Biomonitoring Summary

Acrylamide

CAS No. 79-06-1

General Information

Acrylamide is a small organic molecule existing as a white crystalline powder in its pure state. Commercially, acrylamide is synthesized and used in the production of polyacrylamide polymer, gels, and binding agents. Polyacrylamides are useful water-compatible polymers used in water treatment, mineral processing, pulp and paper production, and in the synthesis or compounding of dye materials, soil conditioners, and cosmetics (NTP-CERHR, 2005). Smaller scale applications of polyacrylamides include additives to paperboard used for food packaging, in permanent press fabrics, in some sealing grouts, as an absorbent in disposable diapers, and in some cosmetics. In 1997, 217 million pounds of acrylamide were produced commercially in the U.S. (NEP-CERHR, 2005). Since acrylamide has limited volatility and high water solubility, environmental releases of acrylamide can enter aquatic systems and soils where it degrades within days and does not bioaccumulate (U.S. EPA, 1994). Recently, it was discovered that acrylamide is formed when starch-rich foods, such as potatoes and some grains, are heated at temperatures used for frying and baking. Natural substances in the food are converted to acrylamide. Foods such as french fries and potato chips can contain acrylamide at levels up to 100 times greater than levels found in cooked fish or poultry (DiNovi and Howard, 2004; FAO/WHO, 2005; FDA, 2006; Tareke et al., 2002).

People may be exposed to acrylamide from foods, smoking, drinking water, and from dermal contact with products that contain residual acrylamide. In the general population, the main source of exposure is from the diet, and an average daily intake is estimated as 0.3-2.0 µg/kg for adults (FAO/WHO, 2005), although additional exposures from cosmetic products could add a similar amount (NTP-CERHR, 2005). Estimated intakes in children are about twice that of adults (DiNovi and Howard, 2004). These estimated intakes are hundreds of times lower than occupational exposures, and well below doses known to cause nerve damage or carcinogenicity in animals, but are generally above the U.S. EPA reference dose of 0.2 µg/kg/day (U.S. EPA, 2006). Animal studies indicate that acrylamide is well absorbed, widely distributed in tissues, and is either metabolized to the reactive epoxide, glycidamide, or to glutathione conjugates (Calleman et al., 1990; Fennell et al., 2005). Elimination occurs mainly in the urine as mercapturic acid conjugates. Acrylamide is not thought to accumulate in the body at environmental doses, but can covalently bind to form adducts with proteins.

In humans, acrylamide has produced upper airway irritation following inhalation of high levels, ocular and dermal irritation from direct contact with acrylamide containing materials, and peripheral neuropathy following chronic occupational exposures. Axonal degeneration, presynatic nerve terminal binding (LoPachin, 2005), and neuronal DNA reactivity (Doerge et al., 2005) have been demonstrated in animals. Animal studies have shown that acrylamide can cause nerve damage (neuropathy), reproductive effects (reduced litter size, fetal death, male germinal cell injury, dominant lethality), and cancer (mammary, adrenal, thyroid, scrotal, uterine, and other sites) (FAO/WHO, 2005; NTP-CERHR, 2005, Rice, 2005; U.S. EPA, 2006). Glycidamide has been shown to react with DNA (Doerge et al., 2005; Klaunig et al., 2005; Maniere et al., 2005; Puppel et al., 2005), to increase the unscheduled synthesis of DNA in tumor susceptible tissues (Klaunig et al., 2005), and to increase DNA reactivity when glutathione is availability is reduced (Klaunig et al., 2005; Puppel et al., 2005). In addition, altered gene expression in testicular tissues (Yang et al., 2005) and sperm DNA adducts (Xie et al., 2006) have been demonstrated after acrylamide dosing. Acrylamide is clastogenic and can produce dominant lethal mutations, probably through its epoxide metabolite, glycidamide (NTP-CERHR, 2005; U.S. EPA, 2006). IARC classifies acrylamide as probably carcinogenic to humans. Additional information is available from U.S. EPA at: https://www.epa.gov/iris/ and from the Food and Agriculture Organization of the United Nations and WHO at: http://www.who.int/ipcs/food/jecfa/summaries/summary_report_64_final.pdf.

Biomonitoring Information

Acrylamide and glycidamide hemoglobin adducts (AHA and GHA, respectively) are markers of integrated acrylamide exposure over the preceding few months. Adducts are formed when either acrylamide or glycidamide react to form a permanent covalent bond with hemoglobin in the blood. After exposure ceases, levels of AHA adducts decline but may remain detectable for several months (Hagmar et al., 2001). AHA levels have been shown to increase with dietary intake (Hagmar et al., 2005, Vesper 2005) and smoking (Bergmark, 1997; Schettgen et al., 2002, 2004).

Levels of AHA and GHA reported the NHANES 2003–2004 sample are generally similar to those seen in several previous studies of non-occupationally exposed subjects (Bergmark et al., 1997; Hagmar et al., 2005; Schettgen et al., 2002, 2003, 2004; Vesper et al., 2006, 2008), although different analytic methods can affect results. Several of these studies have shown that smokers have adduct levels that are three to fourfold higher than non-smokers; most non-smokers had levels less than about 100 pmol/gram hemoglobin. The degree of formation of the more toxic glycidamide and levels of GHA can be influenced by polymorphisms in several of the enzymes that metabolize acrylamide (Duale et al., 2009). Younger children may have slightly higher levels possibly due to increased intake of acrylamide-containing foods relative to body size (Dybing et al., 2005, Mucci et al., 2008).

In occupational settings, AHA levels were several fold to several hundredfold higher than levels in non-exposed non-smokers (Bergmark et al., 1993; Hagmar et al., 2001; Perez et al., 1999). AHA levels correlated with a neurologic symptom index and specific physiologic measures in an occupational setting and correlated better with clinical signs and symptoms than urinary excretion of the mercapturic acid metabolite (Calleman et al., 1994). In another study, symptoms of numbness or tingling in the extremities did not occur in exposed workers whose AHA levels were below 510 pmol/gram hemoglobin, and 39% of workers with levels above 1000 pmol/gram hemoglobin had these symptoms (Hagmar et al., 2001).

Finding a measurable amount of acrylamide or glycidamide hemoglobin adducts in blood does not imply that these levels of acrylamide or glycidamide hemoglobin adducts cause adverse health effects. Biomonitoring studies of acrylamide or glycidamide hemoglobin adducts provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels of acrylamide than are found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.

References

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Calleman CJ, Bergmark E, Costa LG. Acrylamide is metabolized to glycidamide in the rat: evidence from hemoglobin adduct formation. Chem Res Toxicol 1990;3:406-412.

Calleman CJ, Wu Y, He F, Tian G, Bergmark E, Zhang S, et al. Relationships between biomarkers of exposure and neurological effects in a group of workers exposed to acrylamide.Toxicol Appl Pharmacol 1994;126(2):361-71.

DiNovi M and Howard D. The Updated Exposure Assessment for Acrylamide. 2004 Acrylamide in Food Workshop: Update - Scientific Issues, Uncertainties, and Research Strategies. April 13-15, 2004, Chicago, Illinois.

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