efsa-opinion-chromium-food-drinking-water

Chromium in food and drinking water
various tissues. In such a situation below the threshold, reduction would be efficient and allow only
low level systemic absorption of Cr(III). Exceedance of the threshold would be expected to appear as
a positive change in the slope of the tissue Cr concentration versus drinking water concentration. Stern
et al. (2010) reported that analysis of available experimental data (NTP, 2007; NTP 2010) indicated
that the dose-reponse data were inconsistent with the existence of such a reduction threshold since the
curves were supra-linear across all doses. The authors concluded that their findings do not support the
hypothesis that the reduction capacity of the mouse gastroitestinal tract was exceeded within the dose
range of the NTP study, where hyperplasia was seen as all doses. Thus at least some Cr(VI) seems to
escape gastric reduction. The authors further corroborated this conclusion by comparing the estimated
Cr(VI) intake rate to the estimated reducing capacity of the mouse gastric fluid, domstrating that only
the estimated intake rate for female mice at the highest Cr(VI) water concentration in the NTP study
exceeds the estimated reduction rate. Furthermore, the authors added the arguments that the half-time
for gastric emptying of liquids in the mouse has been reported to amount to < 5-9 minutes and that
Cr(VI) can be absorbed directly through the stomach membranes. Thus, they argued that even when
the hourly rate of Cr(VI) reduction would greatly exceed the hourly rate of Cr(VI) intake, a substantial
fraction of the ingested Cr(VI) can be expected to escape reduction by being transported from the
stomach to the small intestine. Finally, the authors concluded that, based on pharmacokinetic data in
both mice and humans, even low, environmentally relevant doses of Cr(VI) are likely to escape
reduction in the stomach, due to the ability of absorption and gastric emptying to successfully compete
with reduction.
Zhitkovich (2011) concluded that a review of the literature showed that hexavalent chromium was not
completely converted to trivalent chromium in animal or human stomachs and that bioavailability
results and kinetic considerations suggest that 10-20 % of ingested low dose Cr(VI) would not be
reduced in the GI system of humans. Zhitkovich argued that on the basis of the reported high
reduction capacity of the stomach (> 80 mg/day), the rate of reduction by gastric juice under fasting
conditions could exhibit pseudo first-order kinetics in a broad range of low to moderate Cr(VI)
concentrations. Since a fundamental property of first-order reactions is independence of the reaction
half-time on concentration it is argued that the extent of gastric reduction should be the same for both
very small and very large amounts of Cr(VI). It was pointed out that in line with first-order kinetics,
the initial rates of reduction by human gastric juice were found to be independent of Cr(VI)
concentrations and that the reduction of 0.1 mg/L Cr(VI) (the current EPA standard for total
chromium) by artificial gastric juice was a first-order reaction. Furthermore, it was pointed out that a
similar bioavailability of Cr(VI) for small and large doses further supports the first-order reaction
kinetics of gastric reduction. In addition the review analyses literature data to estimate the percentage
of Cr(VI) that would escape the stomach detoxification and concluded that overall bioavailability and
gastric reduction rate-based estimations suggest that 10-20 % Cr(VI) ingested with water escapes the
gastric inactivation and reaches the small intestine. For example the fact that 10.6 % and 2.1 % of an
equal dose of Cr(VI) was excreted in urine upon dosing directly into the duodenum or upon oral
ingestion, respectively, was taken to calculate that upon oral intake 2.1/10.6 x 100 % = 19.8 % of the
oral dose of Cr(VI) reached the duodenum and escapes reduction in the stomach. The author notes
that these estimates do not apply to the consumption of water with food, which is expected to promote
Cr(VI) reduction through increased stomach residence time and delivery of additional reducers. The
Panel noted that these calculations assumed that Cr(III) would not be absorbed at all which is not fully
correct.
The author also compared estimated reduction rates for Cr(VI) by human gastric juice at physiological
temperature (t 1/2 =7 min) and the time for human stomach emptying (t1/2 = 15.2 min) to calculate that
22.2 % of Cr(VI) will reach the duodenum. Taking all together Zhitkovic concluded that the
bioavailability results and kinetic considerations indicate incomplete gastric detoxification of Cr(VI)
at environmental levels of exposure.
Proctor et al. (2012) performed ex vivo studies using stomach contents of rats and mice to quantify
Cr(VI) reduction rate and capacity for loading rates amounting to 1-400 mg Cr(VI)/L stomach
contents, which are in the range of recent bioassays. Cr(VI) reduction followed mixed second-order
kinetics, dependent on the concentrations of both Cr(VI) and the native reducing agents.
EFSA Journal 2014;12(3):3595 105