National Academies Press: OpenBook
« Previous: Appendix B JP-8 Final Risk Assessment: Contents, Executive Summary, and Introduction (TIEHH 2001)
Suggested Citation:"Appendix C." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 201
Suggested Citation:"Appendix C." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 202
Suggested Citation:"Appendix C." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 203
Suggested Citation:"Appendix C." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 204
Suggested Citation:"Appendix C." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 205
Suggested Citation:"Appendix C." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 206
Suggested Citation:"Appendix C." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 207

Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Appendix C

Review of Tests Assessing Neurologic Function in Persons Exposed to Jet Fuels This appendix described four types of tests that have been used to assess the neurotoxicity potential of jet-propulsion fuel 8 and related fuels in humans: clinical neurological examinations, posturograms, nerve conduction studies, vibration sensation studies, and blink reflex classical conditioning studies. For each test, a critical analysis of its use in assessing neurotoxicity from exposure to jet fuels is presented. Limitations of these tests are also presented. CLINICAL NEUROLOGIC EXAMINATIONS Neurological examinations of 29 aircraft factory workers chronically exposed to jet fuel vapors revealed findings consistent with central and periph- eral nervous system involvement (Knave et al. 1976). The exposed subjects were classified into two groups: heav ily exposed (n = 13) and less heavily exposed (n = 16). Subjects from both groups (all of the heavily exposed workers and 7 of the 16 less heavily exposed workers) reported having repeat- edly experienced acu te effects of jet fuel exposure such as dizziness, headache, nausea, respiratory tract symptoms, heart palpitations, and a feeling of pres- sure on the chest. Symptoms indicative of peripheral neuropathy included mu scle cramps, distal paresthesias, numbness, and paresis. Signs indicative of peripheral neuropathy on clinical neurological examination included re- 202

Appendix C 203 duced sensory perception particularly of pain and temperature sense among the subjects from the heavily exposed group. A high rate of symptoms indica- tive of CNS involvement (neurasthenia and psychasthenia) was also observed in the two exposed groups on comparison with the reference groups. POSTUROGRAM Posturogram measures spontaneous body sway, which is considered to be a quantitative version of the Romberg test, which is a simple clinical test of the integrated postural pathways and mechanisms (i.e., peripheral nerve fibers, spinal cord pathways, vestibular system components, and the cerebellum). The posturogram is a way of measuring a person's ability to maintain an up- right posture against variable perturbatio ns. Perform ance on posturogram is a function of gender, age, and vision (Kollegger et al. 1992; Black et al. 1982; Thyssen et al. 1982). Various posturography techniques are available to pro- vide quantitative measures. Posturogram performance deficits have been associated with exposures to various solvents including toluene, xylene, and jet fuel (Sm ith et al. 1997; Y okoyam a et al. 1997). The validity and reliability of the posturogram as a measure of central and peripheral nervous system function has been demonstrated in various studies. Posturogram findings have been shown to positively correlate with other measures of vestibular function such as positional nystagmus demonstrating the validity of this test (Kubo et al. 1990). Studies in subjects who consumed ethanol immediately before testing showed disturbances in body sway that correlated with the amount of ethanol consumed indicating that this test is a sensitive and valid measure of CN S dysfunction induced by neurotoxicants that are known to affect balance and the severity of the deficit can reflect the exposure dose (M ills and Bisgrove 1983; Lukas et al. 1989; Kubo et al. 1989). Studies by Benvenuti et al. (1999) dem onstrated the consistency of posturo- gram findings on test-retest among geriatric subjects with disequilibrium dem- onstrating the reliability of this test as well as its validity. Although the results of a study by Uimonen et al. (1995) indicate that the posturogram of a malingerer can be differentiated from that of a subject with vestibular neuritis by body sway velocity, these findings should be interpreted with caution. The administration of neuropsychological tests sensitive to malingering and motivation such as the Test of Mem ory and Motivation (TOMM) can be administered along with the posturogram and other conven- tional tests of neurological function to further differentiate those patients with a true performance deficit from those with deficits induced by factors such as secondary gain. Patients involved in litigation who have abnormal TOMM

204 Appendix C scores and abnormal posturograms may have motivational influences that are affecting their performances. Unfortunately, although the sensitivity of posturography is relatively high, the specificity of this test as a measure of neurotoxicant exposure-induced effects is relatively low as it reveals deficits due to many factors (e.g., diabetes and head injury). Thus, the findings on posturogram must also be interpreted in light of their correlation with other measures of neurophysiological and neuropsychological function as well as with the patient’s medical history and his or her history of neurotoxicant exposure to parse out the locus of the lesion (i.e., central v. peripheral). For example, the Digit Symbol Test is a neuropsychological measure of psychomotor function that has been shown to positively correlate with posturography findings among patients exposed to ethanol and central acting pharmaceuticals (Lukas et al. 1989; Allen and Lader 1992). Nerve conduction studies have been shown to positively corre- late with posturography findings among patients with diabetic neuropathy (Uccioli et al. 1995). In conclusion, posturography is a reasonable test to use to corroborate with data from neurophysiological and neuropsychological tests but perfor- mance on this test cannot be relied upon exclusively to establish exposure limits for neurotoxicants encountered in the workplace. NERVE CONDUCT ION STUDIES Peripheral neuropathy has been reported in subjects exposed to various solvents including n-hexane and jet fuels. Neurological and neurophysiological examinations of 29 aircraft factory workers chronically exposed to jet fuel vapors findings consistent with peripheral neuropathy (Knave et al. 1976). The exposed subjects were classified into two groups: heavily exposed (n = 13) and less heavily exposed (n = 16). Clinical neurological examinations, nerve conduction velocities studies, and assessments of vibration sensation thresholds were perform ed on all subjects. All subjects in the heavily exposed group and 7 of 16 from the less heavily exposed reported having repeatedly experienced acute effects such as dizziness, headache, nausea, respiratory tract symptom s, heart palpitations, a feeling of pressure on the chest during expo- sures to jet fuel vapors in their 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 com bined in comparison with reference groups. Nerve conduction studies have been used extensively to study peripheral nerve function. These tests have been shown to be valid marker of nerve damage and a correlated with pathological findings. These tests have been

Appendix C 205 shown to be reliable with good retest reliability and good interrator reliability due to established normal values and stringent testing procedures and proto- cols (Kimura 2001). Based on its review of the literature, the subcommittee concludes that nerve conduction studies are a good marker of neurological injury due to exposures to neurotoxicants and that the findings from this test can be relied upon to establish occupational and environmental exposure limits. VIBRATION SENSATION Vibration sensation thresholds were used to assess functioning in 29 aircraft factory workers chronically exposed to jet fuel vapors and who re- ported symptoms consistent with peripheral neuropathy (Knave et al. 1976). The exposed subjects were classified into two groups: heavily exposed (n = 13) and less heavily exposed (n = 16) and were com pared with unexposed controls. Comparison of the subjects from the high-exposure group with controls revealed significant differences on vibration sensation thresholds. The vibration sensation test is purported to be a quantitative measure of perception of a vibrating stimulus. It is used to see if a person can volitionally tell the examiner when a stimulus is first perceived. It is intended to reveal impairment in the ability of a peripheral nerve to conduct an impulse. If the subject has a high threshold for this test, it is suggested by the amount of time the subject requires for acknowledging his/her perception of the stimulus. This test is subject to embellishment by the examinee and to observer bias by the test ad ministrator. Such impairments detected on screening tests such as this must be correlated w ith other more objective tests for evidence of periph- eral neuropathy such as nerve conduction velocities, tendon reflex responses, and patterns of sensory loss detected by pin prick perception. In conclusion, the subcommittee’s review of the literature suggests that the use of this test to assess peripheral nerve function among persons exposed to neurotoxicants is reasonable if corroborated with data from conventional validated neurophysiological tests. However, performance on this test cannot be relied upon by itself to establish exposure levels for neurotoxicants. BLINK REFLEX CLASSICAL CONDITIONING The use of blink reflex classical conditioning to investigate motor learning in subjects exposed to neurotoxicants has been suggested. Bekkedal et al. (2001) reported that the blink reflex conditioning response may be affected by exposure to JP-8. It has been shown that the cerebellum is involved in the

