Long-term exposure to jet fuel: an investigation on occupationally exposed workers with special reference to the nervous system.

Long term exposure to jet fuel: An investigation on occupationally exposed workers with special reference to the nervous system. Scand. j. work environ. & health 3 (197~) 152-164. In the present study the results of a neurological and neuro physiological health examination of 29 aircraft £actory workers chronically exposed to jet fuel vapors are presented. The exposed subjects were classified into a heavily exposed and a less heavily exposed group. The examination included a stan dardized clinioal neurological examination, measurements of the conduction v·elocities in the per1pheral nerves, and threshold determinations of vibratory sensations in the extremities. All 13 persons examined in the heavily exposed group and 7 of the 16 in the less heavily exposed group stated tha,t they had repeatedly experienced 'acute effects (dizziness, respiratory tract symptoms, heart palpitations, a feeling of pressure on the chest, nausea, headache) of the jet fuel vapors in the inhaled air. A high rate of symptoms indicative of neurasthenia and psychasthenia and symptoms and signs indicative of polyneuropathy was observed both in the heavily exposed group and in the two groups combined in comparison with reference groups. Considering the presented facts concerning (a) the acute effects on repeated ,occasions, (b) the high rates of symptoms indicative of neurasthenia and psychastheni'a and symptoms and signs indicative of polyneuro pathy, and (c) the differences in the observations made between the two groups with varying degrees of exposure to jet fuel, ,the authors interpreted the results as indicative of a possible effect of long-term exposure to jet fuel on the nervous system.

were compared with those from studies of different reference groUiPs of industrial workers. The actual jet fuels, commonly referred to as MC 75 and MC 77, have raw gasoline and kerosene as their principal components. For an evaluation of the health hazards which may arise from exposure to these jet fuels, oonsideration must be given to their oontents of aliphatic hydrocarbons as well as aromatic hydrocarbons such as benzene, toluene, xylene, and trimethylbenzene.
Acute ga'soline exposure is known to cause a depression of the central nervous system in man. Felix (14) tried to use gasoline as a general anesthetic. He found that the inhalaUon of 5-15 gm during a period of 7 to 12 min caused dizziness, nausea, vomiting, drowsiness, eye irritation, and a burning sensaUon in the chest. Anesthesia and sleep followed the administraUon of 20-40 gm given over a period of 8 to 12 min. Several cases of acute gasoline 'and kerosene poisoning by inhalation have since been reported. [For an early review the reader is referred to Potts (33) and also VlOn Oettingen (32), Gerharde (16) and Jacobziner and Raybin 23).] Cases of slight intoxication may show inebriation with an atactic, staggering gait. With increasing intoxication sympto.ms such as nausea, Vlomiting, and headache may develop. These symptoms have also been described in a case of in-fli~ht intoxication due to jet fuel fumes (9).
Se60us neurological after-effects have been described in the early literature after recovery from acute heavy gasoline poisonings, e.g., epilepsy (15,39), retrobulbar neuritis (5), encephalitis (15,33), a condition similar to multiple sclerosis (11), and vertigo and nystagmus (34). In a recent long-term follow-up study on 35 industrial workers focal neurological symptoms were reported to develop after acute heavy poisonings from different industrial hydrocarbons (36).

THE WORKPLACE
At the factory fI"'Om which the subj.ects of the present study came, the personnel were exposed to jet fuels during the production and installation of fuel systems for planes in isolated test cells and in a specially constructed fuel rig and during work on the fuel system in the complete airplanes (adjustments, repairs, etc.) at several workshops within the factory.
In the fuel rig the fuel system was set up on a scaffold ("rig") where it was tested under condihons simulating actual flight.
The tests usually resulted in jet fuel vapors throughout the testing area. In the test cells the fuel pumps and vents were subjected to careful checks as the jet fuel flowed through them.
With the fuel system installed in the planes another category of personnel, the mechanics, were exposed to fumes from the fuel. DUTiing inspections, repairs, etc, a worker often had to place his head in the narrow and semiclosed tanks containing residual jet fuel. During precision work of a technically difficult nature, the exposure time could amount to an hour or two.

