Internal Dose Benchmarking of Acrylamide Exposure and Peripheral Neuropathy Risk: A National Population-Based Validation Study
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Background
Acrylamide, a neurotoxicant in heated foods and smoke, is linked to occupational neuropathy, but evidence regarding chronic, low-level population exposure remains limited. We evaluated the association between acrylamide exposure biomarkers and peripheral neuropathy among U.S. adults.
Methods
A total of 2,266 NHANES 2003–2004 participants (age ≥40) were analyzed. Exposure was assessed via hemoglobin adducts (HbAA/HbGA); neuropathy via monofilament testing (≥1 site). Survey-weighted logistic regression models adjusted for confounders. Sensitivity analyses included cubic splines, diabetes stratification, and multiple imputation.
Results
Neuropathy prevalence was 15.5%. In adjusted models, neither adduct was associated with neuropathy (HbAA OR: 0.98, 95% CI: 0.82–1.17; HbGA OR: 0.91, 95% CI: 0.77–1.08). No dose-response gradient was observed. Expected risk factors (age, diabetes) showed strong associations, validating model sensitivity. The null result remained robust across sensitivity analyses, including a stricter outcome definition and multiple imputation (pooled OR: 0.97, 95% CI: 0.83–1.14).
Conclusions
Acrylamide adducts were not associated with peripheral neuropathy in this national sample. General population levels (∼55–70 pmol/g) lie well below established occupational no-observed-adverse-effect levels (∼510 pmol/g) and clinical neuropathy thresholds (∼6,000 pmol/g), providing a mechanistically coherent explanation for this null result.