206 Appendix C acquisition of motor skills and procedural learning (Corkin 1968; Sanes et al. 1990; Laforce and Doyon 2001). The data reviewed indicate that the blink reflex classical conditioning test is a valid marker of cerebellar function (Bracha et al. 1997; Glocker et al. 1999; Sears et al. 2000; Somm er et al. 2001). However, there are few com prehensive studies supporting the validity of this test by showing that it correlates positively with other measures of motor function and does not correlate positively w ith irrelevant measures (Somm er et al. 2001). Furthermore, the interrator reliability and test-retest reliability have not been fully established for this test. In addition, it has not been shown that this test would be practical to use from both a cost and risk versus benefits perspective in research studies. The subcomm ittee concludes that the use of this test to assess cerebellar function among persons exposed to neurotoxicants is reasonable, but the data shou ld not be relied upon exclusively and must be corroborated with data from conventional validated neuropsychological and neurophysiological tests particularly if it is to be used to establish exposure levels for neurotoxicants. REFERENCES Allen, D., and M. Lad er. 1992. The interactions of ethanol with single and repeated doses of suriclone and diazepam on physio logical and psychom otor functions in normal subjects. Eur. J. Clin. Pharmacol. 42(5):499-505. Bekkedal, M.Y.V., S.M. McInturf, G.D. Ritchie, and J. Rossi III. 2001. Eyeblink conditioning response test used to assess performance in JP-8 exposed air force personn el. Pp. 69-71 in JP 8 Final R isk Assessment. T he Institute of Environ- mental and Human Health (TIEHH), Lubbock, TX. August 2001. Benvenuti, F., R. Mecacci, I. Gineprari, S. Bandinelli, E. Benvenuti, L. Ferrucci, A. Baroni, M. Rabuffe tti, M. Hallett, J.M. Dambrosia, and S.J. Stanhope. 1999. Kinem atic characteristics of standing disequilibrium: Reliability and validity of a posturographic protocol. Arch. Phys. Med. Rehabil. 80(3):278-287. Black, F.O., C. Wall III, H.E. Rockette Jr., and R. Kitch. 1982. Normal subject pos- tural sway during the Romberg test. Am. J. Otolaryngol. 3(5):309-318. Bracha, V., L. Zhao, D.A. Wunderlich, S.J. Morrissy, and J.R. Bloedel. 199 7. Patients with cere bellar lesions cannot acquire but are ab le to re tain conditioned eyeblink reflexes. Brain 120(Pt 8):1401-1413. Corkin, S. 1968. Acquisition of m otor skill afte r bilateral m edial tem poral-lobe exci- sion. Neuropsycologia 6(3):255-265. Glocker, F.X., M. Lauk, D. Foll, B. Koster, B. Guschlbauer, J. Tim mer, G . Deuschl, and C.H. Lucking. 1999. Classical conditioning of the electrically elicited blink reflex in humans: A new method of data analysis. J. Neurosci. Methods 89(2): 133-140.

