CAS RN:79-06-1

Toxicity Summary

IDENTIFICATION AND USE: Acrylamide is a white crystalline solid. Acrylamide is mainly used in the production of polymers and copolymers for various purposes. All acrylamide in the environment is man-made, the main source being the release of the monomer residues from polyacrylamide used in water treatment or in industry. HUMAN EXPOSURE AND TOXICITY: Acrylamide is toxic and an irritant. Cases of acrylamide poisoning show signs and symptoms of local effects due to irritation of the skin and mucous membranes and systemic effects due to the involvement of the central, peripheral, and autonomic nervous systems. Local irritation of the skin or mucous membranes is characterized by blistering and desquamation of the skin of the hands (palms) and feet (soles) combined with blueness of the hand and feet. Effects on the central nervous system are characterized by abnormal fatigue, sleepiness, memory difficulties, and dizziness. With severe poisoning, confusion, disorientation, and hallucinations occur. Truncal ataxia is a characteristic feature, sometimes combined with nystagmus and slurred speech. Excessive sweating in the limb extremities is a common observation. Sign of central nervous system and local skin involvement may precede peripheral neuropathy by as much as several weeks. Peripheral neuropathy can involve loss of tendon reflexes, impairment of vibration sense, loss of other sensation, and muscular wasting in peripheral parts of the extremities. Nerve biopsy shows loss of large diameter nerve fibers as well as regenerating fibers. Autonomic nervous system involvement is indicated by excessive sweating, peripheral vasodilation, and difficulties in micturition and defecation. After cessation of exposure to acrylamide, most cases recover, although the course of improvement is prolonged and can extend over months to years. There are no epidemiological data available on cancer due to exposure to acrylamide. There is no evidence in man of any teratogenic effects resulting from acrylamide exposure. ANIMAL STUDIES: In rats, biotransformation of acrylamide occurs through glutathione conjugation and through decarboxylation. At least 4 urinary metabolites have been found in rat urine, of which mercapturic acid and cysteine- S-propionamide have been identified. Acrylamide and its metabolites are accumulated (protein-bound) in both nervous system tissue and blood (hemoglobin-bound). Accumulation in the liver and kidney as well as the male reproductive system has also been demonstrated. In animal studies, early changes in visual-evoked potentials (VEP), preceding clinical signs, as well as changes in somatosensory-evoked potentials (SEP), have been seen. Degenerative changes have been described in peripheral nerve axons, with less severe changes in the longer fibers of the CNS. Degeneration of Purkinje cells has been observed in chronically-intoxicated animals. The changes are most pronounced in the nerve endings of myelinated sensory fibers. The nerve endings show enlarged "boutons terminaux" and a widespread enlargement of nerve terminals from the accumulation of neurofilaments. This occurs in both the peripheral and central nervous systems. Impairment of axonal transport has been found in sensory fibers, and interference with glycolysis and protein synthesis has been observed in biochemical studies. Studies of neurotransmitter distribution and receptor binding in the brains of rats have revealed changes induced by acrylamide. In rats, changes in the concentration of neurotransmitters and in striatal dopamine receptor binding have been related to behavioral changes. Degenerative changes in renal convoluted tubular epithelium and glomeruli and fatty generation and necrosis of the liver have been seen in monkeys given large doses of acrylamide. In rats, acrylamide disrupted the metabolism of lipids and amino acids, induced oxidative stress, impaired hepatic porphyrin metabolism. Acrylamide was not mutagenic in Salmonella typhimurium with or without metabolic activation. Acrylamide induced chromosomal aberrations in the spermatocytes of male mice and increased cell transformation frequency in Balb 3T3 cells with a metabolic activation. Acrylamide was shown to be an initiator for skin tumors in mice. It increased the incidence of lung tumors in mice-screening assays. Absorption of acrylamide by the fetus has been demonstrated in animal (pig, dog, rabbit, and rat) studies. Oral administration of acrylamide, between the 7-16th days of gestation in rats, decreased the binding of dopamine receptors in the striatal membranes in 2-week-old pups. Degeneration of seminiferous tubules and chromosome aberrations in spermatocytes has been seen in acrylamide-treated male mice. Depressed plasma levels of testosterone and prolactin have also been observed. A statistically-significant increase in the incidence of mesothelioma of the scrotal cavity was observed in rats after long-term (2-year) administration of acrylamide in the drinking-water. Administration over 2 years of acrylamide not only increased the incidence of a variety of tumor types (both benign and malignant) but also decreased the life expectancy in both male and female rats. ECOTOXICITY STUDIES: Acrylamide was genotoxic in C. auratus peripheral blood cells. The fish exposure also produced a dose-dependent increase in total DNA strand breakage, the formation of erythrocytic nuclear abnormalities and in the levels of hepatic cytochrome P4501A (CYP1A) and glutathione S-transferase (GST) activity. Acrylamide may induce gonadotoxicity in mussels.
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