In our study, the geometric mean concentrations of various arsenic species in urine were 3.0, 1.4, 24.7, and 41.4 ㎍/L of inorganic arsenic, MMA, DMA, and AsB, respectively; therefore, TmetAs and TsumAs were 30.9 and 84.7 ㎍/L, respectively. The urinary arsenic level in the general adult population of Korea was considerably higher than that of the United States (7.3 ㎍/L < no seafood > and 24.5 ㎍/L < with seafood > of the median total arsenic, Navas-Acien et al., 2011; 4.76 ㎍/L of the median TmetAs and 5.79 ㎍/L of the median AsB, Gilbert-Diamond et al., 2013), France (3.75 ㎍/L of of the geometric mean TmetAs and 13.42 ㎍/L of the geometric mean total arsenic, Saoudi et al., 2012), Germany (4.9 ㎍/L of the arithmetic mean TmetAs and 10.8 ㎍/L of the arithmetic mean TsumAs, Heitland and Köster, 2008), and United Kingdom (3.6 ㎍/L of the arithmetic mean TmetAs and 33.9 ㎍/L of the arithmetic mean TsumAs, Morton and Leese, 2011), but was similar to or lower than that of Taiwan (86.08 ㎍/L of the arithmetic mean TmetAs and 267.05 ㎍/L of the arithmetic mean total arsenic in a previously contaminated area, Hsueh et al., 1998; 57.08 ㎍/L of the arithmetic mean TmetAs in a previously contaminated area, Huang et al., 2009; 20.94 ㎍/g creatinine of the arithmetic mean TmetAs, Huang et al., 2012), Japan (141.3 ㎍/L of the median total arsenic, Hata et al., 2007; 132.2 ㎍/L of the median total arsenic, Suzuki et al., 2009), and China (28.3 ㎍/L of the arithmetic mean TmetAs of the control, Wen et al., 2011; 56 ㎍/L of the arithmetic mean TmetAs, Cui et al., 2013). In addition, approximately 44.0% of this study subjects (900/2,044) had urinary TmetAs over 35 ㎍/L of the biological exposure index (BEI, ACGIH, 2014); approximately 26.3% of study subjects (537/2,044) had urinary TmetAs exceeding 50 ㎍/L of the biological limit value (BLV, DFG, 2017).
Diet, especially seafood, was the main source of arsenic exposure in the general population who lived in arsenic non-polluted areas. Previously, several studies reported that seafood intake was associated with urinary arsenic concentrations (Navas-Acien et al., 2011; Bae et al., 2017; Signes-Pastor et al., 2017). In our study, urinary concentrations of various arsenic species, such as InAs, DMA, and AsB, were significantly higher in people who ate seafood, including fish/shellfish and seaweeds, during the 3 days before the personal interview than in those who did not. Additionally, the urinary concentrations of arsenic were higher in inhabitants of the coastal area than in those living inland, highlighting that seafood may be a major source of arsenic exposure in the general population (Luvonga et al., 2020). In our study, the distributions of urinary arsenic profiles were quite different from those in Western countries, including the United States. The relative proportions of AsB and TmetAs in relation to TsumAs were approximately 57% and 43%, respectively, in our study population. In contrast, the relative proportions of AsB in relation to TsumAs or the levels of AsB in urine were much lower in the general populations of Western countries, such as the United States, Germany, and France, than in Koreans (Heitland and Köster, 2008; Caldwell et al., 2009; Saoudi et al., 2012). Thus, the Korean general population is exposed to a higher arsenic level than the populations of Western countries, and AsB was a dominant contributor to the total arsenic exposure.
