Bilateral Vestibular Dysfunction Associated With Chronic Exposure to Military Jet Propellant Type-Eight Jet Fuel

Abstract

We describe three patients diagnosed with bilateral vestibular dysfunction associated with the jet propellant type-eight (JP-8) fuel exposure. Chronic exposure to aromatic and aliphatic hydrocarbons, which are the main constituents of JP-8 military aircraft jet fuel, occurred over 3–5 years’ duration while working on or near the flight line. Exposure to toxic hydrocarbons was substantiated by the presence of JP-8 metabolite n-hexane in the blood of one of the cases. The presenting symptoms were dizziness, headache, fatigue, and imbalance. Rotational chair testing confirmed bilateral vestibular dysfunction in all the three patients. Vestibular function improved over time once the exposure was removed. Bilateral vestibular dysfunction has been associated with hydrocarbon exposure in humans, but only recently has emphasis been placed specifically on the detrimental effects of JP-8 jet fuel and its numerous hydrocarbon constituents. Data are limited on the mechanism of JP-8-induced vestibular dysfunction or ototoxicity. Early recognition of JP-8 toxicity risk, cessation of exposure, and customized vestibular therapy offer the best chance for improved balance. Bilateral vestibular impairment is under-recognized in those chronically exposed to all forms of jet fuel.

Full text

May 2018 | Volume 9 | Article 3511
CASE REPORT
published: 16 May 2018
doi: 10.3389/fneur.2018.00351
Frontiers in Neurology | www.frontiersin.org
Edited by:
Bryan Kevin Ward,
Johns Hopkins University,
United States
Reviewed by:
Pierre-Paul Vidal,
Université Paris Descartes, France
Jorge Kattah,
University of Illinois College of
Medicine, United States
*Correspondence:
Terry D. Fife
tfe@email.arizona.edu
Specialty section:
This article was submitted
to Neuro-Otology,
a section of the journal
Frontiers in Neurology
Received: 06March2018
Accepted: 01May2018
Published: 16May2018
Citation:
FifeTD, RobbMJA, SteenersonKK
and SahaKC (2018) Bilateral
Vestibular Dysfunction Associated
With Chronic Exposure to Military
Jet Propellant Type-Eight Jet Fuel.
Front. Neurol. 9:351.
doi: 10.3389/fneur.2018.00351
Bilateral Vestibular Dysfunction
Associated With Chronic Exposure
to Military Jet Propellant Type-Eight
Jet Fuel
Terry D. Fife1*, Michael J. A. Robb2, Kristen K. Steenerson3 and Kamala C. Saha1
1 Barrow Neurological Institute, Phoenix, AZ, United States, 2 Robb Oto-Neurology Clinic, Phoenix, AZ,
United States, 3 Stanford University, Palo Alto, CA, United States
We describe three patients diagnosed with bilateral vestibular dysfunction associated
with the jet propellant type-eight (JP-8) fuel exposure. Chronic exposure to aromatic
and aliphatic hydrocarbons, which are the main constituents of JP-8 military aircraft jet
fuel, occurred over 3–5years’ duration while working on or near the ight line. Exposure
to toxic hydrocarbons was substantiated by the presence of JP-8 metabolite n-hexane
in the blood of one of the cases. The presenting symptoms were dizziness, headache,
fatigue, and imbalance. Rotational chair testing conrmed bilateral vestibular dysfunc-
tion in all the three patients. Vestibular function improved over time once the exposure
was removed. Bilateral vestibular dysfunction has been associated with hydrocarbon
exposure in humans, but only recently has emphasis been placed specically on the
detrimental effects of JP-8 jet fuel and its numerous hydrocarbon constituents. Data
are limited on the mechanism of JP-8-induced vestibular dysfunction or ototoxicity.
Early recognition of JP-8 toxicity risk, cessation of exposure, and customized vestibular
therapy offer the best chance for improved balance. Bilateral vestibular impairment is
under-recognized in those chronically exposed to all forms of jet fuel.
