Document pmxo5jRyE8BEgGOakbxvGKXK6

*4^. =/-* *^:=V, ^Bi)'i.OfefeK.^~ - ,'~'&5&t?*'r-;- I .: - w-r"'-: *; J. TOXICOL.-CUN. TOXICOL., 19(1), pp. 27-34 (1982) - '? rteieSrv / Paraoccupational Exposure to Mixed Solvents EDWARD L. BAKER, MD, MPH Occupational Health Program Harvard School of Public Health Boston University School of Medicine Boston, Massachusetts 02118 ROBERT G. FELDMAN, MD Department of Neurology Boston University School of Medicine Harvard School of Public Health Boston, Massachusetts 02115 ABSTRACT Exposure to solvent vapors resulted in a sensory neuropathy and mild encephalopathy in a 44-yr-old female cook. The route of ex posure was unusual: a ventilation system cross-connection between her restaurant and an adjacent upholstery shop. Possible "para occupational" exposures should be sought in cases of neurologic or other unexplained symptoms possibly caused by toxic substances. The role of solvent mixtures in the genesis of nervous system dis orders is reviewed. Exposure of persons to toxic materials within the work place or from adjacent sources may contribute to the development of certain neurologic disorders. Syndromes of "paraoccupational illness" have been seen in persons living or working near plants handling toxic Cop\ right 1^82 b> Marcel Dekkcr, Inc, 27 SL 033907 f JH 4-* m ill -.... -- zKZs'--'?' "'.i<'-c^- "'("_ * _^-. -ir- j ' ' ~':\a ''S^gSgl --- c`"*E5r^.W-*ti "V'lU.^C 28 BAKER AND FELDMAN substances or in families of workers who are indirectly exposed to toxic dust carried home on workers' clothing. Persons living near lead, zinc, and copper smelters have been shown to have increased absorption of heavy metals emitted by the smelters [1-3] and to suffer neuropsychologic damage [2, 4]. Children of workers employed in secondary lead smelters and in battery plants have been found to have excessive lead absorption and even overt lead poisoning following ex posure to lead dust carried home on parents' clothing [5-7]. Further more, family members of workers employed in the beryllium and as bestos industries have been found to have developed berylliosis [8] and mesothelioma [9] from similar paraoccupational exposures. This re port describes the development of sensory neuropathy and mild en cephalopathy in a woman with unwitting recurrent paraoccupational ex posure to a mixture of volatile solvents. CASE HISTORY The patient, a 44-yr-old woman, began work as a cook in a familyowned restaurant in October 1975. In February 1976 she began to notice unusual odors in the vicinity of her work area and stove where she spent 1C to 15 h per day preparing food. At this time she also be gan to notice headaches, dizziness, difficulty in coordination, nausea, and diarrhea. These symptoms persisted until April 1977 when she began to notice, in addition, intermittent burning paresthesiae of the face, hands, legs, and back. She also noted during this period persis tent fatigue, lethargy, and feelings of depression and anxiety. She ceased working in the restaurant in April 1977, and medical evaluations described below were performed during the subsequent 2 yr. After removal from exposure, she noted a gradual reduction in the frequency of episodes of burning paresthesiae and did not experi ence further symptoms of nausea, headache, dizziness, or diarrhea. Difficulty in coordination persisted. The depressive symptoms con tinued despite psychotherapy and several drug-treatment regimens. She did not experience significant muscie weakness during the course of her illness. She also denies having had any numbness or loss of sensation in her extremities. There is a negative history of excessive alcohol consumption, diabetes, or trauma to her extremities. There is no family history of neurologic disease. Neurologic Examinations Serial neurologic examinations performed between 1977 and 1979 revealed no abnormality in cranial nerve function, tendon reflexes, or tests of coordination. Vibration sensation was variably reduced in the legs. Sensation to pinprick was reduced in a patchy distribution over PARAOCCUPATIC | TABLE L Result Nerve parameter Right Median N. Motor C.V. (M/s) Right Peroneal N. Motor C.V. (M/s) Right Sural N. Sensory C.V. (M/ Amplitude (uv) the forearms and laboratory testing prandial blood glu | 1977 