Dataset Information

Chronic dietary exposure to inorganic arsenic.

ABSTRACT: Following an official request to EFSA from the European Commission, EFSA assessed the chronic dietary exposure to inorganic arsenic (iAs) in the European population. A total of 13,608 analytical results on iAs were considered in the current assessment (7,623 corresponding to drinking water and 5,985 to different types of food). Samples were collected across Europe between 2013 and 2018. The highest mean dietary exposure estimates at the lower bound (LB) were in toddlers (0.30 ?g/kg body weight (bw) per day), and in both infants and toddlers (0.61 ?g/kg bw per day) at the upper bound (UB). At the 95th percentile, the highest exposure estimates (LB-UB) were 0.58 and 1.20 ?g/kg bw per day in toddlers and infants, respectively. In general, UB estimates were two to three times higher than LB estimates. The mean dietary exposure estimates (LB) were overall below the range of benchmark dose lower confidence limit (BMDL ₀₁) values of 0.3-8 ?g/kg bw per day established by the EFSA Panel on Contaminants in the Food Chain in 2009. However, for the 95th percentile dietary exposure (LB), the maximum estimates for infants, toddlers and other children were within this range of BMDL ₀₁ values. Across the different age classes, the main contributors to the dietary exposure to iAs (LB) were 'Rice', 'Rice-based products', 'Grains and grain-based products (no rice)' and 'Drinking water'. Different ad hoc exposure scenarios (e.g. consumption of rice-based formulae) showed dietary exposure estimates in average and for high consumers close to or within the range of BMDL ₀₁ values. The main uncertainties associated with the dietary exposure estimations refer to the impact of using the substitution method to treat the left-censored data (LB-UB differences), to the lack of information (consumption and occurrence) on some iAs-containing ingredients in specific food groups, and to the effect of food preparation on the iAs levels. Recommendations were addressed to improve future dietary exposure assessments to iAs.

SUBMITTER: European Food Safety Authority (EFSA)

PROVIDER: S-EPMC7845508 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Chronic dietary exposure to inorganic arsenic.

Arcella Davide D Cascio Claudia C Gómez Ruiz Jose Ángel JÁ

EFSA journal. European Food Safety Authority 20210129 1

Following an official request to EFSA from the European Commission, EFSA assessed the chronic dietary exposure to inorganic arsenic (iAs) in the European population. A total of 13,608 analytical results on iAs were considered in the current assessment (7,623 corresponding to drinking water and 5,985 to different types of food). Samples were collected across Europe between 2013 and 2018. The highest mean dietary exposure estimates at the lower bound (LB) were in toddlers (0.30 μg/kg body weight ( ...[more]

PMID: 33537067

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Project description:Inorganic arsenic in the drinking water is a multisite human carcinogen that potentially targets the kidney. Recent evidence also indicates that developmental arsenic exposure impacts renal carcinogenesis in humans and mice. Emerging theory indicates that cancer may be a disease of stem cells (SCs) and that there are abundant active SCs during early life. Therefore, we hypothesized that inorganic arsenic targets SCs, or partially differentiated progenitor cells (PCs), for oncogenic transformation. Thus, a rat kidney SC/PC cell line, RIMM-18, was chronically exposed to low-level arsenite (500 nM) for up to 28 weeks. Multiple markers of acquired cancer phenotype were assessed biweekly during arsenic exposure, including secreted matrix metalloproteinase (MMP) activity, proliferation rate, colony formation in soft agar, and cellular invasiveness. Arsenic exposure by 10 weeks and after also induced marked and sustained increases in colony formation, indicative of the loss of contact inhibition, and increased invasiveness, both cancer cell characteristics. Compared to the passage-matched control, chronic arsenic exposure caused exposure-duration dependent increases in secreted MMP-2 and MMP-9 activity, Cox-2 expression, and more rapid proliferation (all >2-fold), characteristics typical of cancer cells. Dysregulation of SC maintenance genes and signaling pathways are common during oncogenesis. During arsenite exposure, expression of several genes associated with normal kidney development and SC regulation and differentiation (i.e., Wt-1, Wnt-4, Bmp-7, etc.) were aberrantly altered. Arsenic-exposed renal SCs produced more nonadherent spheroid bodies that grew much more aggressively in Matrigel, typical of cancer SCs (CSCs). The transformed cells also showed gene overexpression typical of renal SCs/CSCs (CD24, Osr1, Ncam) and arsenic adaptation such as overexpression of Mt-1, Mt2, Sod-1, and Abcc2. These data suggest that inorganic arsenic induced an acquired cancer phenotype in vitro in these rat kidney SCs potentially forming CSCs and, consistent with data in vivo, indicate that these multipotent SCs may be targets of arsenic during renal carcinogenesis.