Keywords: JP-8, jet propulsion fuel-8, JP-8 jet fuel, bilateral vestibular dysfunction, ototoxicity, vestibulotoxicity,
rotational chair, hydrocarbons
INTRODUCTION
e primary jet fuel used in the United States Air Force and NATO military operations is jet
propellant type-eight (JP-8). JP-8 is a kerosene-based fuel comprised of over 228 aromatic and
aliphatic hydrocarbons (1). During 1992–1996, the Air Force transitioned from using JP-4 to JP-8
due to the improved safety prole of the latter. JP-8 is also used as a multipurpose fuel for ground
vehicles, generators, tent heaters and air conditioners, lamps, and cooking stoves allowing for
an array of exposure opportunities. JP-8 typically contains 18% aromatic hydrocarbons and 82%
aliphatic hydrocarbons, in particular, 9% C8–C9, 65% C10–C14, and 7% C15–C17 (2). JP-8 diers
from commercial airline fuel due to its military additives including static electricity/corrosion/
icing inhibitors, thermal stability enhancers, and antioxidants.
Vestibulotoxicity from JP-8 has been suggested but not well-documented in previous studies.
Several studies indicate an association with impaired balance (3, 4), hearing, and central auditory
processing (5–8).
We present a case study of three patients who had chronic complaints of dizziness, headache,
fatigue, and imbalance. One patient performed fuel-tank maintenance for the Air National Guard

FIGURE 1 | Example of vestibular hypofunction seen across all frequencies for Case 1. A sinusoidal rotation at 0.04Hz, 60deg/s by rotational chair testing. The
smooth sinusoid is the chair/head rotation at 0.04Hz, and the scatter line represents the slow phases of compensatory nystagmus in response to the sinusoidal
head (and chair) rotations. The abscissa is time measured in seconds. LB, left beating nystagmus; RB, right beating nystagmus. Performed using Micromedical
Technologies (Chatham, IL, USA).
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for over a decade, while the other two worked 4–6years in admin-
istrative positions in a small under-ventilated building proximate
to the ight line. Each developed documented-bilateral vestibular
dysfunction most probably related to chronic inhaled JP-8 fumes
over a long period of time.
CASE REPORTS
Case 1: Military Flight Refueler
A 37-year-old woman presented with several years of progres-
sively worsening continuous dizziness, headache, and fatigue.
e dizziness consisted of sensations of spinning, tilting, disequi-
librium, and head fullness. She did not report tinnitus or hearing
loss. She was employed as a military ight refueler and exposed to
JP-8 vapors and exhaust while working full-time on and around
a KC-135E tanker aircra, a plane used for performing in-ight
refueling missions. She worked in a large enclosed hangar that
housed all but the tail section of the tanker aircra. During
inspection and maintenance of the aircra, up to 9,750 gallons of
fuel would be loaded. Jet fuel vapors were always present in the
hangar due to venting, small leaks, and fuel residue. Fuel vapor
concentrations were even greater when engine maintenance
necessitated removal of fuel lters and fuel components, drain-
ing of fuel into buckets, and opening of fuel lines. She worked in
engine maintenance with over 4years of inhalational and dermal
exposure to JP-4 and JP-8.
Her examination showed moderately impaired equilibrium
to walk only three steps in tandem before taking a sidestep.
Romberg testing revealed more sway during eye closure but no
falling. Her medical and neurological examinations were nor-
mal. ere was no spontaneous, gaze, or positional nystagmus.
Qualitative head impulse test was not performed at that time.
A brain SPECT study at an outside facility revealed mild-
right frontal hypoperfusion that persisted on a repeated study
the following year. Neurocognitive examination showed overall
memory function in the 97th percentile. An MRI brain without
gadolinium and an EEG were normal. An initial hydrocarbon
assay revealed the presence of 3-methylpentane and n-hexane
in the blood at concentrations of 27 and 15.7ng/ml (parts per
billion), respectively (none should be measurable in normal
individuals). Ten months later, 3-methylpentane and n-hexane
remained present although at signicantly lower concentra-
tions. Eighteen months aer presentation, 3-methylpentane
and n-hexane persisted in the blood and had only diminished
an additional 20%. Rotational chair, more so than caloric ves-
tibular testing, demonstrated bilateral vestibular dysfunction
(Figures 1 and 2) with reduced gain values on step velocity
along with a reduced time constant. Gain was also reduced on
all sinusoidal rotations with increase phase lead at 0.01, 0.02,
and 0.04Hz rotations. e patient reported that her headaches,
dizziness, fatigue, and mild unsteadiness improved somewhat
following a transfer to the nance department where no JP-8
exposure existed. ere was a long interval of 15years since her
initial visit when she was lost to follow up. Now, 16years aer
her initial presentation, she reports that the dizziness is mild
but headaches and severe fatigue persist. She has continued
to work but plans to retire earlier than originally anticipated
due to the ongoing symptoms. Recently, cervical and ocular
vestibular-evoked myogenic potential (cVEMP and oVEMP,
respectively) and video head impulst testing for each canal were
performed and all results were normal.
Cases 2 and 3
e following two patients were employees in a small-purchasing
warehouse, located 75feet south of the ight path, which was
separated from the blast and heat emissions from jet aircra
engines by a metal-coated and chain-link fence. Neither air
conditioning vents nor carpet had not been cleaned or replaced
for over a decade. On inspection, the vents were found to be mal-
functioning such that air was able to enter the building but unable
to escape. Subsequent inspection by the U. S. Occupational Safety
and Health Administration (OSHA) conrmed poor ventilation
evidenced by carbon dioxide concentrations >1,500ppm (nor-
mal <1,000 ppm according to the U.S. Department of Labor).
Hydrocarbons discovered in the carpet via an independent
analysis using gas chromatography/mass spectrometry included

FIGURE 2 | The summary of average gain values at frequencies between 0.01 and 0.64Hz sinusoidal rotations. The gain values were below normal for all
frequencies tested for Cases 1 and 2 and were reduced at most frequencies for Case 3.
TABLE 1 | Caloric vestibular test results of each case.
TimingbRCaRWaLCaLWaVR% DP%
Case 1 0 16 12 14 20 9 Right 16 Left
Case 2 0 5 7 6 8 7 Right 0
Case 2 16 Months 19 32 30 21 0 22 Right
Case 3 0 23 17 11 10 31 Left 8 Right
Case 3 7 Months 20 32 20 36 3 Right 3 Left
All studies performed with water caloric irrigation using ICS Chartr VNG, now GN
Otometric (Schaumburg, IL).
aPeak slow phase velocity in degrees/second of caloric-induced nystagmus.
bTime 0=initial presentation. Subsequent studies designated as months subsequent
to presentation.
RC, right cool irrigation, LC, left cool irrigation, RW, right warm irrigation, LW, left warm
irrigation; VR, vestibular response asymmetry as a percentage using Jongkees formula;
DP, directional preponderance which reects the direction (rightward versus leftward) of
the bithermal caloric-induced nystagmus expressed as a percentage using Jongkees
formula.
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undecane (C11), dodecane (C12), tridecane (C13), tetradecane
(C14), and toluene (C8)—all known JP-8 constituents (2). e
chemicals present in the oce carpet likely reected poor indoor
air quality. Vapor, aerosol, dermal, and eye absorption of JP-8 are
presumed.
Case 2: Warehouse Employe 1
A 45-year-old female contracting ocer for the National Guard
reported several years of imbalance, headache, fatigue, eye and
skin irritation, coughing, sinus congestion, recurrent urinary
tract infections, chest tightness, irritability, depression, shortness
of breath, palpitations, and numbness. She described her dizzi-
ness as an intermittent oating and a rightward tilting sensation
with imbalance lasting minutes to hours without any particular
pattern. She had a history of asthma and allergies including
reaction to aspirin causing urticaria and airway obstruction. In
1998, she developed syncope and dizziness though no specic
cause was found. She started working in the building in 1994 and
worked there full-time for 5years.
Her examination was normal except that she fell on Romberg
testing and could only walk a few steps in tandem. Brain MRI,
EEG, audiogram, and pulmonary function tests were normal.