AsB is essentially a non-toxic and rapidly excreted compound, with a relatively high concentration in seafood (Wolle and Conklin, 2018). In our previous study, total urinary arsenic concentrations measured using ICP-MS were associated with the amount of seafood consumption (Bae et al., 2017). Furthermore, the speciation analyses of urinary arsenic indicated a major source of organic arsenic, namely, AsB, which was significantly associated with the consumption of fish/shellfish but not of seaweeds. Moreover, the urinary AsB concentration increased with the amount of fish/shellfish consumption in a dose-dependent pattern; seaweeds intake positively correlated with urinary InAs and DMA concentrations, and dose-dependent increases of InAs and DMA were observed according to the seaweeds consumption. However, seaweeds intake was not statistically associated with urinary concentrations of AsB. These findings indicate that seaweeds might afford inorganic arsenic rather than organic species (from fish/shellfish) in the Korean population. Nonetheless, the urinary concentrations of InAs and DMA positively correlated with fish/shellfish intake and increased according to the amount of fish/shellfish consumption, which might indicate that fish/shellfish is a part of InAs exposure source in Koreans.
However, the contributing mechanism remains to be understood as to whether a little amount of InAs in fish/shellfish, which is much consumed favorite food in Korea (Sirot et al., 2009; Seo et al., 2016), any kind of labile organic arsenic in fish/shellfish (Choi et al., 2010; Luvonga et al., 2020) as well as both and other foods might be source of arsenic exposure.
Inhabitants in arsenic contaminated area could be exposed to arsenic mainly through contaminated drinking water or harvested crops in the contaminated soil, which has previously caused the so-called “black foot disease” in Taiwan, Bangladesh, and elsewhere (Tseng, 1977; Smith et al., 2000; Nordstrom, 2002; Sun et al., 2007). Others could be exposed through inhalation or ingestion in the industry or accidentally (Morton and Mason, 2006; Heitland and Köster, 2008; Wen et al., 2011). However, urinary arsenic profiles show a different pattern according to the exposure source of arsenic. Our data present a high proportion of AsB (56.7%) and a relatively low proportion of TmetAs (43.3%) in TsumAs, but a relatively high proportion of DMA (80.8%) in TmetAs with low proportions and concentrations of InAs and MMA. Despite a relatively low concentration of AsB and high concentration of TmetAs, a relatively low concentration of DMA with a high concentration of InAs and MMA in TmetAs were observed in inhabitants of arsenic-contaminated areas or in workers occupationally exposed to arsenic in industries (Morton and Mason, 2006; Sun et al., 2007; Wen et al., 2011). Differences in urinary arsenic profiles by arsenic exposure levels could be explained based on a previous study by Huang et al. (2009), which presented changes in urinary arsenic profiles, such as the decreased proportion of InAs (–4.9%) and MMA (–6.8%) and increased DMA (11.7%), after cessation of arsenic ingestion for 15 years in people residing in the arsenic-contaminated area of Taiwan. Therefore, the speciation analyses of arsenic are essential for evaluating the health risk from arsenic exposure, especially in countries where populations mainly consume seafood, such as Korea.
In our previous study, increased urinary excretion of DMA was observed after seafood consumption in volunteers (Choi et al., 2010). Thus, a labile organoarsenic such as arsenosugar and arsenolipd could be metabolized to DMA, which is more toxic than the original form of organoarsenic (Molin et al., 2014; Luvonga et al., 2020). Furthermore, this study showed significantly higher urinary DMA concentrations in subjects who consumed seafood during the 3 days before the personal interview than in those who did not. Seafood is known as a healthy food, especially for growing children, pregnant women, and the elderly, as it is a rich source of essential amino acids, unsaturated fatty acids (omega 3 & 6), vitamins, and minerals (Mozaffarian and Rimm, 2006; Venugopal and Gopakumar, 2017). However, it remains to be elucidated whether overconsumption of seafood may increase exposure to hazardous arsenic species and result in toxicological implications.
