Substances Included Synonyms

Therapeutic Toxic Class

A)

Specific Substances

1) Acrylamide
2) Acrylic amide
3) Akrylamid (Czech)
4) Ethylenecarboxamide
5) Propenamide
6) 2-Propenamide
7) Propanoic acid, amide
8) CAS 79-06-1
9) References: RTECS, 1983; EPA, 1985

1.2.1) MOLECULAR FORMULA
1) C3H5NO

Available Forms Sources

A)

1) Sold as colorless to pale yellow liquid. Half of the product is water (OHM/TADS , 2000).
2) Odorless, crystalline, white solid (NIOSH , 2000).
3) Acrylamide is a vinyl monomer (Harbison, 1998).
4) Acrylamide is a colorless solid that can be dissolved in solvents (AAR, 1998).

B)

1) Converted into acrylamide from acrylonitrile by a number of different processes (HSDB , 2000).
2) Acrylonitrile is treated with sulfuric acid (H2SO4) or hydrogen chloride (HCl) to form acrylamide (Budavari, 1996).
3) Acrylonitrile and copper-based, or microbiological, catalysts undergo a catalytic hydration reaction to form acrylamide (Harbison, 1998).

C)

1) Used in adhesives, chemical grouting, polymers and co-polymers for plastics, making dyes, soil conditioning, flocculants, and treating sewage and waste water (AAR, 1998; (OHM/TADS , 2000).
2) Used in the production of organic chemicals and ore processing, to synthesize dyes, as a cross-linking agent, permanent press fabrics, and for construction of foundations in dams and tunnels (HSDB , 2000).
3) Used in fibers, molded parts, paper sizing, textiles, and in water coagulation products (ACGIH, 1991).
4) Used as a carboxylated comonomer (Ashford, 1994).
5) Acrylamide monomer is used to make polyacrylamides and is a component in contact lenses and oil recovery additives (Budavari, 1996).
6) Acrylamide is an ingredient in biotechnical electrophoretic gels (Harbison, 1998).
7) Used in cosmetic additives (Hathaway et al., 1996).
8) Acrylamide is used to stabilize soil and in gel chromotography (Sittig, 1991).
9) Acrylamide is used in the dyeing, photographic processing, plastic, paper, hair sprays, textile, ceramic, and paint industries, and in laboratories (Garland & Patterson, 1967).
10) Polyacrylamides are used as flocculants to separate solids from liquid solutions in waste disposal, mining operations, water supply purification, and in laboratories for filtration and centrifugation (Tilson, 1981). Polyacrylamides are found in construction (particularly in mines), and in adhesive-making, textile-working, well-drilling, synthetic-fiber manufacturing, for electrophoresis in laboratories, and in electrode gels in medicine. The polymer is non-toxic, but is often contaminated with as much as 10 percent acrylamide monomer.
11) Most toxic exposures to acrylamide occur as a result of pyrolysis during fires or from its use as a soil waterproofing agent in mining and tunneling operations (Ellenhorn & Barceloux, 1988).
12) Over 70 million pounds are distributed throughout the US each year (Miller et al, 1982).

Overview

Life Support

A)

Clinical Effects

0.2.1)

A) WITH POISONING/EXPOSURE

1) Toxic effects depend on the duration, total dose and rate of exposure. The effects of acute high-dose exposure may be delayed in onset for several hours. Following large exposures, these include somnolence, confusion, hallucinations, disorientation, incoordination, tremors, and possibly seizures with cardiovascular collapse. Peripheral neuropathy may appear several weeks following significant acute exposure or following significant chronic exposures. Encephalopathy may occur in severe acute poisonings.
2) In sub-acute toxicity (exposure over days to weeks), and if of sufficient concentration, drowsiness, somnolence, loss of concentration, truncal ataxia, dysarthria, nystagmus, and urinary retention may occur. Polyneuropathy and peripheral neuropathy, with mainly motor and proprioceptive disturbances, may follow several weeks later.
3) Neurotoxic effects may include muscle weakness, numbness of limbs and extremities, tingling fingers, speech difficulties, unsteadiness, tremors, fatigue, lethargy, memory difficulties, and a sensory polyneuropathy if of sufficient dose. Excessive sweating is also common after exposure.
4) Dermal contact is a common route of exposure and may result in skin irritation with numbness, tingling, blistering and peeling with direct contact of high concentrations. Visual impairment and eye irritation also occur with significant exposure. Inhalation may produce a cough and sore throat. Ingestion, the least common route, may result in abdominal pain.
5) Complete recovery over a few weeks to months may be expected with mild symptoms, including prolonged weakness, but in cases of severe exposure, gradual and incomplete recovery may occur with residual ataxia, loss of reflexes, distal extremity weakness, and sensory disturbances.

0.2.3)

A) Hypotension, tachycardia, respiratory depression, hypothermia, and cardiovascular collapse may occur. Hypertension was reported in experimental animals.

0.2.4)

A) Visual impairment and eye irritation may occur. Rhinorrhea and mucosal irritation may occur in sub-acute exposures.

0.2.5)

A) WITH POISONING/EXPOSURE

1) Hypotension, peripheral cyanosis, and cool extremities may occur.
2) Cardiac failure was reported in one patient following ingestion of water contaminated with acrylamide.

0.2.6)

A) WITH POISONING/EXPOSURE

1) A persistent cough has been reported in sub-acute ingestions, but pulmonary findings were absent.
2) Respiratory failure was reported in one patient following ingestion of water contaminated with acrylamide.

0.2.7)

A) WITH POISONING/EXPOSURE

1) Neurological effects include hallucinations, confusion, tremors, myoclonus, opisthotonos, seizures, memory loss, euphoria, peripheral neuropathy, autonomic nervous system effects, and ataxia.
2) Alteration in the levels of dopamine, serotonin, and 5-hydroxyindoleacetic acid in regions of the brain and EEG abnormalities have also been noted.
3) Permanent peripheral and central neurological sequelae may occur following severe intoxication or prolonged occupational exposures.

0.2.8)

A) Anorexia and gastrointestinal disturbances may be seen in patients with sub-acute exposure. Pancreatitis following ingestion has been reported.
B) Weight loss, despite tube feeding, and fecal incontinence have been observed in experimental animals.

0.2.9)

A) WITH POISONING/EXPOSURE

1) Hepatic toxicity has been reported in humans and experimental animals.
2) Hepatic failure has been reported in one patient following ingestion of water contaminated with acrylamide.

0.2.10)

A) WITH POISONING/EXPOSURE

1) Renal toxicity and oliguria may occur from acute exposure. Overflow urinary incontinence may result from chronic exposure.
2) Renal failure was reported in one patient following ingestion of water contaminated with acrylamide.

0.2.11)

A) WITH POISONING/EXPOSURE

1) In severe poisonings, metabolic acidosis may occur.

0.2.12)

A) Excessive sweating may cause fluid losses and hyponatremia.

0.2.13)

A) WITH POISONING/EXPOSURE

1) In acute and sub-acute exposures, severe thrombocytopenia, disseminated intravascular coagulation, ecchymoses, and alteration in phagocyte function have been reported.

0.2.14)

A) An exfoliative, erythematous rash of the hands may be seen with chronic dermal exposure.

0.2.15)

A) WITH POISONING/EXPOSURE

1) Weakness, distal extremity muscle wasting, muscle pain, cramping, and rhabdomyolysis have been reported.

0.2.16)

A) Pituitary, thyroid, and adrenal gland tumors developed in chronically exposed rats.

0.2.17)

A) WITH POISONING/EXPOSURE

1) Weight loss is a consistent finding in patients with sub-acute exposure.

0.2.18)

A) Emotional disturbances such as emotional lability, insomnia, anxiety, irritability, and agitation have been reported, but causation cannot be determined.