Quantitative rotational chair and caloric vestibular tests revealed
bilateral peripheral vestibular dysfunction (Tabl e  1 ; Figure 2).
Her caloric responses improved following removal from the
under-ventilated environment (Table1).
Case 3: Warehouse Employe 2
A 54-year-old female National Guard contract specialist pre-
sented with 2 years of intermittent dizziness, blurred vision,
and occasional palpitations. Dizziness was experienced at least
3days a week. She reported intermittent problems with erratic
heart beats, cough, sneezing, headaches, fatigue, recurrent sinus
infections, upper respiratory tract, and bladder infections. She
worked in the purchasing warehouse full-time for 3years. When
away from the workplace her symptoms were improved. Aer
moving with her colleagues into a new building, the frequency of
dizziness was lessened.
Her medical, neurological, and oto-neurological examina-
tions were normal. Electronystagmography revealed somewhat
reduced caloric vestibular responses for age and a 33% reduced
vestibular response on the le. Rotational testing showed reduced
gain with sinusoidal rotational stimuli at frequencies from 0.02
to 0.16Hz (Figure2). Her caloric responses improved follow-
ing removal from the “sick-building” environment (Tab l e  1).
Computerized dynamic posturography showed falls on conditions
4, 5 and 6 indicating some general impairment of equilibrium and
a predominant vestibular decit pattern. Audiometric tests were
normal except for mild-sensorineural hearing loss in the right ear
from 250 to 8,000Hz and borderline normal le-sided hearing
from 250 to 2,000Hz sloping to a moderate loss between 3,000
and 8,000Hz.
DISCUSSION
ese case reports describe three women working in close pro-
ximity to JP-8 jet fuel who developed bilateral vestibulopathy
aer 3–5years of exposure. Serum studies in one of the patients
(Case 1) demonstrated JP-8 fuel metabolites 3-methylpentane

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Frontiers in Neurology | www.frontiersin.org May 2018 | Volume 9 | Article 351
and n-hexane (1). ese compounds are not present in human
blood normally. e levels of these metabolites diminish over
time once the individual is removed from repeated exposure.
Quantitative vestibular testing revealed bilateral vestibular
dysfunction in all three patients aer JP-8 exposure. ere was
no other probable identiable explanation for the vestibular
dysfunction. Although causal relationship cannot be deni-
tively proven yet, this collection of data suggests a relationship
between prolonged exposure to JP-8 fuel and development of
bilateral vestibular dysfunction which has not previously been
documented in humans.
The presence of bilateral vestibular dysfunction in these
cases may be due to a process localizing to the vestibular
ner ves, the vestibular end-organs, or a combination of both.
However, the constituent hydrocarbons in JP-8 are lipophilic
and have been shown to aect the CNS so a peripheral vestibu-
lar mechanism is assumed but not assured. Indeed, for Case 1
on whom we have long-term follow up, headaches and severe
fatigue have persisted for years, which are symptoms associated
with CNS hydrocarbon toxicity. A CNS toxicity contribution
might also explain the chronicity of symptoms and lackluster
res ponse to vestibular rehabilitative eorts. e relative
preservation of caloric vestibular responses (Table  1 ) in the
presence of prominent pan-frequency vestibular dysfunction
on rotational chair testing raises the possibility of some degree
of frequency-specic ototoxicity (9). Furthermore, improve-
ment in the caloric responses with removal from continued
exposure implies the possibility of some degree of reversibility
of vestibular dysfunction. Dedicated occupational studies in
humans on the vestibular eects of chronic JP-8 exposure are
limited and data are still sparse on the direct mechanisms of
ototoxicity due to jet fuel.
Human Studies
A study of the eects of low-level exposure to JP-8 fuel vapor in
U.S. Air Force aircra maintenance personnel found a correla-
tion between solvent exposure (benzene, toluene, xylene) and
increased postural sway implying vestibular or proprioceptive
impairment (3). Another study of 37 Air Force personnel with
short-term work day exposure to JP-8 did not identify increases
in postural sway (4). Long-term exposure to jet fuel in a subset
of eight subjects assessed by vestibular testing found minor ves-
tibular abnormalities but those patients actually reported more
cognitive symptoms than vestibular ndings (10).
