efsa-opinion-chromium-food-drinking-water

Chromium in food and drinking water
7.1.2. Hexavalent chromium
Absorption
Following oral administration, Cr(VI) is absorbed to a greater extent than Cr(III) but its absorption
from the gut is also poor. Studies report 1 - 6.9 % of the administered dose of Cr(VI) to be recovered
in the urine in humans (Kerger et al., 1996; Finley et al., 1996, 1997; Paustenbach et al., 1996) and
2 % in the rat (MacKenzie et al., 1959; Donaldson and Barreras, 1966; Febel et al., 2001).
Both plasma and RBC levels of chromium (peak levels and plasma under the plasma time curve) were
much higher in individuals ingesting on 5 mg dose of Cr(VI) than when Cr(III) was ingested (Kerger
et al., 1996).
The intestinal absorption of Cr(VI) has been reported to be markedly affected by contact with gastric
juices (MacKenzie et al., 1959; Donaldson and Barreras, 1966; De Flora et al., 1987; Kerger et al.,
1997; Febel et al., 2001). The infusion of Cr(VI) into the duodenum or jejunum (bypassing the
stomach) resulted in a marked increase in absorption in humans (Donaldson and Barreras, 1966; De
Flora et al., 1987) and experimental animals (MacKenzie et al., 1959; Donaldson and Barreras, 1966;
Febel et al., 2001). Donaldson and Barreras (1966) recovered 11 to 30 % of the administered dose of
Cr(VI) in human urine following the infusion of 1 ng/L of Na 2 51 CrO 4 into the intestine (under these
conditions only 1-2 % of the dose of Cr(III) administered as Cr(Cl) 3 was absorbed). Upon
intraduodenal administration of Na 2 51 CrO 4 to humans (avoiding contact with gastric juices),
approximately half of the chromium was absorbed based on faecal excretion (De Flora et al., 1987).
Similar results were observed following intrajejunal administration in rats, where 57 % of the dose of
Cr(VI) administered into the ligated jejunum of rats was recovered in the jejunum after 60 minutes
while approximately 98 % of the dose of Cr(III) was recovered in the jejunum under the same
experimental conditions (Febel et al., 2001). Following the oral administration of Cr(VI) to humans,
increased recovery of chromium in the urine was observed under conditions of low stomach acidity
(pernicious anemia) compared to control (8 % vs. 2 %) (Donaldson and Barreras, 1966).
Incubation of Cr(VI) with gastric juices prior to intraduodenal or intrajejunal administration in humans
and rats, respectively, virtually prevented the absorption of chromium (De Flora et al., 1987). The
authors concluded that reduction of Cr(VI) to the trivalent form in the stomach significantly reduces
absorption by the oral route (De Flora et al., 1987). Absorption of Cr(VI) following intestinal
administration of Na 2 51 CrO 4 was found to be increased three- to five-fold in comparison with oral
administration, consistent with reduction of Cr(VI) during passage through the stomach to Cr(III)
which is less well absorbed (MacKenzie et al., 1959).
Both Cr(III) and Cr(VI) are better absorbed from the gastrointestinal tract in the fasted than in the fed
state, (MacKenzie et al., 1959; O’Flaherty, 1996). Based on urinary excretion, Cr(VI) absorption was
estimated to be 6 % in fasted rats and 3 % in nonfasted rats (MacKenzie et al., 1959).
Kerger et al. (1996) administered Cr(VI) to humans mixed with orange juice to determine to what
degree the acidic-organic environment (somewhat analogous to the stomach) reduces oral absorption.
Four adult male volunteers ingested a single dose of 5 mg Cr (in 0.5 litres deionized water) in three
chromium mixtures: (1) Cr(III) chloride (CrCl 3 ), (2) potassium dichromate reduced with orange juice
(Cr(III)-OJ); and (3) potassium dichromate (Cr(VI)). Blood and urine chromium levels were followed
for 1–3 days prior to and up to 12 days after ingestion. The three mixtures showed quite different
pharmacokinetic patterns. CrCl 3 was poorly absorbed (estimated 0.13 % bioavailability) and rapidly
eliminated in urine (excretion half-life, about 10 hours), whereas Cr(VI) had the highest
bioavailability (6.9 %) and the longest half-life (about 39 hours). Thus, the fraction of the dose of
chromium recovered in the urine appeared to be greater for Cr(VI) than when Cr(III) was administered
(6.9 % versus 0.13 %). The absorbed fraction was considerably less when Cr(VI) was administered
with orange juice (0.6 %) than when Cr(VI) was administered in water (6.9 %).
Kerger et al. (1997) investigated the absorption, distribution and excretion of Cr(VI) after oral
exposure of adult male human volunteers to 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
EFSA Journal 2014;12(3):3595 66