DESCRIPTION

Acrylamide (C₃H₅NO, vinyl amide) is a water soluble vinyl monomer that is used to make polyacrylamide.

FORMS AND USES

• Acrylamide is used mainly in the production of polyacrylamide, in the synthesis of dyes, and in construction of dam foundations, tunnels, and sewers.
• The polymerized form of the acrylamide monomer is relatively nontoxic and is used in the treatment of sewage and industrial waste, weather control (to dissipate fog), mining and timber operations, preparation of gels for chromatography, and grouting agents.

TOXIC DOSE

• Acute ingestion of 50 to 100 mg/kg can cause neurologic effects.
• Chronic ingestion of contaminated water (400 ppm) for 1 month can cause severe neurologic effects.

PATHOPHYSIOLOGY

• Exposure occurs via inhalation, dermal absorption, or ingestion.
• Acrylamide monomer is neurotoxic, producing progressive degeneration of axons in the peripheral, autonomic, and central nervous systems (e.g., dying-back polyneuropathy).
• Toxicity associated with the polymer form of acrylamide is thought to be related to the contamination of the product with acrylamide monomer.
• Acrylamide is a probable human carcinogen.

EPIDEMIOLOGY

• Poisoning is uncommon.
• The toxic effects following exposure range from mild to severe; incomplete recovery has been documented in a few cases.
• Death may occur after massive acute exposure.

CAUSES

Poisoning is usually associated with chronic occupational skin exposure. However, acute poisoning following the ingestion of contaminated underground water supply has been reported.

PREGNANCY AND LACTATION

Human data have not been compiled. Animal data suggest sperm changes and decrease in fertility, as well as DNA inhibition and mutagenicity.

WORKPLACE STANDARDS

Work place standards for acrylamide monomer:

• ACGIH. TLV is 0.03 mg/m³.
• OSHA. PEL TWA is 0.3 mg/m³.
• NIOSH. PEL TWA is 0.03 mg/m³. IDLH is 60 mg/m³.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• PREGNANCY AND LACTATION
• WORKPLACE STANDARDS

DIFFERENTIAL DIAGNOSIS

• Toxicologic causes of peripheral neuropathy include alcoholism, carbon disulfide, heavy metals, hexane, n-butyl ketone, and organophosphates, among others.
• Nontoxicologic causes include diabetes, nutritional deficiency states, hand-arm vibration injury, as well as multiple sclerosis or other disease states causing combined central and peripheral neuropathy.

SIGNS AND SYMPTOMS

• Acute high-dose exposure may produce confusion, disorientation, ataxia, tremors, and seizures, with cardiovascular collapse after a delay of several hours. Peripheral neuropathy may begin 1 to 2 days later.
• First signs of chronic exposure are numbness and weakness of hands and feet and occur after weeks to months of exposure.
• Most toxic effects follow chronic exposure.

HEENT

Inhalation may produce irritation in the eyes and throat.

Dermatologic

• Abnormal sweating of the limbs may occur.
• Handling of acrylamide monomer causes erythema and peeling of the skin as well as red or blue discoloration where skin contact occurred.

Pulmonary

Persistent cough without parenchymal disease has been described.

Gastrointestinal

• Anorexia, constipation, and weight loss have been observed following chronic exposure.
• Liver injury has also occurred.
• Pancreatitis has been reported in one case.

Renal

Urinary retention and overflow urinary incontinence may develop if neuropathy develops.

Musculoskeletal

Weakness of the wrist and ankle extensor muscles, as well as loss of deep tendon and plantar reflexes, may occur as part of neuropathy.

Hematologic

Decreased platelet count may develop after large acute exposure.

Neurologic

• Acute CNS effects range from nervousness, sleeplessness, and difficulty in concentration to disorientation, confusion, hallucination, slurred speech, lethargy, and seizure.
• Peripheral signs include numbness, paresthesia, and weakness of the hands and feet (first signs of chronic exposure).
• Cerebellar effects may occur in severe cases.

Reproductive

Acrylamide is teratogenic in animal models.

PROCEDURES AND LABORATORY TESTS

Essential Tests

No tests may be needed for brief acute exposure or asymptomatic patients.

Recommended Tests

• Complete blood count, serum electrolytes, glucose, lipase BUN, creatinine and liver function tests are used to assess renal, hepatic, bone marrow, and pancreatic function in symptomatic patients.
• Lumbar puncture in the symptomatic patient may show increased protein levels.
• Heavy metal screens for arsenic, mercury, and thallium may be useful in the differential diagnosis.
• Serial nerve conduction studies may be used to document the extent and progression of peripheral neuropathy.
• The EEG may be abnormal in severe poisoning.

