UPTAKE, DISTRIBUTION, AND FORMATION OF HEMOGLOBIN AND DNA-ADDUCTS AFTER INHALATION OF C2-C8 1-ALKENES (OLEFINS) IN THE RAT

Absorption, distribution, elimination and hemoglobin and DNA adduct fo rmation were studied in the rat after inhalation of individual C2-C8 1 -alkenes (olefins) at 300 p.p.m., 12 h a day for 3 consecutive days. T he concentrations of olefins were measured in blood, lung, brain, live r, kidney and perirenal fat immediately after each exposure and 12 h a fter the third exposure, DNA adducts were determined by P-32-postlabel ing in liver, and lymphocytes sampled immediately after the last expos ure. Hemoglobin adducts were determined by GC/MS and GC/MS/MS in eryth rocytes sampled immediately after the last exposure, Concentrations of 1-alkenes in blood and organs reached a steady-state level after the first 12 h exposure, and the concentrations 12 h after the last exposu re were generally low, except in fat. tissue. Concentrations of 1-alke nes in blood and the different tissues increased with increasing numbe r of carbon atoms. In contrast, levels of hemoglobin and DNA adducts d ecreased with increasing number of carbon atoms. The decrease was most pronounced from C2 to C3. The decrease through the whole homologous s eries from ethene to 1-octene was most pronounced for hemoglobin adduc ts followed by the DNA adducts in the lymphocytes. All 1-alkenes cause d formation of detectable levels of hemoglobin and DNA adducts, althou gh the levels of hemoglobin adducts after C4-C8 exposure were low. The project illustrates important aspects of the use of biomarkers. The s tructure-activity approach gives possibilities for extrapolation withi n the homologous series.