Liquid hydrocarbon fractions are distilled from petroleum
based on density. Although there may be variations in composi-
tion, these hydrocarbon mixtures have toxic eects on the human
body similar to jet fuels (11). Some organic solvents com monly
used in commercial industries are also hydrocarbon mixtures and
would be expected to have similar toxicities. Indeed, dizziness,
sometimes but not always resulting in vestibular test abnor-
malities, is a common symptom among individuals exposed to
organic solvents (12). Workers exposed chronically to toluene
and ethanol for many years exhibited reduced pursuit tracking
and increased postural sway; and the latter suggests possible
impairment of vestibular function (13). A study of three weld-
ers with short-term exposure to hydrocarbons found vestibular
nystagmus and vestibular abnormalities that persisted for 3–18+
months aer exposure (14).
It has been suggested that aliphatic and aromatic hydrocarbon
toxicity may be associated with bilateral vestibular dysfunction,
dizziness, and abnormal performance on posturography testing
(3, 15). Although, organic solvents may have toxic eects on
peripheral vestibular function or brainstem vestibular pathways
(16), most of the data simply suggest increased sway in those
exposed, which is not necessarily a specic indicator of vestibu-
lar dysfunction. A small study of 18 individuals with exposure
to organic solvents found a signicantly greater number with
abnormal vestibular function including oVEMP and cVEMP,
and caloric testing when compared to unexposed controls. e
authors suggest that organic solvent toxicity may adversely aect
the function of the utricle and saccule to a greater degree than
hearing or semicircular canal function (17).
Animal Studies
Studies in rats exposed to JP-8 vapor for 6h per day, 5days per
week for a total of 1month showed that pure-tone hearing thresh-
olds, outer hair cell function, and hair cell numbers remained
unaected with exposure of 1,500mg/m3. However, when rats
were exposed to JP-8 plus noise, marked decreases in distortion
produce otoacoustic emissions amplitude, increases in pure-
tone auditory threshold along with a small reduction (<1%) in
the number of cochlear outer hair cells were detected (18, 19).
A study of 26 pigmented rats exposed to toluene in a prosptec-
tive cross-over control study found a dose-related reduction in
VOR suppression and reduced VOR gain and time constants
(20). Another study in rats exposed to 1,000mg/m3 of JP-8 found
impaired encoding of stimulus intensity both in rats exposed
only to JP-8 and in those exposed to JP-8 and noise. ere were
no changes in auditory thresholds and no loss of cochlear outer
hair cells; however, there was impaired brainstem encoding of
stimulus intensity indicating dysfunction of central auditory
processing (6, 8).
ere are no studies of the long-term eects of JP-8 specically
on peripheral vestibular function in humans. is may be in part
because many exposed personnel tolerate limited exposure well,
and those that do have symptoms have not been evaluated and
reported in published literature. Bilateral vestibular dysfunction,
regardless of cause, is probably under-recognized in clinical
medicine (21). Hence, the true incidence of vestibulopathy from
jet fuel exposure is unknown.
Human Exposure and Absorption
of Jet Fuel
Military duties such as fuel transportation, aircra fueling and
defueling, aircraft maintenance, cold aircraft engine starts,
main tenance of equipment and machinery, use of tent heaters,
and cleaning or degreasing with fuel may result in jet fuel expo-
sure. Fuel handlers, mechanics, ight line personnel, especially
crew chiefs, and even incidental workers remain at risk for
developing illness secondary to chronic JP-8 fuel exposure in
aerosol, vapor or liquid form. JP-8 is one of the most common
occupational chemical exposures in the US military (1). e Air

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Force has set recommended exposure limits for JP-8 at 63ppm
(447mg/m3 as an 8-h time-weighted average) (22).