showed no at status were not dc marked deficits it responses. Electrodiagnc I Electrodiagnos August 1977 and 1 of a mild sensory tentials and slowe city, which were the subsequent ex exposure. Electr generation were n the lower extremi tern in the extens muscles, increase insertional activit tensor digitorum Environment Investigations usual odor deteett to arise from an ing and which sha The odor was ide SL 033908 JV's-.' `5-i- . ff&i -T-v j.. -- PARAOCCUPATIONAL EXPOSURE TO MIXED SOLVENTS 29 TABLE 1. Results of Nerve Conduction Studies Nerve parameter Study 1 (8-15-77) Control values Study 2 (6-30-78) Right Median N. Motor C.V. (M/s) Right Peroneal N. Motor C.V. (M/s) Right Sural N. Sensory C.V. (M/s) Amplitude (uv) 55 44 Absent Absent 57.2 2.0 51.0 4.7 51.0 39.0 64 54 45.5 14 the forearms and legs. Sensation of position was normal. Clinical laboratory testing revealed normal hematologic studies and 2-h post prandial blood glucose determinations. An electroencephalogram in 1977 showed no abnormalities although obvious disturbances in mental status were not detected. Formal neuropsychological testing revealed marked deficits in sustained attention, particularly for visual motor responses. Electrodiagnostic Peripheral Nerve Studies Electrodiagnostic peripheral nerve studies were performed in August 1977 and in June 1978. These studies (Table 1) show evidence of a mild sensory neuropathy as evidenced by absent sural nerve po tentials and slowed median and peroneal motor nerve conduction velo city, which were noted in the first examination, and improvement of the subsequent examination performed 9 months after removal from exposure. Electromyographic signs of denervation and motor unit re generation were noted during the last examination in the muscles of the lower extremities. These consisted of reduced interference pat tern in the extensor digitorum brevis, gastrocnemius, and hamstring muscles, increased number of polyphasic potentials with increased insertional activity and bizarre high frequency discharges in the ex tensor digitorum brevis muscle. Environmental Studies Investigations were performed to document the source of the un usual odor detected in the patient's work area. The odors were found to arise from an upholstery shop which was located in the same build ing and which shared a common ventilation system with the restaurant. The odor was identified as caused by an aerosol lacquer used in the .^v,-z , V->- -?crr' 30 BAKER AND FELDMAN upholstery operation. It appeared that the ventilation system hood, which operated over the stove where the patient cooked, was convey ing fumes to the area where the patient worked. The lacquer com pound was analyzed and found to contain a mixture of 7% resin solids, 43% solvents, and 50% propellent. The solvent was a mixture of esters, ketones, alcohols, and hydrocarbons. Among these were toluene, methyl isobutyl ketone, and ethyl acetate. An air sample was taken over a period of 10 min during which 3 min of spraying with the lacquer took place. The effect was a noticeably strong odor. Ethyl acetate, methyl ethyl ketone, and isopropyl alcohol were identi fied as well as other nonspecified hydrocarbons. An on-site visit focused on potential air exchange routes between the upholstery shop and the restaurant. Two basic direct air paths were identified. One was the single heating and ventilation system which served both the restaurant and the upholstery shop. The single central heating unit and fan system serving both tenants encouraged mixing of air from one side of the building to the other during normal fan operation. A second possible route of air transfer between sides of the building was the return duct system which had back-to-back openings on the bottom of the wall separating the two business estab lishments. The openings connected immediately below the floor to form a single return duct. Under normal fan operation, both return ducts were maintained at negative pressure to both rooms, causing air to be drawn continually into the return vent from each room to the fans, mixed, and returned to the supply ducts when the ventilation fan was on. However, at the time the odors were most noticeable, a ven tilation hood system over the stove was in place, producing a negative