Human exposure to organic arsenic species from seafood

Abstract

Seafood, including finfish, shellfish, and seaweed, is the largest contributor to arsenic (As) exposure in many human populations. In contrast to the predominance of inorganic As in water and many terrestrial foods, As in marine-derived foods is present primarily in the form of organic compounds. To date, human exposure and toxicological assessments have focused on inorganic As, while organic As has generally been considered to be non-toxic. However, the high concentrations of organic As in seafood, as well as the often complex As speciation, can lead to complications in assessing As exposure from diet. In this report, we evaluate the presence and distribution of organic As species in seafood, and combined with consumption data, address the current capabilities and needs for determining human exposure to these compounds. The analytical approaches and shortcomings for assessing these compounds are reviewed, with a focus on the best practices for characterization and quantitation. Metabolic pathways and toxicology of two important classes of organic arsenicals, arsenolipids and arsenosugars, are examined, as well as individual variability in absorption of these compounds. Although determining health outcomes or assessing a need for regulatory policies for organic As exposure is premature, the extensive consumption of seafood globally, along with the preliminary toxicological profiles of these compounds and their confounding effect on assessing exposure to inorganic As, suggests further investigations and process-level studies on organic As are needed to fill the current gaps in knowledge.

Keywords: Arsenolipid; Arsenosugar; Organic arsenic; Seafood.

Fig. 1

As compounds found in seafood.

Fig. 2

Estimated intake scenarios of As species from different seafood diets. A) Estimated distributions of As species found in different seafood types. Total As concentrations are based on mean concentrations from EFSA, 2009, plotted demersal vs. pelagic fish concentrations were estimated from the EFSA mean As concentration for fish and the ratio of mean As in demersal to pelagic fish from the Norwegian fish survey (Julshamn, 2012); proportions of As species are estimated from literature reports (see Section 2). The range of total As concentrations (5%–95% confidence limit) from EFSA, 2009, are given in brackets. B) Seafood consumption by country based on FAOSTAT Food Consumption Database. Countries were chosen to provide a side distribution of dietary patterns, rather than to analyze a particular population. C) Hypothetical intake of As species based on estimated distributions of As compounds and seafood consumption data.

Fig. 3

Hypothetical intake of As species based on seafood consumption data for two populations (Japan and the USA), using estimated distributions of As compounds from median total As concentrations (EFSA, 2009) and distributions from the literature (Fig. 2a), compared with the same diet but where Bluefin tuna having 50% AsLipid and 3.2 mg/kg As wet wt (converted from 5.9 mg/kg As dry weight, present as equal parts fat soluble and water soluble As reported by Taleshi et al., 2010, assuming 80% water content) as the source of pelagic fish, or where mussels with elevated concentrations of iAs (42% of 13.8 mg/kg As wet wt reported by Sloth et al., 2008) were the source of bivalves.

Fig 4

Major urinary metabolites from ingestion of AB, AsSugars, AsLipids and iAs. Dashed lines represent large variability in excretion between individuals.

Fig. 5

Broad overview of identification/determination of As compounds in seafood.

Fig. 6

Comparative permeability, bioaccessability and effect on cell number for As species are summarized from previously published data (Ebert et al.; Leffers et al., 2013a, 2013b; Meyer et al., 2014, 2015). A) Permeability of As species (apical to basolateral) after 48 hour apical incubation with Caco-2 cells. Permeability of As species was determined at the following concentrations: 1 µM iAs; 2.5 µM thio-DMA; 50 µM AsHC332, AsHC 360 and AsHC444; 100 µM thio- AsSugar-Gly, and 500 µM AB, AsSugar-Gly, AsSugar-SO₃, oxo-DMA, thio-DMA, oxo-DMAE and thio-DMAE. Data represent percent applied apical concentration detected on basolateral side. B) Bioavailability of arsenic at 48 hours in UROTSA cells. Data are presented as percent of applied concentration detected in cells after 48h incubation. Concentrations of arsenic species applied are as follows: 1 µM AsHC332, AsHC 360, AsHC444, iAs and thio-DMA; 100 µM thio-AsSugar-Gly and DMA; and 500 µM AB, AsSugar-Gly, AsSug-SO₃, oxo-DMA, thio-DMA, oxo-DMAE and thio-DMAE. C) Effect of As species on UROTSA cell number at 48 hours. Data are presented as 1/IC50 values, calculated from cell number data (minimum of 6 concentrations) fit with a Weibull (type 1) 3-parameter curve in R (DRC package).