In vitro reduction kinetics of hexavalent chromium in human blood.

This study examines time- and concentration-dependent changes in distribution of hexavalent chromium [Cr(VI)] and total chromium [Cr-(TOT)] in reconstituted human blood following addition of potassium dichromate. Fresh human blood stabilized with EDTA was obtained from human volunteers soon after meal ingestion and at 2.5 h after a light meal (herein defined as "2.5-h fasted" conditions). Cr(VI) spiked into plasma under 2.5-h fasting conditions at 3.0-12.5 micrograms/L was stable for several hours, indicating a lack of appreciable reductive capacity in isolated plasma. Spiked plasma following a recent meal exhibited immediate but variable reduction of Cr(VI) up to 300 micrograms/L. When the spiked plasma was recombined with the red blood cell (RBC) fraction, rapid reduction occurred in both the plasma and the RBC fractions based on measurement of Cr(VI) and Cr(TOT). The data indicate that plasma reduction capacity is enhanced by a recent meal, but may be overwhelmed at Cr(VI) concentrations between 2000 and 10,000 micrograms/L. These data also suggest that the RBC fraction apparently has the capacity to reduce Cr(VI) at concentrations in blood up to 15,000 micrograms/L, and that the rate of Cr(VI) uptake into RBCs may not exceed the rate of intracellular reduction at these concentrations.

Ingestion of chromium(VI) in drinking water by human volunteers: absorption, distribution, and excretion of single and repeated doses.

This study examines the magnitude of hexavalent chromium [Cr(VI)] absorption, distribution, and excretion following oral exposure to 5 and 10 mg Cr(VI)/L in drinking water administered as a single bolus dose (0.5 L swallowed in 2 min) or for 3 d at a dosage of 1 L/d (3 doses of 0.33 L each day, at 6-h intervals). Adult male volunteers ingested deionized water containing various concentrations of potassium chromate, and samples of urine, plasma, and red blood cells (RBCs) were collected and analyzed for total chromium throughout the studies. In the bolus dose studies, a fairly consistent pattern of urinary chromium excretion was observed, with an average half life of about 39 h. However, 4-d total urinary chromium excretion and peak concentrations in urine and blood varied considerably among the 5 volunteers. Studies of repeated exposure to smaller volumes ingested at a more gradual rate (i.e., 0.33 L over 5-15 min) showed similar urinary chromium excretion patterns but generally lower chromium uptake/excretion. Given that sustained elevations in RBC chromium levels provide a specific indication of chromium absorption in the hexavalent state, these data suggest that virtually all (> 99.7%) of the ingested Cr(VI) at 5 and 10 mg Cr(VI)/L was reduced to Cr(III) before entering the blood-stream. The interindividual differences in total chromium uptake and excretion are plausibly explained by ingestion of appreciable doses on an empty stomach, which likely results in the formation of well-absorbed Cr(III) organic complexes in gastrointestinal tissues and possibly the blood. The lack of any clinical indications of toxicity in the volunteers and the patterns of blood uptake and urinary excretion of chromium are consistent with a predominant uptake of Cr(III) organic complexes [derived from Cr(VI)] that are excreted more slowly than inorganic forms of Cr(III). Therefore, it appears that the endogenous reducing agents within the upper gastrointestinal tract and the blood provide sufficient reducing potential to prevent any substantial systemic uptake of Cr(VI) following drinking-water exposures at 5-10 mg Cr(VI)/L. Based on these data, the chemical environment in the gastrointestinal tract and the blood is effective even under relative fasting conditions in reducing Cr(VI) to one or more forms of Cr(III).

Observation of steady state in blood and urine following human ingestion of hexavalent chromium in drinking water.

