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Toxic Neuropathy Treatment & Management

  • Author: Jonathan S Rutchik, MD, MPH; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
Updated: Feb 03, 2016

Medical Care

See the list below:

  • Advise removal from occupational or environmental exposure.
  • Advise discontinuation of medication or recreational drug habit. Also provide information regarding how alcohols affect those with exposures.
  • Acute care for those intoxicated with recreational, industrial, or other agents is discussed in other articles on this web site.
  • Preventive care and supportive care should include consideration of life stressors, diet, and overall behavior modifications.
  • Treatment options also include the following:
    • Nonpharmacologic options include cool soaks, heat, massage, elevation or lowering of the limbs, shoe tightness, and/or exercise.
    • Pharmacological options include tricyclic antidepressants, anticonvulsants, opiates, or topical capsaicin cream. Other options include intravenous gamma globulin, aldose reductase inhibitors, nerve growth factor, anti–tumor necrosis factor-α; these are mainly research ideas. Three that may be helpful presently include lipoic acid, evening primrose, and vitamin E.
      • Alpha lipoic acid is well reviewed by Halat and Dennehy.[56] Thiolic acid is a free radical scavenger and chelator. It is approved for use in Germany for neuropathy. The best studies suggest parenteral use followed by oral use relieves symptoms and improves nerve blood flow. Oral preparations are available in United States. Two studies suggest increased nerve conduction (600/1200 mg for 2 y, oral) and reduced symptoms (1800 mg/d for 3 wk, oral). The mechanism of action includes chelation and, thus, a concern for mineral shortage exists. Monitoring iron levels is suggested, and persons with alcoholism need to take vitamin B.
      • Evening primrose is also well summarized by Halat and Dennehy.[56] It includes omega 6 essential fatty acids: gamma linoleic acid (GLA) and linoleic acid. It is an essential component of myelin and the neuronal cell membrane. Dosages ranging from 360-480 mg/d for 6 months to 1 year improved nerve function measurements. It has mild side effects including inhibition of platelet aggregation. Concern also exists for those with seizure disorders.
      • Vitamin E is discussed in the article Argyriou et al.[57] Vitamin E has been administered to patients on chemotherapy for prevention of neuropathy at doses of 600 mg/d during treatment and then for 3 months after treatment. A reduced peripheral neuropathy score has been noted. A neuroprotective effect has been described.


See the list below:

  • Occupational therapist
  • Environmental medicine specialist


Although diet does not play a specific role in reparation of the PNS, a balanced diet is important for various reasons related to general health. Since various B vitamins have been implicated in the development of neuropathies, some physicians suggest supplementation.

Contributor Information and Disclosures

Jonathan S Rutchik, MD, MPH Associate Clinical Professor, Division of Occupational Medicine, Department of Medicine, University of California, San Francisco, School of Medicine; Neurology, Environmental and Occupational Medicine Associates (

Jonathan S Rutchik, MD, MPH is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, International Parkinson and Movement Disorder Society, Society of Toxicology, Western Occupational and Environmental Medical Association, American College of Occupational and Environmental Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Glenn Lopate, MD Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Consulting Staff, Department of Neurology, Barnes-Jewish Hospital

Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, Phi Beta Kappa

Disclosure: Nothing to disclose.

Chief Editor

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS Professor Emeritus of Neurology and Psychiatry, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Neuroscience Director, Department of Neurology, Crouse Irving Memorial Hospital

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS is a member of the following medical societies: American College of International Physicians, American Heart Association, American Stroke Association, American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners Institute, National Association of Managed Care Physicians, American College of Physicians, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, Royal Society of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Milind J Kothari, DO Professor, Department of Neurology, Pennsylvania State University College of Medicine; Consulting Staff, Department of Neurology, Penn State Milton S Hershey Medical Center

Milind J Kothari, DO is a member of the following medical societies: American Academy of Neurology, American Neurological Association, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

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Table 1. Exposure Limits, Common Organic Solvents and Metals
Compound OSHA


ppm (mg/m3)


TWA: ppm (mg/m3),



ppm (mg/m3) TLV,


Acrylamide(0.3)(0.03), 60 Ca 
Arsenic, inorganic(0.01)C (0.002)(0.01), -
Arsenic, organic0.5 mg/m3  
Carbon disulfide20, 30, 100 for 30 min1 (3),

10 STEL (30),


10 (31)
Ethylene oxide 1 < 0.1,

< 0.18, 5 C,


1 (1.8)
n -hexane500 (1800)50 (180), 110050, (176)
Lead0.05 mg/m30.100 mg/m3(0.05), -
Mercury, inorganicC 0.1 mg/m30.05 mg/m3,

C 0.01 mg/m3,

10 mg/m3

0.025 mg/m3
Mercury, organic0.01 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)
Perchloroethylene100, 200 C,

300 for 5 min

in 3 h

150 Ca25 (170),

100 (685)

