ACRYLAMIDE
Overview
CAS number
79-06-01
Functional Class
Food Contaminant
CONTAMINANT
CONTAMINANT
Evaluations
Evaluation year: 2011
Comments:
While adverse neurological effects are unlikely at the estimated average exposure,
morphological changes in nerves cannot be excluded for individuals with a high dietary exposure to acrylamide. For a compound that is both genotoxic and carcinogenic, these MOEs indicate a health concern.
The Committee noted that mitigation after 2003 has been reported for food types with high acrylamide levels or single products that contain higher levels within their food type. Although this might significantly reduce the exposure for some individuals or population subgroups, the Committee noted that this will have little effect on the dietary exposure of the general population in all countries. In line with this, neither the estimated average acrylamide exposure for the general population (0.001 mg/kg bw per day) nor the exposure for consumers in the high percentile (0.004 mg/kg bw per day) had changed since the sixty-fourth meeting. The MOE calculated relative to the NOAEL of 0.2 mg/kg bw per day for the most sensitive non-carcinogenic end-point— namely, morphological changes in nerves, detected by electron microscopy, in rats—therefore remains unchanged. For the general population and consumers with high exposure, the MOE values are 200 and 50, respectively. Consistent with the conclusion made at the sixty-fourth meeting, the Committee noted that while adverse neurological effects are unlikely at the estimated average exposure, morphological changes in nerves cannot be excluded for individuals with a high dietary exposure to acrylamide. When average and high dietary exposures are compared with the BMDL10 of 0.31 mg/kg bw per day for the induction of mammary tumours in rats, the MOE values are 310 and 78, respectively. For Harderian gland tumours in mice, the BMDL10 is 0.18 mg/kg bw per day, and the MOE values are 180 and 45 for average and high exposures, respectively. The Committee considered that for a compound that is both genotoxic and carcinogenic, these MOEs indicate a human health concern. The Committee recognized that these MOE values were similar to those determined at the sixty-fourth meeting and that the extensive new data from cancer bioassays in rats and mice, PBPK modelling of internal dosimetry, a large number of epidemiological studies and updated dietary exposure assessments support the previous evaluation.
Intake:
Mean: 0.001 mg/kg bw per day; high: 0.004 mg/kg bw per day, based on GEMS data
Tolerable Intake:
NONE ESTABLISHED; genotoxic carcinogen
Meeting:
72
Report:
Tox Monograph:
Toxicological study
Pivotal Study:
GLP-compliant dietary carcinogenicity studies in mice & rats (Beland, 2010): F344 rats and B6C3F1 mice (48/species/sex/dose) received acrylamide at a concentration of 0, 0.0875, 0.175, 0.35 or 0.70 mmol/l in their drinking-water for 2 years (equivalent to: 0, 1.05, 2.23, 4.16 and 9.11 mg/kg bw/d (males) & 0, 1.11, 2.25, 4.71 and 9.97 mg/kg bw/d (females) in mice & 0, 0.34, 0.67, 1.36 and 2.78 mg/kg bw/d (males) & 0, 0.45, 0.90, 1.88 and 4.09 mg/kg bw/d (females) in rats). Decreased body weight gain in high-dose rats starting at Week 8 resulted in significantly reduced body weight at terminal necropsy. Significantly increased incidences of thyroid follicular adenomas, peritesticular mesotheliomas, phaeochromocytomas, heart schwannomas, and pancreatic islet tumours were noted in male rats. In females, significant increases were noted in mammary tumours, glial tumours, thyroid follicular adenomas or adenocarcinomas, oral cavity squamous papillomas, uterine adenocarcinomas, clitoral gland adenomas and pituitary adenomas. The study NOAEL for toxicity in rats was 0.67 mg/kg bw/d (males) and 1.88 mg/kg bw/d (females) for sciatic nerve axonal degeneration. High-dose male mice and 0.35 and 0.70 mmol/l females had reduced survival. Sporadic changes in body weight that did not exceed 6% of control weights occurred throughout the study. Water consumption was unaffected in males but was dose-relatedly increased in females, beginning at week 80. Significantly increased incidences of lung, Harderian gland, forestomach, mammary gland, and ovaries were noted. The study did not reach a NOEL/NOAEL for toxicity in mice due to the finding of increased Hardarian gland adenoma & lung tumors (males) at the lowest dose tested of 1.05 mg/kg bw/d.
Animal Specie:
Rats & mice
Effect:
Rats: neurotoxicity; mice: Hardarian gland & lung tumors (males)
NOAEL:
Rats only: 0.67 mg/kg bw/d (males) and 1.88 mg/kg bw/d (females)
LOEL:
Mice: 1.05 mg/kg bw/d
Point of departure:
0.31 mg/kg bw/d (mammary tumors in rats), 0.18 mg/kg bw/d (Hardarian gland tumors in mice)
Evaluation year: 2005
Comments:
For morphological changes in nerves the no-observed-effect level was 0.2 mg/kg bw per day; the margin of exposure at mean intake was 200 and at high intake was 50. For reproductive, developmental, and other non-neoplastic effects the no-observed-effect level was 2 mg/kg bw per day; the margin of exposure at mean intake was 2000 and at high intake was 500. The Committee concluded that adverse effects based on the above endpoints are unlikely at the estimated mean intakes, but that morphological changes in nerves cannot be excluded for some individuals with very high intake. For cancer the benchmark dose lower confidence limit was 0.3 mg/kg bw per day; the margin of exposure at mean intake was 300 and at high intake was 75. The Committee considered these margins of exposure to be low for a compound that is genotoxic and carcinogenic and that they may indicate a human health concern. Therefore, appropriate efforts to reduce acylamide concentrations in foodstuffs should continue.
Intake:
Mean: 0.001 mg/kg bw per day; high: 0.004 mg/kg bw per day
Report: