TOXICOLOGICAL PROFILE FOR CHROMIUM - Davidborowski.com

CHROMIUM 1622. HEALTH EFFECTSInterroute extrapolation. The model was developed initially using kinetic data from intravenousstudies and then refined using data from oral and intratracheal routes. The final model was able toreasonably predict the results from an inhalation exposure experiment.Two kinetic models describing distribution and clearance in humans have been developed based onstudies in volunteers. A model for distribution and clearance of chromium(III) as chromium(III)trichloride was developed by Lim et al. (1983) that has fast, medium, and slow exchange compartments.The model’s parameters were based on distribution measurements obtained from whole body scintillationscanning after intravenous injections of radiolabeled chromium into volunteers. Total chromiumremaining in the body as a function of time was determined with a whole-body scanner, plasma clearancewas determined by measurement of radiolabel in the blood. Measurements taken immediately afterinjection showed that 96% of the label was bound to plasma proteins while 4% was free, after 24 hoursthe label was too low to measure. Whole-body scanning showed labeled chromium primarily in the liver,spleen, body soft tissues, and bone with highest concentrations in the liver and spleen. Examination ofthe scanning images over time revealed three major accumulation and clearance components in eachorgan, half-lives were 0.5–12 hours, 1–14 days, and 3–12 months. Each organ exhibited this pattern, i.e.,each organ has varying proportions of fast, medium, and slow components for chromium clearance. Amodel was constructed based on a central compartment of plasma chromium in equilibrium with threepools defined by clearance rate and elimination from the body taking place at the kidney through filtrationof unbound chromium and loss of bound chromium by shedding of epithelial cells. The model indicatesthat in a normal individual in chromium balance, absorbed chromium distributes into three pools, a fastpool containing approximately 0.13 µg, and a clearance half-time of 5.2 minutes, a medium poolcontaining 0.8 µg and a half-time of 2.2 days, and a slow pool containing 24.7 µg and a half-time of315 days.Gargas et al. (1994) employed a three compartment model describing the urinary excretion of chromium(Aitio et al. 1988) to estimate the bioavailability of chromium(III) from chromium(III) picolinate involunteers ingesting capsules containing 400 µg. The model contained 3 compartments, a fast-exchangecompartment receiving 40% of absorbed chromium with a half-life of 7 hours, a medium-exchangecompartment receiving 50% of absorbed chromium with a half-life of 15 days, and a slow-exchangecompartment receiving 10% of absorbed calcium with a half-life of 3 years. Estimates of absorbedchromium were used as inputs to the model and predicted urinary excretion was compared to thatobserved. Adjustments to the estimate of absorbed chromium were made until the predictions agreed