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Melatonin, a pineal hormone present in the blood of humans and other species, has a distinct diurnal variation in its biosynthesis and, therefore, in its concentration. This variation has suggested the possibility of a regulatory function in day/night-dependent physiological processes such as sleep and has led scientists to explore the effects of administered melatonin on the modulation of circadian rhythms. For the self-treatment of sleep disorders and other benefits, melatonin use has been extolled to the extent that 20 million new consumers were added to the U.S. retail market in 1995. Its principal aeromedical application has been in the experimental treatment of jet-lag effects. For aircraft passengers, melatonin administration at destination bedtime appears to improve sleep quality and to decrease the time required to reestablish normal circadian rhythms. For international aircrews that travel through multiple time zones without time to adapt to new environments, taking melatonin before arriving home may further impair already disturbed circadian rhythms. Its use to adjust to shiftwork changes by air traffic controllers, aircraft maintenance workers, and support personnel is even more controversial. Limited studies suggest that giving this hormone to shift workers should be done only under controlled conditions and that taking it at the wrong time may actually impair job performance. Because of its possible interaction with certain medications and the changes in its concentrations observed in some clinical conditions, the practitioner must exercise caution during the medical certification of airmen. The variations in the concentration of melatonin can be effectively determined by radioimmunoassay, high-performance liquid chromatography, and gas chromatography-mass spectroscopy analytical techniques. These techniques are capable of measuring the human daytime (10 pg/mL) and nighttime (30-120 pg/mL) melatonin in plasma/serum. Melatonin measurements in victims of accidental death may allow forensic scientists and accident investigators to use the relationship between its concentration and the time of day when death occurred. The most accurate estimations of the time of death result from analysis of melatonin content of the whole pineal body, whereas less accurate estimates are obtained from serum and urine analyses. Pineal levels of melatonin are unlikely to be altered by exogenous melatonin, but its blood and urine levels would change. High blood levels in a daytime crash victim would suggest exogenous supplementation. The possible interfering effects of postmortem biochemical processes on melatonin concentrations in whole blood and in other tissues are not well understood, and there is a need for the continuing research into melatonin's chronobiological properties to define its proper applications and limitations. The indiscriminate use of melatonin by aviation professionals may pose unacceptable safety risks for air travel.

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The measurement of combustion gases produced by burning aircraft cabin materials poses a continuing limitation for smoke toxicity research. Because toxic effects of gases depend on both their concentrations and the duration of exposure, frequent atmosphere sampling is necessary to define the gas concentration-exposure time curve. A gas chromatographic (GC) method was developed for the simultaneous analyses of carbon monoxide (CO), hydrogen sulfide (H2S), sulfur dioxide (SO2), and hydrogen cyanide (HCN). The method used an MTI M200 dual-column gas chromatograph equipped with 4-m molecular sieve-5A and 8-m PoraPlot-U wall-coated capillary columns and two low-volume, high-sensitivity thermal conductivity detectors. Detectability (in parts per million [ppm]) and retention times (in seconds) for the gases were as follows: CO, 100 ppm, 28 s; H2S, 50 ppm, 26 s; SO2, 125 ppm, 76 s; and HCN, 60 ppm, 108 s. The method was effective for determining these gases in mixtures and in the combustion atmospheres generated by burning wool (CO, HCN, and H2S) and modacrylic fabrics (CO and HCN). Common atmospheric gaseous or combustion products (oxygen, carbon dioxide, nitrogen, water vapor, and other volatiles) did not interfere with the analyses. However, filtration of the combustion atmospheres was necessary to prevent restriction of the GC sampling inlet by smoke particulates. The speed, sensitivity, and selectivity of this method make it suitable for smoke toxicity research and for evaluating performance of passenger protective breathing equipment. Also, this method can potentially be modified to analyze these gases when they are liberated from biosamples.

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In-flight fires in modern aircraft are rare, but post-crash fires do occur. Cabin occupants frequently survive initial forces of such crashes but are incapacitated from smoke inhalation. According to an international study, there were 95 fire-related civil passenger aircraft accidents worldwide over a 26-yr period, claiming approximately 2400 lives. Between 1985 and 1991, about 16% (32 accidents) of all U.S. transport aircraft accidents involved fire and 22% (140 fatalities) of the deaths in these accidents resulted from fire/smoke toxicity. Our laboratory analyses of postmortem blood samples (1967-93) indicate that 360 individuals in 134 fatal fire-related civil aircraft (air carrier and general aviation) accidents had carboxyhemoglobin saturation levels (> or = 20%), with or without blood cyanide, high enough to impair performance. Combustion toxicology is now moving from a descriptive to a mechanistic phase. Methods for gas analyses have been developed and combustion/animal-exposure assemblies have been constructed. Material/fire-retardant toxicity and interactions between smoke gases are being studied. Relationships between gas exposure concentrations, blood levels, and incapacitation onset are being established in animal models. Continuing basic research in smoke toxicity will be necessary to understand its complexities, and thus enhance aviation safety and fire survival chances.

