Acrylamide

Characteristics

Uses

Environmental Transport

Environmental Deposition

Methods for Monitoring in the Environment

Methods for Monitoring Human Exposure

Safeguards Against Acrylamide Exposure


Harmful Effects

Dose Response

Absorption, Distribution and Metabolism

Primary Sites for Toxicity

Biomarkers

Mechanism of Action

Risk Assessment and Management

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Acrylamide Policy

Introduction to Policy

Decision Makers and Stakeholders

Current Policy

Policy Recommendations


References

BIOMARKERS OF DISEASE

Whereas hemoglobin adduct is a biomarker of exposure, there are currently few reports on biomarkers of response

BLOOD
Pieces of the acrylamide molecule will bind to specific amino acids such as valine and cysteine on hemoglobin molecules. When it reacts in human blood with N-terminal valine, the hemoglobin adduct N-(2-carbomoylethyl)valine (CEV) is created. In the lab hemoglobin is digested so that amino acids with bound pieces of the acrylamide molecules can be detected and quantified.

TUMORS
It is found that acrylamide is a rodent carcinogen at high doses (75-300 mg/kg/day) in mice. These studies are conflicted by acute exposure leading to neurotoxicity at approximately the same levels. It is also a scrotal carcinogen in rats at 2 mg/kg-dosed in drinking water. (49)
Choronic exposure in rat’s drinking water caused increased tumors of the vaginalis testis, mammary fibroadenomas, and adenomas of follicular cells of the thyroid. (47,48)

TESTES
One characteristic symptom of acute exposure is testicular atrophy and degeneration of germinal epithelium.

REPRODUCTION
Acrylamide affects the spermatid-spermatozoa stages when male rats are exposed to acrylamide in drinking water. Reproduction is hindered as pre-implantation and post-implantation losses occur causing more spontaneous abortions. High doses abnormally affect sperm causing decreased motility and morphology thereby affecting how often mating occurs. Reduced fertility is elevated in treated rodents.

Even at low doses acrylamide exposure decreases the litter sizes of rats and mice. Fertilized eggs do not implant on the uterus and embryos were aborted due to dominant lethal mutations in the sperm cell chromosome. When female rats are infected instead of male reproduction is not affected.(47,48,49)

NERVES
Long term exposure results in peripheral nerve and spinal cord lesions at 20mg/kg of body weight per day. Exposure to acrylamide produces a distal axonopathy in both humans and experimental animals. Both CNS and PNS are affected although CNS damage appears to require exposure to much higher concentrations. There are some potential for regeneration of PNS neurons but damage to CNS is permanent.

Acrylamide has been shown to decrease CNS concentrations of noradrenalin, dopamine and 5-hydroxytryptamien. Acrylamide and glycidamide interfer with neuronal intracellular transport and sperm motility. They inhibit the activity of kinesin and dyneine by binding to dopamine receptors and spermatid protamines. (47) It also appears to affect postsynaptic dopamine receptor affinity and density. The mechanism for this distal axonopathy is produced is unknown although several theories have been advanced, all supported by experimental evidence. It appears that acrylamide interferes with axonal retrograde transport mechanisms essential for the survival of the axon.

DEVELOPMENTAL
Adverse developmental and reproductive effects are also observed at acute exposure. In neonatal rodents, nerve degeneration and abnormal changes in intestinal enzymes are observed. Acrylamide may induce slight dose-dependent increase in plasma thyroxine and a slight dose-dependent decrease in plasma thyroid stimulating hormone. Thyroid gland morphometry showed significant decrease in the colloid area and a significant increase in the follicular cell height of treated rats as compared to controls. (45, 49)

DNA
Acrylamide does cause chromosome damage to mammalian cells. Acrylamide has been shown to bind to DNA which may result in the production of unsound structural proteins essential for axonal function. As such it is regarded as a potential mutagen since it can bind to DNA. (51)