NICOTINE AND COTININE ACCUMULATION IN PIGMENTED AND UNPIGMENTED RAT HAIR

This study was performed to assess the contribution of systemic and ex ternal uptake to nicotine accumulation in hair. The systemic nicotine uptake in hair was determined in pigmented rats (Brown Norway) and alb ino rats (Sprague-Dawley) after subcutaneous administration of 3 doses of nicotine with osmotic minipumps [5, 10, and 20 mg/(kg x day) for 3 weeks], the highest dose also following metabolic enzyme induction. T he external nicotine uptake was determined in cut hair of both strains after exposure to room-aged cigarette sidestream smoke, a surrogate f or environmental tobacco smoke (nicotine concentration: 5 mu g/liter f or 1, 2, and 3 weeks). Nicotine and its metabolite cotinine were deter mined using capillary GC after complete alkaline digestion of the hair sample and solvent extraction. Systemic uptake: Nicotine and cotinine concentrations in hair were dose-dependent and correlated with plasma concentrations. The nicotine concentration was similar to 20 times hi gher in pigmented than in unpigmented hair. The cotinine concentration was similar to 10 times lower than the nicotine concentration in pigm ented hair. After enzyme induction before administration, nicotine and cotinine concentrations in hair were significantly reduced in paralle l to the reduced plasma concentrations, showing the influence of metab olism. External uptake: Nicotine was found in the hair of both strains , the concentration in pigmented hair being a factor of 1.5 higher tha n in unpigmented hair. Thus, hair pigmentation had a major influence o n systemic uptake in hair and a minor influence on external uptake in hair. In the rat model, the contribution of both routes to the nicotin e concentration in hair can be roughly estimated to be in the same ord er of magnitude, when compared on a basis applicable to the human situ ation. For this estimate, the experimental data were extrapolated to t he lower concentrations of nicotine found in the plasma of smokers and in environmental tobacco smoke.