Hemoglobin Adducts Of Acrylamide Research Articles

Estimation of intake and quantification of hemoglobin adducts of acrylamide in adolescents in Sweden.

Blood samples (n = 600) from participants in the Swedish dietary survey Riksmaten Adolescents 2016-17 were analyzed with respect to hemoglobin (Hb) adducts from acrylamide (AA) and its metabolite glycidamide (GA) as biomarkers of internal dose/exposure. The results are presented from statistical analyses of food consumption data (2-day dietary recall and questionnaires) and measured Hb adduct levels. The estimated exposure as well as consumption data were examined in relation to non-dietary factors such as sex, age (group medians of 12, 15, and 18 years), place of residence (urban/rural), smoking status, and parental education level. The median AA adduct level was estimated to be 34 pmol/g Hb (range 14-225). No significant difference was found for place of residence, parental education, sex, or age. A significant difference was found between the median adduct levels of daily smokers (n = 8) and never smokers (n = 323) in the older age groups, but not between occasional smokers (n = 47) and never smokers. The median differences between daily smokers and never smokers were 76, 40, and 128 pmol/g Hb for AA, GA, and AA + GA, respectively. The median AA intake for the whole group of adolescents, as estimated from dietary recall data combined with reported concentrations in food, was 0.40 μg/kg bw/day. The corresponding median intake estimated from measured Hb adduct levels of AA was 0.20 μg/kg bw/day. A significant, although low, positive Spearman correlation was found between the two intake estimates (p-value = 8 × 10-3; ρ = 0.11). From the estimated intake of AA from food frequency questionnaires, significance was found for the 15-year-old children with higher AA adduct levels observed at higher consumption frequencies of fried potatoes/French fries. AA is considered a genotoxic carcinogen. For the estimated intake of AA for any age group and method (dietary recall or AA adduct), both a calculated margin of exposure as well as lifetime quantitative cancer risk estimates indicate health concern. A future study on food consumption designed with respect to AA exposure would provide a better understanding of the correlation between consumption and exposure and should give a more reliable estimate of the contribution of dietary AA to the overall cancer risk.

Relationship between acrylamide and glycidamide hemoglobin adduct levels and osteoarthritis: a NHANES analysis.

Osteoarthritis (OA) is the most prevalent degenerative joint disease, and acrylamide is a chemical produced when foods are processed at high temperatures. Recent epidemiological research linked acrylamide exposure from the diet and environment to a number of medical disorders. However, whether acrylamide exposure is associated with OA is still uncertain. This study was aimed at assessing the relationship between OA and hemoglobin adducts of acrylamide and its metabolite glycidamide (HbAA and HbGA). Data were taken from four cycles of the US NHANES database (2003-2004, 2005-2006, 2013-2014, 2015-2016). Individuals aged between 40 and 84years who had complete information on arthritic status as well as HbAA and HbGA levels were eligible for inclusion. Univariate and multivariate logistic regression analysis s was performed to determine associations between study variables and OA. Restricted cubic splines (RCS) were used to examine non-linear associations between the acrylamide hemoglobin biomarkers and prevalent OA. A total of 5314 individuals were included and 954 (18%) had OA. After adjusting for relevant confounders, the highest quartiles (vs. lowest) of HbAA (adjusted odds ratio (aOR) = 0.87, 95% confidence interval (CI), 0.63-1.21), HbGA (aOR = 0.82, 95% CI, 0.60-1.12), HbAA + HbGA (aOR = 0.86, 95% CI, 0.63-1.19), and HbGA/HbAA (aOR = 0.88, 95% CI, 0.63--1.25) were not significantly associated with greater odds for OA. RCS analysis revealed that HbAA, HbGA, and HbAA + HbGA levels were non-linearly and inversely associated with OA (p for non-linearity < 0.001). However, the HbGA/HbAA ratio displayed a U-shaped relationship with prevalent OA. In conclusion, acrylamide hemoglobin biomarkers are non-linearly associated with prevalent OA in a general US population. These findings implicate ongoing public health concerns for widespread exposure to acrylamide. Further studies are still warranted to address the causality and biologic mechanisms underlying the association.

