contributor to photochemical air pollution in urban air, the presence of O₃ in the upper troposphere and lower stratosphere provides a necessary health benefit to humans by screening out harmful ultraviolet radiation. As discussed in Chapter 3, many commercial flight paths are at altitudes where O₃ concentration might be greater than those typically found at ground level. O₃ in the cabin is required not to exceed 0.25 ppm (250 ppb) during a flight (FAR 25.832¹ ). Mean O₃ measured on aircraft has ranged from 22 ppb (Nagda et al. 1989) to 200 ppb (Waters 2001). The health effects of ground-level O₃ have been well studied (EPA 2001). Those effects are relevant to travelers who might be exposed to increased O₃ during high-altitude flights if the aircraft is not equipped with an O₃ converter or the equipment is not operating properly. The ground-level national ambient air-quality standard for O₃, established by the Environmental Protection Agency (EPA) in 1997, is 0.12 ppm by volume for a 1-h exposure and 0.08 ppm by volume for 8-h exposures (EPA 1997).

O₃ can cause acute respiratory problems, aggravate asthma, and impair the body's immune system making people more susceptible to respiratory illnesses, including bronchitis and pneumonia (EPA 1996). Exposures to O₃ as low as approximately 0.08–0.10 ppm for about 6 h have resulted in impairments of the immune system (EPA 1996). Inflammatory responses occurred within 1 h after a 1-h exposure to O₃ at 0.3 ppm or more. Exposures for up to 7 h to O₃ as low as 0.08 ppm caused small decrements in lung function and increases in respiratory symptoms (EPA 1996). Those effects are exacerbated by exercise. In a study of healthy adults exposed during exercise to ambient O₃ at 21–124 ppb, there was a statistically significant decrement in lung function (Spektor et al. 1988a). Similar lung function decrements were seen in healthy children (at a summer camp) exposed to O₃ at the ambient air standard of 120 ppb, where average forced vital capacity (FEV), forced expiratory volume in the first second (FEV₁), peak expiratory flow rate (PEFR), and forced expiratory flow (FEF_25–75) decrements were 4.9%, 7.7%, 17%, and 11%, respectively (Spektor et al. 1988b).

Asthmatics, particularly children, show an increase in respiratory symptoms and decrements in peak expiratory flow rate with increasing O₃ (EPA 1996). Studies on children with moderate-to-severe asthma found that increasing O₃ from 84 to 160 ppb for 1 h resulted in increased medication use and an increase in the number of chest symptoms (Thurston et al. 1997). The long-term sequelae of inhalation exposure are unknown, but continued exposure O₃ at low concentrations could result in chronic effects in humans (EPA 1996).

The committee was able to identify only one study that examined the possible effects of O₃ on flight attendants (Tashkin et al. 1983). The authors attempted to determine, on the basis of symptoms reported on a questionnaire distributed to flight attendants on high-altitude flights of Boeing 747SP aircraft, whether the symptoms were consistent with possible exposure to increased O₃. Although the authors concluded that the reported symptoms were consistent with exposure to toxic concentrations of O₃ (0.4–1.09 ppm, measured onboard other 747SP aircraft), no O₃ measurements were made on flights where the questionnaire was used. There were substantial limitations in the study, as discussed in Chapter 6.

Engine Oils and Hydraulic Fluids

Engine lubricating oils and hydraulic fluids are complex mixtures of primarily organic compounds (see Table 3–12 for major components). Among the major additives to the petroleum base of these mixtures are organophosphate compounds, of which those organophosphates, of greatest toxicological concern are tricresyl phosphate (TCP) derivatives and the generation of trimethylolpropane (TMPP). Other organophosphates that can be present in the oils and fluids are tributyl phosphate, dibutyl phenyl phosphate, and triphenyl phosphate. The general toxicity of these agents is discussed below.

Engine lubricating oils and hydraulic fluids have been reported to enter the passenger cabin of aircraft through the environmental control system (ECS) as discussed in Chapter 3. The fluids (and their possible pyrolysis products) can result in mists, fumes, vapors, and smoke in the cabin. The major pyrolysis products of jet engine oils and hydraulic fluids, at less than very high temperatures, will probably be volatile organic compounds (VOCs) and carbon monoxide (CO). Although there is considerable toxicological information on the major constituents of engine oils and hydraulic fluids, there are few data on the toxicity of the formulated oils and fluids themselves. Only a couple of studies were found in the published literature, and they are discussed below.