Styrene100, 200 C,

600 for 5 min

in 3 h

50 (215),

100 ST (425), 700

50 (213),

100 (428)

Thallium0.1 mg/m3 skin0.1 mg/m3,

15 mg/m3

0.1 mg/m3
Toluene200, 300, 500 for 10 min100 (375),

150 ST (560),


50 (188)


(methyl chloroform)

350 (1900)C 350(1900)

for 15 min,


350 (1910),

450 (2460)

Trichloroethylene100, 200 C,

300 for 5 min

in 2 h

1000 Ca50 (269),

100 (1070)

Vinyl chloride1, 5 for 15 minND 
Xylene100 (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
Table 2. Agency for Toxic Substances and Disease Registry Biological Exposure Indices
Compound Urine Blood Expired


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

monomethyl-arsonic acid, cacodylic acid (days)

  Hair (ingestion chronic)
Carbon disulfide2-TTCA* 5 mg/gCarbon disulfideCarbon disulfide 
Ethylene oxide    
n -hexane2-5 hexanediol: end of shift, 5 mg/g

2 hexanol, total metabolites

n -hexanen -hexane 
LeadLeadLead 30 μg/100 mL Erythrocyte protopor-phyrin
Mercury, inorganicMercury: start of shift, 35 µg/gMercury: end of shift at end of work week, 15 µg/L  
Methyl n -butyl ketone 2,5 hexane dione  
Perchloro-ethylenePerchloro-ethylene, trichloroacetic acidPerchloroethylene 1 mg/LPerchloro-ethylene: before last shift of week, 10 ppm† 
StyreneMandelic 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  
TolueneHippuric acidTolueneToluene 
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† 
Trichloro-ethyleneTrichloroethylene, trichloroacetic acid: end of work week, 100 mg/g or trichloroacetic acid plus trichloroethanol, 300 mg/gTrichloroethylene: end of work week, 4 mg/LTrichloro-


Vinyl chloride    
XyleneMethylhippuric acid: end of shift, 1.5 mg/gXyleneXylene 
*2-TTCA - 2-thiothiazolidine-4-carboxylic acid

† ppm - parts per million

Table 3. Industrial Uses of Common Organic Solvents and Metals
Compound Industrial Uses
AcrylamideMining and tunneling, adhesives, waste treatment, ore processing, paper, pulp industry, photography, dyes
ArsenicPesticides, pigments, antifouling paint, electroplating, seafood, smelters, semiconductors, logging
Carbon disulfideViscose rayon, explosives, paints, preservatives, textiles, rubber cement, varnishes, electroplating
Ethylene oxideInstrument sterilization, chemical precursor
n -hexaneGlues and vegetable extraction, components of naphtha, lacquers, metal-cleaning compounds
LeadSolder, lead shot, illicit whiskey, insecticides, auto body shops, storage batteries, foundries, smelters, lead-based paint, lead stained glass, lead pipes
MercuryScientific instruments, electrical equipment, amalgams, electroplating, photography, felt making, taxidermy, textiles, pigments, chloroalkali industry
Methyl n -butyl ketonePaints, varnishes, quick-drying inks, lacquers, metal-cleaning compounds, paint removers
PerchloroethyleneDry cleaning, degreaser, textile industry
StyreneFiberglass component, ship building, polyester resin
ThalliumRodenticides, fungicides, mercury and silver alloys, lens manufacturing, photoelectric cells, infrared optical instruments
ToluenePaint, fuel oil, cleaning agents, lacquers, paints and paint thinners

Trichloroethane (methyl chloroform)

Degreaser and propellant
TrichloroethyleneCleaning agent, paint component, decaffeination, rubber solvents, varnish
Vinyl chlorideIntermediate for polyvinyl chloride (PVC) resins for plastics, floor coverings, upholstery, appliances, packaging
XyleneFixative for pathologic specimens, paint, lacquers, varnishes, inks, dyes, adhesives, cements
Table 4. Differential Diagnosis of Peripheral Neuropathy With Selective Lab Testing (Recommended lab tests in bold.)
Inflam-matory Metabolic and Nutritional Infective and Granulo-matous Vasculitic Neoplastic and Para-proteinemic Drug-Induced and Toxic Hereditary
Acute idiopathic polyneuro-pathy (Anti-Gm1, anti-Gd1a, anti-GQ1b)Diabetes ( Fasting blood glucose , 2-hour glucose tolerance test) AIDS ( HIV) Mixed CT disease (ESR)Compression and infiltration ( chest radiograph) AlcoholHMSN
Chronic inflammatory demyelin-ating polyneuro-pathyEndocrino-pathies: hypo-thyroidism, acromegaly ( TSH , Electrolytes, GH) Leprosy, syphilis ( RPR , FTA , MHA-TP) Poly-arteritis nodosaParaneo-plastic syndromes (anti-Hu, anti-RII, etc; CBC)See TableHSN
 Uremia ( BUN/CR) Diphtheria, Lyme ( Serology) Rheu-matoid arthritis ( RF) Paraprotein-emias ( SPEP , immuno-fixation , anti-MAG, M protein)  Friedreich ataxia
 Liver disease ( LFTs) Sarcoidosis ( ACE) SLE ( ANA) Amyloidosis (nerve biopsy) Familial amyloid (nerve biopsy)
 Vitamin B-12 deficiency ( B12) Sepsis and multi-organ failure ( ESR)    Porphyria (porphobil-inogen, amino-levulinic acid),