Reconstructing population exposures to acrylamide from human monitoring data using a pharmacokinetic framework

BackgroundAcrylamide toxicity involves several metabolic pathways. Thus, a panel of blood and urinary biomarkers for the evaluation of acrylamide exposure was deemed appropriate. ObjectiveThe study was designed to evaluate daily acrylamide exposure in US adults via hemoglobin adducts and urinary metabolites using a pharmacokinetic framework. MethodsA cohort of 2798 subjects aged 20–79 was selected from the National Health and Nutrition Examination Survey (NHANES, 2013–2016) for analysis. Three acrylamide biomarkers including hemoglobin adducts of acrylamide in blood and two urine metabolites, N-Acetyl-S-(2-carbamoylethyl)cysteine (AAMA) and N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine (GAMA) were used to estimate daily acrylamide exposure using validated pharmacokinetic prediction models. Multivariate regression models were also used to examine key factors in determining estimated acrylamide intake. ResultsThe estimated daily acrylamide exposure varied across the sampled population. Estimated acrylamide daily exposure was comparable among the three different biomarkers (median: 0.4–0.7 μg/kg/d). Cigarette smoking emerged as the leading contributor to the acquired acrylamide dose. Smokers had the highest estimated acrylamide intake (1.20–1.49 μg/kg/d) followed by passive smokers (0.47–0.61) and non-smokers (0.45–0.59). Several covariates, particularly, body mass index and race/ethnicity, played roles in determining estimated exposures. DiscussionEstimated daily acrylamide exposures among US adults using multiple acrylamide biomarkers were similar to populations reported elsewhere providing additional support for using the current approach in assessing acrylamide exposure. This analysis assumes that the biomarkers used indicate intake of acrylamide into the body, which is consistent with the substantial known exposures due to diet and smoking. Although this study did not explicitly evaluate background exposure arising from analytical or internal biochemical factors, these findings suggest that the use of multiple biomarkers may reduce uncertainties regarding the ability of any single biomarker to accurately represent actual systemic exposures to the agent. This study also highlights the value of integrating a pharmacokinetic approach into exposure assessments.

Inverse relationship between dietary fiber intake and environmental exposure to acrylamide.

Dietary fiber intake was thought to decrease some environmental pollutant exposure by increasing gastrointestinal excretion. While diet is considered the major source of exposure to acrylamide (AA), the impact of dietary fiber intake on acrylamide (AA) exposure is still unknown. We analyzed the associations between dietary fiber intake and AA hemoglobin biomarkers [hemoglobin adducts of acrylamide (HbAA) and glycinamide (HbGA), and sum of HbAA and HbGA (HbAA + HbGA)] among 3448 US adults who participated in the National Health and Nutrition Examination Survey (NHANES) 2013-2016. Multivariable linear regression and cubic spline models were conducted to estimate the associations between dietary fiber intake and AA hemoglobin biomarkers. Dietary fiber intake had a strong inverse and J-shaped association with AA hemoglobin biomarkers. In the fully adjusted linear regression model, compared with participants in the lowest dietary fiber quantile, the adjusted percent change with 95% confidence intervals (CIs) in HbAA for the highest dietary fiber quantile was - 19.7% (- 26.7%, - 13.1%); for HbGA, it was - 12.2% (- 18.9%, - 4.9%), and for HbAA + HbGA, it was - 17.3% (- 23.7%, - 10.4%). Associations between higher dietary fiber intake and lower levels of environmental exposure to acrylamide hemoglobin biomarkers suggest the need to increase dietary fiber intake.

Association between acrylamide exposure and the odds of developmental disabilities in children: A cross-sectional study.