Human exposure to the most hazardous metals, such as lead, mercury, and cadmium, are generally influenced by individual lifestyles, such as smoking and alcohol consumption, socioeconomic status, as well as sex and age in the general population (McKelvey et al., 2007; Eom et al., 2018). However, there were no observed prominent differences in urinary arsenic levels based on sex, smoking and alcohol consumption, economic and educational levels, residential area size, and pesticide used in our study. The factors affecting arsenic exposure in humans were quite different from those for other metals. Diet, especially seafood, and residential area (inland or coastal) mainly contributed to determining the human exposure levels to various arsenic species in our study population. Additionally, the amount of rice intake associated with the urinary levels of inorganic arsenic and its metabolites. Our finding is consistent with previous reports where rice consumption contributed to inorganic arsenic exposure (Wei et al., 2014; Signes-Pastor et al., 2017). Rice is a staple food and one of the major sources of inorganic arsenic exposure in Koreans (Seo et al., 2016). However, the levels of human arsenic exposure among individuals or countries could be affected by several factors, including lifestyles, dietary habits, and geological contamination (Vahter et al., 2000; Mandal and Suzuki, 2002; Minatel et al., 2018). Moreover, it is well known that drinking water is a principal contributing factor to arsenic exposure (Smith et al., 2000; Sun et al., 2007; Huang et al., 2009). In this study, there was no difference in the urinary concentrations of various arsenic species in the study subjects according to the type of drinking water used. The concentration of arsenic in drinking water is well regulated, with a standard limit of < 10 ㎍/L in Korea. Water supply is available for 99.3% of the population, the mean arsenic concentration in the water supply is < 1 ㎍/L, and only 3 times were reported as exceeding a standard limit in the supplied water during the last 10 years (MOE, 2021). Nevertheless, as the concentration of arsenic in drinking water was not analyzed in this study, our findings do not suggest that groundwater is safe from arsenic contamination. In a previous nationwide survey of arsenic concentrations in groundwater, about 98% of 722 groundwater had < 10 ㎍/L (Park et al., 2016).
Taken together, the big difference in the urinary concentrations of TmetAs, which is a toxicologically relevant arsenic species, between Korean (30.9 ㎍/L) and European/American (3–5 ㎍/L) populations could be possibly explained mainly by their dietary habits. Particularly, the amount of rice consumption is much higher in Koreans, at 62 ㎏/person/year, than in Europeans, at 6 ㎏/person/year (OECD/FAO, 2021). Moreover, Koreans eat higher amounts of seafood and fish, at 56 ㎏/person/year, than Europeans, at 23 ㎏/person/year (OECD/FAO, 2021). The significant portion of the seafood consumed by Koreans is made up of crustacean and mollusk which contain relatively high levels of inorganic arsenic and DMA compared to fish (Sioen et al., 2009; Taylor et al., 2017). Seaweeds, such as dried tangle, dried laver, and kelp, contain high levels of inorganic arsenic (Seo et al., 2016). Koreans consume considerably more seaweeds, at 33 kg/person/year, than Europeans/Americans, who consume very little seaweeds, if at all (FAO, 2021). Nevertheless, it is necessary a more comprehensive study to assess the risk conferred by contributing factors to the arsenic exposure of Koreans and to develop effective exposure-reduction measures.
Previous epidemiologic studies suggested that chronic arsenic exposure may induce metabolic syndrome, diabetes, atherosclerosis and cancer, which could be associated with the increased oxidative stress (De Vizcaya-Ruiz et al., 2009; James et al., 2015; Kuo et al., 2017; Spratlen et al., 2018). C-peptide is a small peptide by-product of insulin synthesis from proinsulin that may be associated with metabolic disease (Suzuki et al., 1997; Kim and Lee, 2017; Yaribeygi et al., 2019). In our study, the increase of MDA and c-peptide concentrations was shown to occur in a dose-dependent pattern according to the urinary concentrations of various arsenic species. These findings suggest that environmental arsenic exposure might be a potential cause of metabolic diseases, such as diabetes mellitus and atherosclerosis, through oxidative stress and endogenous endocrine effects; however, further studies are needed to improve our understanding and to protect the general public from environmental pollutants.
In summary, urinary arsenic concentrations in the adult population in the Republic of Korea was similar to or lower than those in other Asian countries but higher than those in Western countries, including the United States. Overall, our findings suggest that seafood and rice are the main sources of arsenic exposure in Korean adults. Furthermore, overconsumption of seafood might be the main source of exposure to organic arsenic also additional exposure source to inorganic arsenic, which primarily exposed by rice. All of this might have a potentially detrimental effect on human health.