Not Recommended Tests

Acrylamide levels are not clinically useful.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • HEENT
  • Dermatologic
  • Pulmonary
  • Gastrointestinal
  • Renal
  • Musculoskeletal
  • Hematologic
  • Neurologic
  • Reproductive
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests
  • Not Recommended Tests

• Treatment should focus on terminating exposure, performing decontamination (following acute exposure), and providing general supportive care.
• The dose and time of exposure should be determined for all substances involved.

DIRECTING PATIENT COURSE

The health-care professional should call the poison control center when:

• CNS toxicity or other severe effects are present.
• Toxic effects are not consistent with acrylamide toxicity.
• Coingestant, drug interaction, or underlying disease presents unusual problems.

The patient should be referred to a health-care facility when:

• The patient or caregiver seems unreliable.
• Any toxic effects are present.
• A coingestant, drug interaction, or underlying disease presents unusual problems.

Admission Considerations

Inpatient management is warranted for patients with CNS effects.

DECONTAMINATION

Out of Hospital

• Induction of emesis is not recommended.
• For inhalation exposure, move the patient to fresh air.
• For skin exposure, wash the skin with soap and water.
• For eye exposure, irrigate the eyes with room-temperature water for 15 to 20 minutes. Seek health-care evaluation if irritation or visual defect persists.

In Hospital

• Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients for large ingestion presenting within 1 hour of ingestion or if serious effects are present.
• One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a large ingestion has occurred within the previous few hours.

ANTIDOTES

• A specific antidote is not available for acrylamide poisoning.

ADJUNCTIVE TREATMENT

• Seizures should be treated as explained in SECTION II, Seizures chapter.
• The patient should be ensured of an adequate airway and oxygenation.
• A benzodiazepine provides initial control.
  • Cardiac and respiratory monitoring should be performed continuously.
  • Diazepam
    • Adult dose is 5 to 10 mg intravenously initially, repeated every 10 minutes, as needed.
    • Pediatric dose is 0.2 to 0.5 mg/kg every 10 minutes, as needed.
  • Lorazepam
    • Adult dose is 2 to 4 mg intravenous push over 2 to 5 minutes; this should be repeated every 10 minutes as needed.
    • Pediatric dose is 0.1 mg/kg intravenous push over 2 to 5 minutes, not to exceed 4 mg/dose. This dose should be repeated every 10 minutes as needed.
• If seizures persist or recur, the patient should be treated with an additional anticonvulsant, such as phenobarbital or phenytoin and neuromuscular blockade should be considered.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
• ADJUNCTIVE TREATMENT

PATIENT MONITORING

• Renal and hepatic function, complete blood count, amylase and serum glucose levels should be monitored in patients subjected to an extensive, acute exposure.
• Duration of monitoring in asymptomatic patients has not been investigated.
• Outpatient followup with occupational physician or clinical toxicologist is recommended.

EXPECTED COURSE AND PROGNOSIS

• Most patients develop mild effects and recover over several months. Patients with severe exposure often develop permanent sequelae and may die.
• Peripheral neuropathy often improves but may leave residual sensory and motor defects.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department
  • Asymptomatic patients can be discharged after gastrointestinal decontamination, if needed.
  • Patients with transient respiratory symptoms may be monitored as outpatients.
  • Patients with extensive, acute exposures should be observed for at least 6 to 12 hours.
• From the hospital. Patients may be discharged when toxic effects are improving, and they can care for themselves.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS

• Detailed occupational history or examination of the workplace may be needed to detect acrylamide exposure.
• If a patient working with acrylamide develops a rash or becomes accident prone (for example, frequently dropping items or stumbling), he or she should be evaluated for peripheral neuropathy.
• Patients recovering from acrylamide intoxication may be more susceptible to repeat exposure.

Poisoning by other central nervous system depressants and anesthetics.

RECOMMENDED READING

Donovan JW, Pearson R. Ingestion of acrylamide with severe encephalopathy, neurotoxicity and hepatotoxicity. Vet Hum Toxicol 1987;29:462.

Mulloy KB. Two case reports of neurological disease in coal mine preparation plant workers. Am J Ind Med 1996;30:56-61.

Tilson HA. The neurotoxicity of acrylamide: an overview. Neurol Behav Toxicol Teratol 1981;3:445-461.

Author: Martha M. Foley

Reviewer: Luke Yip