BackgroundThe association between acrylamide exposure and the odds of developmental disabilities (DDs) is unclear. We conducted this analysis to explore whether acrylamide exposure is related to DDs.MethodsWe analyzed a sample of 1,140 children aged 6–17 years old from the US National Health and Nutrition Examination Survey 2013–2014 to 2015–2016. DDs were determined by reports of parents. Acrylamide exposure was evaluated by the hemoglobin adducts of acrylamide (HbAA) and its major metabolite glycidamide (HbGA). We investigated the association using binomial logistic regression analysis by taking HbAA and HbGA as continuous or quartile variables. Restricted cubic splines (RCS) were used to explore the non-linear relationship between HbAA or HbGA and the odds of DDs. Interaction analysis and propensity score matching (PSM) were used to validate the results.ResultsA total of 134 participants were reported to have DDs. The median level of HbAA and HbGA was 41.6 and 40.5 pmol/g Hb, respectively. HbAA and HbGA were not associated with the odds of DDs when taken as continuous variables. When divided into quartiles, there was no evidence for a linear trend for HbAA and HbGA. RCS showed that there was a J-shaped association between HbGA and the odds of DDs (P for non-linearity, 0.023). The results were consistent in interaction analysis by age, gender, and race, and after PSM.ConclusionHbGA level was associated with the odds of DDs in a J-shaped manner among children. Further investigation is warranted to determine the causality and underlying mechanisms.

The association between biomarkers of acrylamide and cancer mortality in U.S. adult population: Evidence from NHANES 2003-2014.

The association between acrylamide (AA) and the development of cancer has been extensively discussed but the results remained controversial, especially in population studies. Large prospective epidemiological studies on the relationship of AA exposure with cancer mortality were still lacking. Therefore, we aimed to assess the association between AA biomarkers and cancer mortality in adult population from National Health and Nutrition Examination Survey (NHANES) 2003-2014. We followed 3717 participants for an average of 10.3 years. Cox regression models with multivariable adjustments were performed to determine the relationship of acrylamide hemoglobin adduct (HbAA) and glycidamide hemoglobin adduct (HbGA) with cancer mortality. Mediation analysis was conducted to demonstrate the mediated role of low-grade inflammation score (INFLA-score) in this correlation. Compared with the lowest quintile, participants with the highest quintile of HbAA, HbGA and HbAA+HbGA had increased cancer mortality risk, and the hazard ratios(HRs) were 2.07 (95%CI:1.04-4.14) for HbAA, 2.39 (95%CI:1.29-4.43) for HbGA and 2.48 (95%CI:1.28-4.80) for HbAA+HbGA, respectively. And there was a considerable non-linearity association between HbAA and cancer mortality (p for non-linearity = 0.0139). We further found that increased INFLA-score significantly mediated 71.67% in the effect of HbGA exposure on increased cancer mortality risk. This study demonstrates that hemoglobin biomarkers of AA are positively associated with cancer mortality in adult American population and INFLA-score plays a mediated role in this process. Our findings can raise public awareness of environmental and dietary exposure to acrylamide and remind people to refrain from smoking or having acrylamide-rich foods.

Associations of Hemoglobin Adducts of Acrylamide and Glycidamide with Prevalent Metabolic Syndrome in a Nationwide Population-Based Study.

Environmental and dietary exposures to acrylamide (AA) have been linked with various metabolic-related outcomes, but the results are mixed. However, the association between long-term exposure to AA and the prevalence of metabolic syndrome (MetS) remains unknown. In this study, we aimed to assess the relationship between hemoglobin adducts of AA, biomarkers of internal exposure to AA, and MetS prevalence among a U.S. nationwide population. MetS patients were defined by meeting three or more of the following five characteristics: elevated blood pressure, high fasting glucose, abdominal obesity, hypertriglyceridemia, and lower high-density lipoprotein cholesterol (HDL-C). Multivariate-adjusted logistic regression models and restricted cubic spline models were used to analyze the associations between AA hemoglobin biomarkers and MetS prevalence. A total of 1552 MetS cases were documented. After adjustment for the potential confounders, the odds ratios (95% confidence intervals) of MetS prevalence in the highest quartile of AA hemoglobin biomarkers were 0.60 (0.40-0.89), 1.26 (0.84-1.89), 0.93 (0.71-1.21), and 1.61 (1.18-2.20) for HbAA, HbGA, the sum of HbAA and HbGA (HbAA + HbGA), and the ratio of HbGA to HbAA (HbGA/HbAA), compared with the lowest quartile, respectively. HbAA was significantly and inversely associated with blood pressure, fasting glucose, abdominal obesity, hypertriglyceridemia, and low HDL-C, while the HbGA/HbAA ratio was also positively associated with abdominal obesity, hypertriglyceridemia, and low HDL-C. The restricted cubic spline models revealed a positive relationship between the HbGA/HbAA ratio and the prevalence of MetS, while the HbAA level was inversely associated with MetS prevalence. Our current findings provided epidemiological evidence that HbAA and the HbGA/HbAA ratio were significantly associated with MetS prevalence among general U.S. adults. Further studies should be conducted to examine the association between internal exposure to AA and MetS prevalence.