In an early study to determine whether the introduction of engine oils or hydraulic fluids or their combustion products into the ECS would impair aircraft crew, rats were exposed via inhalation to synthetic engine lubricating oils (Exxon turbo oil 2380 or Mobil II jet oil) or one synthetic hydraulic fluid (Skydrol 550B) (Crane et al. 1983). The authors concluded that for combustion of the engine oils at 400°C, the major toxic component was CO, whether or not combustion produced flames or only smoke. The hydraulic fluid Skydrol, under flaming conditions, was more toxic (the animals became incapacitated and died more quickly) than the engine oils, but it was not toxic under non-flaming (smoking) conditions.

In another study, the hydraulic fluid Skydrol 500B-4 (manufactured by Monsanto), containing primarily tributyl phosphate and dibutyl phenyl phosphate (80–90% phosphate esters) was tested with rats via inhalation. The animals were exposed for 6 h/d, 5 d/wk, to very high Skydrol concentrations (up to 300 mg/m³, with about 95% of particles less than 10 μm in diameter) for up to 13 wk. Rats exhibited reddish nasal discharge and salivation, suggesting irritation. No pathological changes were seen in animals exposed at 100 mg/m³ (the no-observed-adverse-effect level). Pathological changes at 300 mg/m³ included increased liver weight with hepatocellular hypertrophy, decreased hematocrit in both males and females, and decreased plasma cholinesterase in females only (Healy et al. 1992). In other animal studies with organophosphate ester hydraulic fluids, rabbits exposed for less than 4 h/d, 5 d/wk, for 11 or 22 d, to aerosols of Cellulube 200 hydraulic fluid at 2,000 mg/m³ died with severe dyspnea and mild diarrhea (Carpenter et al. 1959, as cited in ATSDR 1997).

Deicing Fluids

Glycols (ethylene glycol and propylene glycol) are the main constituents of deicing fluids used for aircraft. Exposure to deicing fluids is expected to be season- and climate-dependent. Deicing fluid is typically applied hot. As noted in Chapter 3, there are no published studies on the potential for deicing fluids to enter the cabin air via bleed air.

Ethylene glycol can be extremely toxic, particularly if ingested at high doses or if high concentrations of heated vapors are inhaled. Most known cases of ethylene glycol toxicity resulted from ingestion; ethylene glycol has a low vapor pressure. Ingestion of small amounts can cause drowsiness and slurred speech. Ingestion of antifreeze fluids containing ethylene glycol, often accidentally or suicidally, causes serious metabolic acidosis and renal toxicity (tubular necrosis) in humans—because of the toxic metabolite oxalic acid—and CNS depression, cardiopulmonary disturbances, pulmonary edema, and congestive heart failure (Snyder and Andrews 1996). The minimal lethal oral dose of ethylene glycol for adults is 1.4 mL/kg (1,330 mg/kg of body weight) (ATSDR 1997). Because of its poor absorption through the skin, systemic effects through skin contact are unlikely.

There are few data on inhalation exposures to ethylene or propylene glycol and no reports of death following exposure by this route (ATSDR 1997). After inhalation exposure to ethylene glycol aerosol at 3–67 mg/m³ for 20–22 h/d for about 4 wk, human volunteers complained of upper respiratory tract irritation and occasionally of slight headache and low backache. Ethylene glycol at above 140 mg/m³ was highly irritating and above 200 mg/m³ was intolerable. No ethylene glycol or its metabolites were found in the blood or urine of the subjects (Wills et al. 1974).