In addition to exposure by JP-8 vapor inhalation, toxicity may
also occur by absorption through the skin, which is proportional
to the amount of skin exposed and the duration of exposure
(23, 24). In addition to the standard operating procedure and
safety guidelines, double gloving, immediate onsite laundering
of contaminated/soiled jumpsuits, regular washing of safety
goggles and masks, reduced foam handling time, smoking
cessation, adequate cross ventilation, and frequent shi breaks
may reduce the overall risk of JP-8 induced illness (1, 2).
At this time, OSHA has not determined a legal limit for jet fuels
in workroom air. e U.S. National Institute of Occupational
Safety and Health set a recommended limit of 100mg/m3 for
kerosene in air averaged over a 10-h work day. Multi-organ
toxicity has been documented from JP-8 exposure in animal
experiments over the past 15years. More recently, toxicology
researchers are investigating the adverse tissue eects of JP-8 jet
fuel in concentrations well below permissible exposure limits.
Ultimately, the new data may help us to better understand the
emerging genetic, metabolic and inammatory mechanisms
underpinning JP-8 cellular toxicity—including auditory and
vestibular toxicity—and lead to a reassessment of the safe JP-8
exposure limits (25, 26). In the meantime, bedside vestibular
screening for vestibular dysfunction can be performed by
dynamic visual acuity testing or by head impulse testing.
Are there any known JP-8 biomarkers? Yes. Breath, blood,
urine, and microRNA tissue biomarkers have been studied and
aid in conrming JP-8 exposure. Self-reported JP-8 exposure in
the workplace is a reliable indicator and a stronger predictor
of measured exposure than job title (27). Aer controlling for
work shi smoking, measurements of blood volatile organic
compounds (ethylbenzene, toluene, xylene) are higher among
US Air Force personnel self-reporting JP-8 exposure in asso-
ciation with elevated hydrocarbons in the breathing zone (28).
Urinary biomarkers 1- and 2-naphthol, the metabolites of naph-
thalene, are the most sensitive and useful short-term surrogates
of JP-8 exposure due to their strong correlation with breathing
zone naphthalene, greater abundance, and slower elimination
kinetics (29, 30). Blood microRNAs (miRNAs) may be unique
biomarkers for volatile organic compounds and have been com-
pared recently to urinary biomarkers in human dockyard work-
ers found to have toluene, xylene, and ethylbenzene in whole
blood. Fiy subjects underwent miRNA microarray analysis
and 211–695 mRNAs were identied for toluene, xylene, and
ethylbenzene suggesting higher sensitivity, specicity, and accu-
racy than urinary biomarkers (31). e analysis of circulating
miRNAs in the blood of military veterans exposed to JP-8 is
worthy of future research.
CONCLUSION
Bilateral vestibular dysfunction in these three patients with pro-
longed vapor and dermal JP-8 fuel exposure should raise aware-
ness in people with occupations that expose them to jet fuels,
liquid hydrocarbons, or organic solvents. Dizziness and mild
imbalance may be the main initial symptoms. Early recognition
and limiting further exposure as well as treatment with vestibular
therapy (32) may improve their function and quality of life.
ETHICS STATEMENT
Written informed consent to publish the report was obtained from
each patient. is report was approved by the local Institutional
Review Board at Barrow Neurological Institute/DignityHealth,
Inc., case series tracking number Case Series 18-004.
AUTHOR CONTRIBUTIONS
TF attended to the three patients in oto-neurological consulta-
tion, contributed to project conception, data collection and anal-
ysis, critical revision, and nal approval of the manuscript. MR
contributed to project conception, scientic poster presentation,
data collection and analysis, draing of the article and critical
revision, and nal approval of the manuscript. KriS contributed
to draing of the article and critical revision and nal approval
of the manuscript. KaS contributed to critical revision and nal
approval of the manuscript.
ACKNOWLEDGMENTS
e authors wish to thank Dana L. Day, AuD for obtaining the
vestibular laboratory data; John B. Sullivan, Jr.,; Mark L. Witten,
Laurence D. Fechter, and O’neil W. Guthrie for their personal
explanations and insights on JP-8 research; Terence Risby, at the
University of Arizona Health Sciences Department of Toxicology.
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