Association between Acrylamide Hemoglobin Adduct Levels and Depressive Symptoms in US Adults: NHANES 2013-2016.

Acrylamide (AA) is widely present in heat-processed carbohydrate-rich food, cigarette smoke, and the environment. Prolonged exposure to AA may cause central nervous system damage. However, few epidemiologic studies assessed the association between hemoglobin adduct levels of AA or its metabolite glycidamide (GA) and depressive symptoms. We included 3595 US adults (≥18 years) from the National Health and Nutrition Examination Survey (NHANES) 2013-2016. Data for hemoglobin adduct levels from AA and GA (HbAA and HbGA) were used as a measure of internal dose. Depressive symptom data were from mental health questionnaires and measured by nine-item Patient Health Questionnaire (PHQ-9) scores. Results of logistic regression models showed a positive association between HbAA in quartile 4 and depressive symptoms with ORs and 95% CI of 2.47 (1.29, 4.77) [ORcontinuousHbAA and 95% CI: 1.006 (1.000, 1.013)], but an inverse association was detected in quartiles 2 and 3 of HbGA/HbAA [0.62 (0.38, 0.99) and 0.54 (0.32, 0.92), respectively]. Especially, an association between HbAA and depressive symptoms was strengthened in smokers, in age 18-39 and 40-59 years and BMI 25-30 kg/m2 groups. Further explorations are needed to study the found associations between HbAA, HbGA, and depressive symptoms.

Vitamin D mediates the association between acrylamide hemoglobin biomarkers and obesity.

Mediation analysis aims to discover the role of intermediate variables from exposure to disease. The current study was performed to evaluate how vitamin D mediates the association between acrylamide hemoglobin biomarkers and obesity. Data were collected on 10,377 adults participating in the National Health and Nutrition Examination Survey (NHANES) 2003-2006 and 2013-2014 aged ≥ 18years. Obesity was assessed through body mass index and abdominal circumference measurements. Generalized linear and restricted cubic spline (RCS) regression were used to estimate the association between vitamin D and acrylamide hemoglobin biomarkers, and the mediation effect of vitamin D was also discussed. After adjusting for potentially confounding factors, vitamin D had strong negative associations with serum concentrations of acrylamide hemoglobin adducts (HbAA, HbGA, and HbAA + HbGA). The RCS plots demonstrated that vitamin D was inversely and nonlinearly associated with HbAA and HbAA + HbGA while inversely and linearly associated with HbGA, and also a striking difference when vitamin D was lower than 60nmol/L. Mediation analysis suggested that a negative correlation between acrylamide and obesity was mediated by vitamin D. The current studyis expected toofferafresh perspective on reducing the toxicity of acrylamide.

The health risks of dual use of electronic and combustible cigarettes: exposure to acrylamide and glycidamide