Project description:Among nonoccupationally exposed U.S. residents, drinking water and diet are considered primary exposure pathways for inorganic arsenic (iAs). In drinking water, iAs is the primary form of arsenic (As), while dietary As speciation techniques are used to differentiate iAs from less toxic arsenicals in food matrices.Our goal was to estimate the distribution of iAs exposure rates from drinking water intakes and rice consumption in the U.S. population and ethnic- and age-based subpopulations.The distribution of iAs in drinking water was estimated by population, weighting the iAs concentrations for each drinking water utility in the Second Six-Year Review data set. To estimate the distribution of iAs concentrations in rice ingested by U.S. consumers, 54 grain-specific, production-weighted composites of rice obtained from U.S. mills were extracted and speciated using both a quantitative dilute nitric acid extraction and speciation (DNAS) and an in vitro gastrointestinal assay to provide an upper bound and bioaccessible estimates, respectively. Daily drinking water intake and rice consumption rate distributions were developed using data from the What We Eat in America (WWEIA) study.Using these data sets, the Stochastic Human Exposure and Dose Simulation (SHEDS) model estimated mean iAs exposures from drinking water and rice were 4.2 ?g/day and 1.4 ?g/day, respectively, for the entire U.S. population. The Tribal, Asian, and Pacific population exhibited the highest mean daily exposure of iAs from cooked rice (2.8 ?g/day); the mean exposure rate for children between ages 1 and 2 years in this population is 0.104 ?g/kg body weight (BW)/day.An average consumer drinking 1.5 L of water daily that contains between 2 and 3?ng?iAs/mL is exposed to approximately the same amount of iAs as a mean Tribal, Asian, and Pacific consumer is exposed to from rice. https://doi.org/10.1289/EHP418.Among nonoccupationally exposed U.S. residents, drinking water and diet are considered primary exposure pathways for inorganic arsenic (iAs). In drinking water, iAs is the primary form of arsenic (As), while dietary As speciation techniques are used to differentiate iAs from less toxic arsenicals in food matrices.Our goal was to estimate the distribution of iAs exposure rates from drinking water intakes and rice consumption in the U.S. population and ethnic- and age-based subpopulations.The distribution of iAs in drinking water was estimated by population, weighting the iAs concentrations for each drinking water utility in the Second Six-Year Review data set. To estimate the distribution of iAs concentrations in rice ingested by U.S. consumers, 54 grain-specific, production-weighted composites of rice obtained from U.S. mills were extracted and speciated using both a quantitative dilute nitric acid extraction and speciation (DNAS) and an in vitro gastrointestinal assay to provide an upper bound and bioaccessible estimates, respectively. Daily drinking water intake and rice consumption rate distributions were developed using data from the What We Eat in America (WWEIA) study.Using these data sets, the Stochastic Human Exposure and Dose Simulation (SHEDS) model estimated mean iAs exposures from drinking water and rice were [Formula: see text] and [Formula: see text], respectively, for the entire U.S. population. The Tribal, Asian, and Pacific population exhibited the highest mean daily exposure of iAs from cooked rice ([Formula: see text]); the mean exposure rate for children between ages 1 and 2 years in this population is [Formula: see text] body weight (BW)/day.An average consumer drinking 1.5 L of water daily that contains between 2 and [Formula: see text] is exposed to approximately the same amount of iAs as a mean Tribal, Asian, and Pacific consumer is exposed to from rice. https://doi.org/10.1289/EHP418.

Dataset Information

Chronic dietary exposure to inorganic arsenic.

Publications

Chronic dietary exposure to inorganic arsenic.

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