Acrylamide
Information extracted from:
Guidelines
for drinking-water quality, 2nd ed. |
1. General description
Identity
CAS no.: 79-06-1
Molecular formula: C3H5NO
Physicochemical properties (1)
| Property | Value |
| Physical state | White crystalline solid |
| Melting point | 84B85 °C |
| Boiling point | 125 °C at 3.33 kPa |
| Density | 1.122 g/cm3 at 30 °C |
| Water solubility | 2150 g/l at 30 °C |
| Vapour pressure | 0.009 kPa at 25 °C |
Major uses
Most of the acrylamide produced is used as a chemical intermediate or as a monomer in the production of polyacrylamide. Both acrylamide and polyacrylamide are used mainly in the production of flocculants for the clarification of potable water and in the treatment of municipal and industrial effluents. They are also used as grouting agents in the construction of drinking-water reservoirs and wells (1).
Environmental fate
Acrylamide is highly mobile in aqueous environments and readily leachable in soil. As it has a higher mobility and lower rate of degradation in sandy soils than in clay soils (2), it may contaminate groundwater. However, its behaviour in subsurface soil, where most grouting takes place, has not been studied.
Acrylamide is susceptible to biodegradation in soil and surface water. Its concentration decreased from 20 to 1 µg/litre in 24 h in the effluent from a sludge dewatering process (3). One of the most important mechanisms for the removal of acrylamide from soils is enzyme-catalysed hydrolysis; nonbiological hydrolysis may be important in natural water. Volatilization is not an important removal process. As acrylamide is both highly soluble in water and degraded by microorganisms, it is not likely to bioconcentrate significantly (4).
2. Analytical methods
The methods used for measuring acrylamide include polarography, electron-capture gas chromatography, and high-performance liquid chromatography. A high-performance liquid chromatography/ultraviolet absorption detection procedure for the determination of acrylamide in water has a detection range of 0.2–100 µg/litre (5).
3. Environmental levels and human exposure
Air
Because of its low vapour pressure and high water solubility, acrylamide is not expected to be a common contaminant in air. Available monitoring data are insufficient to confirm this.
Water
The most important source of drinking-water contamination by acrylamide is the use of polyacrylamide flocculants containing residual levels of acrylamide monomer. Generally, the maximum authorized dose of polymer is 1 mg/litre. At a monomer content of 0.05%, this corresponds to a maximum theoretical concentration of 0.5 µg/litre monomer in water (6). In practice, concentrations may be lower by a factor of 2–3. This applies to both the anionic and nonanionic polyacrylamides, but residual levels from cationic polyacrylamides may be higher.
Acrylamide was detected at levels of less than 5 µg/litre in both river water and tapwater in an area where polyacrylamides were used in the treatment of potable water. Samples from public drinking-water supply wells in West Virginia (USA) contained 0.024–0.041 µg of acrylamide per litre. In one study in the United Kingdom, tapwater levels in the low microgram per litre range were reported (5).
Food
No studies on the occurrence of acrylamide in foods were identified. However, polyacrylamide is used in the refining of sugar, and small amounts of acrylamide may remain in the final product.
4. Kinetics and metabolism in laboratory animals and humans
Acrylamide is readily absorbed by ingestion and inhalation, and through the skin (1), and is then widely distributed in body fluids. It can cross the placental barrier. The tissue distribution following intravenous injection of l-[14C]acrylamide (100 mg/kg of body weight) into male Porton strain rats was highest (up to 1360 µmol per g of tissue) in blood; progressively lower amounts were present in kidney, liver, brain, spinal cord, sciatic nerve, and plasma (7).
In rats, biotransformation of acrylamide occurs through glutathione conjugation and decarboxylation. At least four urinary metabolites have been found in rat urine; N-acetyl-S(3-amino-3-oxypropyl)cysteine accounted for 48% of the oral dose, and unmetabolized acrylamide (2%) and three non-sulfur-containing metabolites (total 14%) were also present. Acrylamide and its metabolites are accumulated (protein-bound) in both nervous system tissues and blood, where it is bound to haemoglobin. Accumulation in the liver and kidney as well as in the male reproductive system has also been demonstrated (8).
The results of animal studies indicate that acrylamide is largely excreted as metabolites in urine and bile. Because of the enterohepatic circulation of biliary metabolites, faecal excretion is minimal. Two-thirds of the absorbed dose is excreted with a half-life of a few hours. However, protein-bound acrylamide or acrylamide metabolites in the blood, and possibly in the central nervous system, have a half-life of about 10 days. Acrylamide has been identified in rat milk during lactation (8).
There are no data indicating any major differences in acrylamide metabolism between humans and other mammals (1).
5. Effects on laboratory animals and in vitro test systems
Acute exposure
Oral LD50s for acrylamide were reported to range from 100 to 270 mg/kg of body weight in various strains of mice and rats. The dermal LD50 in rats was reported to be 400 mg/kg of body weight (9–12).