A combustible cigarette is a significant source of acrylamide, which is associated with numerous adverse effects. Electronic cigarette (e‑cigarette) is an emerging smoking device with uncertain health effects. OBJECTIVES The aim of the study was to explore the exposure risks of acrylamide (AA) by measuring biomarkers, hemoglobinadducts of AA (HbAA) and of glycidamide (HbGA), in serum samples of the general adult population with regard to different smoking status (smoking vs nonsmoking). This was a cross‑sectional study of 1657 participants aged 18 years or older from the United States National Health and Nutrition Examination Survey (2015-2016) with recorded patient smoking status and concentrations of HbAA and HbGA. Multivariable linear regression models were used to analyze HbAA and HbGA in different smoking groups (nonsmokers, cigarettes smoking only, e‑cigarettes smoking only, and dual users). Dual users had the highest HbAA and HbGA concentrations (median [interquartile range], 83.75 [53.28-128.25] pmol/gHb and 61.20 [40.73-89.78] pmol/gHb, respectively). There was a positive association between the use of e‑cigarettes and the HbAA concentration. The standardized β coefficients of HbAA and HbGA between the combustible cigarette smokers and nonsmokers in the fully adjusted model were 0.312 and 0.255 (both P <0.001) and those between the dualusers and nonsmokers in the fully adjusted model were 0.396 and 0.342, respectively (both P <0.001). E‑cigarette users are exposed to AA, and users of both combustible and e‑cigarettes have highest measures of HbAA and HbGA. Aside from the adverse effects caused by e‑cigarette smoking, coexposure risks of combustible cigarettes and e‑cigarettes need to be communicated to the public. Further studies are warranted to aid in health promotion.

Hemoglobin adducts of acrylamide in human blood – what has been done and what is next?

BACKGROUND AND AIM: Acrylamide is found in many commonly consumed foods. Dietary exposure is of concern and food is being monitored worldwide as acrylamide is neurotoxic, crosses the placenta, restricts intrauterine growth and increases the risk of certain cancers and obesity. In animals, acrylamide causes heritable mutations, tumors, developmental, reproductive, and neurotoxicity. The impact on human health of dietary exposure to acrylamide remains poorly understood and it is impossible to say what level can be deemed safe as the assessment of acrylamide from diet is uncertain. We aim to summarize the internal dose of acrylamide in humans measured through quantification of hemoglobin (Hb) N-terminal valine adduct levels from acrylamide using mass spectrometric methods METHODS: We performed a search up to February 2020 and included peer-reviewed articles and reports in English. Data were extracted and mean Hb adduct levels by smoking status and country of origin were calculated. RESULTS:Methods and results from a total of 75 studies of 31,202 individuals from 15 countries were reviewed. Adduct levels were highest in occupational exposed individuals and three-fold higher in smokers as compared to non-smokers. Adducts ranged from 3 to 210 pmol/g Hb in non-smokers and this wide range suggests that dietary exposure to acrylamide varies largely. Relative to smoking, the correlation between estimated dietary intake of acrylamide and Hb adducts was weak and the validity of the methods used for assessment of dietary intake vary. Non-smokers from the USA and Canada had higher levels as compared with non-smokers from Europe and Asia. Within Europe, individuals from UK had the highest levels. CONCLUSIONS:Large studies starting with early-life exposures using validated high-throughput analyses of adducts from acrylamide and other heat-generated compounds, together with comprehensive assessment of diet, smoking and socio-economic factors, would improve evaluation of the effects of dietary acrylamide on health. KEYWORDS: Biomarkers of exposure, Food, Internal exposome

Association of acrylamide and glycidamide haemoglobin adduct levels with diabetes mellitus in the general population.

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.

Association between acrylamide exposure and sex hormones in males: NHANES, 2003-2004.

IntroductionAcrylamide is widely present in heat-processed food, cigarette smoke and environment. Reproductive toxicity was reported in animals treated with acrylamide, particularly in males. The reproductive toxicity of acrylamide and its active metabolite, glycidamide, was reported to be mainly mediated through DNA damage in spermatocytes. However, the effect of acrylamide on sex hormones in men is unknown.MethodsThere were 468 male subjects (age ≧ 12 years) enrolled to determine the relationships between hemoglobin adducts of acrylamide (HbAA) and hemoglobin adducts of glycidamide (HbGA) with several sex hormones using the National Health and Nutrition Examination Survey (NHANES), 2003 to 2004. All potential confounding variables in the data set were properly adjusted.ResultsWe found that one unit increase in the natural log-transformed HbAA level was associated with an increase in natural log transformed serum inhibin B level by 0.10 (SE = 0.05; P = 0.046), and natural log transformed serum sex hormone binding globulin (SHBG) by 0.15 (SE = 0.15; P = 0.036). With respect to HbGA, one unit increase in the natural log-transformed HbGA level was associated with an increase in natural log transformed serum anti-Müllerian Hormone (AMH) level by 0.31 (SE = 0.00; P = 0.003).ConclusionIn this representative cohort, we identified positive associations between acrylamide exposure and several sex hormones in men. The HbAA is positively associated with inhibin B and SHBG, and HbGA is positively associated with AMH. Other than genotoxicity, our findings suggested that altered sex hormones might also play a role in acrylamide-related reproductive toxicity in males.