meta-chromatic leukodys-trophy, Krabbe, abetalipo-proteinemia, Tangier disease, Refsum disease, Fabry disease

Table 5. Neuropathies With Unusual Features
Small Fiber Neuropathies Facial Nerve Involvement Autonomic Involvement Sensory Ataxia Pure Motor Involvement Skin, Nail, or Hair Manifestation
DiabetesGuillain-BarréParaneo-plasticPolyganglio-nopathiesMotor neuron diseaseVasculitis: purpura, livedo reticularis
AmyloidCIDPGBSParaneo-plasticMultifocal motor neuropathyCryoglo-binemia: purpura
HIV-associatedLyme diseasePorphyriaSjögren syndromeGBsFabry disease: angiokera-tomas
Hereditary sensory and autonomic neuropathySarcoidosisVincristine, vacorCisplatin analogsAcute motor axonal neuropathyLeprosy: skin hypopig-mentation
Fabry diseaseHIVDiabetesVitamin B-6 toxicityPorphyriaOsteo-sclerotic myeloma: skin hyperpig-mentation
Tangier diseaseTangierAmyloidGBS (Miller-Fisher variant) CIDPVariegate porphyria: bullous lesions
Sjögren syndrome HIVIgM monoclonal gammopathy of undetermined significanceOsteosclerotic myelomaRefsum disease: ichthyosis
  Hereditary sensory and autonomic neuropathy Diabetic lumbar radiculoplex-opathyArsenic or thallium intoxication: Mees lines
    Hereditary motor sensory neuropathy (Charcot-Marie-Tooth)Thallium intoxication: alopecia
    LeadGiant axonal neuropathy: curled hair
Table 6. Industrial Agents and Pharmaceuticals Associated With Peripheral Neuropathy
Almitrine (s)“Spanish toxic oil”
Arsenic (s)(d) 2-t-Butylazo- 2- hydroxyl- 5 methylhexane
Carbamate pesticides (nm) Allyl chloride
Carbon disulfide (m)(d) Amiodaron e (d)
Chloramphenicol (s) Amitriptyline
Cimetidine (m)Carbamates (nm)
Cisplatin (s)Carbon monoxide
CytarabineDichloroacetic acid
Dapsone (m) Disulfiram (m)
Dichloroacetylene (cr)Ethionamide
Didoxynucleosides (s) (ddC, ddI, d4T) Ethyl alcohol
DimethylaminopropionitrileEthylene glycol (cr)
Doxorubicin (m)Ethylene oxide
Ethambutol (s) Germanium dioxide
Etoposide (s)Gold
Hydralazine (s) Indomethacin
Hyperinsulinemia/ hypoglycemia (m)Isoniazid
Imipramine (m)Lincomycin (nm)
Interferon alpha (nm)Lithium
Lead (m) L-Tryptophan
LidocaineMercury, inorganic
Methyl n-butyl ketone (m)(d)Mercury, organic
Metronidazole (s) Methaqualone
Misonidazole (s) Methyl bromide
MuzolimineMethyl methacrylate
Nitrous Oxide (s) N hexane (d)
Organophosphates (m) Naproxen
Organophosphorus compounds (nm) Nitrofurantoin (m)
Polychlorinated biphenyls (s)Penicillamine (nm)
Polymyxin (nm)Perhexiline (d)
Pyrethroids (ic) Phenol
Pyridoxine (s) Phenytoin
Succinylcholine (nm)Quinine (nm)
Sulfonamides (m), sulfasalazineStatins
TacrolimusStilbamidine (cr)
Taxanes (paclitaxel, docetaxel) (s) Suramin
Thalidomide (s) Tetrachloroethane
Thallium (s) Tetracyclines (nm)
Trimethaphan (nm) Trithiozine
VidarabineTubocurarine (nm)
Vincristine (m) Vincristine  (m), Vinca alkaloids
ZimeldineVinyl chloride
(s): Predominantly sensory

(m): Predominantly motor

(d): Possibly demyelination with conduction block

(cr): Associated with cranial neuropathy

(nm): Associated with neuromuscular transmission syndromes

(ic): Associated with axon ion channel syndromes

Bold: A rating for common or strong association

Unbolded: B rating for less common or less than strong association

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