0.2.20)

A) At the time of this review, no studies on the possible reproductive effects of acrylamide in humans were found.
B) In rodent studies, teratogenic effects, maternal and paternal toxic effects such as pre-implantation and post-implantation mortality, changes in litter size, and changes in sperm morphology were observed.

0.2.21)

A) Sufficient evidence exists to indicate that acrylamide is carcinogenic in experimental animals.

Laboratory Monitoring

A)

B)

Treatment Overview

0.4.2)

A) EMESIS NOT RECOMMENDED

1) EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression and seizures.

B) ACTIVATED CHARCOAL

1) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.

C) GASTRIC LAVAGE

1) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.

a) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.

D) PYRIDOXINE

1) Pyridoxine use in humans has been reported in a case of acrylamide ingestion, but with unproven effect. In cases of high-dose exposure or in symptomatic patients, pyridoxine use should be strongly considered.

E) SEIZURES

1) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).

a) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
b) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.

F) HYPOTENSION

1) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.

0.4.3)

A) Aerosolization readily occurs.
B) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.

0.4.4)

A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.

0.4.5)

A) OVERVIEW

1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
2) Exfoliative rashes can be treated symptomatically. Thorough neurologic examination should be performed to detect peripheral neuropathies.

Range Of Toxicity

A)

Clinical Effects

Summary Of Exposure

A)

1) Toxic effects depend on the duration, total dose and rate of exposure. The effects of acute high-dose exposure may be delayed in onset for several hours. Following large exposures, these include somnolence, confusion, hallucinations, disorientation, incoordination, tremors, and possibly seizures with cardiovascular collapse. Peripheral neuropathy may appear several weeks following significant acute exposure or following significant chronic exposures. Encephalopathy may occur in severe acute poisonings.
2) In sub-acute toxicity (exposure over days to weeks), and if of sufficient concentration, drowsiness, somnolence, loss of concentration, truncal ataxia, dysarthria, nystagmus, and urinary retention may occur. Polyneuropathy and peripheral neuropathy, with mainly motor and proprioceptive disturbances, may follow several weeks later.
3) Neurotoxic effects may include muscle weakness, numbness of limbs and extremities, tingling fingers, speech difficulties, unsteadiness, tremors, fatigue, lethargy, memory difficulties, and a sensory polyneuropathy if of sufficient dose. Excessive sweating is also common after exposure.
4) Dermal contact is a common route of exposure and may result in skin irritation with numbness, tingling, blistering and peeling with direct contact of high concentrations. Visual impairment and eye irritation also occur with significant exposure. Inhalation may produce a cough and sore throat. Ingestion, the least common route, may result in abdominal pain.
5) Complete recovery over a few weeks to months may be expected with mild symptoms, including prolonged weakness, but in cases of severe exposure, gradual and incomplete recovery may occur with residual ataxia, loss of reflexes, distal extremity weakness, and sensory disturbances.

Vital Signs

3.3.1)

A) Hypotension, tachycardia, respiratory depression, hypothermia, and cardiovascular collapse may occur. Hypertension was reported in experimental animals.

3.3.2)

A) Respiratory depression is apparent when severe CNS depression and seizures occur (Donovan & Pearson, 1987).

3.3.3)

A) Excessive sweating caused by acrylamide may lead to hypothermia (Donovan & Pearson, 1987).

3.3.4)

A) Severe hypotension and cardiovascular collapse were reported with acute high-dose exposure (Donovan & Pearson, 1987).

1) Hypotension may occur as a result of effects on the sympathetic nervous system (Post & McLeod, 1977) or an effect on responses of the dopamine system (Tilson, 1981).

B) Hypertension was reported to occur soon after acutely poisoning experimental animals (Sterman et al, 1983a).

3.3.5)

A) Tachycardia was reported to occur soon after acutely poisoning experimental animals (Sterman et al, 1983a).

Heent

3.4.1)

A) Visual impairment and eye irritation may occur. Rhinorrhea and mucosal irritation may occur in sub-acute exposures.

3.4.3)

A) Visual impairment may occur due to retinal neuronal damage (Eskin et al, 1985). Severely poisoned patients with occupational exposure may have cerebellar and ocular involvement (Myers & Macun, 1991).

1) MONKEYS - Acrylamide-induced visual impairment was found in an experimental study in monkeys; visual acuity recovered only partially and stabilized below control values more than 90 days after exposure (Merigan et al, 1982).

B) RABBITS - A 40% acrylamide solution placed in rabbit eyes and not irrigated produced pain, conjunctival irritation, and corneal injury. All signs resolved within 24 hours (ACGIH, 1991).

3.4.5)

A) WITH POISONING/EXPOSURE

1) Rhinorrhea has been reported in patients with sub-acute exposure (Igisu et al, 1975).

3.4.6)

A) WITH POISONING/EXPOSURE

1) Transient mucosal irritation may develop in patients with sub-acute exposure (Igisu et al, 1975).

Cardiovascular

3.5.1)

A) WITH POISONING/EXPOSURE

1) Hypotension, peripheral cyanosis, and cool extremities may occur.
2) Cardiac failure was reported in one patient following ingestion of water contaminated with acrylamide.

3.5.2)

A) HYPOTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) Hypotension may occur as a result of effects on the sympathetic nervous system (Post & McLeod, 1977) or an effect on responses of the dopamine system (Tilson, 1981).

B) CYANOSIS

1) WITH POISONING/EXPOSURE

a) Peripheral cyanosis and cool extremities may occur, particularly in patients with chronic exposure (Miller & Spencer, 1985).

C) HEART FAILURE

1) WITH POISONING/EXPOSURE

a) CASE REPORT - A 36-year-old man developed cardiac failure within 24 hours after ingesting mineral water contaminated with a high concentration of acrylamide. The patient recovered following treatment with high doses of N-acetylcysteine (Mehrhof et al, 2008).

Respiratory

3.6.1)

A) WITH POISONING/EXPOSURE

1) A persistent cough has been reported in sub-acute ingestions, but pulmonary findings were absent.
2) Respiratory failure was reported in one patient following ingestion of water contaminated with acrylamide.

3.6.2)

A) COUGH

1) WITH POISONING/EXPOSURE

a) Persistent cough and upper respiratory tract symptoms have been reported in cases of sub-acute ingestion, but pulmonary findings were absent (Igisu et al, 1975).

B) RESPIRATORY FAILURE

1) WITH POISONING/EXPOSURE

a) CASE REPORT - A 36-year-old man developed respiratory failure within 24 hours after ingesting mineral water contaminated with a high concentration of acrylamide. The patient recovered following treatment with high doses of N-acetylcysteine (Mehrhof et al, 2008).

Neurologic

3.7.1)

A) WITH POISONING/EXPOSURE

1) Neurological effects include hallucinations, confusion, tremors, myoclonus, opisthotonos, seizures, memory loss, euphoria, peripheral neuropathy, autonomic nervous system effects, and ataxia.
2) Alteration in the levels of dopamine, serotonin, and 5-hydroxyindoleacetic acid in regions of the brain and EEG abnormalities have also been noted.
3) Permanent peripheral and central neurological sequelae may occur following severe intoxication or prolonged occupational exposures.