THE EXPOSED PERSONNEL
With the aid of employer records and interviews of the personnel (the individual's own description of his earlier and present work conditions) 32 employees considerably exposed to fuel fumes from 1955 on were selected for the present investigation. During the evaluation of the results three of the examined persons were excluded because of the existence of a di,sease whkh per se might give rise to symptoms of neurasthenia and polyneuropathy (organic nervous diseases and juvenile diabetes mellitus).
The exposed persons were divided into two groups with regard to degree of exposure, group A being heavily exposed and group B being less heavily exposed. These classifications took into consideration both the duration and the intensity of the exposure. All 29 of the persons examined had been eX!posed for at least 5 years of employment. For exposure intensity the following criteria were used: group A: continuous exposure for several hours daily to high concentrations of jet fuel fumes in the fuel rig or the test cells or intermittent exposure to high concentrations for at least 20-30 min each time with an a'verage frequency of at least every second or third week; group B:~ess frequent intermittent exposure than group A. 'The majority of persons in group B stated a va-rying pattern of eX!posure with several days of heavy, intermittent exposure alter-nating with weeks or months without exposure. Employees with intermi'ttent, heavy exposure of less ,than 20-30 min each time were excluded from the investigation. After gmup allocation the heavily exposed and less heavily exposed groups consisted of 13 and 16 persons, respectively. The examined persons were grouped independently of the examination and prior to the evaluation of the results.

Personal history
In the general part of the personal history information was recorded on heredity, prev10us health, occupational history, tobacco smok'ing, use of alcohol, etc, as well as current symptoms associated with acute exposure and symptoms which had developed successively during the period 1960-1974. In a specific part of the personal history the persons were asked about Table 1. Evaluation and gradation of early neurological signs upon examina,tion of the peripheral nerve function [from lJindblom (3)]. Needle-priCk on the foot and leg. Grade 1: reduced in the feet (if a prick is felt more on the knee than on the foot, a slight reduction in the response of the foot is considered to have occurred, Le., grade 1).

Subject of evaluation
The metallic part of a percussion hammer was placed against the dorsum of the foot and the knee-cap; one percussion hammer had been cooled in water at roam temperature (about 20°C) and another warmed up with warm tap-water (about 40°C). Grade 1: reduced in the feet. the occurrence of symptoms considered indicative for neurasthenia and polyneuropathy. As to neurasthenia a standardized inquiry was used that was earlier applied in studies on industrial workers exposed to lead (26,27). As to polyneuropathy a standardized inquiry was used which had been worked out by Lindblom and used in studies on the perilphera1l nerve function of uremic patients (3). This inquiry was used by the present authors in earlier investigations on industrial workers exposed to carbon disulfide (25) and lead (26,27). The examined persons were thus questioned as to the occurrence of restless legs (6,24), muscle cramps, pain in the extremities, distal paresthesia and numbness, and paresis. For the evaluation of neurasthenia and polyneuropathy symptoms the same standardized criteria were used as in our earlier investigations on industrial workers, i.e., a symptom was considered "positive" when the subject experienced it at a frequency exceeding once a month. It should be emphasized that "positive" symptoms according to these criteria do not necessarily indicate manifest disease in terms of a olinical evaluation.

Neurological examination
The clinical examination included a general neurological examination and a neurological examination especially designed to detect early aberrations indicative of polyneuropathy. A basis for such an evaluation was developed by Lindblom in studies on uremic patients with sUibclinical and manifest polyneuropathy (3) and was later used by the present authors in investigations on industrial workers (25,26,27). The method allows the examination signs to be graded between 0 and 3 (0 = normal, 1 = earliest and mildest changes, 2 and 3 = different grades of manifest polyneuropathy). The criteria used for grade-1 changes are given in table 1. This standardized neurological examination is sensitive in detecting slight aberrations from normal.

Conduction velocities in peripheral motor nerves
In the present study measurements were made of the maximal conductton velocity in the median (MCVmed) and the ulnar nerve (MCVuln), as well as the conduction velocity of the slow fibers in the ulnar nerve (CVSFuln). The technique of measuring CVSFuln has previously been used by SeppiiHiinen and Herniberg (35). Accordingto these authors this method is a more sensitive detedor of nerve dysfuncUon due to lead exposure than c'onventi:onal conduction velocity measurements.