pressure in the kitchen area. The heat of the stove added to the nega tive draft effect, drawing air containing vapors from the solvents into the restaurant kitchen. DISCUSSION An indirect route, paraoccupational, of toxic exposure leading to the development of a peripheral neuropathy and a mild encephalop athy is described in this report. The association of central nervous system symptoms with acute exposure to solvents is well recognized [24]. That the symptoms and signs in the patient resolved almost completely after removal from exposure to the solvents is consistent with the findings of previous studies of solvent-induced neuropathy [10, 13]. Exposure to mixtures of volatile industrial solvents is extremely frequent in industry. Reports of peripheral neuropathy following ex posure to solvents are not uncommon [9, 18]. The term "mixed sol vent neuropathy" may be used to describe the syndrome characterized by insidious distal, symmetrical sensory, and motor impairment fol lowing exposure to mixtures of industrial solvents in which a specific SL 033910 ' ''J * .i-T- ~y^::ZXJ i:-C PARAOCCUPATION. | neurotoxic chemical ous absorption appea specific substances insult, the complexit the particular offend Substances comm xylene, butyl acetate | alcohol, nitropropam panol, pentane, hepta stances were found 1 case reports have in neurotoxic potential, neurotoxic effects is used singly or in con I to cause peripheral s butyl ketone [10, 11], | bon disulfide [16], ar I toxic effects may be ' may not be listed In i tiation of the neuroto another solvent (met appears likely that tt solvent mixtures ma; formulations whose i toxicity may exhibit i combined. Many solvents, inc toms of lightheadednt | nausea. The acute s: noticing unusual odor acute solvent toxicity lethargy, and signs o; tests are symptoms e associated with chror In a recent study c j ture of solvents, Sepp paired nerve conduct!I vealed exposure to a isobutyl ketone, and t was exposed. In that nerve testing has bee tion of toxic peripher. Such studies were qui measure of periphera cessation of neurotox A nerve biopsy wa of Means et aL [25] a the course of her illn< tron microscopic patl -IBr-' r% -tv^uS---'' ----- SkA^S 'if _ ---^rt^eTj1 * +< PARAOCCUPATIONAL EXPOSURE TO MIXED SOLVENTS 31 neurotoxic chemical is not identified. Both inhalation and percutane ous absorption appear to be important routes of exposure. Although specific substances are undoubtedly responsible for the neurologic insult, the complexity of the exposure often makes identification of the particular offending agents impossible. Substances commonly contained in such mixtures include toluene, xylene, butyl acetate, methyl isobutyl ketone, n-heptanone, isobutyl alcohol, nitropropane, isopropyl acetate, isobutyl isobutyrite, isopro panol, pentane, heptane, and acetone [9, 18, 19]. Some of these sub stances were found in the environment of this case. Although isolated case reports have indicated that agents from this group may have neurotoxic potential, clear evidence linking specific substances with neurotoxic effects is lacking. In contrast, several other solvents, used singly or in combination in industry, have been shown definitively to cause peripheral and central nervous system damage: methyl nbutyl ketone [10, 11], n-hexane [12, 13], trichlorethylene [14, 15], car bon disulfide [16], and ethanol [19], These agents with known neuro toxic effects may be present in solvent mixtures as contaminants and may not be listed in the product1 s chemical formulation. Since poten tiation of the neurotoxic effect of a solvent (methyl butyl ketone) by another solvent (methyl ethyl ketone) has been demonstrated [20], it appears likely that the neurotoxic potential of certain constituents of solvent mixtures may be enhanced by metabolic interactions. Thus formulations whose individual constituents have relatively little neuro toxicity may exhibit significant effects when these constituents are combined. Many solvents, including toluene, are associated with acute symp toms of lightheadedness, difficulty in coordination, and occasionally nausea. The acute symptoms, experienced by this patient when first noticing unusual odors in February 1976, were quite likely due to acute solvent toxicity. The associated