3.7.2)

A) CENTRAL NERVOUS SYSTEM FINDING

1) WITH POISONING/EXPOSURE

a) Central nervous system effects in patients acutely exposed to large amounts may include confusion, hallucinations, tremors, agitation, disorientation, myoclonus, opisthotonos, hyperreflexia, seizures, encephalopathy, and a depressed level of consciousness (Donovan & Pearson, 1987).
b) In patients with significant sub-acute exposures for days to weeks there may be dizziness, euphoria, memory loss, vivid visual hallucinations, slurred speech, normal or hyperactive reflexes, somnolence, and truncal ataxia. These may be followed weeks later by peripheral neuropathy with distal extremity paresthesias and mildly decreased touch and vibration senses (Igisu et al, 1975; Garland & Patterson, 1967).
c) CASE REPORT - A 36-year-old man experienced balance and gait problems, confusion, and visual hallucinations several hours after ingesting mineral water that tasted bitter. Over the next 24 hours, the patient developed multi-organ failure and signs of disseminated intravascular coagulation and rhabdomyolysis. Three days post-admission, toxicologic analysis of the patient's blood and the mineral water revealed a high concentration of acrylamide. The patient was given high doses of N-acetylcysteine, and cardiac and renal function, platelet count and coagulation parameters improved; however, he developed severe peripheral polyneuropathy, and occasional confusion and hallucinations continued to persist (Mehrhof et al, 2008).

B) SECONDARY PERIPHERAL NEUROPATHY

1) WITH POISONING/EXPOSURE

a) Cerebellar disturbances, autonomic nervous system symptoms, and severe peripheral neuropathy due to acrylamide exposure are characteristic (Hashimoto & Ando, 1971; He et al, 1989) and in severe intoxication incidents may leave RESIDUAL DEFICITS with permanent neurologic sequelae (Aminoff, 1985; HSDB , 1999). Manifestations of encephalopathy may occur with acute high-level exposures (Le Quesne, 1985).

1) Pathological changes include demyelination, axonal degeneration, proliferation of Schwann cells (Hashimoto & Ando, 1971), and degenerating fibers (Fullerton, 1969).

b) Maximal motor nerve conduction velocity in 3 patients was normal or only slightly reduced except for 1 nerve; the author suggested that the slow conduction was due to degeneration followed by regeneration of the distal parts of the fibers (Fullerton, 1969).
c) CASE REPORT - Murray et al (1994) report a case of a mine worker exposed by acrylamide inhalation. Symptoms of central and peripheral neuropathy developed one month following the initial exposure. Following a total 4 year exposure period, the patient was incapacitated with polyneuropathy. Some improvement occurred following discontinuation of exposure, but the worker remained disabled 10 years later.
d) NEUROTOXIC INDEX - Calleman et al (1994) and Bergmark et al (1993) describe neurotoxic indexes for the determination of peripheral neuropathies in occupational exposures. The index is based on numbness, loss of position, pain, touch, and vibration sensation, clumsiness of hands, difficulty grasping, ataxia, decreased ankle reflexes, muscular atrophy, and abnormal EMG and ENG findings.

1) The index, which predicted the clinical diagnosis of peripheral neuropathy, correlates with levels of mercapturic acids in 24 hour urine, hemoglobin adducts of acrylamide, accumulated in vivo doses of acrylamide, and employment duration (Bergmark et al, 1993a).

e) Electroneuromyography findings have shown no spontaneous denervation potentials of sampled muscles, indicating more involvement of distal sensory fibers than distal motor fibers in acrylamide neuropathy. This probably reflects a central-peripheral distal axonopathy (Calleman et al, 1994).
f) Permanent peripheral or central neurological sequelae may occur in patients with severe intoxication (HSDB , 1999).
g) CASE REPORT - A 36-year-old man developed severe peripheral polyneuropathy approximately 6 days after ingesting mineral water contaminated with high concentration of acrylamide. The neuropathy initially presented as tetraplegia, progressing to bilateral affection of the vagal nerve and resulting in laryngoplegia. Despite intensive supportive care, the patient was still unable to walk 21 days post-ingestion (Mehrhof et al, 2008).

C) CHRONIC POISONING

1) WITH POISONING/EXPOSURE

a) Chronic exposure of weeks to months may be manifested by lassitude, sleepiness, nervousness, irritability, nerve degeneration, paresthesias, asthenia, and distal peripheral neuropathies.

1) Motor and proprioceptive disturbances exceed sensory losses, and are associated with foot drop, absent deep tendon reflexes, muscle wasting, and persistent ataxia (Fullerton, 1969; Satchell & McLeod, 1981) Auld & Bedwell, 1967). Severe cases may have cerebellar and ocular involvement (Myers & Macun, 1991).
2) The early, prominent signs and symptoms of chronic acrylamide poisoning have been demonstrated in workers as numbness in hands and feet, fatigue, sweating of the hands and feet, and peeling of skin. Difficulty in grasping, dizziness, and weak legs with an unsteady gait were also present. Impairment of vibration sensation appears to be an early sign of acrylamide neuropathy (Calleman et al, 1994; (Bachmann et al, 1992; Myers & Macun, 1991; He et al, 1989).

D) HYPOREFLEXIA

1) WITH POISONING/EXPOSURE

a) CASE SERIES - The Achilles tendon reflex and the knee-jerk reflex had completely disappeared in 3 patients who had worked for 3 to 12 months in a factory where acrylamide was being manufactured from acrylonitrile (Fujita et al, 1960). A patient exposed for 29 weeks with absent reflexes had little improvement after 1 year (Kesson et al, 1977).

E) CLOUDED CONSCIOUSNESS

1) WITH POISONING/EXPOSURE

a) Mental confusion and ataxia were reported in a family whose well water contained a large amount of acrylamide (Igisu et al, 1975).

F) ELECTROENCEPHALOGRAM ABNORMAL

1) WITH POISONING/EXPOSURE

a) The EEG was abnormal but non-specific in workers who had been handling acrylamide (Takahashi et al, 1971).

G) DISORDER OF AUTONOMIC NERVOUS SYSTEM

1) WITH POISONING/EXPOSURE

a) Autonomic nervous system symptoms are characteristic of acrylamide poisoning (Hashimoto & Ando, 1971).

H) PARESTHESIA

1) WITH POISONING/EXPOSURE

a) Paresthesias of the hands and asthenia and disturbances of sensitivity and motion in the lower limbs may develop. In 2 patients exposed for more than 22 weeks, there was little recovery after 1 year (Cavigneaux & Cabasson, 1972; Kesson et al, 1977; He et al, 1989).

3.7.3)

A) ANIMAL STUDIES

1) NEUROPATHY

a) Thioctic acid treatment enhanced recovery after partial denervation of muscles in acrylamide-poisoned experimental animals. The results suggest that thioctic acid is able to react with acrylamide before it has a chance to bind and deplete axonal and nerve terminal glutathione (Kemplay et al, 1988).
b) In experimental animals, incorporation of exogenous sodium pyruvate in the diet of rats receiving acrylamide retarded the onset and development of functional, morphological, and biochemical measures of acrylamide neuropathy (Sabri et al, 1989).
c) RATS - Studies in rats have demonstrated an acrylamide inhibition of creatine kinase activity in the brain causing apparent neurological signs. Areas in the hypothalamus showed the most significant CK activity (54 percent) while activity in the cerebellar vermis was less (27 percent) (Kohriyama et al, 1994).
d) RATS - intoxicated with acrylamide over a 4 week period developed significant increases in the number of axon terminal branches and frequency of swellings of preterminal, terminal, and ultraterminal axons. An increase of myelinated fibers showing axonal degeneration in the extensor digitorum longus muscle was also demonstrated (Madrid et al, 1993).
e) MONKEYS - trained to report detection of vibration or an electrical stimulus were intoxicated with acrylamide. Vibration sensitivity was reduced in the treated monkeys. Repeat exposures produced a similar reduction in vibration sensitivity. Vibration sensitivity may be a useful monitoring tool for following the time course of acrylamide-induced peripheral neuropathies (Maurissen et al, 1990).
f) RATS - Peripheral nerve degeneration appeared to have completely reversed after 3 days in lower-dosed rats (Burek et al, 1980).
g) Poisoned adult baboons confirmed both motor and sensory nerve degeneration, affecting particularly the distal parts of the longest nerve fibers (Hopkins & Gilliat, 1967).
h) RATS - Intraperitoneal injection of acrylamide in rats induced alteration in the levels of dopamine, serotonin, and 5-hydroxyindoleacetic acid in different regions of the brain (HSDB, 1991).

