efsa-opinion-chromium-food-drinking-water

Chromium in food and drinking water
In contrast, once inside the cells reduction of Cr(VI) to Cr(III) may reflect its bioactivation to a DNA
reactive form.
Reduction of Cr(VI) to Cr(III) upon oral intake has been well described (see Section 7.1.2). The
question remaining, however is whether this reduction of Cr(VI) to Cr(III) is efficient and fast enough
to prevent hexavalent chromium from reaching and being taken up by tissues and cells.
Arguments in favour of this fast reduction, especially at low dose levels when no saturation of
reducing capacity occurs, are mainly based on kinetics studies comparing uptake and distribution of
different forms of chromium using red blood cell (RBC) chromium concentrations as a biomarker for
systemic absorption of unreduced Cr(VI) (Kerger et al., 1996, 1997; Finley et al., 1997). This
approach is based on the fact that upon systemic availability of Cr(VI), Cr(VI) would be taken up in
the RBC and upon its reduction to Cr(III) be withheld in the RBC resulting in kinetics for the decrease
of RBC chromium being different (slower) than those for the decrease of chromium in plasma. Studies
reporting on this fast and complete reduction of Cr(VI) upon oral exposure are the following:
De Flora et al. (1987) reported that incubation of Cr(VI) with gastric juices prior to intraduodenal or
intrajejunal administration in humans and rats, respectively, virtually eliminated absorption of
chromium. Absorption of trivalent chromium ( 51 CrCl 3 ) was not increased by intraduodenal or
intrajejunal administration. The authors concluded that reduction of Cr(VI) to Cr(III) in the stomach
significantly reduces absorption by the oral route.
Kerger et al. (1996) studied the absorption of Cr(III) and Cr(VI) alone or mixed with orange juice in
four adult male volunteers to investigate the effects of the acidic-organic environment on oral
absorption. Cr(III) was poorly absorbed (estimated 0.13 % bioavailability) and rapidly eliminated in
urine (excretion half-life, about 10 hr) whereas Cr(VI) had the highest bioavailability (6.9 %) and the
longest half-life (about 39 hr). The absorbed fraction was considerably less when Cr(VI) was
administered in orange juice (0.6 %) than in water (6.9 %). The authors concluded that the data
suggested that nearly all the ingested Cr(VI) was reduced to Cr(III) before entering the bloodstream
based on comparison to RBC and plasma chromium patterns in animals exposed to high doses of
Cr(VI) and that their findings supported their other work (Kerger et al., 1997), which suggested that
water-soluble organic complexes of Cr(III) formed during the reduction of Cr(VI) in vivo explain the
patterns of blood uptake and urinary excretion in humans at drinking water concentrations of 10 mg/L
or less. Zhitkovich (2011) argued however that the approximately 10-fold higher bioavailability of
ingested Cr(VI) compared to that of Cr(VI) reduced with orange juice prior to ingestion suggests that
the bulk of absorbed Cr from Cr(VI) was likely a cell-permeable chromate.
In a following study in human volunteers, Kerger et al. (1997) treated adult male subjects with
potassium chromate at 5 or 10 mg Cr(VI)/L in drinking water, administered either as a single bolus
dose (0.5 L swallowed in 2 minutes) or for 3 days at a dose of 1 L/day (3 doses of 0.33 L at 6-h
intervals). The authors reported a low or no increase in Cr concentration in RBC following the
exposure period, suggesting a rapid reduction of Cr(VI) to Cr(III) in the upper gastrointestinal tract or
plasma prior to RBC uptake and systemic distribution. The author concluded that volunteers ingesting
5-10 mg Cr(VI)/L in drinking water showed a pattern of blood uptake and urinary excretion consistent
with Cr(III) uptake and distribution, and thus that the endogenous reduction to the less absorbable
species within the upper gastrointestinal tract and the blood prevent any substantial systemic uptake of
Cr(VI) under the experimental conditions described.
Paustenbach et al. (1996) studied uptake and elimination of Cr(VI) in a male volunteer who ingested 2
L/day of water containing 2 mg/L for 17 consecutive days. Steady state chromium concentrations in
urine and blood were achieved after 7 days. From the fact that both plasma and red blood cell (RBC)
chromium concentrations returned rapidly to background levels within a few days after cessation of
dosing the authors concluded that concentrations of 10 mg Cr(VI)/L or less in drinking water of
exposed humans appear to be completely reduced to Cr(III) prior to systemic distribution. The authors
indicated that their data added to an increasing weight of evidence that relatively low concentrations
of Cr(VI) in drinking water (less than 10 mg/L) do not produce adverse effects in humans.
EFSA Journal 2014;12(3):3595 103