Sensation thresholds of vibration in the extremities
The vibration threshold was determined from the lapplication of a 100-Hz sine wave stimulus from an electromagnetic biothesiometer (Bio-Medical Instruments Inc., Chagrin Falls, Ohio). The stimulator head consisted ofa plastic probe 6 mm in diameter with a l"ounded edge. An accelerometer was mounted on the shaft of the stimulator, the movement of which was displayed after amplification on an oscilloscope and oalibrated in {tm peak to peak. The stimulator was applted with the pressure of its own weight (440 g) and wi'th the moving shaH in a posibon a,s near to vertical as possible, and, at the same time, perpendicular to the skin surface. Care was taken to apply the stimulator to the underlying bone by p1acing it where the subcutaneous tissue was the thinnest. This application gave the least variation in threshold in repeated tests. The threshold was determined with the method of limits. A full description of the method, including normal threshold values for commonly used stimulus sites such as the metatarsal and metacarpal regions, is being prepared by Goldberg and Lindblom.

Personal history
Acute symptoms in connection with exposure to jet fuel vapors. All persons in the heavily exposed gl"OUp stated that they Table 2. Symptoms and examination signs in the jet fuel exposed groups. Table 3. Symptoms indicative of polyneuropathy in the jet fuel exposed groups.

Symptom
Group A GroupB (n = 13) (n = 16) "Restless legs" 8 3 Musde cramps 3 3 Diffuse pain in the extremities From table 2 it is evident that the exposed persons successively developed a number of symptoms which could be referred to as symptoms of neurasthenia and psychasthenia, I.e., dizziness, respiratory tract symptoms (feeling of suffocation, pain upon inhalation), palpitations, pressure on the chest, depression, anxiety, sleep disturbances, headache, memory impairment, and irritability. The presence of these symptoms was found to be remarkably consistent in many of the oases. Twelve of the 13 heavily exposed and 9 of the 16 less heavily exposed reported one or more of these symptoms. Among the 12 persons in group A with neura,sthenic and psychasthenic symptoms 10 had consulted a physician and had been treated for the symptoms long before the present study (in 8 cases since the middle and late 1960s and in the remaining 2 cases since 1971 and 1972, respectively). Five out of seven in group B had been treated by physicians for the same reasons (4 since the 1960s and 1 since 1972).
of dizziness was described in various ways, e.g., as "a feeling of whirling around," "swaying sensation," "felt his mind was not all there." The respiratory tract symptoms were described as "feeling of suffocation," "pain upon inhalation," "slight cough," "ache in the chest," etc. All of the examined persons who had experienced acute symptoms (including also the persons with acute symptoms in the less hetavily exposed group) reported that on such occasions they repeatedly had to interrupt their work to "get a breath of fresh air" for relief of symptoms. Seven of the 16 less heavily exposed workers also reported acute symptoms in the form of dizziness (5 persons), headache (5 persons), nausea (2 persons), respiratory tract symptoms (3 persons), palpita,tions and pressure on the chest (2 persons). Symptoms and examination signs TabLe 4. Signs indicative of polyneuropathy in the jet fuel exposed groups.
on the occurrence of oorresponding symptoms and examination signs in the reference group of an investigation of the effects of chronic carbon disulfide exposure in a vis'Cose factory (25) and in the reference group of an investigation on the effects of lead exposure in a heavy metals industry (27). Although they are not reference groups, a group of persons moderately exposed to lead in a storage battery factory (26) and a group of persons moderately exposed to lead in a heavy metals industry (27) have been included in the table for comparison. These groups, named group C, D, E, and F, respectively, were investigated with the same standardized methods as were used in the present study. Table 5 shows an increased rate of neurasthenic and psychasthenic symptoms, as well as symptoms and signs indicative of polyneuropathy, in the group heavily exposed to jet fuel (Le., group A) in conparison to that of the other groups. The symptoms and signs are also more frequent in the group less heavily exposed to . jet fuel (Le., group B) than in the reference groups, but less frequent than in group A.
Age must be regarded as an important factor when the frequency of polyneuropathy signs is considered. Since groups A and B combined bear the most resemblance to group D as far as age composition is concerned, it is preferable to compare the present results with the observations made on group D. When groups A and D are compared for the frequency of polyneuropathy signs, the i'ous symptoms among the examined persons is presented in table 3. Subjects who experienced at least one of the symptoms listed in table 3 were classified as "positive" in table 2. According to these criteria, 11 out of the 13 heavily exposed and 6 out of the 16 less heavily exposed showed symptoms which might be indicative of polyneuropathy.
Other neuroLogicaL diseases. Four of the 29 workers had been examined in the hospital for neurological disease, viz., epilepsy, mental confusion of unknown etiology, rhizopathy, and inactivation atvophy in the hands due to chronic joint disease.
Skin changes. Three of the examined persons had skin changes. Two had eczema; and one, suspected psoriasis.