2) TREMOR

a) MONKEYS - Forelimb tremor was noted in monkeys poisoned with acrylamide, and persisted for up to 2 weeks after cessation of dosing (Maurissen et al, 1983).

3) ATAXIA

a) MONKEYS - Loss of balance was noted in monkeys poisoned with acrylamide, and persisted for up to 2 weeks after cessation of dosing (Maurissen et al, 1983).

4) EEG ABNORMAL

a) CATS - EEG abnormalities were noted prior to the development of ataxia in cats treated with acrylamide (HSDB , 1999).

5) NEOPLASM

a) In experimental animals, exposure to acrylamide for 3 weeks lead to progressive loss of Purkinje cells (HSDB , 1999) and tumors (Johnson et al, 1986).

Gastrointestinal

3.8.1)

A) Anorexia and gastrointestinal disturbances may be seen in patients with sub-acute exposure. Pancreatitis following ingestion has been reported.
B) Weight loss, despite tube feeding, and fecal incontinence have been observed in experimental animals.

3.8.2)

A) LOSS OF APPETITE

1) WITH POISONING/EXPOSURE

a) Anorexia and gastrointestinal disturbances may be seen in patients with sub-acute or chronic exposure (Garland & Patterson, 1967).

B) PANCREATITIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT - Pancreatic injury was reported in one case of acute ingestion, with hyperglycemia and elevated amylase levels (Donovan & Pearson, 1987).

3.8.3)

A) ANIMAL STUDIES

1) WEIGHT DECREASE

a) Weight loss occurs in experimental animals despite tube feedings, and there may be regurgitation due to development of megaesophagus (Satchell & McLeod, 1981). Fecal incontinence also occurs in experimental animals.

Hepatic

3.9.1)

A) WITH POISONING/EXPOSURE

1) Hepatic toxicity has been reported in humans and experimental animals.
2) Hepatic failure has been reported in one patient following ingestion of water contaminated with acrylamide.

3.9.2)

A) LIVER ENZYMES ABNORMAL

1) WITH POISONING/EXPOSURE

a) Hepatic toxicity as evidenced by elevated transaminase levels has been reported in humans and experimental animals after acute exposure (McCollister et al, 1964; Donovan & Pearson, 1987; Fujita et al, 1981).

B) ABNORMAL LIVER FUNCTION

1) WITH POISONING/EXPOSURE

a) CASE SERIES - Slight abnormalities of liver function were reported in 3 patients who had worked for 3 to 12 months in a factory where acrylamide was manufactured from acrylonitrile (Fujita et al, 1981).

C) HEPATIC FAILURE

1) WITH POISONING/EXPOSURE

a) CASE REPORT - A 36-year-old man developed hepatic failure within 24 hours after ingesting mineral water contaminated with a high concentration of acrylamide. The patient recovered following treatment with high doses of N-acetylcysteine (Mehrhof et al, 2008).

Genitourinary

3.10.1)

A) WITH POISONING/EXPOSURE

1) Renal toxicity and oliguria may occur from acute exposure. Overflow urinary incontinence may result from chronic exposure.
2) Renal failure was reported in one patient following ingestion of water contaminated with acrylamide.

3.10.2)

A) TOXIC NEPHROPATHY

1) WITH POISONING/EXPOSURE

a) Renal toxicity and decreased urinary output have been reported in humans and experimental animals following acute exposure (McCollister et al, 1964; Donovan & Pearson, 1987).

B) RENAL FAILURE SYNDROME

1) WITH POISONING/EXPOSURE

a) CASE REPORT - A 36-year-old man developed renal failure within 24 hours after ingesting mineral water contaminated with a high concentration of acrylamide. The patient recovered following treatment with high doses of N-acetylcysteine (Mehrhof et al, 2008).

C) RETENTION OF URINE

1) WITH POISONING/EXPOSURE

a) Urinary retention and overflow urinary incontinence have been reported in patients with sub-acute or chronic exposure (LeQuesne, 1985).

3.10.3)

A) ANIMAL STUDIES

1) URINARY TRACT DISORDER

a) Urinary bladder function in rats exposed to a total of 300 mg/kg acrylamide became abnormal within one week of dosing. Low average bladder pressures and absence of bladder contractions were noted (Kudlacz et al, 1989).

2) TESTIS DISORDER

a) Reproductive function was disrupted in rats chronically exposed to acrylamide, which interfered with ejaculation, sperm transport and uterine implantation (Zenick et al, 1986). There have been reports of testicular atrophy with chronic high-dose acrylamide in laboratory animals and increased chromosomal aberrations in germ cells of male mice (Shiraishi, 1978).

Acid-Base

3.11.1)

A) WITH POISONING/EXPOSURE

1) In severe poisonings, metabolic acidosis may occur.

3.11.2)

A) ACIDOSIS

1) WITH POISONING/EXPOSURE

a) In patients with severe poisoning, metabolic acidosis may occur due to lactate accumulation from agitation, seizures, and hypoperfusion (Donovan & Pearson, 1987).

Hematologic

3.13.1)

A) WITH POISONING/EXPOSURE

1) In acute and sub-acute exposures, severe thrombocytopenia, disseminated intravascular coagulation, ecchymoses, and alteration in phagocyte function have been reported.

3.13.2)

A) THROMBOCYTOPENIC DISORDER

1) WITH POISONING/EXPOSURE

a) Severe thrombocytopenia and ecchymoses have been reported in patients with acute or sub-acute exposure (Igisu et al, 1975; Donovan & Pearson, 1987).

B) DISSEMINATED INTRAVASCULAR COAGULATION

1) WITH POISONING/EXPOSURE

a) CASE REPORT - Disseminated intravascular coagulation was reported in a 36-year-old man who ingested mineral water contaminated with a high concentration of acrylamide. The patient recovered following treatment with high doses of N-acetylcysteine (Mehrhof et al, 2008).

C) IMPAIRED PHAGOCYTOSIS

1) WITH POISONING/EXPOSURE

a) In vitro, high concentrations of acrylamide had an inhibitory effect on several human polymorphonuclear leukocyte phagocytic functions (HSDB , 1999).

3.13.3)

A) ANIMAL STUDIES

1) ERYTHROCYTES ABNORMAL

a) RATS - Packed cell volume, red blood cell, and hemoglobin values were slightly decreased in rats exposed to acrylamide for up to 93 days (Burek et al, 1980).

2) CHOLINESTERASE DECREASED

a) RATS - Serum cholinesterase activity was decreased in female rats dosed with 20 mg/kg/day of acrylamide for up to 93 days (Burek et al, 1980).

Dermatologic

3.14.1)

A) An exfoliative, erythematous rash of the hands may be seen with chronic dermal exposure.

3.14.2)

A) ERUPTION

1) WITH POISONING/EXPOSURE

a) An exfoliative, erythematous rash, particularly on the hands, may occur with dermal exposure (Garland & Patterson, 1967) Auld & Bedwell, 1967). Excessive sweating, coldness, and cyanosis of the hands and feet also occurs (Igisu et al, 1975).

B) CONTACT DERMATITIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT - Eczema developed on both hands of a laboratory worker despite the wearing of gloves. A patch test with acrylamide was positive (Dooms-Goossens et al, 1991). Contact dermatitis has been reported in workers with occupational exposure (HSDB , 1999).

Musculoskeletal

3.15.1)

A) WITH POISONING/EXPOSURE

1) Weakness, distal extremity muscle wasting, muscle pain, cramping, and rhabdomyolysis have been reported.

3.15.2)

A) MUSCLE PAIN

1) WITH POISONING/EXPOSURE

a) Distal extremity muscle wasting, muscle pain, and cramping are reported to occur (Garland & Patterson, 1967).

B) RHABDOMYOLYSIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT - Rhabdomyolysis was reported in a 36-year-old man who ingested mineral water contaminated with a high concentration of acrylamide. The patient recovered following treatment with high doses of N-acetylcysteine (Mehrhof et al, 2008).

C) MUSCLE WEAKNESS

1) WITH POISONING/EXPOSURE

a) Asthenia and disturbances of sensitivity and motion in the limbs may develop. In 2 patients exposed for more than 22 weeks, there was little recovery after 1 year (Cavigneaux & Cabasson, 1972; Kesson et al, 1977; He et al, 1989).

Endocrine

3.16.1)

A) Pituitary, thyroid, and adrenal gland tumors developed in chronically exposed rats.

3.16.3)

A) ANIMAL STUDIES

1) NEOPLASM

a) RATS - given oral acrylamide for 2 years developed adrenal pheochromocytomas, follicular adenomas of the thyroid, and an increased incidence of pituitary adenomas, thyroid follicular tumors, and mammary adenomas (HSDB , 1999).

Reproductive

3.20.1)

A) At the time of this review, no studies on the possible reproductive effects of acrylamide in humans were found.
B) In rodent studies, teratogenic effects, maternal and paternal toxic effects such as pre-implantation and post-implantation mortality, changes in litter size, and changes in sperm morphology were observed.

3.20.2)

A) ANIMAL STUDIES

1) In laboratory animals, prenatal exposure had no neurologic effect on the offspring, although long-term alterations in gastrointestinal enzymes occurred (Edwards, 1975; Walden et al, 1981).
2) RAT - The embryos are not affected at doses up to 15 milligrams/kilogram/day; however, maternal toxicity does occur at this dose (Field et al, 1990).
3) Acrylamide was not teratogenic in developing chick embryos (Kankaapaa et al, 1979), but paternal dosing with acrylamide, 50 mg/kg intraperitoneally for 5 days, induced morphologically abnormal preimplantation mouse embryos. Also found were increased numbers of micronuclei in normal and abnormal embryos (Titenko-Holland et al, 1998).
4) When male mice were treated with the acrylamide metabolite glycidamide and mated to normal females, there was a decrease in the litter size, a decreased number of living implants, and an increase in resorption moles (Generoso et al, 1996).
5) In a continuous breeding study in mice, acrylamide exposure in drinking water caused dominant lethal effects and heritable translocations in males and an 11 percent decrease in the number of pups, but did not cause neurotoxicity (Chapin et al, 1995).
6) Fetal mice showed hypoplasia of the lymphatic organs and of the centers for hematopoiesis in liver and bone marrow after prenatal acrylamide exposure. Hemorrhages of the placenta were also frequently seen (HSDB , 1996).
7) Prenatal exposure had no neurologic effect in rats, but long-term alterations in gastrointestinal enzymes occurred in some animals (Edwards, 1975; Edwards, 1976; Walden et al, 1981). Acrylamide was not teratogenic in mice or rats; there was a dose-related increase in incidence of normal variations, such as an extra rib (Field et al, 1990).
8) Observed toxic effects on the newborn rat were biochemical and metabolic changes and changes in growth statistics (RTECS , 1999).
9) Field et al (1990) reported that the incidence of variations, primarily an extra rib, increased with dose. Maternal treatment with acrylamide induced hindlimb splaying in the offspring (Field et al, 1990).

3.20.3)

A) PLACENTAL BARRIER-HUMANS

1) In a study of 11 pregnant women, the concentration of the specific acrylamide hemoglobin adduct, N-2-carbamoylethylvaline, in neonatal blood was approximately 50% of the maternal blood level. In 1 mother who was a smoker, exposure to acrylamide was increased significantly for both the mother and the neonate as compared to non-smoking mothers and their neonates (Schettgen et al, 2004).

B) ANIMAL STUDIES

1) PLACENTAL BARRIER

a) Acrylamide crosses the placental barrier and causes decreased birth weight (Edwards, 1975) Zelnick et al, 1986). It caused depression in rat pups, but no other evidence of adverse fetal effects (Edwards, 1975; Edwards, 1976; Zenick et al, 1986).

3.20.4)

A) ANIMAL STUDIES

1) Weight gain was depressed in rat pups during breast feeding when the dams were exposed to acrylamide (Zenick et al, 1986; Walden et al, 1981).

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS79-06-1 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) IARC Classification

a) Listed as: Acrylamide
b) Carcinogen Rating: 2A

1) The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans. This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent (mixture) may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals and strong evidence that the carcinogenesis is mediated by a mechanism that also operates in humans. Exceptionally, an agent, mixture or exposure circumstance may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans.

3.21.2)

A) Sufficient evidence exists to indicate that acrylamide is carcinogenic in experimental animals.

3.21.3)

A) CARCINOMA

1) The ACGIH (1991) and NIOSH (1999) list acrylamide as a suspected human carcinogen. Acrylamide should be considered a carcinogenic risk to humans (IARC, 1986; Dearfield et al, 1988).

B) DIETARY ACRYLAMIDE AND CANCER

1) In a prospective study of 61,467 women, no evidence of an association between dietary intake of foods with elevated acrylamide, and colorectal cancer was found (Mucci et al, 2006). In a large series of case-controlled studies, no association was found between dietary acrylamide and oral, pharyngeal, laryngeal, esophageal, colorectal, breast, ovary, or prostate cancers (Pelucchi et al, 2006).
2) A prospective cohort study of 120,852 participants (male, n=58,279; female, n=62,573; age range, 55 to 69 years) in the Netherlands found an association between dietary intake of acrylamide and increased risk for multiple myeloma in all men and men who never smoked, as well as an increased risk for follicular lymphoma in all men. After 16.3 years of follow-up (from September 1986 through December 2002), 1233 confirmed cases of lymphatic malignancies were identified that had complete data for covariables and were included in the analysis. Increased risk for multiple myeloma was present for the continuous acrylamide variable in all men (smokers and non-smokers combined; HR per 10 mcg acrylamide/day, 1.14; 95% CI, 1.01 to 1.27), with a trend across the quintiles of acrylamide intake (p=0.02), and in men who never smoked (HR per 10 mcg acrylamide/day, 1.98; 95% CI, 1.38 to 2.85). Increased risk for follicular lymphoma was also present for the continuous acrylamide variable in all men (HR per 10 mcg acrylamide/day, 1.28; 95% CI, 1.03 to 1.61). No associations were observed between acrylamide intake and the risk of diffuse large cell lymphoma, Waldenstrom macroglobulinemia, or immunocytoma in men or in women, or mantle cell lymphoma or T-cell lymphoma in men (too few women were in the latter 2 groups for meaningful analyses). No clear association was observed for chronic lymphocytic leukemia and the continuous acrylamide variable (HRs in men for the second and third tertiles after 8 years of follow-up, 0.85 and 0.8, respectively; 95% CIs, 0.45 to 1.63, and 0.41 to 1.55, respectively). The results of this study should be interpreted cautiously, as they may reflect true biological effects or chance findings. Further studies into the observed associations are needed to discern this (Bongers et al, 2012).

C) LACK OF EFFECT

1) In a study of workers chronically exposed to acrylamide, there were no increases in the death rate, no increases in malignant neoplasms, and no relationship to any specific cancers (Sobel et al, 1986). A similar study with a much larger sample size also found no connection between chronic occupational acrylamide exposure and mortality (Collins et al, 1989).