Short-term exposure
Studies have shown that acrylamide is a cumulative neurotoxin. Rats, cats, and dogs receiving 5–30 mg/kg of body weight per day in the diet exhibited weakness and ataxia in hind limbs for 14–21 days, which progressed to paralysis with continued exposure (13,14). Other characteristic symptoms were testicular atrophy and degeneration of germinal epithelium (15).
Long-term exposure
Signs of acrylamide toxicity in animals exposed for longer periods of time (several months to 1 year) are generally the same as those in animals exposed for short times, but average daily doses as low as 1 mg/kg of body weight per day sometimes produce effects. When male and female F344 rats were exposed to 0, 0.05, 0.2, 1.5, or 20 mg/kg of body weight per day in drinking-water for 90 days, definite peripheral nerve and spinal cord lesions and testicular atrophy were observed in the group receiving 20 mg/kg of body weight per day; although 1.5 mg/kg of body weight per day caused no external signs of toxicity, histological evidence of neuropathy was noted. The NOAEL was 0.2 mg/kg of body weight per day (16).
Reproductive toxicity, embryotoxicity, and teratogenicity
Male Long-Evans rats exposed to acrylamide doses of up to 5.8 mg/kg of body weight per day for 10 weeks in their drinking-water experienced increased pre-implantation and post-implantation loss after mating (17). Another series of experiments carried out by the same authors suggested that acrylamide affected the spermatid–spermatozoa stages (18).
Acrylamide was administered to pregnant Porton rats either as a single intravenous dose (100 mg/kg of body weight) on day 9 of gestation or in the diet as a cumulative dose of either 200 or 400 mg/kg of body weight between days 0 and 20 of gestation. Apart from a slight decrease in the weight of individual fetuses from rats dosed with 400 mg/kg of body weight, no fetal abnormalities were seen, even at doses that induced neuropathy in the dams (19).
When fertilized chicken eggs were injected with 0.03–0.6 mg of acrylamide on days 5, 6, or 7 of incubation, embryonic mortality increased and leg deformities were observed in hatched chicks (20).
Mutagenicity and related end-points
Acrylamide does not cause mutations in bacterial test systems but does cause chromosome damage to mammalian cells both in vitro and in vivo (1,21,22).
Carcinogenicity
Recent results indicate that acrylamide may be a carcinogen. Male and female Fischer 344 rats were given 0, 0.01, 0.02, 0.5, or 2 mg/kg of body weight per day in drinking-water for 2 years. In male rats receiving doses of 0.5 and 2 mg/kg of body weight per day, there was an increase in the frequency of scrotal, thyroid, and adrenal tumours. In female rats receiving 2 mg/kg of body weight per day, there was an increased incidence of malignant tumours of the mammary gland, central nervous system, thyroid, and uterus (23).
Eight-week-old A/J male and female mice given oral doses of 6.3, 12.5, or 25.0 mg/kg of body weight three times per week for 3 weeks or intraperitoneal doses of 1, 3, 10, 30, or 60 mg/kg of body weight three times per week for 8 weeks showed a dose-dependent increased incidence of lung adenomas at 9 and 8 months of age, respectively (22).
6. Effects on humans
Subacute toxic effects were experienced by a family of five exposed through the ingestion and external use of well-water contaminated with 400 mg of acrylamide per litre as the result of a grouting operation (24). Symptoms of toxicity developed about a month later and included confusion, disorientation, memory disturbances, hallucinations, and truncal ataxia. The family recovered fully within 4 months.
Many other cases of human exposure to acrylamide have been reported, generally the result of the dermal or inhalation exposure of workers in grouting operations or factories manufacturing acrylamide-based flocculants (25–28). Typical clinical symptoms were skin irritation, generalized fatigue, foot weakness, and sensory changes, which reflect dysfunction of either the central or peripheral nervous system.
7. Guideline value
In mutagenicity assays, acrylamide does not cause mutations in bacterial test systems but does cause chromosome damage to mammalian cells in vitro and in vivo. In a long-term carcinogenicity study in rats exposed via drinking-water, it induced tumours at various sites (23). IARC has placed acrylamide in Group 2B (29).
On the basis of the available information, it was concluded that acrylamide is a genotoxic carcinogen. Therefore, the risk evaluation was carried out using a non-threshold approach. On the basis of combined mammary, thyroid, and uterus tumours observed in female rats in a drinking-water study (23) and using the linearized multistage model, guideline values associated with excess lifetime cancer risks of 10-4, 10-5, and 10-6 are estimated to be 5, 0.5, and 0.05 µg/litre, respectively.
The most important source of drinking-water contamination by acrylamide is the use of polyacrylamide flocculants that contain residual acrylamide monomer. Although the practical quantification level for acrylamide is generally of the order of 1 µg/litre, concentrations in drinking-water can be controlled by product and dose specification.
