Acrylamide (AA), an environmental pollutant, has been linked to neurotoxicity, genotoxicity and carcinogenicity. AA is widely used to synthesize polymers for industrial applications, is widely found in Western-style carbohydrate-rich foods and cigarette smoke, and can also be detected in human umbilical cord blood and breast milk. This is the first study that demonstrated the cardiac developmental toxicity of AA in zebrafish embryos. Post-fertilization exposure to AA caused a clearly deficient cardiovascular system with a shrunken heart and abortive morphogenesis and function. Disordered expression of the cardiac genes, myl7, vmhc, myh6, bmp4, tbx2b and notch1b, as well as reduced number of myocardial cells and endocardial cells, indicated the collapsed development of ventricle and atrium and failed differentiation of atrioventricular canal (AVC). Although cell apoptosis was not affected, the capacity of cardiomyocyte proliferation was significantly reduced by AA exposure after fertilization. Further investigation showed that treatment with AA specifically reduced the expressions of nkx2.5, myl7 and vmhc in the anterior lateral plate mesoderm (ALPM) during the early cardiogenesis. In addition, AA exposure disturbed the restricted expressions of bmp4, tbx2b and notch1b during atrioventricular (AV) valve development and cardiac chambers maturation. Our results showed that AA-induced cardiotoxicity was related to decreased cardiac progenitor genes expression, reduced myocardium growth, abnormal cardiac chambers morphogenesis and disordered AVC differentiation. Our study demonstrates that AA exposure during a time point analogous to the first trimester in humans has a detrimental effect on early heart development in zebrafish. A high ingestion rate of AA-containing products may be an underlying risk factor for cardiogenesis in fetuses.

The potential hazards of acrylamide (AA) have been proposed due to its lifelong exposure. However, the association between AA exposure and mortality remains unclear.We evaluated the prospective association of AA hemoglobin adducts (HbAA and HbGA) with all-cause and cardiovascular disease (CVD) mortality in U.S. population from National Health and Nutrition Examination Survey (NHANES) 2003–2006.We followed 5504 participants who were ≥25 years of age for an average of 6.7 years at the baseline examination with annual linkage to the NHANES statistics database. Using AA hemoglobin biomarkers [HbAA, HbGA, sum of HbAA and HbGA (HbAA + HbGA), and ratio of HbGA to HbAA (HbGA/HbAA)], we determined mortality from all-causes and CVD through Cox proportional hazard regression analysis with multivariable adjustments both in non-smoker group and smoker group. In addition, subgroup analyses and sensitivity analyses were further conducted.After adjusting for sociodemographic, life behavioral and cardiovascular risk factors in non-smoker group, HbAA was positively associated with all-cause mortality (p for trend = 0.0197) and non-CVD mortality (p for trend = 0.0124). HbGA and HbGA/HbAA were inversely associated with all-cause mortality (p for trend = 0.0117 and 0.0098, respectively) and CVD mortality (p for trend=0.0009 and 0.0036, respectively). The multivariable adjusted hazard ratios (HRs) [95% confidence intervals (CIs)] of the upper three quartiles were 0.472 (95% CI: 0.283–0.786), 0.517 (95% CI: 0.299–0.894) and 0.470 (95% CI: 0.288–0.766) between HbGA/HbAA and all-cause mortality comparing with the lowest quartile, respectively. No significant associations were found between HbAA + HbGA and mortality in non-smoker group, and between all AA hemoglobin biomarkers and mortality in smoker group.Hemoglobin biomarker levels of AA were strongly associated with mortality in general U.S. non-smoker adults. These findings proposed a continuous public health concern in relation to environmental and dietary exposure to AA.

Acrylamide (AA) is an organic contaminant that naturally forms in starchy foods during high-temperature cooking under low-moisture conditions. It is mainly produced from the sugars and amino acids present in food by the Maillard reaction. When humans are exposed to AA, AA is eliminated in the urine as mercapturic acid conjugates, primarily including N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA), N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA3), and N-acetyl-3-[(3-amino-3-oxopropyl)sulfinyl]-L-alanine (AAMA-Sul), which are used as exposure biomarkers of AA in human biomonitoring studies. Although the carcinogenic effects of AA on humans have not been demonstrated yet, some studies have shown that AA may negatively affect children's health. The main objective of this study was to evaluate the exposure of Spanish children (n = 612) to AA. For this purpose, the levels of AAMA, AAMA-Sul, and GAMA3 in first-morning urine samples were analyzed by “dilute and shoot” and liquid chromatography coupled to tandem mass spectrometry. The three metabolites were detected in all the children involved in this study in the following order (geometric mean (GM)): AAMA (79 ng ml⁻¹) > AAMA-Sul (28 ng ml⁻¹) > GAMA3 (18 ng ml⁻¹). Statistical analysis suggested that the intake of fried potato products and biscuits could be associated with higher levels of AA metabolites in urine. Estimated daily intakes of AA in the children under study were in the range of 1.2–1.5 μg AA·kg-body weight⁻¹·day⁻¹ (GM). Risk assessment calculations indicate that the health risk of AA exposure cannot be overlooked and the exposure of Spanish children to AA should be closely monitored.

