Fact sheet: Acrylamide Toxicity
Human exposure to acrylamide primarily comes from dermal contact with inhalation of dust and vapor in the industrial environment. The public may be exposed to acrylamide through the ingestion of drinking water that is contaminated with acrylamide or the intake of acrylamide from food.
Major health effects of acrylamide are skin irritation such as redness and peeling of the skin of palms and neuropathy regarding the central nervous system and the peripheral nervous system. Acute and subacute intoxication with a large dose by ingestion water drink contaminated with acrylamide can cause severe symptoms of the central nervous system. Long term exposure to acrylamide produces a motor and sensory polyneuropathy. Although severe exposure may result in permanent sequelae, affected humans recovered within several months to one year after cessation of exposure.
# CNS (central nervous system) symptoms : drowsiness, disturbance of balance, and mental changes characterized by confusion, hallucinations, memory loss Peripheral polyneuropathy : numbness of lower limbs, tingling of the fingers, tenderness to the touch, decreased pinprick sensation, vibratory loss, weak or absent tendon reflexes such as knee jerk, positive Romberg’s sign, ataxic gait, foot drop and muscular atrophy of the extremities
1. Acute toxicity : Acrylamide is a skin and respiratory tract irritant in humans. Reported oral LD50 values are in the range of 159 mg/kg to 300 mg/kg body weight (bw) in rats (14).
2. Subchronic/Chronic Toxicity : Acrylamide is a human neurotoxicant. Adverse effects in rats administered small amounts of acrylamide include general systemic toxicity and hematological changes. Acrylamide is also a neurotoxicant to animals.
In rats, repeated oral administration of acrylamide at doses of 20 mg/kg bw/day and above produced peripheral neuropathy, atrophy of skeletal muscle, and decreased erythrocyte parameters. At 5 mg/kg bw/day in a 90-day study in rats, peripheral lesions occurred and slight changes in peripheral nerve tissue could see only by electron microscopy at 1 mg/kg bw/day. No effects were seen at 0.2 mg/kg bw/day (16).
In monkeys, clinical signs of peripheral neuropathy occurred at doses of 10 mg/kg bw/day for up to 12 weeks(16).
# Carcinogenicity : Although inadequate evidence is available from human studies, several laboratory animal studies have shown that acrylamide causes a variety of tumors in rats and mice. Acrylamide has been classified by the U.S. EPA as a B2, a probable human carcinogen, by IARC as a 2B, a possible human carcinogen, and by ACGIH as an A3, confirmed animal carcinogen with unknown relevance to human.
Although two cohort mortality studies of occupational exposure to acrylamide have been conducted, they were inadequate to evaluate the potential carcinogenicity of humans (14).Two long-term studies in male and female rats were given the range of 0 to 3.0 mg/kg bw/day acrylamide in drinking water for 2 years. At the two highest doses, they observed the incidence of tumors increased in the scrotum, adrenal, thyroid, mammary, oral cavity, and uterus. Tumors of the brain and spinal cord were also seen in studies, but they did not show clear dose responses and did not attain statistical significance. Male and female mice given 6.25, 12.5, or 25 mg/kg bw/day, 3 times/week, for 8 weeks by gavage had a dose-responsive increase in lung adenoma.
# Genotoxicity : Acrylamide causes chromosomal aberrations, dominant lethality, sister chromatid exchanges and unscheduled DNA synthesis in various in vitro and in vivo systems. When administered at a level of 500 ppm in the diet for 3 weeks in mice, acrylamide caused a high frequency of sister chromatid exchanges and breaks.
# Developmental/Reproductive Toxicity : No information was found on the developmental/reproductive effects of acrylamide in humans. Acrylamide does not appear to cause structural developmental defects by oral administration to rats. Testicular atrophy and decreased fertility have been reported in male mice given acrylamide by mouth.
Impaired fertility associated with effects on sperm count and sperm mobility parameters has been demonstrated in male rats exposed to 15 mg/kg bw/day or more for 5 days. But in other rat studies effects on fertility were less clear. No effects on fertility in rats were observed in a 2-generation reproduction study in which males and females of each generation received 5 mg/kg bw/day for 10 to 11 weeks. Male mice treated with 0.035 g/kg by gavage 2 times/week, for 8 weeks had testicular atrophy, reduced numbers of spermatozoa, degenerating spermatids and spermatocytes, and multinucleate giant cells.
# Neurotoxicity : Acrylamide is a neurotoxin by either oral (in animals) or inhalation exposure (in humans and in animals). Toxic effects are central and peripheral neuropathy causing drowsiness, hallucinations, distal numbness, and ataxia. Recovery is possible after cessation of exposure. EPA has derived an oral reference dose (RfD) of 0.0002 mg/kg/day for acrylamide, based on adverse nervous system effects in laboratory animals.
A study of factory workers exposed to 0.07 to 2.5 times the NIOSH recommended exposure limit (REL 0.03 mg/m3, is roughly equivalent to 0.004 mg/kg bw/day for an 8-hour work day) showed a dose response relationship for abnormal sensation, decreased motor strength, abnormal gait, and skin abnormalities.