Propylene glycol has almost no intrinsic oral toxicity and is widely used in foods, cosmetics, and pharmaceuticals. Its low toxicity is explained by its metabolic conversion to lactic acid and pyruvic acid, normal body constituents (Snyder and Andrews 1996). Both propylene glycol and ethylene glycol are rapidly metabolized by humans and cannot be detected in tissues 48 h after exposure. Repeated, short-term exposures to propylene glycol may result in some irritation of the eyes, skin, and nasal and oral mucosa; some skin sensitization is possible (ATSDR 1997). Over the last 5 yr, the market share of propylene glycol used in deicing fluids has grown from 10% (124 million pounds) to 70% (140 million pounds), primarily at the expense of ethylene glycol (Ritter 2001). The increased use of propylene glycol in deicing fluids has reduced the potential for toxic effects after accidental exposure to these compounds.

Pyrethroid Pesticides

Today, only a few foreign countries require the use of insecticides on aircraft coming from other countries, including aircraft from the United States. Consequently, the interiors of U.S. aircraft destined for those countries must be disinsected, a practice the United States discontinued in 1979 (see Chapter 3). The pesticides are usually synthetic pyrethroids, primarily phenothrin and permethrin. Chapter 3 describes the application methods for these pesticides.

The disinsection practices of some countries are expected to result in the exposure of cabin crews and passengers to pesticides. Although pyrethroid pesticides have very low toxicity in humans, they can cause adverse effects in some people and are recognized as neurotoxicants at very high doses. The acute oral dose that is lethal to 50% of rats is 0.5–5 g/kg; the dose that is lethal to 50% of animals in 4-h is 2,280 mg/kg; and the concentration that is lethal to 50% of animals via inhalation with intermittent exposure is 500 mg/m³ (NRC 1994). The pesticides act by slowing inactivation of the neuronal sodium channels, thus causing hyperexcitability of the nerves. That hyperexcitability produces signs of CNS and peripheral nerve disturbances. CNS toxicity is manifested as coarse tremors, involuntary muscle movements, and excessive lacrimation. Although their lethality is low, the pyrethroids are recognized as dermal irritants and, when they are in fume or vapor form, as respiratory and ocular irritants (Ecobichon and Joy 1994).

Systemic poisoning is less likely from dermal exposure than from oral exposure oral because absorption through the skin is considerably less than absorption through the gastrointestinal tract. In general, dermal exposure to pyrethroids results in a localized tingling sensation of the skin (paresthesia) without loss of normal sensation within 0.5–5 h and persists for up to 3 d (WHO 1995). Because skin appears to bind pyrethroids, localized effects can be expected to last for long periods, and the skin might act as a reservoir; this could result in symptoms that last for several weeks in acute cases of pyrethroid poisoning (He et al. 1989), although thorough cleaning of the skin may prevent or minimize this effect. In a study with 184 human volunteers, a 21 -d repeat patch test with a 40% solution of permethrin did not result in any skin sensitization, although there were some reports of transient burning, stinging, and itching (NRC 1994). Patch tests with permethrin have shown no allergic response (Naumann and McLachlan 1999).

Areas on the body where skin is thin are affected first, because the agent can interact more readily with nerve endings. The average threshold dose for producing paresthesia is 0.2 mg/cm² of skin in humans (WHO 1995). About 2% of permethrin applied directly to human skin is expected to be absorbed (NRC 1994). In a scabies-control program involving about 1,000 people, skin application of a cream containing 5% pyrethroids resulted in no complaints of paresthesia (Yonkosky et al. 1990). There appear to be individual susceptibilities to the effect; this may be related to the variation in the concentrations of carboxyesterase enzymes in the skin (Leng et al. 1999). Thus, lymphocyte carboxyesterase activity might serve as a biomarker of the effect (Leng et al. 1999). It has been suggested that persons with pre-existing disease (including skin disease and lowered immunity), infants, and children can be more sensitive than healthy adults to the effects of permethrin (Naumann and McLachlan 1999). Phenothrin is used to control headlice in children and has been reported to have relatively few adverse health effects (Naumann and McLachlan 1999).