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Carbon monoxide (CO) and hydrogen cyanide (HCN) are generated during aircraft interior fires in sufficient amounts to incapacitate cabin occupants. For typical post-crash and in-flight fires, minimum protection periods of 5 and 35 min, respectively, have been suggested for breathing devices to protect the occupants from smoke. Relationships of blood carboxyhemoglobin (COHb) and cyanide (CN-) levels to incapacitation have not been well defined for these gases. Therefore, time to incapacitation (ti) and blood COHb and CN- at incapacitation were examined in rats exposed to CO (5706 ppm for 5-min ti; 1902 ppm for 35-min ti), HCN (184 ppm for 5-min ti; 64 ppm for 35-min ti) and their mixtures (equipotent concentrations of each gas that produced 5- and 35-min ti). Blood CO and HCN uptakes were evaluated at the two concentrations of each gas. With either gas, variation in ti was higher for the 35-min ti than the 5-min ti The COHb level reached a plateau prior to incapacitation at both CO concentrations, and COHb levels at the 5- and 35-min ti were different from each other. Blood CN- increased as a function of both HCN concentration and exposure time, but CN- at the 5-min ti was half of the 35-min ti CN- level. The HCN uptake at the high concentration was about three times that at the low concentration. In the high concentration CO-HCN mixture, ti was shortened from 5 to 2.6 min; COHb dropped from 81 to 55% and blood CN- from 2.3 to 1.1 microgram ml(-1). At the low-concentration CO-HCN mixture, where ti was reduced from 35 to 11.1 min, COHb decreased from 71 to 61% and blood CN- from 4.2 to 1.1 microgram ml(-1). Any alteration in the uptake of either gas by the presence of the other was minimal. Our findings suggest that specific levels of blood COHb and CN- cannot be correlated directly with the incapacitation onset and that postmortem blood COHb and CN- levels should be evaluated carefully in fire victims.

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Polymeric aircraft cabin materials have the potential to produce toxic gases in fires. Lethality (LC50) in animal models is a standard index to rank polymers on the basis of their combustion toxicity. However, the use of times-to-incapacitation (ti) may be more realistic for predicting relative escape times from a fire. Therefore, LC50 and ti for polymers, polyamide (I), polystyrene (II), Nylon 6/6 (III), polysulfone (IV), polyethylene (V) and chlorinated polyethylene (VI), of different chemical classes were determined and compared. Male rats, 12/fuel loading, were exposed to the pyrolysis products from selected weights of each polymer for 30 min in a 265-L combustion/exposure system, and LC50 values were determined following a 14-d observation period. For each polymer, ti was measured at 16 g and at its respective LC50 using the inability of rats (n greater than or equal to 12) to walk in rotating cages as a criterion for incapacitation. LC50 (45.7-87.5 mg/L) of the polymers had the order of I less than II approximately III less than IV less than V less than VI, while their ti (6.6-21.1 min) at 16 g (60 mg/L) had the order of III approximately I less than V approximately II less than VI less than IV. Based on ti at LC50, polymers were grouped into III & V; I, II & VI; and IV. LC50 and ti did not exhibit the same relative toxic hazard rankings for these polymers; ti were also not equal at the LC50 concentrations. These findings demonstrate the possible involvement of different mechanisms of action for the combustion products of these polymers at the selected end points.

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A foundation population derived from nine different rat strains was subjected to genetic selection for high and low rearing activity. A rapid response to selection was demonstrated, the two selected lines showing virtually no overlap in scores after 10 generations. Heritability estimates were assessed from parent-offspring regressions in the unselected control line and from comparisons of the achieved response with the selection pressure applied in the selected lines. Overall, the heritability of rearing activity in the rat was assessed to be about 0.25. In addition, a major gene effect was revealed, albinism being associated with low rearing activity scores.

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Spinal cord ischemia was produced by an occlusion of the thoracic descending aorta on experimental cats for the periods of 3, 5, 10, and 15 minutes. The reduction/oxidation (redox) ratio of cytochrome a,a3 was measured in vivo by reflectance spectrophotometry, simultaneously with the measurement of the following: blood pressure in the aorta distal to the occlusion; relative blood volume in the cord; oxygen tension in cord tissue; and cord potential in response to dorsal root stimulation. During aortic occlusion, the maximum increase in the redox ratio was reached somewhat more slowly than the maximum decrease in blood pressure, blood volume, and oxygen tension. Interneuron potentials began to decrease as the redox level increased, and completely disappeared soon after the redox ratio increased, and completely disappeared soon after the redox ratio increased maximally. During ischemia, therefore, oxygen consumption in the mitochondria was slightly lower than the decrease in oxygen tension; impairment of ADP phosphorylation, and accordingly that of ion pump, occurs simultaneously with the increase in the redox ratio. Recovery of the redox ratio after completion of aortic occlusion was also slightly slower than the recovery of blood pressure, blood volume, and oxygen tension. Complete recovery of interneuron potentials was much more delayed than that of the redox ratio; after 15-minute ischemia, uncoupling of ADP phosphorylation was noted. It can be concluded that the spinal cord function and metabolism are severely impaired after 15-minute occlusion.

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The Roman high-avoidance (RHA) and low-avoidance (RLA) strains of rats were tested and compared with Maudsley reactive (MR) and non-reactive (MNR) strains to assess the relative contributions of emotionality and conditionability to differences between the two Roman strains. The RHA learned significantly faster in active avoidance, but slightly slower in passive avoidance, significantly faster in acquisition of an active approach task, but slighty slower in extinction of active approach tasks despite extensive adaptation and gentling. The RHA showed more 'rearing', more activity in the open field and more variety-seeking. Crossing with MNR showed the RHA less reactive in the open field. Results show RLA equivocal in conditionability, more emotional, and perhaps less active.

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