efsa-opinion-chromium-food-drinking-water
efsa-opinion-chromium-food-drinking-water
efsa-opinion-chromium-food-drinking-water
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Chromium in <strong>food</strong> and <strong>drinking</strong> <strong>water</strong><br />
of 1 L/day ( three doses of 0.33 L at 6-hour intervals). Samples of urine, plasma, and RBCs were<br />
collected and analyzed for total <strong>chromium</strong>. Upon taking the bolus dose urinary <strong>chromium</strong> excretion<br />
with an average half life of about 39 hours was observed. However, total urinary <strong>chromium</strong> excretion<br />
and peak concentrations in urine and blood varied considerably between the five volunteers. Upon the<br />
3 days exposure to repeated low dose levels generally lower <strong>chromium</strong> uptake/excretion was<br />
observed. The authors concluded, based on low or even absent levels of elevated RBC <strong>chromium</strong><br />
content in the weeks following Cr(VI) ingestion, that the Cr(VI) was reduced rapidly to Cr(III) in the<br />
upper gastrointestinal tract or plasma prior to RBC uptake and systemic distribution. Thus they<br />
concluded that volunteers ingesting highly soluble chromate (Cr(VI)) at concentrations of<br />
5 – 10 mg Cr(VI)/L in <strong>drinking</strong> <strong>water</strong> have a pattern of blood uptake and urinary excretion consistent<br />
with uptake and distribution of <strong>chromium</strong> in the trivalent state. They also concluded that the<br />
endogenous reducing agents within the upper gastrointestinal tract and the blood provided sufficient<br />
reducing potential to prevent any substantial systemic uptake of Cr(VI) following <strong>drinking</strong>-<strong>water</strong><br />
exposures at 5-10 mg Cr(VI)/L.<br />
Finley et al. (1997) reported the urinary recovery in human subjects following dose levels of 0.1, 0.5,<br />
1.0, 5.0 or 10 mg/day of Cr(VI) for four days to amount to respectively 1.7 %, 1.2 %, 1.4 %, 1.7 %<br />
and 3.5 %. A dose-related increase in urinary <strong>chromium</strong> excretion was observed in all volunteers. The<br />
authors indicated that the RBC <strong>chromium</strong> profiles suggested that the ingested Cr(VI) was reduced to<br />
Cr(III) before entering the bloodstream, since the <strong>chromium</strong> concentration in RBCs dropped rapidly<br />
post-exposure. The authors concluded that the RBC and plasma <strong>chromium</strong> profiles are consistent with<br />
systemic absorption of Cr(III) not Cr(VI).<br />
Collins et al. (2010) demonstrated that exposure of male F344/N rats and female B6C3F1 mice to<br />
Cr(VI) resulted in significantly higher tissue <strong>chromium</strong> levels compared with Cr(III) following similar<br />
oral doses. This indicates that a portion of the Cr(VI) escaped gastric reduction and was distributed<br />
systemically. Linear or supralinear dose responses of total <strong>chromium</strong> in tissues were observed<br />
following exposure to Cr(VI), indicating that these exposures did not saturate gastric reduction<br />
capacity. The study also reports that in vitro experiments demonstrated that Cr(VI) but not Cr(III), is a<br />
substrate of the sodium/sulphate cotransporter, providing a partial explanation for the greater<br />
absorption of Cr(VI).<br />
Distribution<br />
Hexavalent <strong>chromium</strong> readily penetrates cell membranes. As a result Cr(VI) is found in both RBC and<br />
plasma. When incubated with washed isolated RBCs, almost the entire Cr(VI) dose is taken up by the<br />
cells and remains there for the lifetime of the RBC. It is reduced inside the cells to Cr(III), essentially<br />
trapping it inside the RBC. Kerger et al. (1997) indicated that sustained elevations in RBC <strong>chromium</strong><br />
levels provide a specific indication of <strong>chromium</strong> absorption in the hexavalent state. However, when<br />
incubated with whole blood or RBCs plus plasma, only a fraction (depending on conditions) of the<br />
Cr(VI) is taken up by the RBC (Lewalter et al., 1985; Wiegand et al., 1985; Coogan et al., 1991a;<br />
Corbett et al., 1998). This may be due to the reduction of a portion of the administered Cr(VI) to<br />
Cr(III) outside the RBC (Korallus et al., 1984; Richelmi and Baldi, 1984; Capellmann and Bolt, 1992).<br />
Oral administration of Cr(VI) results in increased levels of <strong>chromium</strong> in a number of tissues including<br />
especially the liver, spleen, kidney and bone (marrow) (MacKenzie et al., 1958; Witmer et al., 1989;<br />
Witmer and Harris, 1991; Thomann et al., 1994; Sutherland et al., 2000; NTP, 2008). Thompson et al.<br />
(2011a, 2012b) reported significant increases in total Cr concentrations in the oral cavity, glandular<br />
stomach, duodenum, jejunum, and ileum of rats and mice following 90 days of exposure to sodium<br />
dichromate dihydrate (SDD) in <strong>drinking</strong> <strong>water</strong>.<br />
Substantial uptake of <strong>chromium</strong> by the liver is indicated by elevated levels of <strong>chromium</strong> in the bile<br />
following intravenous administration of Cr(VI), (Cikrt and Bencko, 1979; Manzo et al., 1983;<br />
Cavalleri et al., 1985).<br />
Increased concentrations of <strong>chromium</strong> in the blood, kidney and femur were detected in rats, mice and<br />
guinea pigs administered 1, 3, 10, 30, 100 or 300 mg/L of Cr(VI) as sodium dichromate in their<br />
EFSA Journal 2014;12(3):3595 67