The uptake and elimination of Cr(VI) in a male volunteer who ingested 2 L/d of water containing 2 mg/L for 17 consecutive days was measured. Total chromium was measured in urine, plasma, and red blood cells (RBCs) for 4 d prior to and 2 wk after dosing (34 d total). The estimated bioavailability (2%) and the plasma elimination half-life (36 h) were consistent with our previous studies of Cr(VI) ingestion in humans. Steady-state chromium concentrations in urine and blood were achieved after 7 d of Cr(VI) ingestion. Both plasma and red blood cell (RBC) chromium concentrations returned rapidly to background levels within a few days after cessation of dosing. Since the concentration of chromium in the RBC should not decrease quickly if the chromium had entered the RBC as Cr(VI), these data support our prior work suggesting that concentrations of 10 mg Cr(VI)/L or less in drinking water of exposed humans appears to be completely reduced to Cr(III) prior to systemic distribution. Clinical chemistry data indicate that no toxicity occurred.

Refined exposure assessment for ingestion of tapwater contaminated with hexavalent chromium: consideration of exogenous and endogenous reducing agents.

Laboratory studies were conducted to determine how rapidly and completely chromium (VI) [Cr(VI)] is reduced upon contact with common beverages mixed with tapwater. Studies were performed for five common beverages (coffee, tea, orange juice, Kool Aid, and powdered lemonade) spiked with either 10 or 50 mg Cr(VI)/l. The concentrations of Cr(VI) were measured at several time intervals for up to four hours. It was demonstrated that each of these beverages had the capacity to reduce a concentration of > or = 8 mg Cr(VI)/l within a 15-minute time frame, and that continued monitoring of the beverages revealed greater reduction of the Cr(VI). These findings are consistent with the observation that many foods and beverages, as well as endogenous body fluids such as saliva and gastric juices, are capable of reducing substantial quantities of Cr(VI) to Cr(III). Our exposure assessment shows that the estimated high-end ingested dose of Cr(VI) from tapwater at both 1 and 5 mg Cr(VI)/l is generally two to three orders of magnitude below doses shown to have no adverse health effect in animal studies. When considered in conjunction with studies demonstrating that the reductive capacity of gastric juices may exceed 50 mg Cr(VI) daily, these observations suggest that little or no Cr(VI) is likely to be absorbed orally at a reasonable water concentration of Cr(VI), since tapwater is bright yellow at 5 mg Cr(VI)/l.

Assessment of airborne hexavalent chromium in the home following use of contaminated tapwater.

Field studies were conducted to estimate the plausible uptake of hexavalent chromium [Cr(VI)] aerosols inhaled during indoor residential use of a shower or an evaporative cooler supplied with water containing Cr(VI). In the evaporative cooler study, water concentrations of 20 mg Cr(VI)/L did not produce an increased concentration of airborne Cr(VI). The indoor air concentration of Cr(VI), measured over 24 hours of use, was 0.3-2.7 ng/m3, about the same as the concurrent outdoor concentrations. In the shower study, the average airborne concentrations of Cr(VI) aerosols at breathing-zone height ranged from 87 to 324 ng Cr(VI)/m3 when the water concentration of Cr(VI) was 0.89 to 11.5 mg/L. The Cr(VI) concentration in air was correlated directly to water concentration. The lifetime average daily doses and incremental cancer risk estimates corresponding to 30-year residential exposures were calculated using the measurements in this study and published exposure guidelines. The plausible upperbound lifetime cancer risk associated with continuous exposure to "background" Cr(VI) in outdoor air was estimated at 6.9 per million for a person exposed during ages 0-30, and 4.0 per million for ages 30-60. Similarly estimated upperbound cancer risks due to inhalation of shower aerosols from water containing 2-10 mg Cr(VI)/L over the same exposure period ranged from 0.9 to 5.5 per million. Our calculations demonstrate that shower aerosols do not contribute appreciably to background Cr(VI) exposures and risks, even at concentrations exceeding 2 mg Cr(VI)/L, which exhibit a discernible and unaesthetic yellow color that may limit the potential for long-term exposures of this type. We conclude that exposure to indoor aerosols from water containing Cr(VI) is unlikely to create a health hazard at concentrations up to 10 mg Cr(VI)/L. Furthermore, these aerosol measurements may be relevant to estimating airborne exposures to other nonvolatile chemicals.