Protective effect of a dietary flavonoid-rich antioxidant from bamboo leaves against internal exposure to acrylamide and glycidamide in humans.

Polyphenolic antioxidants may effectively reduce acrylamide contents in processed foods. However, few studies focused on their detoxification effects via estimating the profile change of internal exposure biomarkers. Here we showed the protective effect of a water-soluble flavone-C-glycoside-rich antioxidant from bamboo leaves (AOB-w) against acrylamide-induced toxicity in college students. The participants were randomly assigned to either the AOB-w or control group and served potato chips, corresponding to 12.6 μg per kg·bw of dietary exposure to acrylamide, followed by capsules containing 350 mg AOB-w or equivalent placebo. The kinetics of acrylamide, glycidamide, and mercapturic acid metabolites was profiled, and their hemoglobin adducts were measured. The toxicokinetic study showed that AOB-w promoted the excretion of acrylamide and shortened the distribution but prolonged the excretion of N-acetyl-S-(2-carbamoylethyl)-l-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine. The intervention with AOB-w reduced the peak concentration and area under curve of AAMA by 42.1% and 49.8%, respectively. Besides, AOB-w gender-dependently altered the toxicokinetic profile and reduced the amount of a human-specific urinary biomarker, N-acetyl-S-(2-carbamoylethyl)-l-cysteine-sulfoxide in women. AOB-w accelerated the metabolism of hemoglobin adducts of acrylamide and glycidamide in blood of women. Compared with the baseline levels on the beginning day, we observed a significant enhancement of hemoglobin adducts on the 10th day after serving them potato chips, showing 54.5% and 20.9% higher levels of the hemoglobin adducts of acrylamide and glycidamide, respectively, which thus indicated a lower level of glycidamide-to-acrylamide ratio in blood of participants. Overall AOB-w could effectively reduce the internal exposure to acrylamide in college students, which provides advanced insights into protective functions of natural antioxidants against in vivo toxicity of chemical contaminants from diet.

Exposure to acrylamide and the risk of cardiovascular diseases in the National Health and Nutrition Examination Survey 2003–2006

BackgroundLong-term exposure to acrylamide (AA) from diet sources may induce oxidative stress and chronic inflammation. However, the association between AA exposure and the prevalence of cardiovascular diseases (CVD) remains unclear. ObjectivesWe aimed to examine the association between blood exposure levels of AA biomarkers and the prevalence of main types of CVD in a general population of US adults. MethodsWe analyzed the associations between AA hemoglobin biomarkers [hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA), sum of HbAA and HbGA (HbAA+HbGA), and ratio of HbGA to HbAA (HbGA:HbAA)] and self-reported diagnosis of CVD in 8290 adults (≥20 years of age) from the National Health and Nutrition Examination Survey (NHANES) 2003–2006. Multivariable logistic regression models were employed for estimating the associations in three groups classified by the combination of smoking status and serum cotinine levels. ResultsIn people exposed to environmental tobacco smoke (n = 4670), HbGA, HbAA+HbGA, and HbGA:HbAA were significantly and inversely associated with the prevalence of total CVD (p < 0.0001, p = 0.0155, and p = 0.0014 for trend, respectively) after adjusting for various covariates. The odd ratios (ORs) for total CVD in the highest quartiles of HbGA, HbAA+HbGA, and HbGA:HbAA were 0.311 [95% confidence interval (CI): 0.193–0.500], 0.664 (95% CI: 0.485–0.911), and 0.495 (95% CI: 0.326–0.752) when compared with the individual lowest quartiles. In active smokers (n = 2432), HbAA was positively associated with CVD risk (p = 0.0088 for trend), while HbGA:HbAA was inversely related to total CVD (p = 0.0137 for trend). However, no significant associations of any AA hemoglobin biomarker with total and individual CVD prevalence were observed in the nonsmoking group (n = 1188). ConclusionsAA hemoglobin biomarkers are significantly associated with CVD in the active smoking group and the group exposed to environmental tobacco smoke but not in the nonsmoking group. Further prospective studies should clarify the causal relationship between HbAA and HbGA and the prevalence of CVD.

