efsa-opinion-chromium-food-drinking-water

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