What is toxic neuropathy?

Updated: Dec 06, 2017
  • Author: Jonathan S Rutchik, MD, MPH, FACOEM; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
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Lewis P. Rowland, in Merritt's Textbook of Neurology, defines the terms peripheral neuropathy and polyneuropathy as describing "the clinical syndrome of weakness, sensory loss and impairment of reflexes caused by diffuse lesions of peripheral nerves." The diagnosis most often is based on the clinical picture and is confirmed with electrodiagnostic techniques, most commonly electromyography (EMG) and nerve conduction studies. Facial nerve and blink reflex testing also are used commonly. Apparatuses, such as the neurometer, vibrometer, and sensory nerve perception threshold-testing device, often are used in research settings or to evaluate clusters of patients.

Patients with toxic etiologies for neuropathy are less common than patients with other neuropathies such as those due to hereditary, metabolic, or inflammatory causes. Drug-related neuropathies are among the most common toxic neuropathies. Neuropathies from industrial agents (either from occupational or environmental sources), presenting after either limited or long-term exposure, are insidious. Patients may present with subtle pain or weakness. Subclinical abnormalities found on electrodiagnostic testing may herald a progressive neuropathy if exposure continues at a similar dose. Attributing neuropathy to such an exposure often is difficult. In some patients, extensive search for an etiology may fail to uncover the exact cause of neuropathy.

Many chemicals are known to cause neuropathy in laboratory animals. Some of these have been associated with neuropathy in clinical epidemiologic studies, confirming their ability to injure the human peripheral nervous system (PNS). Other chemicals have been reported to be associated with PNS dysfunction and neuropathy on the basis of retrospective and cross-sectional epidemiologic studies. Designs for many of these studies have been criticized. Other associations have been made from many case reports and case series.

Human studies infrequently have associated exposure to environmental sources with peripheral neuropathy. As compared to nonexposed controls, exposed individuals have statistically significant differences in nerve conduction velocity (NCV) and EMG findings. Exposures have been estimated for duration and intensity based on point source extrapolation, a common method of environmental risk assessment. When reviewing the literature, a critical analysis of study designs and electrodiagnostic techniques is important.

An algorithm to assess patients with suspected neurotoxic illness is detailed in Medical/Legal Pitfalls. It describes occupational and environmental history as an important aspect of the medical history. In cases of positive occupational or environmental exposure, estimating dose and duration of exposure and level of protection afforded by personal protective equipment is emphasized. Government and professional organizations publish exposure limits for workers using various chemicals. Physicians may use this information to compare with industrial hygiene data. These are outlined in Table 1.

Table 1. Exposure Limits, Common Organic Solvents and Metals (Open Table in a new window)




ppm (mg/m3)


TWA: ppm (mg/m3),



ppm (mg/m3) TLV,




(0.03), 60 Ca


Arsenic, inorganic


C (0.002)

(0.01), -

Arsenic, organic

0.5 mg/m3



Carbon disulfide

20, 30, 100 for 30 min

1 (3),

10 STEL (30),


10 (31)

Ethylene oxide


1 < 0.1,

< 0.18, 5 C,


1 (1.8)

n -hexane

500 (1800)

50 (180), 1100

50, (176)


0.05 mg/m3

0.100 mg/m3

(0.05), -

Mercury, inorganic

C 0.1 mg/m3

0.05 mg/m3,

C 0.01 mg/m3,

10 mg/m3

0.025 mg/m3

Mercury, organic

0.01 mg/m3,

C 0.04 mg/m3

0.01 mg/m3,

ST 0.03 mg/m3,

2 mg/m3

0.01 mg/m3,

0.03 mg/m3

Methyl n -butyl


100 (410)


5 (20)


100, 200 C,

300 for 5 min

in 3 h

150 Ca

25 (170),

100 (685)


100, 200 C,

600 for 5 min

in 3 h

50 (215),

100 ST (425), 700

50 (213),

100 (428)


0.1 mg/m3 skin

0.1 mg/m3,

15 mg/m3

0.1 mg/m3


200, 300, 500 for 10 min

100 (375),

150 ST (560),


50 (188)



(methyl chloroform)

350 (1900)

C 350(1900)

for 15 min,


350 (1910),

450 (2460)


100, 200 C,

300 for 5 min

in 2 h

1000 Ca

50 (269),

100 (1070)

Vinyl chloride

1, 5 for 15 min




100 (435)

100 (435),

150 ST (655)

100 (434),

150 (651)

Abbreviations: OSHA - Occupational Safety and Health Association; NIOSH - National Institute of Occupational Safety and Health; ACGIH - American Congress of Governmental Industrial Hygienists; TWA - time-weighted average; TLV - threshold limit value; PEL - permissible exposure limit; REL - recommended exposure limit; ppm - parts per million; STEL - short-term exposure limit; Ca - level for carcinogenicity; C - ceiling, should never be exceeded; ND - not determined

Utilizing neurophysiologic testing, neuropsychological testing, and neuroimaging to support a clinical suspicion is encouraged. When the exposure has ended, retesting also is appropriate after a period of time. Perform biological testing of serum and urine to assess absorbed dose. Values have been published for these data. These are outlined in Table 2.

Table 2. Agency for Toxic Substances and Disease Registry Biological Exposure Indices (Open Table in a new window)













Inorganic arsenic: end of work week, 50 µg/g

monomethyl-arsonic acid, cacodylic acid (days)



Hair (ingestion chronic)

Carbon disulfide

2-TTCA* 5 mg/g

Carbon disulfide

Carbon disulfide


Ethylene oxide





n -hexane

2-5 hexanediol: end of shift, 5 mg/g

2 hexanol, total metabolites

n -hexane

n -hexane




Lead 30 μg/100 mL


Erythrocyte protopor-phyrin

Mercury, inorganic

Mercury: start of shift, 35 µg/g

Mercury: end of shift at end of work week, 15 µg/L



Methyl n -butyl ketone


2,5 hexane dione




Perchloro-ethylene, trichloroacetic acid

Perchloroethylene 1 mg/L

Perchloro-ethylene: before last shift of week, 10 ppm†



Mandelic acid: start of shift, 300 mg/g; end of shift, 800 mg/g

Phenylglyoxylic acid: start of shift, 100 mg/g; end of shift, 240 mg/g

Styrene: start of shift, 0.02 mg/L; end of shift, 0.55 mg/L









Hippuric acid




1,1,1 Trichloroethane (methyl chloroform)

Trichloroacetic acid: end of work week, 10 mg/L

total trichloroethanol: end of shift at end of work week, 30 mg/L

Total trichloroethanol

1 mg/L

Methyl chloroform: prior to last shift of work week, 40 ppm†



Trichloroethylene, trichloroacetic acid: end of work week, 100 mg/g or trichloroacetic acid plus trichloroethanol, 300 mg/g

Trichloroethylene: end of work week, 4 mg/L




Vinyl chloride






Methylhippuric acid: end of shift, 1.5 mg/g




*2-TTCA - 2-thiothiazolidine-4-carboxylic acid

† ppm - parts per million

Use of the medical literature to associate an agent with an abnormality is important. Ascertain existence of supporting evidence that suggests exposure at a specific dose and duration that can cause such dysfunction and whether animal data are helpful to extrapolate an estimated dose that may lead to a health effect in humans.

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