3.21.4)

A) CARCINOMA

1) Acrylamide was found to be carcinogenic by RTECS criteria in rats with testicular tumors and uterine tumors. In the mouse, acrylamide was found to be neoplastic and carcinogenic by RTECS criteria with lungs, thorax or respiratory tumors and skin and appendages tumors (RTECS , 2002).
2) In an experimental study, acrylamide acted as a tumor initiator on the skin of mice (Bull et al, 1984).
3) Rats given oral acrylamide over a 2-year period developed mammary adenocarcinomas, mesotheliomas of the tunica of the testes, and uterine adenocarcinomas (HSDB , 1999).
4) In a lifetime acrylamide exposure study in rats, there was an increased incidence of benign tumors of the thyroid and mammary glands at a dose which not cause overt neurotoxicity (Friedman et al, 1995).
5) Chronic acrylamide treatment in rodents has been shown to induce tumors in both rats and mice. Park et al (2002) have proposed an acrylamide-induced cellular transformation involvement in tumor production. Their studies have demonstrated that acrylamide reduces GSH levels in Syrian hamster embryo (SHE) cells, while coadministration with N-acetylcysteine prevents acrylamide-induced reduction of GSH. Acrylamide treatment for 7 days continuously induced morphological transformation in SHE cells. The authors proposed that clastogenic activity of acrylamide, as well as, acrylamide reactivity to macromolecules with GSH depletion in SHE cells (causing structural and cellular functional changes), may be involved in acrylamide-induced SHE cell morphological transformation.
6) Significant increases in tumors of the mammary gland, nervous system, oral cavity, scrotum, thyroid, and skin were seen in rats given acrylamide at 2 mg/kg/day (Johnson et al, 1986). Acrylamide also acted as a tumor initiator in a mouse skin painting study (Bull et al, 1984).

B) MESOTHELIOMA

1) RATS who received acrylamide over a 2-year period had a significantly increased incidence of scrotal mesothelioma when compared with controls (Johnson et al, 1986; Friedman et al, 1995).

Genotoxicity

A)

B)

C)

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Cerebrospinal fluid may have a slightly increased protein level.
B) Monitor renal and hepatic function tests, CBC, platelet count, amylase and blood glucose in patients with significant exposure.

4.1.2)

A) TOXICITY

1) There are no data available relating plasma levels to degree of toxicity. The rapid elimination half-life of acrylamide from blood suggests a poor correlation with clinical effects (Miller et al, 1982).

B) BLOOD/SERUM CHEMISTRY

1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count and liver and kidney function tests is suggested for patients with significant exposure.
2) As pancreatic injury may occur with acute exposure, monitor serum amylase and blood glucose (Donovan & Pearson, 1987).

C) HEMATOLOGIC

1) Monitor platelet count.

4.1.3)

A) URINALYSIS

1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring urinalysis is suggested for patients with significant exposure.

4.1.4)

A) OTHER

1) CEREBROSPINAL FLUID

a) Cerebrospinal fluid may have a slightly increased protein content (Garland & Patterson, 1967; Igisu et al, 1975) Auld & Bedwell, 1967).

2) ELECTROPHYSIOLOGICAL TESTING

a) Nerve conduction studies (particularly sensory nerve action potentials and somatosensory evoked potentials) can be used to evaluate the toxic effects of acrylamide (Aminoff, 1985). Sensory nerve action potentials appear to be the most sensitive indicator (Takahashi et al, 1971; Fullerton, 1969). Sensory nerve conduction studies reveal decreased action potential amplitudes and conduction velocities in distal sensory nerves, but little change in motor nerves (Takahashi et al, 1971).
b) EEG - abnormalities have also been reported in some chronically exposed patients (Igisu et al, 1975; Donovan & Pearson, 1987; Takahashi et al, 1971).

3) OTHER

a) ANNUAL EXAMINATION - should be performed annually for all workers chronically exposed to acrylamide. Examination should stress the CNS, eyes, skin, and the peripheral nervous system. Individuals with CNS diseases should not work with acrylamide.

Methods

A)

1) Acrylamide may be measured in tissues and blood by HPLC, and in solution by gas chromatography (Miller et al, 1982; LeQuesne, 1980).

B)

1) Quantitation of airborne acrylamide vapors and dust is made by differential pulse polarographic methods (Betso & McLean, 1976; McLean et al, 1978).

Treatment

Life Support

A)

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Patients with significant exposure who display any CNS symptoms should be hospitalized. Any patient with a single large exposure should be admitted or observed for a minimum of 6 to 12 hours due to possible delayed onset of toxicity (Donovan & Pearson, 1987).

6.3.1.2) HOME CRITERIA/ORAL

A) Patients with acute exposure who remain asymptomatic for 6 to 12 hours post-exposure may be discharged to home, but follow-up examination is advised due to possible delayed development of peripheral neuropathy (Donovan & Pearson, 1987). Nerve conduction studies may be indicated.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Onset of symptoms may be delayed for several hours following acute exposure to a high dose (Donovan & Pearson, 1987). All such patients should be observed for a minimum of 6 to 12 hours for development of CNS symptoms.

6.3.5)

6.3.5.3) CONSULT CRITERIA/DERMAL

A) If rash occurs from chronic acrylamide dermal exposure, the patient should be evaluated for peripheral neuropathies and nerve conduction studies considered.

Monitoring

A)

B)

Oral Exposure

6.5.1)

A) EMESIS/ NOT RECOMMENDED

1) EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression and seizures.

B) ACTIVATED CHARCOAL -

1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION

a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).

1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).

2) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

6.5.2)

A) EMESIS/NOT RECOMMENDED

1) EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression and seizures.

B) ACTIVATED CHARCOAL

1) Adsorption of acrylamide to activated charcoal has not been established. In theory, this highly water-soluble substance may not be well adsorbed by activated charcoal, but there is no contraindication to its use in acrylamide ingestions.
2) CHARCOAL ADMINISTRATION

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

3) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

C) GASTRIC LAVAGE

1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).

a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.

2) PRECAUTIONS:

a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.

3) LAVAGE FLUID:

a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.

4) COMPLICATIONS:

a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).

5) CONTRAINDICATIONS:

a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.

6.5.3)

A) PYRIDOXINE

1) Pyridoxine (vitamin B6) delayed the onset and reduced the severity of acrylamide neurotoxicity in laboratory animals (Loeb & Anderson, 1981). The mechanism of action may be partial reversal of acrylamide-induced inhibition of glycolytic enzymes. Pyridoxine use in humans has been reported in a case of acrylamide ingestion, but with unproven effect (Donovan & Pearson, 1987). In cases of high-dose exposure or in symptomatic patients, pyridoxine use should be strongly considered.
2) Optimum dosage is unknown, but may be similar to that used for treatment of other toxicant-induced peripheral neuropathies. Doses of pyridoxine hydrochloride recommended in such cases for severe acute symptoms are 3 to 10 grams of 10 percent solution intravenously in D5W over 30 to 60 minutes (Wason et al, 1981; Yarbrough & Wood, 1983). It is questionable whether pyridoxine has any effect once neuropathy has become established (Wason et al, 1981).
3) Pyridoxine has been shown to have neurotoxic effects with chronic administration, but single doses of 70 to 357 milligrams per kilogram have been used without toxicity (Wason et al, 1981).
4) Pyridoxine hydrochloride is available as a 10 percent solution (100 milligrams per milliliter) in 30 milliliter (3 gram) vials.

B) PYRUVIC ACID

1) Blockade of glycolysis in nerve axons by neurotoxicants such as acrylamide may be bypassed by providing pyruvate, the end product of glycolysis. Pyruvate has been shown to delay the appearance of axonal degeneration and neurotoxicity in laboratory animals, but there was no difference in the final outcome (Sterman et al, 1983b). Pyruvate had no neurotoxicity in these studies when given alone. Even if effective, optimal dosage is unknown and sodium pyruvate has limited availability.