Occupational exposure to or inappropriate handling of synthetic pyrethroids has been found to produce dizziness, burning, itching, or tingling of the skin. More severe contact, such as spilling of the pesticides onto the skin, resulted in lacrimation, photophobia, and eye irritation. Accidental swallowing may cause headaches, dizziness, vomiting, fatigue, anorexia, chest tightness, blurred vision, paresthesias, and, in severe cases, convulsive attacks. However, the signs and symptoms of pyrethrin toxicity are usually fully reversible, and no long-term human toxicity has been reported after single or repeated exposure (He et al. 1989; Ecobichon and Joy 1994; Harp 1998; Leng et al. 1999; Vandenplas et al. 2000). It is possible that after exposure sensitive people will develop a rash or allergy-like symptoms such as wheezing, cough, and shortness of breath. That might happen particularly in people who have atopy or bronchial asthma, although the relationship between asthma and pyrethroid exposure is not clear (WHO 1995). Aerosolized pesticides can trigger a “nonspecific” asthmatic response—bronchoconstriction and respiratory symptoms—although it is has been difficult to link sensitization in nonasthmatics to exposure to aerosolized pyrethroid insecticides (WHO 1995).

Aside from the obvious inhalation and dermal exposures that occur when passengers and crew are actively sprayed, typically with phenothrin, residual exposures can occur when permethrin is used to treat unoccupied cabins. Residual exposures are likely to be dermal and oral. See Chapter 3 for a more detailed description of possible exposures resulting from disinsection practices.

Pyrethroid pesticides are rapidly destroyed by carboxyesterase enzymes in the liver and to a lesser extent in skin, muscle, kidney, brain, and serum (Leng et al. 1999). Organophosphates are also destroyed by carboxyesterases and so can compete with pyrethroids for the enzymes, the competition can result in a synergism that increases overall toxicity. The enzyme cholinesterase, which is also inhibited by organophosphates, does not appear to be important in pyrethroid metabolism (Leng et al. 1999). There is little information on long-term exposure to permethrin and none such on exposure of humans (Naumann and McLachlan 1999).

Most flight attendants' reports of pesticide incidents describe lung, eye, throat, or skin irritation as the primary adverse effect. Sensitization, or enhanced responsiveness with successive pesticide exposures, may be a problem faced by cabin attendants because they are intermittently exposed; such an exposure regimen is ideal for inducing sensitization or magnified responses to the same exposures (Weiss and Santelli 1978; Gilbert 1995; Jones et al. 1996).

If people are exposed to both pyrethroid and some enzyme inhibitors, there is a potential for synergistic effects. Pyrethroids are lipophilic and are rapidly absorbed and metabolized after ingestion by mammals. However, they do not accumulate in mammalian tissues. In mammals and insects, pyrethroids are generally metabolized by carboxylases and the mixed-function oxidase (MFO) system of the microsomes (Casida et al. 1983). Piperonyl butoxide, a potent inhibitor of the MFO system, is often added to the pesticide formulations to increase the toxicity by a factor of 10–300 (Casida et al. 1983). Carboxyesterase inhibitors may also act synergistically to enhance the toxicity of pyrethroids. The synergism is an asset for insect control, but it can have potentially serious implications for humans in the rare event that a leak of engine oils or hydraulic fluids causes these compounds to enter the cabin and causes simultaneous exposure to carboxyesterase inhibitors. No incidents of such interactions have been documented in humans, but engine-oil seal failures and hydraulic-fluid leaks into the ECS of aircraft have been reported (Parliament of Commonwealth of Australia 2000; van Netten 2000; van Netten and Leung 2000, 2001). See Chapter 3 for a more detailed discussion of engine-oil and hydraulic fluid leaks.

Two other features of possible pyrethroid toxicity may warrant further research and discussion: their potential as developmental neurotoxicants (Ericsson, 1997; Landrigan et al, 1999) and their potential as endocrine disruptors in vivo, which so far has been demonstrated only in vitro (Go et al. 1999).

Aldehydes

Aldehydes, such as acetaldehyde and acrolein (an unsaturated aldehyde), could be found in cabin air in the case of leaking or pyrolysis of engine oil or hydraulic fluids. Concentrations of aldehydes (and ketones) measured in aircraft cabins are “lower than those encountered in ground level buildings” (Nagda et al. 2001).

