efsa-opinion-chromium-food-drinking-water

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