Clinical Toxicology

ISSN: 0009-9309 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/ictx18

Methyl Ethyl Ketone Polyneuropathy in Shoe Factory Workers Frances M. Dyro To cite this article: Frances M. Dyro (1978) Methyl Ethyl Ketone Polyneuropathy in Shoe Factory Workers, Clinical Toxicology, 13:3, 371-376, DOI: 10.3109/15563657808988244 To link to this article: http://dx.doi.org/10.3109/15563657808988244

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CLINICAL TOXICOLOGY 1 3 ( 3), pp. 371-376 (1978)

Methyl Ethyl Ketone Polyneuropathy

in Shoe Factory Workers

FRANCES M. DYRO, M.D. Assistant Professor of Neurology Department of Neurology Temple University Philadelphia, Pennsylvania

Polyneuropathies in chronic inhalers of glues and paint thinners have been described with increasing frequency in recent years. The substances implicated in the production of the now typical changes of fiant axonal swelling have been 2-hexane, acrylamide, and m o r e recently methyl butyl ketone [l-31. Methyl butyl ketone (MBK) was felt to be the cause of severe polyneuropathy in workers in an Ohio plant even though the solvent mixture used contained methyl ethyl ketone as well. Reports from Altenkirch e t al. [4] in West Berlin have suggested that methyl ethyl ketone (MEK) may be capable of synergizing the effect of MBK and 2-hexane given in high concentrations. This laboratory h a s recently studied three women who developed polyneuropathy while exposed to concentrations of MEK and acetone o r MEK and toluene well below the threshold limit values f o r these substances.

371 Copyright 0 1979 hy Marcel Dekker, Inc All Rights Reserved Neither this work nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanlcal. Including photocopying, microfilming, and recording. or by any information storage and retrieval system. without permission in writing from the publisher

DYRO

372 CASE R E P O R T S

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Case 1 The most severely involved patient, N. M., a 34-year-old woman, presented on November 22, 1976 complaining of "pins and needles" paresthesias in the feet, weakness, fatigue, heaviness in the chest, and true vertigo. She had no shortness of breath on exertion but had proximal muscle fatigue and cramping of gastrocnemii. She had worked as a cementer in the same shoe manufacturing plant in Maine for 6; years. A new ventilating system had been installed about three y e a r s after she began working at the plant. The cement used was Supergrip 335 SAC (sole attaching cement) made by the Bostik Division of USM Corporation. This cement contains 51% MEK and 27% toluene as solvents. When tested the patient had been out of work and not exposed to the cement f o r three months. On physical examination she showed evidence of neuropathy. Her deep tendon reflexes were sluggish and difficult to elicit in the lower extremities, and she had glove and stocking hyperesthesia. Motor nerve conduction velocities (listed in Table 1) were slowed with prolongation of distal motor latencies (Table 2). Electromyography, performed using standard TECA equipment, showed an increase in the number of complex and polyphasic motor unit potentials with voluntary contraction. Motor units were decreased in total number, and fasiculations and occasional fibrillation potentials were seen. The changes are consistent with denervation. On February 8, 1977 conductions velocities were improved, but distal motor latencies were still prolonged. The patient was hospitalized at that time for investigation of other possible causes of neuropathy. Glucose tolerance testing, thyroid function studies, vitamin B12 and foiate levels, complete blood count, and SMA 12/60 (blood chemist r y screening) were normal; x-rays of the chest and lumbosacral spine revealed only a slight scoliotic curve. Electroencephalogram was essentially normal. Pulmonary function studies showed changes consistent with bronchitis due to exposure to an irritative substance. No specific treatment was given. The patient was followed at intervals, and on August 6, 1977 conduction velocities and distal motor latencies had returned to normal. Case 2 J. D., a 33-year-old woman, was tested on March 14, 1977. She had worked for the same shoe company as the f i r s t patient for four years. She terminated employment after two years of exposure to the cement in November 1976 (3$ months before testing). She complained of aching

METHYL ETHYLKETONE POLYNEUROPATHY

373

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TABLE 1. Conduction Velocities of Patient N.M. Nerve

11/22/76

R. peroneal

R. p. tibial

Mean normal value, m/sec

2/8/77

8/6/77

41.1

48.0

46.3

51.0

37.4

41.6

5U 8

48.7

L. peroneal

36.0

41.3

68.2

51.0

L. p. tibial

42.7

48.4

50.6

48.7

TABLE 2. Distal Motor Latencies of Patient N.M. Nerve

11/22/76,

2/8/77,

8/6/77,

msec

msec

msec

-~~ ~

R. median

Upper limit of normal, msec

~

4.7

4.5

R. ulnar

3.4

4.0 3.3

R. peroneal

8.0

7.8

6.7

6.8

R. p. tibial

9.5

6.9

4.9

7.6

L. peroneal

7.8

7.9

5.9

6.8

L. p. tibial

9.6

9.6

6.2

7.6

3.4

in the legs, numbness in the hands, and headaches and irritability, which had improved somewhat since she stopped working. She had a contact dermatitis when seen, but she did not feel that it was related to exposure to the cement. She denied being on any medication and also denied diabetes, renal disease, and anemia. Motor nerve conduction velocity testing revealed slowing of the left peroneal nerve, as well as dispersion of the evoked potential recorded on stimulation of the right peroneal and posterior tibial nerves. Median sensory latencies were at the upper limits of normal. Case 3 B. S. is a 31-year-old woman who was exposed to a cement containing MEK and acetone for one year. Although h e r complaints were primarily related to alterations of consciousness with demonstrated EEG changes, she did complain of aching muscles and numbness in the hands and feet. Evaluations focused on her CNS symptoms, but when

DYRO

374

tested two years after cessation of exposure to cement, she had a persistent mild peroneal neuropathy. H e r right peroneal conduction velocity was 43.9 m/sec with a dispersed 2 mV evoked potential.