NeuroLogicaL examination
Signs indicative of poLyneuropathy. All the signs noted as indicative of polyneuropathy in the present study were classified as grade-l changes (table 4). Three of the subjects in group A had no positive polyneuropathy signs. Six persons had one positive sign and 4 persons had two positive signs. In the less heavily exposed group 9 persons had no positive signs, 5 persons had one positive sign, and 2 persons had two or more positive signs. One of the subjects in this group had four positive signs.
Other neurological signs. Two of the examined persons were found to have other pathological signs in the neurological examination. One subject showed a functional psychogenic disturbance upon performance of Romberg's test, and another had obvious muscular atrophies and pareses in his hands and fingers.

Sign
Group A Group B (n = 13) (n = 16) Frequency of symptoms indicative of neurasthenia and psychasthenia and symptoms and signs indicative of poLyneuropathy in the groups exposed to jet fueL in comparison with reference groups In  In 'table 6 the age factor is taken into consideration through the subdivision of the examined persons into two groups with 50 years of age as the dividing line. The trend of high rat.es of signs indica'tive of polyneuropathy in the jet fuel exposed groups can be seen be'low as well as above the age of 50 years. However, chi square testing becomes less meaningful in this si1tuation because of the small numbers in the groups and the size differences in the samples compared. Fig. 1 shows the MCVnln as a function of age in the heavily exposed group ( fig. 1 A) and in the less heavily e:xcposed group (f1g. 1 B); the continuous and broken lines  Fig. 3. Conduction velocity of the slow fibers of ,the ulnar nerve (CVSFu]n) as a function of age in the groups heavily (A) and less heavily (B) exposed to jet fuel. The continuous and broken lines represent the age regression and ± 2 SD, respectively, in the reference group from the heavy metalls industry (27). represent the regression and the ± 2 SD, respectively, for the reference group (group D in table 5). In the d~agram the values measured for each examined person have subsequently been plotted. In fig. 2 A and B the results from the meaoor€ments of the MCV meu are presented in the same manner. The CVSFuln has been plotted in the di,agram in fig. 3 A and B for the heavily and th€ less heavily exposed groups, respectively.

Conduction velocities in peripheral motor nerves
An analysis of covariance in order to account for age-dependence gave no significant differences either between the heavily exposed group (group A) and the reference group (group D) or between the less heavily exposed group (group B) and the reference group for any of the three variables.

Threshold determinations of vibration sensation
In the present investigation vibration thresholds were compared with the results of the investigation on the reference group of workers in the heavy metals industry (27), i.e., group D in table 5 (figs. 4 and 5). An analysis of covariance for the two measurements of vibration sensation showed a significant difference between the less heavily exposed group and the reference group for th€ measurements on the hand (c'arpal, fig. 5 B). Comparing the measurements of the heavily exposed and the reference group produced a p-valu€ that was somewhat larger than 0.10. For the other vibration measurements there were no significant diff€rences between the expolsed groups and the reference group.