Appendix C 207 Kimura, J. 2001. Electrodiagnosis in Diseases of Nerve and Muscle: Principles and Practice, 3rd E d. New York: O xford U niversity Press. Kollegger, H., C. Baum gartner, C. Wo ber, W. O der, and L. Deecke. 1992. Spontane- ous body sway as a function of sex, age, and vision: Posturograp hic stu dy in 30 healthy adults. Eur. Neurol. 32(5):253-259. Knave, B., H.E. Persson, J.M. Goldberg, and P. W esterholm. 1976. Long-term expo- sure to jet fu el: An investigation on occupationally exposed workers with special reference to the nervous system. Scand. J. Work Environ. Health 2(3):152-164. Kubo, T., Y. Sakata, T. Matsunaga, A. Koshim une , S. Sakai, K . Ameno, and I. Ijiri. 1989. Analysis of body sway pattern after alcohol ingestion in hum an subjects. Acta Otolaryngol. 468(Suppl):247-252. Kubo, T., Y. Sakata, A. Koshimune, S. Sakai, K. Ameno, and I. Ijiri. 1990. Positional nystagmus and body sway after alcohol ingestion. Am. J. Otolaryngol. 11(6):416- 419. Laforce Jr., R., an d J. D oyon. 2001. Distinct contributio n of th e striatum and cere bel- lum to motor learning. Brain Cogn. 45(2):189-211. Luka s, S.E., B.W. Lex, J.P. Slater, N.E. Greenwald, and J.H . Me ndelson . 1989. A microanalysis of ethanol-induced disruption of body sway and psychomotor performance in women. Psychopharmacology (Berl) 98(2):169-175. Mills, K.C., and E.Z. Bisgrove. 1983. Body sway and divided attention performance under the influence of alcohol: Dose-response differences between males and females. Alcohol Clin. Exp. Res. 7(4):393-397. Sanes, J.N., B. Dimitrov, and M. Hallett. 1990. Motor learning in patients with cere- bellar dysfunction. Brain 113(Pt 1):103-120. Sears, L.L., N.C . Andreasen , and D.S . O'L eary. 2000. C erebellar functional abnormal- ities in schizophrenia are suggested by classical eyeblink condition ing. Biol. Psy- chiatry 48(3):204-209. Smith, L.B., A. Bhattacharya, G. Lem asters, P. Succop, E. Puhala II, M. Medvedovic, and J. Joyce. 1997. Effect of chronic low-level exposure to jet fuel on postural balance of US Air Force personnel. J. Occup. Environ. Med. 39(7):623-632. Som mer, M., J. Grafm an, I. Litvan, and M. Hallett. 2001. Im pairmen t of eyeblink classical conditioning in progressive supranuclear palsy. Mov. Disord. 16(2):240- 251. Thyssen, H.H., J. Brynskov, E.C. Jansen, and J. Munster-Swendsen. 1982. Normal ranges and reproducib ility for the quan titative Romberg's test. A cta N eurol. Scand 66(1):100-104. Uc cioli, L., P.G. Giacomini, G. Monticone, A. Magrini, L. Du rola, E . Bruno, L . Parisi, S. Di G irolamo, and G . Menzinger. 1995. Body sw ay in diabetic neuro pathy. Diabetes Care 18(3):339-344. Uimonen, S., K. Laitakari, H. Kiukaanniemi, and M. Sorri. 1995. Does posturography differentiate malingerers from vertiginous patients? J. Vestib. Res. 5(2):117-124. Yokoyama, K., S. Araki, K. Murata, M. Nishikitani, K. Nakaaki, J. Yokota, A. Ito, and E. Sakata. 1997. Postural sway frequency analysis in workers exposed to n-hex- ane, xylene, and toluene: Assessment of subclinical cere bellar dysfunction. Envi- ron Res. 74(2):110-115

Toxicologic Assessment of Jet-Propulsion Fuel 8 Get This Book
×
Buy Paperback | $55.00 Buy Ebook | $43.99
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

This report provides a critical review of toxicologic, epidemiologic, and other relevant data on jet-propulsion fuel 8, a type of fuel in wide use by the U.S. Department of Defense (DOD), and an evaluation of the scientific basis of DOD's interim permissible exposure level of 350 mg/m3

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  6. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  7. ×

    View our suggested citation for this chapter.

    « Back Next »
  8. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!