Maximal concentrations of acetaldehyde were 26.4–30.7 μg/m³ in bleed air and 20.8–70.2 μg/in³ in cabin air (see Chapter 3). Some sensitive people might suffer adverse effects, and there could be repeated exposures. Exposure to other aldehydes results in decreasing toxicity as the chain length of the aldehyde increases in the order of acetaldehyde, propionaldehyde, isobutyraldehyde, n-butyraldehyde, valeraldehyde, and isovaleraldehyde (HSDB 2000). Effects of inhalation exposure to acetaldehyde at high concentrations (about 100–200) ppm include irritation of the mucous membranes (200 ppm for 15 min), irritation of the respiratory tract (134 ppm for 30 min), and lung edema. Prolonged inhalation exposure to acetaldehyde results in symptoms that mimic alcohol intoxication. Repeated dermal or ocular exposures may cause dermatitis or conjuncitivitis, respectively (HSDB 2000). Irritation of the eye may occur at acetaldehyde vapor concentrations as low as 25 ppm after 15 min. Acetaldehyde may facilitate the uptake of other air contaminants by humans because of its ciliotoxic and mucus-coagulating effects (HSDB 2000). Acetaldehyde has been classified as a possible human carcinogen.

The unsaturated aldehyde acrolein may also cause adverse effects when inhaled. However, acrolein was not detected in bleed air or cabin air of several aircraft under normal operating conditions (Nagda et al. 2001). It is an irritant of the eyes and respiratory tract. The odor of acrolein can be perceived at 0.7 mg/m³. The threshold concentrations of acrolein for irritation and health effects are 0.13 mg/m³ for eye irritation, 0.3 mg/m³ for nasal irritation and blinking, and 0.7 mg/m³ for decreased respiratory rate. Exposure to acrolein vapor in air at 1 ppm (2.3 mg/m³) causes lacrimation and marked eye, nose, and throat irritation within 5 min. It irritates the conjunctiva and mucous membranes of the upper respiratory tract. Above 3 mg/m³, it causes injury to the lungs, and respiratory insufficiency may persist for 18 mo or more. A10-min exposure at 350 mg/m³ was lethal (HSDB 2000). Acrolein has been classified as a possible human carcinogen on the basis of an increased incidence of adrenal cortical adenomas in female rats (IRIS 2001). EPA established a reference concentration³ of 0.0002 mg/m³ for acrolein on the basis of squamous metaplasia and neutrophilic infiltration of nasal epithelium in subchronic inhalation studies in rats (Kutzman 1981, as cited in IRIS 2001).

Carbon Dioxide

Carbon dioxide (CO₂) in the aircraft cabin is primarily a “bioeffluent” in that it is released in the exhaled breath of the occupants and is generated by normal metabolism (see also the section on sources inside the cabin in Chapter 3). CO₂ inhaled at 2% in air increases pulmonary ventilation by 50% (Thienes and Haley 1972, as cited in HSDB 2000). Asphyxiant effects may occur as the concentration exceeds 6%, causing shortness of breath, dizziness, tingling, and slowed mentation (Maresh et al. 1997). Adding 1% CO₂ to air increased pulmonary ventilation rate by 37% at sea level. Under a pressure that simulated an altitude of 5,000 m (16,400 ft), pulmonary ventilation rate increased by 7%. CO₂ concentrations of 0.5% or 1% stimulated hyperventilation to a degree that prevented a decrease in psychomotor performance at a simulated altitude of 5,800 m (19,000 ft) but not at 5,000 m (16,400 ft) (Vieillefond et al. 1981, as cited in HSDB 2000). Repeated daily exposures to 0.5–1.5% inspired CO₂ at 1 atm are well tolerated by healthy people (ACGIH 1980).

FAR 25.831 has a set limit for CO₂ in the cabin at 0.5% (5,000 ppm).⁴ Cabin pressure altitude is limited to 2,440 m (8,000 ft) and that limit appears to protect occupants from adverse effects of exposure to CO₂. The highest CO₂ concentrations measured in aircraft cabins and reported in the literature are below the limit (see Table 1–2, Chapter 1). Typical values reported are in the range of 1,100–1,700 ppm, although concentrations as high as 4,200 ppm have been reported (Waters 2001). Backman and Highighat (2000) reported CO₂ concentrations of 455 ppm, 586 ppm, and 706 ppm on an Airbus 320 (altitude, 39,000 ft; 86 passengers), a Boeing 767 (39,000 ft; 70 passengers), and a DC-9 (35,000 ft; 75 passengers), respectively.