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CONCENTRATION MEASUREMENTS The threshold limit values f o r MEK and toluene as given by the manufacturer of Supergrip are 200 ppm for MEK and 100 ppm for toluene. The TLV for acetone is 1000 ppm. Sampling done in the f i r s t plant on January 28, 1976 between 10:20 A.M. and 4:05 P.M. revealed that f o r most of the cementers the levels were in the range of 10 ppm of MEK and 25 ppm of toluene. Near drying racks f o r 96 p a i r s of shoes, the level of toluene rose momentarily to 130 ppm when a new load of shoes arrived at that station. Measurements made in the second factory gave concentrations of MEK as 21-180 ppm and acetone as 36-250 ppm. A direct reading instrument gave solvent vapor concentrations of 50-200 ppm of MEK. DISCUSSION The threshold limit value is defined as that level to which nearly all workers may be repeatedly exposed day after day without adverse

effects. This is a value based on the assumption of a 7-8 h r work day and a 40-hr week. The immediate effects of overexposure are well known and include irritation of the eyes, throat, and nose, headache, nausea, dizziness, and lack of coordination. These effects apply predominantly to acetone and toluene. In 1977 Glatt [5] described dizziness, unreality, and hallucinations with transient paresthesias in glue sniffers following 15-30 min of inhalation. The solvent MEK was thought to be responsible. Chronic exposure to toluene alone has been known to cause cerebral atrophy and cerebellar degeneration with persistent t r e m o r s in patients who had sniffed o r inhaled toluene in large amounts (1 ml at a time 2-4 times a day f o r 10 years [ S ] ) . The combination of MEK and MBK was used in an Ohio fabric plant in which 86 out of 1161 plant workers were found to have some degree of neuropathy [7]. It was felt that MEK was not at fault because it had been previously used in combination with MIBK (methyl iso-butyl ketone) at the plant f o r many years withou causing neuropathy. When MIBK was replaced by MBK, symptoms of neuropathy began to appear in workers. Measurements in that plant were 331-516 ppm of MEK and 9.2-36.0 ppm of MBK. A report by Oh and Kim [8] of a "huffer" o r inhaler with a neuropathy comments that he had been inhaling up to 7.5 liters/ month of two kinds of lacquer thinners containing MEK, MIBK, acetone,

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METHYL ETHYLKETONE POLYNEUROPATHY

375

and toluene. The authors conclude that the giant axonal swelling they were able to demonstrate was caused by the MIBK in the mixture. Altenkirch et al. have reported a toxic neuropathy due to sniffing of a glue thinner containing 16% n-hexane, 11% MEK, and 29% toluene in rather large amounts. On electrical testing, their patients had slow conduction velocities and prolonged distal motor latencies. Their conclusion w a s that MEK enhances the neurotoxic effects of E-hexane and MBK. The neuropathy in their cases and in the Maine cases was of gradual onset with distal sensory complaints appearing before motor deficit. Improvement w a s gradual over the course of many months. The difference between the shoe workers and other reported cases of neuropathy is the amount of exposure that was felt to be within a safe range for the shoe workers. The factor of absorption from skin surfaces by the shoe workers may account f o r this apparent difference. Studies are now in progress to ascertain the effect of absorption versus inhalation. In either case a cumulative effect is probably present. MEK, it appears, is not an innocuous substance and may be responsible for the production of neuropathy by itself as well as for potentiating substances known to cause neuropathy. SUMMARY Three c a s e s of polyneuropathy in shoe factory workers are described. The etiologic agent is felt to be methyl ethyl ketone, a substance previously thought to be a safe solvent. The concentration of this substance in the ambient air of the patients was below the threshold limit value. This suggests that there may be a cumulative effect and that we should reexamine the threshold limit values s e t for all the organic solvents with respect to inhalation and absorption from skin surfaces. REFERENCES N. Allen, J. R. Mendell, D. J. Billmaier, R. E. Fontaine, and J. 0' Neill, Toxic polyneuropathy due to methyl-n-butyl ketone,

Arch. Neurol., 32, 209 (1975). Ishii, and H. Schaumburg, n-hexane neuroA. Herskowitz, pathy: a syndrome occurring as a result of industrial exposure, New~Engl.J. _Med., _ 265, 82 (1971) T. 0. Garland and M. W. H. Patterson, Six cases of acrylamide poisoning, Brit. Med. J., 1968-4, 134. H. Altenkirch, H. Mager, m l t e n b u r g , and J. Helmbrecht, Toxic polyneuropathies after sniffing a glue thinner, J. Neurol., 214, 137 (1977). __

376

M. M. Glatt, Abuse of solvent for kicks, Lancet, 1977-1, 485. M. Sasa, Irreversible brain atrophy founa%&henedict, Hosp. Trib., May 23, 1977. [7] P. S. Spencer, H. N. 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). [8] S. J. Oh and J. M. Kim, Giant axonal swelling in "Huffer' s" neuropathy, Arch. Neurol., 33, 583 ( 1976). 51 61

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DYRO

Methyl ethyl ketone polyneuropathy in shoe factory workers.

Clinical Toxicology ISSN: 0009-9309 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/ictx18 Methyl Ethyl Ketone Polyneuropathy in S...
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