systemic symptoms of fatigue, lethargy, and signs of encephalopathy detected on neuropsychological tests are symptoms also seen in persons with peripheral neuropathy associated with chronic solvent exposure. In a recent study of Finnish automobile painters exposed to a mix ture of solvents, Seppalainen and associates [9] found evidence of im paired nerve conduction velocity. Environmental measurements re vealed exposure to a mixture of solvents including toluene, methyl isobutyl ketone, and butyl acetate, substances to which our patient was exposed. In that study and others, electrodiagnostic peripheral nerve testing has been shown to be particularly useful in the evalua tion of toxic peripheral neuropathies [9, 10, 13, 14, 16, 17, 21-23]. Such studies were quite helpful in our case in providing an objective measure of peripheral nerve function that was seen to improve after cessation of neurotoxin exposure. A nerve biopsy was not performed in our case but the observations of Means et al. [25] are helpful in explaining the pathophysiology of the course of her illness and recovery. They studied light and elec tron microscopic pathology of sural nerve biopsy specimens as well si 339U V 32 BAKER AND FELDMAN as the central and peripheral nervous system from an autopsy of a patient who abused solvents. Isolated teased nerve fibers showed prominent focal paranodal axonal swellings. Segmental demyelination was infrequent; the predominant abnormality was retraction and thin ning of the myelin sheath surrounding the nodes of Ranvier. Electron microscopy revealed neurofilament accumulation in the myelinated axons. Changes in anterior horn cells were taken as evidence of the "dying back" process characteristic of solvent neuropathies [11, 26, 27], Although some deterioration in peripheral nerve function, an apparent delayed effect, may be seen within a few months after re moval from exposure, reevaluation 1 yr later consistently shows im provement in nerve conduction parameters. Complete recovery may not ever occur after axonal degeneration. Sensory nerve conduction velocities measured in the sural nerves of the patient revealed slow ing consistent with axonal changes. These changes were most strik ing, although relative differences in motor conduction velocities be tween 1977 and the later studies of 1979 provide further evidence of peripheral neuropathy. This report emphasizes the important observation that toxic ex posure may emanate from beyond the immediate work environment, thus requiring an extensive search to identify the source. The result of such exposure by our patient was neurotoxic effects of mixed sol vents in the form of neuropathology and mild encephalopathy. REFERENCES P. J. Landrigan et al., Epidemic lead absorption near an ore smelter, N. Engl, J. Med., 292, 1 (1975). P. J. Landrigan et aL, Increased lead absorption with anemia and slowed nerve conduction in children near a lead smelter, J, Pediatr., 89, 904 (1976). [3] E. L. Baker et aL, A nationwide survey of heavy metal absorp tion in children living near primary copper, lead, and zinc smelters, Am. J. Epidemiol., 106, 261 (1977). [*} P. J. Landrigan, E. L. Raker, HTk. Whitworth, and R. G. Feld man, "Neuroepidemiologic Evaluations of Children with Chronic Increased Lead Absorption," in Proceedings of Seminal of Low Level Lead Exposure in Children: The Clinical Implications of Current Research, Raven, New York, I960. [5] . L. Baker et al., Lead poisoning in children of lead workers: Home contamination with industrial dust, N. Engl. J. Med., 296, 260 (1977). [6] W. N. Watson, L. E. Witherell, and G. C. Giguere, Increased lead absorption in children of workers in a lead storage battery plant, J. Occup. Med., 20, 759 (1978). [7] M. Eisenbud et aL, Non-occupational berylliosis, J. Ind. Hyg. Toxicol., 31, 282 (1949). si. 033912 PARAOCCUPATIONAI | [8] H. A. Anderson hold Exposure to (Conference of Cl [9] A. M, Seppalaine logical effects ol solvents, Scand. [10] N. Allen et al., C ketone. An indue [11] P, S. Spencer, H. haar, Nervous s: solvent methyl-n [12] Y. Yamamura, n Neurol. Jpn., 23, [IS] M. lida, Y.~ Yarns and conduction v* i graphy, 9, 247 (: I [14] ft. G. Feldman, I eral neurotoxic i (1970). [15] R.