High-throughput, simultaneous quantitation of hemoglobin adducts of acrylamide, glycidamide, and ethylene oxide using UHPLC-MS/MS

Ethylene oxide (EO), acrylamide (AA) and glycidamide (GA) exposures are associated with mammary tumors in animals. Currently available information about human exposure to these chemicals is limited creating the need for analytical methods to assess their exposure. We developed a sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to simultaneously quantitate hemoglobin (Hb) N-terminal valine adducts of AA (HbAA), GA (HbGA), and EO (HbEO) using modified Edman reaction. The limits of detection of this method were 3.9, 4.9 and 12.9 in pmol/g Hb for HbAA, HbGA and HbEO, respectively. The among-day and within-day precision for all analytes determined with three levels of quality control pools ranged from 2.2–13.0% in percent coefficient of variation (%CV). The accuracy determined by standard addition was between 94 and 111% among all analytes. The median HbAA, HbGA and HbEO values in 34 self-reported non-smokers were 64.9, 45.3 and 113.6 pmol/g Hb and in 70 self-reported smokers were 127.8, 69.6 and 237.1 pmol/g Hb, respectively. HbAA, HbGA, and HbEO were detectable in all samples suggesting that the described method is suitable for measuring hemoglobin adducts of AA, GA and EO in the general population. This high throughput method can process 148 samples in 8 h. The HbEO/HbGA ratio appears independent of the HbAA levels in non-smokers and decreases with increasing HbAA concentration in smokers. This new method is suitable for measuring human exposure to AA, GA and EO and can provide further insight into the metabolism of these chemicals in humans.

Association of acrylamide hemoglobin biomarkers with obesity, abdominal obesity and overweight in general US population: NHANES 2003–2006

Exposure to chemical contaminants is considered as one of risk factors to the current epidemic of obesity. Acrylamide (AA) is a ubiquitous chemical contaminant in environmental waste, mainstream cigarette smoke and carbohydrate-rich foods, and widely used in industrial manufacturers and cosmetics. Few studies have highlighted the association of daily exposure to AA with obesity-related outcomes. We analyzed data from 8364 participants who aged 20–85years and were recruited in National Health and Nutrition Examination Surveys (NHANES) 2003–2006. We established the model of PROC Survey Logistic regressions via using AA biomarkers in blood, hemoglobin adducts of acrylamide and glycidamide (HbAA and HbGA), as the measure of internal exposure to AA, and assessing obesity, abdominal obesity and overweight with body mass index (BMI) or waist circumference (WC). After the adjustment of sociodemographic variables, lifestyle behaviors, and health-related factors, the ratio of HbGA to HbAA (HbGA/HbAA) was significantly associated with obesity (p for trend<0.0001). The odd ratios (ORs) with 95% confidence intervals (CIs) of HbGA/HbAA across increasing quartiles were 1.740 (1.413–2.144), 2.604 (2.157–3.144), and 2.863 (2.425–3.380) compared with the lowest quartile. HbGA was positively associated with obesity [OR (95% CI): 1.226 (1.041–1.443), 1.283 (1.121–1.468), and 1.398 (1.165–1.679); p for trend=0.0004], while HbAA was inversely associated with obesity [OR (95% CI): 0.839 (0.718–0.980), 0.713 (0.600–0.848), and 0.671 (0.554–0.811); p for trend<0.0001]. Negative associations were found between the sum of HbAA and HbGA (HbAA+HbGA) and the body weight outcomes. Similar associations were also observed between the hemoglobin biomarkers of AA and abdominal obesity as well as overweight. Thus, the hemoglobin adducts of AA as long-term internal exposure biomarkers are strongly associated with obesity-related outcomes in a population of US adults.