The frequency and duration of exposure to acrylamide (AA) from the environment and diet are associated with a range of adverse health effects. However, whether long-term AA exposure is related to diabetes mellitus (DM) remains unknown. Data from 3577 adults in the National Health and Nutrition Examination Survey (NHANES) 2005–2006 and 2013–2016 aged ≥ 20 years was analysed. The main analyses applied multivariate logistic regression and restricted cubic spline models to investigate the associations between DM and AA haemoglobin biomarkers, including haemoglobin adducts of acrylamide and glycidamide (HbAA and HbGA), the sum of HbAA and HbGA (HbAA + HbGA), and the ratio of HbGA to HbAA (HbGA/HbAA) levels. After multivariable adjustment, the odds ratios (95% confidence intervals) for DM comparing the highest with the lowest AA haemoglobin biomarker quartiles were 0.71 (0.55, 0.93), 0.92 (0.71, 1.18), 0.80 (0.62, 1.03) and 1.95 (1.51, 2.51) for HbAA, HbGA, HbAA + HbGA and HbGA/HbAA, respectively. The restricted cubic spline model demonstrated that HbAA was linearly and inversely associated with risk of DM (P for trend = 0.013), while HbGA/HbAA was nonlinearly and positively associated with the prevalence of DM (P for trend <0.001). These results support for epidemiological evidence that the HbAA and HbGA/HbAA are significantly associated with DM. Further studies are warranted to infer the causal role of AA exposure in the prevalence of DM.

Acrylamide is a well-known carcinogen and neurotoxic substance that has been discovered in frying or baking carbohydrate-rich foods and is widely found in soils and groundwater. The purpose of this study was to investigate the adverse effects of exposure to acrylamide on skeletal development. After treatment with acrylamide in zebrafish embryos, the survival and hatching rates decreased, and the body length shortened, with cartilage malformation and a decrease in skeletal area. Exposure to acrylamide in maternal rats during the lactation period disturbed bone mineral density, serum levels of parathyroid hormone, and the expression of skeletal development-related genes in neonates. Exposure to acrylamide in pregnant rats during the pregnancy period decreased the trabecular density and inhibited cartilage formation by delaying the differentiation of osteoblasts and promoting the maturation of osteoclasts in rat embryos. Furthermore, acrylamide intervention downregulated the expression of chondrocyte and osteoblast differentiation-related genes (sox9a, bmp2, col2a1, and runx2), and upregulated the expression of osteoclast marker genes (rankl and mcsf) in zebrafish and rat embryos at different gestational stages. Our results indicated that exposure to acrylamide dysregulated signature gene and protein expression profiles of skeletal development by suppressing the differentiation and maturation of osteoblasts and cartilage matrix and promoting the formation of osteoclasts, and ultimately induced skeletal abnormality in morphology, which brings increasing attention to the intergenerational toxicity of acrylamide via mother-to-child transmission.

Acrylamide-induced immunotoxicity and allergic dermatitis have been reported in animal experiments and clinical reports, respectively. However, epidemiological evidence from the general population is limited.The purpose of the present study was to estimate the associations between acrylamide exposure and allergy-related outcomes in the general US population.A total of 6982 subjects were selected from the National Health and Nutrition Examination Survey 2005–2006 (NHANES). Internal exposure was measured by the hemoglobin adducts of acrylamide (HbAA) and its metabolite glycidamide (HbGA). Allergy-related outcomes including asthma, hay fever, allergy, itchy rash, sneeze, wheeze and eczema were obtained by self-administered questionnaires. Allergic sensitization was assessed by the total immunoglobulin E (IgE) levels. The associations of HbAA and HbGA quartiles with allergy-related outcomes were calculated using logistic regression models with multivariable adjustments. Analyses were additionally stratified according to age, gender and serum cotinine levels.When setting quartile 1 of HbAA as reference, the odds ratios (ORs) [95% confidence intervals (CIs)] of quartile 2 to 4 for eczema were 1.18 (0.79–1.76), 1.14 (0.73–1.78) and 1.58 (1.14–2.18), respectively (ptrend = 0.002). Individuals at the highest quartile of HbGA had significantly elevated likelihoods of itchy rash (OR = 1.37, 95% CI = 1.02–1.83, ptrend = 0.032) and eczema (OR = 1.45, 95% CI = 1.06–1.97, ptrend = 0.044). The stratification analyses indicated various results in different subgroups.This study indicated significant associations between HbAA and HbGA levels and the likelihoods of allergy-related outcomes in the general US population, depending on age, gender and smoke exposure status. These findings suggested potential public health concerns for the widespread exposure to acrylamide.

Acrylamide (AA) can have deleterious effects on freshwater fish. However, its adverse effects on euryhaline fish are still unknown. In this study, embryos of Oryzias melastigma were exposed to different concentrations of AA to investigate its effect on early developmental disorders. After 21 days of exposure, AA significantly inhibited the hatching rate and delayed the hatching time of embryos, and led to developmental delay, teratogenesis, and locomotion impairments in larvae. RNA-sequencing data of larvae indicated that AA upregulated the expression of hemoglobin and myoglobin involved in oxygen transport and angiopoietin 1, integrin, and matrix metallopeptidases related to angiogenesis and downregulated the expression of early growth response genes and synaptotagmin-2 related to neural plasticity and neurotransmitter release. Overall, our study showed that AA caused deleterious effects on the early development of euryhaline fish through hypoxic stress and neurotoxicity, providing a scientific basis for the environmental risk assessment of marine AA.