CO₂ is used to assess the adequacy of ventilation. Normally, CO₂ produced as the metabolic byproduct of occupants—respiration—is the primary source of CO₂ generation in an occupied space. Although the CO₂ generated by respiration is unlikely to reach the point at which adverse effects would be expected, other bioeffluents are generated more or less in proportion to CO₂. These other bioeffluents may be responsible for complaints about odors, stale air, lack of fresh air, and stuffiness.

Particulate Matter

Airborne particles in the passenger cabin may comprise coarse particles (such as powders, dusts, dirt, and hair with aerodynamic diameters over 2.5 (μm) and fine and ultrafine particles. Fine particles (aerodynamic diameter, less than 2.5 μm) and ultrafine particles (aerodynamic diameter, less than 0.1 μm) are the products of combustion of materials such as fuels, engine oil, and hydraulic and deicing fluids. Particulate matter (PM), generally with an aerodynamic diameter of less than 10 μm (PM₁₀) has been measured aboard aircraft during normal operations with concentration means ranging from less than 10 μg/m³ (Nagda et al. 2001) to 176 μg/m³ (CSS 1994). Typical indoor air PM concentrations are 3–35 μg/m³ (Burton et al. 2000). Coarse particles, because of their size, are deposited in the upper respiratory airways and can lead to coughing, sneezing, and nasal irritation. Chapter 4 discusses exposure to and health effects of particles of biological origin.

PM₁₀ or smaller may be deposited in the lower (thoracic) regions of the human respiratory tract, including PM_2.5, which deposit primarily in deep lung airways. Exposure to fine and ultrafine PM has been associated with heart rate variability (Peters et al. 2000, as cited in EPA 2001) and may be related to cough. Asthmatics have small decrements in lung function and increases in coughing, phlegm, breathing difficulty, and bronchodilator use after exposure to PM₁₀ and PM_2.5 (EPA 2001). Fine and ultrafine particles, which are deposited in the small airways, may contain toxic constituents that have been shown to cause cardiopulmonary effects. However, few data are available on the acute effects of particle-associated organic carbon constituents (EPA 2001). See Chapter 4 for a more detailed discussion of the possible health effects associated with exposure to biological agents.

Physiological Stressors

In addition to the environmental and chemical stressors discussed above, other stressors may play a role in the perception of and susceptibility to air quality or changes in it.

Fatigue is a common complaint among flight attendants. Work schedules can be erratic, with unplanned layovers and long hours. Furthermore, jet lag can pose a problem. Sleeping accommodations are not always conducive to good rest, and meals can be erratic. Fatigue can also be accentuated by increased CO₂ in the air: other factors contributing to fatigue are the effects of vibration, turbulence, and noise; however, these are beyond the scope of this report and will not be discussed further here.

Multiple and Interactive Factors

As discussed earlier in this chapter, cabin occupants (whether flight crew or passengers) may be subjected to numerous air contaminants and other physiological stessors in some situations. Space et al. (2000) argue that cabin air quality generally is better than that in most indoor environments, according to standard criteria. Although that assessment may describe the experience of passengers under most circumstances, problems do occur. Engine oil and hydraulic fluids, and their pyrolysis products, as noted in other chapters, may contaminate the cabin environment, releasing organic compounds, including cresyl phosphates, some of which are neurotoxic. Because cabin pressurization is limited to a virtual altitude of 8,000 ft, PO₂ declines; this a potential hazard for passengers with cardiovascular impairment. Elevated CO₂ concentrations in that cabin may not present a serious health threat, but in office buildings they are reported to be associated with respiratory symptoms (Apte et al. 2000). Some countries expose passengers to insecticides as part of a program designed to prevent the introduction of nonnative insects.

Although individual factors in isolation might each contribute only a small diminution in well-being, in combination they might be additive, synergistic, or even antagonistic, with their combined influence on the health status of crew and passengers virtually unknown.

Such factors as cramped seating also influence passenger comfort. However, physical activity is more likely to be a potentiating than an additive factor. Unlike the relatively sedentary passengers and cockpit crew, cabin attendants tend to have sustained periods of moderate activity during the course of a flight. As shown for O₃ earlier, exercise could enhance the effects of exposure to many possible cabin air contaminants, including CO and CO₂.

The interactions of CO and high altitude have been examined, and results suggest that the effects are additive (EPA 2000). By binding to hemoglobin, CO may increase the hypoxic effects of high altitude in the elderly and those with coronary arterial disease. At high altitudes on earth (e.g., 15,000 ft), the body adjusts to these hypoxic effects within a few days, but the adjustments do not occur over the duration of even a long-distance flight. In a review of the long-term effects of CO at high altitude, EPA found few effects at CO concentrations of less than 100 ppm and altitudes below 15,000 ft (4,573 m) (EPA 2000).

Passengers and crew members frequently report fatigue, dizziness, headaches, sinus and ear problems, dry eyes, and sore throats during and after air travel. Such symptoms are common to many conditions and can be mistaken for infections (IEH 2001). Other characteristics of air travel, however, can make people more susceptible to infection. For example, travelers are subject to stresses (unrelated to their time on an aircraft) that may reduce their resistance to infectious diseases, such as long hours of waiting, disruption of eating habits, and changes in climate and time zone (Rayman 1997; CDC 2001). Psychological stress has been associated with increased susceptibility to the common cold (Cohen et al., 1991) and may play a role in other infectious diseases. Drying of the nasal mucosa during air travel (due to the low moisture content of the air) may result in nosebleeds and is thought by some to increase susceptibility to respiratory infections, although this is uncertain (BRE 2001). Rose et al. (1999) hypothesized that the reduced-O₂ environment in aircraft leads to mild hypoxia and suppression of the cellular immune system, which in turn contributes to increased susceptibility to infection. If that is borne out, this pathway could explain in part why some frequent flyers complain of infections after air travel.

Other gases, such as those associated with human body odor, are present in the cabin air and may contribute to the discomfort of passengers. Emissions vary widely and depend on individual health, diet, activity, and personal hygiene, such as bathing habits, frequency of clothing change, and use of deodorant (Berg-Munch et al. 1986). Personal-hygiene products and fragrances contain various plant and animal components, such as aldehydes and sterols, that may be in the cabin air. Additional sources of disagreeable biological odors on aircraft are the toilets, waste-storage areas in galleys, and bacterial and fungal growth in the cabin. Evidence of adverse health effects (as opposed to annoyance) of body odors, cosmetics and colognes, or VOCs of microbial origin remains controversial. Respiratory irritation is one condition that could result from exposure to odors on aircraft (Batterman 1995; Ammann 1999; Korpi et al. 1999; Rose et al. 2000).

Susceptibility Factors

Although most members of the traveling public are healthy, given the large number of people who fly each year it is to be expected that many of them will have some level of compromised health. At cabin altitudes during cruise, all crew and passengers are in an environment with decreased O₂. Under ordinary conditions of commercial flight, relatively small O₂ decrements usually cause no symptoms in healthy people, because hemoglobin remains well saturated with O₂ at altitude. Nevertheless, some persons with underlying pulmonary or cardiac disease or significant untreated or partially treated anemia might be sensitive to a lowered PO₂ and might experience any number of symptoms, including headache, lightheadedness, dizziness, fatigue, numbness, and tingling (Sheffield and Heimbach 1996). The health implications of commercial flight for passengers with pre-existing illness are described in greater detail in Medical Guidelines for Airline Travel (Aerospace Medical Association 1997). Air crew and passengers with particular preexisting medical conditions may not tolerate the cabin environment described above as well as would a healthy traveler. People with underlying cardiovascular or respiratory diseases, particularly adults and children with asthma, may also be at increased risk because of the increased O₃ exposures that occur in high-altitude flights. Data are lacking on the relationship between asthma and O₃ in aircraft cabins at high altitudes. People with COPD or emphysema have lung-tissue damage with an abnormal capability for transporting O₂ across the lung tissue into the bloodstream. Consequently, they have less O₂ in their blood than a normal person, whether at sea level or, worse, at altitude. Such passengers may become symptomatic and have shortness of breath, wheezing, and coughing. Schwartz et al. (1984) studied subjects with severe COPD (average resting arterial PO₂, 68.0±7.3 mm Hg) during flights at altitudes of 1,650–2,250 m (about 5,400–7,400 ft) in unpressurized aircraft cabins. PO₂ decreased to an average of 51.0±9.1 mm Hg at an altitude of 1,650 m; there was little further change at 2,250 m.