C) ACETYLCYSTEINE

1) Acrylamide is detoxified by glutathione conjugation and excreted as non-toxic mercapturic acid metabolites (Miller et al, 1982). As depletion of hepatic glutathione stores has been shown to lead to an earlier onset of toxicity, it is theorized that treatment with glutathione precursors such as N-acetylcysteine may modify acrylamide toxicity (Dixit et al, 1981; Donovan & Pearson, 1987). This treatment is speculative and cannot routinely be recommended at this time.
2) CASE REPORT - A 36-year-old man developed confusion, visual hallucinations, multi-organ failure, and signs of disseminated intravascular coagulation and rhabdomyolysis after ingesting mineral water contaminated with a high concentration of acrylamide. Approximately three days post-ingestion, the patient was treated with high-doses of N-acetylcysteine. Between days 4 and 8 , the patient's cardiac function normalized, with improvement of his platelet count, coagulation parameters, and renal function (Mehrhof et al, 2008).

D) SEIZURE

1) SUMMARY

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

2) DIAZEPAM

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

3) NO INTRAVENOUS ACCESS

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

4) LORAZEPAM

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

5) PHENOBARBITAL

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

6) OTHER AGENTS

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

E) HYPOTENSIVE EPISODE

1) SUMMARY

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

2) DOPAMINE

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

3) NOREPINEPHRINE

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

F) METHYLCOBALAMIN

1) Ultra-high doses of methylcobalamin (500 micrograms per kilogram) accelerated recovery from acrylamide-induced peripheral neuropathy in rats (Watanabe et al, 1994). Whether or not this treatment has value in humans is unknown.

Inhalation Exposure

6.7.1)

A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

6.7.2)

A) SUPPORT

1) Acrylamide is readily absorbed by inhalation.

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

6.8.1)

A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

6.8.2)

A) SUPPORT

1) It is unlikely that acute eye exposure would cause systemic symptoms or require further treatment.

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

6.9.1)

A) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

6.9.2)

A) SUPPORT

1) Single acute dermal exposure to acrylamide is unlikely to produce symptoms, but chronic exposure causes an exfoliative rash which can be treated with standard topical therapy and removal from further exposure.
2) Systemic symptoms are most often caused by occupational dermal exposure.

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Abstracts

Case Reports

A)

1) CHRONIC EFFECTS

a) There have been approximately 50 affected patients reported in the medical literature (LeQuesne, 1980). Most of these have been chronic low-dose occupational exposures (Takahashi et al, 1971) Auld & Bedwell, 1967; (Garland & Patterson, 1967).
b) DERMAL - Two cases of manual contact allergy to acrylamide have been reported in laboratory workers who consistently wore gloves. In both cases, patch tests were negative to all but acrylamide. Patch tests on the patients' skin covered by latex were positive, indicating that latex gloves were not protective (Lambert et al, 1988; Dooms-Goossens et al, 1991).
c) DERMAL - Several cases of contact dermatitis have been reported in printers who use Nyloprint(R) photopolymerising printing plates. Four of the 5 chemical fractions that were positive in patch tests on 7 printers were shown to contain secondary acrylamides (Pedersen et al, 1982).
d) DERMAL - Six workers were affected from dermal and inhalation exposure during the polymerization process of acrylamide monomer in the manufacture of flocculators. The main signs and symptoms which occurred after several weeks to months of exposure were numbness, paresthesias and weakness of the distal extremities, increased sweating and peeling of the hands, ataxia, lethargy, generalized tremors, slurred speech, weight loss, and bladder disturbances. Symptoms were thought to be due to midbrain involvement and peripheral neuropathy, and residual effects were still present after 6 months (Garland & Patterson, 1967).
e) The prevalence of occupational acrylamide poisoning in a group of exposed Chinese workers was 73.2 percent. Many of the cases had no clinical signs of intoxication despite abnormal electroneuromyographic (ENMG) findings, suggesting that ENMG may be a sensitive method to detect early signs of toxicity (He et al, 1989).
f) CHRONIC ORAL - Five members of a family in Japan were exposed to 400 ppm of acrylamide in well water for one month. Rhinorrhea, dizziness, confusion, truncal ataxia, urinary retention, ecchymoses, hallucinations, nystagmus, memory loss, somnolence, and hyperactive reflexes were present. CNS effects preceded development of peripheral neuropathy. Symptoms resolved after 4 months. The children were less affected than the adults (Igisu et al, 1975).

2) ACUTE EFFECTS

a) A 23-year-old female ingested approximately 18 grams (375 mg/kg) of acrylamide monomer crystals in water in a suicide attempt. Symptoms did not occur until 4 hours post-ingestion, when vivid visual hallucinations, tremors, extremity paresthesias, and agitation developed. A generalized seizure occurred 12 hours post-ingestion (Donovan & Pearson, 1987).

1) Coma and hypotension occurred. Evidence of hepatic, renal and pancreatic injury developed over several days. Treatment included pyridoxine, N-acetylcysteine, and supportive care. Distal motor weakness and worsening sensory neuropathy occurred after 1 week, and significant peripheral neuropathies were still present after 1 year (Donovan & Pearson, 1987).

Range Of Toxicity

Summary

A)

Minimum Lethal Exposure

A)

1) Death may occur at >1000 ppm (OHM/TADS , 2000)
2) Probable lethal oral dose is 50-500 mg/kg, or 1 teaspoon to 1 ounce, for a person that weighs 150 lbs. (Sittig, 1991).
3) A non-significant increase in pancreatic cancer deaths was seen in a study of four acrylamide plants. Incidence of pancreatic cancer did not increase with increased acrylamide exposure (IARC, 1994).
4) A person committed suicide by ingesting 400 mg/kg of acrylamide in 1993 (Calleman, 1996).
5) Cumulative doses of 100 milligrams/kilogram produce definite neurotoxicity and some deaths in experimental animals (Lowndes et al, 1978).

Maximum Tolerated Exposure

A)

1) Human poisonings are often complicated by skin absorption, so the dose-response relationship has not been established (Hathaway et al, 1996a).
2) A human mortality study was conducted between 1957 and 1970 on 371 workers. Exposures to acrylamide before 1957 were as high as 1.0 mg/m3 and decreased to 0.1 - 0.6 mg/m3 after 1970. No increases in specific cancers or total malignant neoplasms were detected (Hathaway et al, 1996a).
3) A 1990 study of 82 workers at a chemical plant found that employees exposed to atmospheric acrylamide at levels of 0.06-2.39 mg/m(3) had significantly higher prevalences of limb pain, numbness, and sweaty, peeling hands than unexposed workers (Bachmann et al, 1992).
4) More than 8500 workers who were exposed to acrylamide between 1925 and 1994 were studied to identify increased incidence of cancers. Exposures ranged from 0.001 to more than 3.0 mg/m(3).year based on 1950-1954 estimates. No increased risk of cancer death could be associated with acrylamide, except pancreatic cancer. Workers with 0.30 mg/m(3).year, or more, exposure were 2.26 times more likely to develop pancreatic cancer. A 1983 study of the same population found no increase in motality with increased acrylamide exposure (Marsh, 1999; Collins et al, 1989).
5) A 1985 study of 71 exposed workers in a Chinese acrylamide production factory recorded symptoms of peeling skin, excessively sweaty hands, leg muscle weakness, numbness and tingling in hands and feet, anorexia, sleepiness, and more. Air concentrations of acrylamide in the factory averaged 0.0324 mg/m(3), except during a renovation when concentrations were 5.56 - 9.02 mg/m(3). Skin exposures were not quantified, but water used to wash hands was found to have 410 mg/L acrylamide after three workers used it (Fengsheng, 1989).
6) Exposure to 0.3 mg/m(3), on average, does not cause overt neurological symptoms. However, symptoms do develop as exposure is increased to 0.6-0.9 mg/m(3). Neurological symptoms are certain to be present when average air concentrations reach 9 mg/m(3) (Calleman, 1996).
7) Neuropathy in acrylamide workers increased over the course of their first 1-2 years on the job. After two years of exposure, workers appear to reach a steady state neurotoxicity, where neuropathy does not advance because it is balanced by lesion repair (Calleman, 1996).
8) The NOAEL for acrylamide is estimated to be 0.6-0.8 mg/m(3) and the LOAEL to be 1.8-2.5 mg/m(3). These are based on an elimination rate of 0.15/hr and breathing volumes of 100 and 72 m(3) respectively. Acrylamide is predicted to have a human elimination rate 5 times slower than that of rats. However, total acrylamide exposure can not be based on air samples alone since dermal uptake is significant (Calleman, 1996).
9) An acute ingestion of 18 grams (375 mg/kg) produced severe toxicity with life-threatening cardiovascular and CNS effects (Donovan & Pearson, 1987).
10) Ingestion of well water contaminated with 400 parts per million of acrylamide for 1 month caused ataxia, hallucinations, and peripheral neuropathies in a family (Igisu et al, 1975). Children had less severe effects than adults with similar exposures.
11) Single acute doses of 50 - 100 mg/kg, or 75 to 300 mg/kg cumulative subacute dosing, in experimental animals caused neurologic testing deficits (Tilson et al, 1979; Gipon et al, 1977; Agrawal et al, 1981). Younger animals were less susceptible to these effects(Fullerton & Barnes, 1966).

Serum Plasma Blood Concentrations

7.5.2)

A) TOXIC CONCENTRATION LEVELS

1) GENERAL

a) No human data are available, but blood levels are not expected to correlate well with severity of symptoms due to the short elimination half-life.

Workplace Standards

A)

1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.

a) Adopted Value

1) Acrylamide

a) TLV:

1) TLV-TWA: 0.03 mg/m(3)
2) TLV-STEL:
3) TLV-Ceiling:

b) Notations and Endnotes:

1) Carcinogenicity Category: A3
2) Codes: IFV, Skin
3) Definitions:

a) A3: Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.
b) IFV: Inhalable fraction and vapor.
c) Skin: This refers to the potential significant contribution to the overall exposure by the cutaneous route, including mucous membranes and the eyes, either by contact with vapors or, of likely greater significance, by direct skin contact with the substance. It should be noted that although some materials are capable of causing irritation, dermatitis, and sensitization in workers, these properties are not considered relevant when assigning a skin notation. Rather, data from acute dermal studies and repeated dose dermal studies in animals or humans, along with the ability of the chemical to be absorbed, are integrated in the decision-making toward assignment of the skin designation. Use of the skin designation provides an alert that air sampling would not be sufficient by itself in quantifying exposure from the substance and that measures to prevent significant cutaneous absorption may be warranted. Please see "Definitions and Notations" (in TLV booklet) for full definition.

c) TLV Basis - Critical Effect(s): CNS impair
d) Molecular Weight: 71.08

1) For gases and vapors, to convert the TLV from ppm to mg/m(3):

a) [(TLV in ppm)(gram molecular weight of substance)]/24.45

2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:

a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance

e) Additional information:

B) NIOSH REL and IDLH Values for CAS79-06-1 (National Institute for Occupational Safety and Health, 2007):

1) Listed as: Acrylamide
2) REL:

a) TWA: 0.03 mg/m(3)
b) STEL:
c) Ceiling:
d) Carcinogen Listing: (Ca) NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).
e) Skin Designation: [skin]

1) Indicates the potential for dermal absorption; skin exposure should be prevented as necessary through the use of good work practices and gloves, coveralls, goggles, and other appropriate equipment.

f) Note(s): See Appendix A

3) IDLH:

a) IDLH: 60 mg/m3
b) Note(s): Ca

1) Ca: NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A).

C) Carcinogenicity Ratings for CAS79-06-1 :

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A3 ; Listed as: Acrylamide

a) A3 :Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.

2) EPA (U.S. Environmental Protection Agency, 2011): Likely to be carcinogenic to humans ; Listed as: Acrylamide
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 2A ; Listed as: Acrylamide

a) 2A : The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans. This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent (mixture) may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals and strong evidence that the carcinogenesis is mediated by a mechanism that also operates in humans. Exceptionally, an agent, mixture or exposure circumstance may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans.

4) NIOSH (National Institute for Occupational Safety and Health, 2007): Ca ; Listed as: Acrylamide

a) Ca : NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).

5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

D) OSHA PEL Values for CAS79-06-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) Listed as: Acrylamide
2) Table Z-1 for Acrylamide:

a) 8-hour TWA:

1) ppm:

a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.

2) mg/m3: 0.3

a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.

3) Ceiling Value:
4) Skin Designation: Yes
5) Notation(s): Not Listed

Toxicity Information

7.7.1)

A) References: ACGIH, 1991 Hathaway et al, 1996 RTECS, 2002

1) LD50- (INTRAPERITONEAL)MOUSE:

a) 170 mg/kg

2) LD50- (ORAL)MOUSE:

a) 107 mg/kg

3) LD50- (INTRAPERITONEAL)RAT:

a) 90 mg/kg

4) LD50- (ORAL)RAT:

a) 124 mg/kg

5) LD50- (SKIN)RAT:

a) 400 mg/kg -- blood changes; transaminases; peptidases

Pharmacology Toxicology

Toxicologic Mechanism

A)

1) Degeneration of the axon structures occurs initially at the distal ends of sensory nerves and progresses proximally, with lesser vulnerability of motor neurons (Howland, 1985; Miller & Spencer, 1985).
2) Degeneration of cerebellar purkinje cells occurs, as well as degeneration of large myelinated fibers in the sympathetic and parasympathetic nervous systems (Post & McLeod, 1977). The development of ataxia may be due to cerebellar lesions.

B)

1) Direct toxicity to neuron cell bodies may also occur by disruption of protein synthesis (LeQuesne, 1980).
2) Acrylamide also decreases brain dopamine, noradrenaline, and serotonin levels, and may alter responsiveness to dopamine (Tilson, 1981).
3) Glutathione-S-transferase, the conjugating enzyme and binding protein for the elimination of acrylamide, is inhibited by acrylamide (Dixit et al, 1981; Miller et al, 1982). Microsomal enzyme inducing drugs such as phenobarbital may speed the onset and increase the severity of acrylamide toxicity, suggesting the formation of a reactive toxic intermediate (Srivastava et al, 1985; Agrawal et al, 1981).

Physicochemical

Physical Characteristics

A)

Molecular Weight

A)

Other

A)

1) Odorless (HSDB , 2000)

Animal Toxicology

Clinical Effects

11.1.13)

A) OTHER

1) Although clinical reports of animal toxicity due to acrylamide are nonexistent, trial dosing of acrylamide has shown dogs, cats, rats, mice, monkeys, and chickens are susceptible (O'Donoghue, 1985).

Range Of Toxicity

11.3.2)

A) SPECIFIC TOXIN

1) NO-EFFECT LEVEL is between 0.2 and 1 milligram/ kilogram/day for 93 days in rats and 0.3 to 1 milligram/kilogram/day in cats (O'Donoghue, 1985).
2) MINIMUM TOXIC DOSE is 0.075 gram/kilogram to 5 gram/kilogram in cats (O'Donoghue, 1985).

References

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ACRYLAMIDE

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

Hepatic

Genitourinary

Acid-Base

Hematologic

Dermatologic

Musculoskeletal

Endocrine

Reproductive

Carcinogenicity

Genotoxicity

Monitoring Parameters Levels

Methods

Life Support

Patient Disposition

Monitoring

Oral Exposure

Inhalation Exposure

Eye Exposure

Dermal Exposure

Case Reports

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Serum Plasma Blood Concentrations

Workplace Standards

Toxicity Information

Toxicologic Mechanism

Physical Characteristics

Molecular Weight

Other

Clinical Effects

Range Of Toxicity

General Bibliography