Biomarker analysis of hemoglobin adducts of acrylamide and glycidamide enantiomers for mid-term internal exposure assessment by isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry

Hemoglobin (Hb) adducts of acrylamide (AA) and its oxidative metabolite glycidamide (GA) are important biomarkers for evaluating the mid-term exposure of acrylamide toxicity in vivo. Taking pentafluoro-2-methylphenyl isothiocyanates of N-(2-carbamoylethyl)valine (AAVal-PFPTH) and N-(2-carbamoyl-2-hydroxyethy)valine (GAVal-PFPTH) as target analytes, we developed an isotope dilution ultra-high performance liquid chromatograph tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of AA and GA hemoglobin (Hb) adducts under the electroscopy ionization negative (ESI‾) mode in the present work. Among them, the enantiomer pair of GA-Hb adducts was firstly identified and successfully separated at baseline level. The method achieved high sensitivity with the LOD and LOQ ranging 1.43–5.05pmol/g Hb and 4.78–16.82pmol/g Hb, respectively. The recovery rates with low, intermediate and high spiking levels were calculated as 97.0–105.2%, 97.4–106.4% and 100.3–111.2%, respectively. Acceptable within-laboratory reproducibility (RSD < 13.7%) substantially supported the robustness of current UHPLC-MS/MS method, which was successfully applied to measure the hemoglobin adducts of acrylamide and glycidamide enantiomers in blood of both rats and humans. A linear exposure assessment model was developed for estimating the daily exposure to acrylamide in humans via considering acrylamide hemoglobin adducts as variables, indicating a novel connect between biomarker-based internal exposure and dietary-based external exposure. Overall, the present instrumental analysis and related internal exposure assessment model provide a substantially methodological support for profiling the internal biological exposure and estimating the external dietary exposure to acrylamide.

The influence of demographic, physical, behavioral, and dietary factors on hemoglobin adduct levels of acrylamide and glycidamide in the general U.S. population

ABSTRACTPurpose: This study aims to better understand the individual characteristics and dietary factors that affect the relationship between estimated consumption of acrylamide and measured acrylamide hemoglobin adduct levels (HbAA) and glycidamide hemoglobin adduct levels (HbGA). Methods: Acrylamide levels in individual food items, estimated by the U.S. Food and Drug Administration, were linked to data collected in the 2003–2004 National Health and Nutrition Examination Survey. Multivariable linear regression was used to evaluate the relationship between estimated consumption of acrylamide and HbAA. Results: A significant association between acrylamide intake and HbAA was observed, after adjustment for gender, race/ethnicity, smoking status, age, and BMI (R2 = 0.34). Across quartiles of acrylamide consumption, HbAA and HbGA levels increased monotonically. Among nonsmokers, an evaluation of three heavily consumed, high AA concentration foods showed a positive trend between the consumed amount of fried potatoes and HbAA in children, adolescents, and adults. A significant positive trend between the consumed amount of potato chips or coffee was indicated in adolescents, adults, and seniors. Conclusions: Consumption of some individual foods affects HbAA concentrations more strongly and in an age-dependent manner. Our results suggest that effective dietary guidelines for controlling acrylamide intake should be subpopulation specific.

Relationships between acrylamide and glycidamide hemoglobin adduct levels and allergy-related outcomes in general US population, NHANES 2005–2006

BackgroundAcrylamide-induced immunotoxicity and allergic dermatitis have been reported in animal experiments and clinical reports, respectively. However, epidemiological evidence from the general population is limited. ObjectivesThe purpose of the present study was to estimate the associations between acrylamide exposure and allergy-related outcomes in the general US population. MethodsA 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. ResultsWhen 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. ConclusionsThis 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.