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 />
Finley et al. (1997) reported a study in which five healthy male volunteers ingested a liter of deionized<br />
<strong>water</strong> containing Cr(VI) concentrations ranging from 0.1 to 10.0 mg/L. A dose-related increase of<br />
<strong>chromium</strong> was observed in urine, plasma and RBC in all volunteers. The authors indicated that the<br />
RBC <strong>chromium</strong> profiles suggest that the ingested Cr(VI) was reduced to Cr(III) before entering the<br />
bloodstream, since the <strong>chromium</strong> concentration in RBCs dropped rapidly post-exposure. The authors<br />
concluded that the RBC and plasma <strong>chromium</strong> profiles are consistent with systemic absorption of<br />
Cr(III) not Cr(VI). They also indicated that their findings suggest that the human gastrointestinal tract<br />
has the capacity to reduce ingested Cr(VI) following ingestion of up to 1 liter of <strong>water</strong> containing 10.0<br />
mg/L of Cr(VI), and that this is consistent with U.S. EPA position that the Cr(VI) <strong>drinking</strong> <strong>water</strong><br />
standard of 0.10 mg Cr(VI)/L is below the reductive capacity of the stomach.<br />
Coogan et al. (1991a) dosed rats intravenously or orally with Cr(VI). Upon intravenous administration<br />
RBC <strong>chromium</strong> levels were increased significantly 1 hr post dosing and these levels had not decreased<br />
7 days later. When the animals were dosed orally with Cr(VI), RBC <strong>chromium</strong> levels were increased<br />
at the 1 hr time point but returned almost to background levels after 7 days. Thus the toxicokinetics<br />
have the appearance as if Cr(III) had been administered and may reflect the predominance of Cr(III).<br />
De Flora (2000) estimated that saliva may reduce 0.7 to 2.1 mg of Cr(VI) per day and gastric juices<br />
have the capacity to reduce at least 80 to 84 mg of Cr(VI) per day.<br />
O'Flaherty et al. (2001) presented a PBK model for the ingestion of Cr(III) and Cr(VI) by humans.<br />
The model was calibrated against blood and urine <strong>chromium</strong> concentration data from a group of<br />
controlled studies in which adult human volunteers drank solutions generally containing up to 10<br />
mg/day of soluble inorganic salts of either Cr(III) or Cr(VI) (Kerger et al., 1996; Paustenbach et al.,<br />
1996; Finley et al., 1997). Chromium kinetics were shown not to be dependent on the oxidation state<br />
of the administered <strong>chromium</strong> except in respect to the amount absorbed. The fraction absorbed from<br />
administered Cr(VI) compounds was highly variable and was presumable strongly dependent on the<br />
degree of reduction in the gastrointestinal tract, that is, on the amount and nature of the stomach<br />
contents at the time of Cr(VI) ingestion.<br />
Kirman et al. (2012) reported a PBK model for rats and mice orally exposed to <strong>chromium</strong>. The results<br />
on erythrocyte to plasma <strong>chromium</strong> ratios suggested that Cr(VI) entered portal circulation at <strong>drinking</strong><br />
<strong>water</strong> concentrations equal to and greater than 60 mg/L in rodents. The authors also indicated that the<br />
cancer bioassays of NTP were collected at Cr(VI) doses where saturable toxicokinetics may be<br />
expected. They pointed out that at doses above 1 mg Cr(VI)/kg per day (corresponding to <strong>drinking</strong><br />
<strong>water</strong> concentrations of approximately 5-6 mg Cr(VI)/L in rodents), the reductive capacity of the GI<br />
lumen begins to become depleted resulting in a greater fraction of Cr(VI) remaining for uptake. They<br />
also indicated the fraction of total <strong>chromium</strong> remaining as Cr(VI) in the GI lumen was predicted to be<br />
higher in mice than in rats, which can be ascribed to higher transition rates in mice (i.e. less time for<br />
reduction to occur in the stomach lumen), combined with fairly similar rates and capacities for Cr(VI)<br />
reduction.<br />
Arguments against complete reduction of Cr(VI) to Cr(III) upon oral administration can be found in<br />
the following studies/evaluations:<br />
Collins et al. (2010) reported that exposure of male F344/N rats and female B6C3F1 mice to Cr(VI)<br />
resulted in significantly higher tissue <strong>chromium</strong> levels compared with Cr(III) following similar oral<br />
doses. The authors stated that this indicates that a portion of the Cr(VI) escaped gastric reduction and<br />
was distributed systemically.<br />
Stern (2010) compared the concentrations of total Cr retained in various tissues after 25 weeks of<br />
dosing, with either Cr(III) picolinate (NTP, 2010) or sodium dichromate, and concluded that the<br />
concentrations of total Cr were 1.4-16.7 times larger for the rats ingesting Cr(VI), and 2.1-38.6 times<br />
larger for mice ingesting Cr(VI) despite 1.8 and 2.8 times larger doses of Cr(III) in rats and mice,<br />
respectively. From this the authors concluded that despite the assumed capacity of the gastrointestinal<br />
tract to reduce Cr(VI) Cr was absorbed as Cr(VI) rather than as Cr(III). The authors also argued that if<br />
the reduction capacity of the mice was exceeded at the higher Cr(VI) <strong>water</strong> concentrations that were<br />
associated with intestinal tumors, there would be a threshold concentration at which Cr(VI) would<br />
become available for absorption resulting in an increased rate of accumulation of total Cr in the<br />
EFSA Journal 2014;12(3):3595 104