`G. Feldman, ' Neurology, VoL (P. J.Vinken an 1979, p. 457. [16] T. C. Tuttle, G. ' Neurological Evs p&iJe "(C&"), USE ton, E.C., 1976. [17] L. D. Prockop, h Am, Med. Assoc [18] G. Abbritti et at aetlological prob [19] L. D. Prockop, ' tlon of Industrial Solvents (C. W. al Institute on D: [20] K. Saisa, J. R. 1^ changes induced pathoL Exp. Neu: [21] R. G. Feldman, 1 pathy in adults [22] P. M. LeQuesne and minimal toxi [23] A. M. Seppalaine in occupational Health, 1, 1 (19 [24] E. Browning, T< Chemical Publist [25] E. D. Means, L "" t.W- *-" tasmt PARAOCCUPATIONAL EXPOSURE TO MIXED SOLVENTS 33 [8] H. A. Anderson et aL, Asbestos-Related Disease from House hold Exposure to Occupational Dusts, Presented at American Conference of Chest Physicians, New Orleans, 1974. [9] A. M. Seppalainen, K. Husman, and C. Martenson, Neurophysio logical effects of long-term exposure to a mixture of organic solvents, Scand. J. Work Environ. Health, 4, 304 (1978). [10] N. Allen et al., Toxic polyneuropathy due to methyl-n-butylketone. An industrial outbreak, Arch. Neurol., p. 209 (1975). [11] P. S. Spencer, H. H. Schaumburg, R. L. Raleigh, and C. J. Terhaar, Nervous system degeneration produced by the industrial solvent methyl-n-butyl ketone, Arch. Neurol., 32, 219 (1975). [12] Y, Yamamura, n-Hexane polyneuropathy, Foiia"Psychiatr. Neurol. Jpn., 23, 45 (1969). [13] M. lida, yTYamamura, and L Sobue, Electromyographic findings and conduction velocity in n-hexane polyneuropathy, Electromyo graphy, 9, 247 (1969). [14] R. G. Feldman, R. F. Mayer, and A. Taub, Evidence for periph eral neurotoxic effect of trichlorethylene. Neurology, 20, 599 (1970). [15] R. G. Feldman, "Trichlorethylene," in Handbook of Clinical Neurology, Vol. 36, Intoxications of the Nervous System, Part I (P. J. Vinken and G. W. Bruyn, eds.), North-Holland, Amsterdam, 1979, p. 457. [16] T. C. Tuttle, G. C. Wood, and C. B. Grether, Behavioral and Neurological Evaluation of Workers Exposed to Carbon Disul phide (CSi); USDHEW (NIOSH) Publication No. 77-128, Washing ton, >.C., 1976. [17] L. D. Prockop, M. Alt, and J. Tison, "Huffer's" neuropathy, J. Am. Med. Assoc., 229, 1083 (1974). [18] G. Abbritti et al., Shoemakers' polyneuropathy in Italy: The aetiological problem, Br. J. bid. Med., 33, 92 (1976). [19] L. D. Prockop, "Nervous System Damage Secondary to Inhala tion of Industrial Solvents," in Voluntary Inhalation of Industrial Solvents (C. W. Sharp and L. T. Carroll, eds.), USDHEW, National Institute on Drug Abuse, Rockville, Maryland, 1978, p. 198. [20] K. Saisa, J. R. Mendell, and H. S. Weiss, Peripheral nerve changes induced by MBK and potentiation by MEK, J. Neuro- pathol. Exp. Neurol., 35, 207 (1976). [21] R. G. Feldman, M. K. Hayes, and F. D. Aldrich, Lead neuro pathy in adults and children, Arch. Neurol., 34, 481 (1977). [22] P. M. LeQuesne, Neurophysiological investigation of subclinical and minimal toxic neuropathies, Muscle Nerve, 1, 392 (1978). [23] A. M, Seppalainen, Applications of neurophysiological methods in occupational medicine. A review, Scand. J, Work Environ. Health, 1, 1 (1975). [24] E. Browning, Toxicity and Metabolism of Industrial Solvents, Chemical Publishing Co., hJew York, 1965. [25] E. D. Means, L. D. Prockop, and G. S. Hooper, Pathology of St- 033913 'v.'-f- T'; ;s.; -.---Vi ' rv.rr"- 34 BAKER AND FELDMAN lacquer thinner induced neuropathy, Ann. Clin. Lab. Sci.. 6, 240 [26] H. H. Schaumburg, H. M. Wisniewski, and P. S. Spencer, Ultra- structural studies of the dying-back process, L Peripheral nerve terminal and axonal degeneration in systemic acrylamide intoxication, J. Neuropathol. Exp. Neurol.. 33, 260 (1976). [27] P. S. Spencer and H. H. Schaumburg, Ultrastructural studies of the dying-back process. IIL The evolution of experimental peripheral giant axonal degeneration, J. Neuropathol. Exd. Neurol.. 36, 276 (1977). ------------------- --------- SL 033914 5,'^c i 'It-----:-: J. TOXICOL.-CLIN. Podophyllum To: Fatal Case and e DANIEL E. CASSIDY Department of Intern JAN DREWRY,t MD Division of Nephrolot JOSEPH P. FANNINC Department of Pathol Maine Medical Cente Portland, Maine 041 A 59-yr-old male attempt. Previous were observed in until 10 h after in; lactic acidosis. I after ingestion. 1 ^Present address: Medical Center, Ban; tPresent address Southwestern Medica Copyright c !9g: by Marcel De