Several simulation studies have been carried out in hypobaric chambers with COPD patients and healthy subjects (Dillard et al. 1989; Naughton et al. 1995). Declines in PO₂ were observed in all patients at rest; values fell to below 50 mm Hg in many healthy and COPD subjects and the declines were made worse by light exercise (Figure 5–3). Of the 100 patients with COPD, 44 reported traveling by air in the 2 years before the interview (Dillard et al. 1991). Eight of the 44 patients reported increased symptoms during flight (no direct physiological measurements were available). Five of the 8 patients experienced shortness of breath when walking in the cabin, and two requested supplemental O₂ for their symptoms. Variables to consider are clinical evaluation, pulmonary-function tests, and blood-gas analysis. The measurement of arterial blood gas is most useful because it is considered the best predictor of arterial PO₂ at altitude. A ground-level value greater than 9.3 kPa (70 mm Hg) is considered adequate in most cases (Gong et al. 1984; Cottrell 1998). If it is lower, consideration must be given to prescribing inflight medical O₂ or postponing air travel depending on the clinical circumstances. It cannot be overemphasized that the clinical judgment of a physician is essential for a person with COPD in deciding whether to fly. The committee was unable to locate any data to suggest that most people with COPD cannot fly safely.

FIGURE 5–3

PO₂ in six healthy subjects and nine subjects with chronic air-flow limitation (CAL; FEV₁/FVC≤70%) during hypobaric high-attitude simulation. Data at 8,000 ft are at rest and after 2 min of “light exercise” (approximate work rate, (more...)

People with significant coronary arterial disease may also be at increased risk for cardiac symptoms because of reduced PO₂ at altitude. The committee was unable to locate any published studies of air-travel experiences of passengers with coronary arterial disease. Because of the lack of data, the broad spectrum of disease severity, and individual variability, the committee cannot put forward any recommendations other than to note that, as with COPD, a decision on a traveler's fitness to fly should be made by a physician.

A number of characteristics may affect a person's risk of becoming infected if exposed and affect the severity of disease that could result from infection (see Chapter 4 for more information on infectious agents on aircraft). Those characteristics include age, nutritional condition, alcoholism, coexisting (particularly chronic) diseases (such as those discussed above), immune status, and abnormalities in the skin or respiratory tract that allow the entry of infectious agents (Macher and Rosenberg 1999). Many persons with altered immunocompetence are able to travel, but they should consult their physicians before traveling.

People with medical conditions that may require treatment during travel (e.g., COPD, asthma, and autoimmune diseases) should carry letters describing their condition and treatment. Various types of medical alert tags and bracelets are available and should be worn to inform emergency-care providers of appropriate treatments or precautions for various medical conditions and how to reach travelers' health-care providers.

Populations that may be particularly sensitive to CO poisoning are anemic persons who have low hemoglobin concentrations, children who have higher metabolic rates that would exacerbate the adverse effects of CO, persons with a history of coronary heart disease or respiratory disease, and the elderly. Smokers typically have increased COHb and may have an adaptive response to elevated COHb (EPA 2000). People with coronary arterial disease and reproducible exercise-induced angina have decreased exercise tolerance at COHb concentrations of 3–6% (EPA 2000). Pregnant women may be at particular risk. The fetus may be very susceptible to the effects of CO because it readily crosses the placenta and might result in neurological damage to the infant (EPA 2000). Asthmatics may be especially sensitive to formaldehyde.

Cabin crews as a cohort population are relatively healthy. Air-transport pilots are required by FAA to undergo a flight physical examination every 6 mo, and must be granted an exception for significant illness or some classes of medications. Air-transport pilots can no longer fly as pilots once they are 60 yr old. However, flight attendants are required to undergo only an entry physical examination. There is no requirement for periodic medical examinations as there is for pilots. There are no health requirements for passengers.