Evaluation of the neurophysiological recordings
For the assessment of the composite results of the neurophysiological recordings (the conduction velocities and the peripheral vibration thresholds, figs. 1-5), a multivariate analysis of covariance was made. This analysis showed no significant differences between either the heavily exposed group (group A) ,and reference group D or the less heavily exposed group (group B) and reference group D.  4. Thresholds of vibra,tion sensation (logarithmic scale) for the dorsum of the foot as a function of age in the groups heavily (A) and less heavily (B) exposed to jet fuel. The continuous and broken lines represent the age regression and ± 2 SD, respectively, in the reference group from the heavy metals industry (27).
phenomenon ffilay offer an explanlation to the albsence of obvious eye irritahon among the exposed persons in the present investigation.
Increased rates of symptoms indicative of neurasthenia and psychasthenia and symptoms and signs indicative of polyneuropathy in the groups exposed to jet fuel ';n comparison with reference groups  All of the 13 persons in the heavily exposed group and 7 of the 16 persons in the less heavily exposed group had repealtedly experienced acute symptoms (dizziness, respiratory tract symptoms, palpitations, pressure on the chest, nausea, headache) on exposure to jet fuel vapors. The frequency and intensity of such repeated effects are, in analogy with the development of chronic gasoline poisonings (1,30,38) and alcoholism (17), probably relevant for the development of les~ons in the nervous system.
Unfortunately, in the present investigation there is insufficient inforrmation available 'On the fuel concentration in the inhaled air when the acute effects described above occurred. On one occasion (in 1972) however, a piece of Drager equipment (type CH 254) showed a concentration of 3,000 ppm ait one workplrace and ahout 500 ppm in two workrooms. These values are on the same order of magnitude as those measured in a Japanese workplace where polyneuropathy and neurasthenia develroped in four workers engaged in cleaning brocade sashes with petroleum benzine (40). In studies on human volunteers at rest Drinker et al. (12) reported that exposure to 1,000 ppm of gasoline oaused slight dizziness, nausea, and headache. When the concentraiti'On reached 2,600 ppm all subjects were drunk and somewhat anesthetized. In fh~s respect attention must be paid to the increase in the uptake of solvents in blood and bssues as a function of physioal exercise; according to .&strand (2) even light work resuLts in a significant increase in uptake. Drinker et al. (12) also found that in a group exposed to 160 and 270 ppm the most distinotive symptoms ,were irritation of the eyes and throat. Later Davis et al. (10) confirmed that eye irritation was the first symptom to appear during exposure to low concentrations of g'asoline. Kerosene, however, has not been found to have such an eye irritating effecit. The application of kerosene to the human eye causes no discomfort or injury (18), and this  group (A = the heaviiy exposed group; B = the less heavily exposed group; the numbers at the bottom of the figure represent the examined subjects). Nerve conduction v'elocities lower than and thresholds of vibration sensation higher than ,the mean value are denoted wi,th a negative sign. Nerve conduction velocities higher than and thresholds of vibratory sensation lower than the mean value are denoted with a positive sign.
descdptions of chronic fuel intoxications in the literature (4,8,13,19,29,30,37,38,40,42). However, in an examination of a small number of persons limited to one place of work, the possibility of the psychological influence of individuals on one another cannot be excluded. Furthermore, the subjective complaints of the workers were generally discussed by the news media at the time of the investigation. However, the neurasthenic and psychasthenIc symptoms had developed and were diagnosed and treated by physicians many years before the present investigation was undertaken.

Neurophysiological recordings
As already mentioned, analyses of covariance (including a multivariate analysis of covariance) gave no significant differences between exposed and reference groups with the exception of the carpal vibration threSholds of the less heavily exposed group and the reference group.

162
Based on these results, ther,e are two principal alternatives as to whether long-term exposure to jet fuel causes any effect on the peril pheral nerves, Le., (a) in reahty there is no such effect or (b) the sample is too small to show such an effect. However the results show a tendency towards slower conduction velocities (MCVuln' MCVmed, CVSFuln) and higher peripheral vibration thresholds (tarsal and carpal vibrartion thresholds). This tendency is illustrated in ltg. 6 A and B, in which each test Vlalue of group A and B, respectively, is expressed as the deviation from the age-w.eighted mean of the reference group with the standard deviation as the untt of measure. Conduction velocities lower than the mean value and vibration thresholds higher than the mean have been denoted by a negative sign. Nega'tive v;alues, Le., low conduction velocities and high peripheral vibratiJon thresholds are results to be anticipated in the presence of an established nerve lesion. As can be seen in the figure, 41 of the 65 test values in group