TOXICOLOGICAL PROFILE FOR CHROMIUM - Davidborowski.com
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TOXICOLOGICAL PROFILE FOR CHROMIUM - Davidborowski.com

TOXICOLOGICAL PROFILE FOR CHROMIUM - Davidborowski.com TOXICOLOGICAL PROFILE FOR CHROMIUM - Davidborowski.com

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10.07.2015 Views

CHROMIUM 1482. HEALTH EFFECTS2.3.4.2 Oral ExposureGiven the low absorption of chromium compounds by the oral route, the major pathway of excretion afteroral exposure is through the feces.An acute, oral dose of radioactive chromium(III) as chromium chloride or chromium(VI) as sodiumchromate was administered to humans after which feces and urine were collected for 24 hours and 6 days,respectively, and analyzed for chromium. The amount of chromium in the 6-day fecal collection was99.6 and 89.4% of the dose for chromium(III) and chromium(VI) compounds, respectively. The amountof chromium in the 24-hour urine collection was 0.5 and 2.1% of the dose for chromium(III) andchromium(VI) compounds, respectively (Donaldson and Barreras 1966). In subjects drinking0.001–0.1 mg chromium(VI)/kg/day as potassium chromate in water for 3 days,

CHROMIUM 1492. HEALTH EFFECTSresulted in an extended time course of excretion. Approximately 76–82% of the 14-day total amount ofchromium in the urine was excreted within the first 4 days (mean peak concentration 209 µg chromium/gcreatinine; range 29–585 µg chromium/g creatinine). The average urinary excretion half-life for four ofthe volunteers was 39 hours at this dose. All subjects had returned to background concentrations(0.5–2.0 µg chromium/g creatinine) by 14 days post-dosing. About 87% of the total amount of chromiumin the urine measured over 8 days was excreted during the first 4 days for one volunteer ingesting0.03 mg chromium(VI)/kg (peak 97 µg chromium/g creatinine on day of ingestion). Urinary chromiumconcentrations had returned to an average of 2.5 µg chromium/g creatinine within 7 days post-dosing, thelast time point measured. Urinary excretion half-life in this volunteer was 37 hours. Similar time coursesof excretion were observed when volunteers took the same doses as daily doses over 3-day periods. Anearlier study by this group (Kerger et al. 1996a) examined urinary excretion half-lives following a bolusdose of 10 ppm (approximately 0.06 mg chromium/kg) chromium(III) chloride, potassium dichromatereduced with orange juice (presumably, the juice reduced the potassium dichromate to chromium(III)-organic complexes and chromium(III) ions), or potassium dichromate. The calculated urinary excretionhalf-lives for the three chromium solutions were 10.3, 15, and 39.3 hours, respectively. The potassiumdichromate half-life is consistent with the results from the Kerger et al. (1997) study.The urinary excretion kinetics of chromium have also been examined in eight adults that wereadministered chromium(III) at 400 µg/day as chromium(III) picolinate for 3 consecutive days (Gargas etal. 1994). The mean time to peak urinary concentration was 7.18±2.11 hours (range 2.9–13.0 hours), themean peak concentration being 7.92±4.24 µg chromium/g creatinine (range 3.58–19.13 µg/g creatinine).Excretion diminished rapidly after the peak but did not appear to return to background in most of thevolunteers before the next daily dose.Pharmacokinetic models were used to predict the retention and excretion of ingested chromium(III)picolinate (Stearns et al. 1995a). A single dose of 5.01 mg (assuming 2.8% or 140 µg of thechromium(III) picolinate is absorbed) resulted in 11 µg (7.9%) retained after 1 year. The model predictedthat about 1.4 µg would still be present in body tissues 10 years after dosing, and continuous dosing overa 1-year period would result in 6.2 mg of chromium(III) picolinate being retained, requiring about20 years to reduce the retained level to 0.046 mg. These projected retention estimates may be two- tofour-fold lower than results obtained from actual clinical findings. The authors caution that accumulativedaily intake of chromium(III) may result in tissue concentrations that could be genotoxic.

<strong>CHROMIUM</strong> 1482. HEALTH EFFECTS2.3.4.2 Oral ExposureGiven the low absorption of chromium <strong>com</strong>pounds by the oral route, the major pathway of excretion afteroral exposure is through the feces.An acute, oral dose of radioactive chromium(III) as chromium chloride or chromium(VI) as sodiumchromate was administered to humans after which feces and urine were collected for 24 hours and 6 days,respectively, and analyzed for chromium. The amount of chromium in the 6-day fecal collection was99.6 and 89.4% of the dose for chromium(III) and chromium(VI) <strong>com</strong>pounds, respectively. The amountof chromium in the 24-hour urine collection was 0.5 and 2.1% of the dose for chromium(III) andchromium(VI) <strong>com</strong>pounds, respectively (Donaldson and Barreras 1966). In subjects drinking0.001–0.1 mg chromium(VI)/kg/day as potassium chromate in water for 3 days,

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