References
1. Acrylamide. Geneva, World Health Organization, 1985 (Environmental Health Criteria, No. 49).
2. Lande SS, Bosch SJ, Howard PH. Degradation and leaching of acrylamide in soil. Journal of environmental quality, 1979, 8:133-137.
3. Arimitu H, Ikebukuro H, Seto I. The biological degradability of acrylamide monomer. Journal of the Japan Water Works Association, 1975, 487:31-39.
4. Neely WB, Baranson DR, Blau CE. Partition coefficient to measure bioconcentration potential of organic chemicals in fish. Environmental science and technology, 1974, 8:1113-1115.
5. Brown L, Rhead MM. Liquid chromatographic determination of acrylamide monomer in natural and polluted aqueous environments. Analyst, 1979, 104:391-399.
6. National Sanitation Foundation. Drinking water treatment chemicals — health effects. Ann Arbor, MI, 1988 (Standard 60-1988).
7. Hashimoto K, Aldridge WN. Biochemical studies on acrylamide, a neurotoxic agent. Biochemical pharmacology, 1970, 19:2591-2604.
8. Miller MJ, Carter DE, Sipes IG. Pharmacokinetics of acrylamide in Fischer-334 rats. Toxicology and applied pharmacology, 1982, 63:36-44.
9. Fullerton PM, Barnes JM. Peripheral neuropathy in rats produced by acrylamide. British journal of industrial medicine, 1966, 23:210-221.
10. Paulet G, Vidal. [On the toxicity of some acrylic and methacrylic esters, acrylamide and polyacrylamides.] Archives des maladies professionnelles, de médecine du travail et de sécurité sociale, 1975, 36:58-60 (in French).
11. Tilson HA, Cabe PA. The effects of acrylamide given acutely or in repeated doses on fore- and hindlimb function of rats. Toxicology and applied pharmacology, 1979, 47:253-260.
12. Hashimoto K, Sakamoto J, Tanii H. Neurotoxicity of acrylamide and related compounds and their effects on male gonads in mice. Archives of toxicology, 1981, 47:179-189.
13. Leswing RJ, Ribelin WE. Physiologic and pathologic changes in acrylamide neuropathy. Archives of environmental health, 1969, 18:23-29.
14. Thomann P et al. The assessment of peripheral neurotoxicity in dogs: comparative studies with acrylamide and clioquinol. Agents and actions, 1974, 4:47-53.
15. McCollister DD, Oyen F, Rowe VK. Toxicology of acrylamide. Toxicology and applied pharmacology, 1964, 6:172-181.
16. Burek JD et al. Subchronic toxicity of acrylamide administered to rats in the drinking water followed by up to 144 days of recovery. Journal of environmental pathology and toxicology, 1980, 4:157-182.
17. Smith MK et al. Dominant lethal effects of subchronic acrylamide administration in the male Long-Evans rat. Mutation research, 1986, 173:273-278.
18. Sublet V et al. Spermatogenic stages associated with acrylamide (ACR) induced dominant lethality. Toxicology, 1986, 6:292 (abstract).
19. Edwards PM. The insensitivity of the developing rat fetus to the toxic effects of acrylamide. Chemico-biological interactions, 1976, 12:13-l8.
20. Parker RDR, Sharma RP, Obersteiner EJ. Acrylamide toxicity in developing chick embryo. Pharmacologist, 1978, 20:249 (Abstract No. 522).
21. Shiraishi Y. Chromosome aberrations induced by monomeric acrylamide in bone marrow and germ cells of mice. Mutation research, 1978, 57:313-324.
22. Bull RJ et al. Carcinogenic effects of acrylamide in Sencar and A/J mice. Cancer research, 1984, 44:107-111.
23. Johnson KA et al. Chronic toxicity and oncogenicity study on acrylamide incorporated in the drinking water of Fischer 344 rats. Toxicology and applied pharmacology, 1986, 85:154-168.
24. Igisu H et al. Acrylamide encephaloneuropathy due to well water pollution. Journal of neurology, neurosurgery and psychiatry, 1975, 38:581-584.
25. Auld RD, Bedwell SF. Peripheral neuropathy with sympathetic overactivity from industrial contact with acrylamide. Canadian Medical Association journal, 1967, 96:652-654.
26. Garland TO, Patterson MWH. Six cases of acrylamide poisoning. British medical journal, 1967, 4:134-138.
27. Fullerton PM. Electrophysiological and histological observations on peripheral nerves in acrylamide poisoning in man. Journal of neurology, neurosurgery and psychiatry, 1969, 32:186-192.
28. Davenport JG, Farrell DF, Sumi SM. Giant axonal neuropathy caused by industrial chemicals. Neurology, 1976, 26:919-923.
29. International Agency for Research on Cancer. Overall evaluations of carcinogenicity: an updating of IARC Monographs volumes 1-42. Lyon, 1987:56 (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Suppl. 7).