Dose-dependent fate of vinyl chloride and its possible relationship to oncogenicity in rats.

Abstract

Studies on the fate of 14C-labeled vinyl chloride (VC) following oral administration and inhalation exposure in rats demonstrated that the disposition of VC in the body is a function of the dose. More importantly, from the data available, it appears that a correlation exists between doses of VC which cause tumors and those that saturate metabolic or detoxifying pathways. Additional studies characterized the depression of liver nonprotein sulfhydryl content (primarily GSH) with the duration and concentration of exposure to VC. The results of these investigations indicate that statistical projections utilizing data collected from rats exposed to high doses of VC are invalid for predicting the hazard of low level exposure, because such projections violate the a priori assumption that the dynamics governing the fate of VC in the body are unaltered.

Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 1

“…In rats exposed to t4C-labeled vinyl chloride at 20,000 ppm for 5 min, radioactivity was detected in the liver, bile duct, kidney, and gastrointestinal tract within 10 min (Duprat et al, 1977). Similarly, in rats exposed to 14C-labeled vinyl chloride at 50 or 100 ppm for 5 or 6 h, liver and kidney had the highest concentration of radioactivity among all the tissues after the exposure (Bolt et al, 1976;Watanabe et al, 1976).…”

“…Similarly, Buchter et al (1980) discovered that vinyl-chloride metabolism in rhesus monkeys was saturated at 200 ppm. In rats exposed to vinyl chloride at 10, 1000, or 5000 ppm for 6 h, Watanabe's group presented evidence that vinyl chloride metabolism appeared to be saturated at 1000 ppm (Watanabe et al, 1976(Watanabe et al, , 1978aWatanabe and Gehring, 1976). At l0 ppm, 68% of the body burden was excreted in the urine, 12% was expired as CO 2, 4% was excreted in the feces, and about 2% was expired unchanged (Watanabe et al, 1976;Watanabe and Gehring, 1976).…”

“…In rats exposed to vinyl chloride at 10, 1000, or 5000 ppm for 6 h, Watanabe's group presented evidence that vinyl chloride metabolism appeared to be saturated at 1000 ppm (Watanabe et al, 1976(Watanabe et al, , 1978aWatanabe and Gehring, 1976). At l0 ppm, 68% of the body burden was excreted in the urine, 12% was expired as CO 2, 4% was excreted in the feces, and about 2% was expired unchanged (Watanabe et al, 1976;Watanabe and Gehring, 1976). When the exposure level was increased to I000 ppm, however, the fraction of the body burden eliminated in the urine was reduced to 56% and that expired as vinyl chloride increased to 12%.…”

Vinyl chloride

“…Absorption in rats from the gastrointestinal tract is nearly comlete, ranging between 80 and 90% . 35 Withey36 found that blood levels peaked 10-20 min following gavage of a single 10-ml aliquot of 44-92 mg kg-' vinyl chloride in an aqueous solution. Seventy-two hours after ingestion, the greatest concentration of vinyl chloride was found in the liver at concentrations two-to fivefold greater than in the lung, fat, muscle, skin or plasma.…”

“…Seventy-two hours after ingestion, the greatest concentration of vinyl chloride was found in the liver at concentrations two-to fivefold greater than in the lung, fat, muscle, skin or plasma. 35 On average, humans retain 42% of inhaled vinyl ~hloride.~' Animal data indicate that vinyl chloride is rapidly absorbed, but is insufficient to quantitate the proportion of dose absorbed.I8…”