Studies on the computer simulated model of toluene elimination from the brain using HPLC measured urinary hippuric acid and the patient's consciousness level and its medical implications

Abstract

Urine specimens were sampled from toluene exposed persons (2 painters, 2 plasterers and 1 addict of organic solvent), who were admitted to the critical care center of our medical school and the urinary hippuric acid (HA; the metabolite of toluene) was monitored every one hour after admission for 10-12 hours and thence-forth every 4 hours for more than 40 hours. The hourly (t) excretion pattern of HA(Y) was simulated with multiexponential functions; Y = sigma Ai.exp(-Bit).....(1), i = 1 to 3. The HA(Y) level during the term before the admission was estimated by equation (eq.) (1) for the respective cases. The consciousness level was evaluated according to the Japan Coma Scale on the following time points; on the telephone call to the emergency center (t1), on the arrival of the ambulance (t2) and on admission (t3). We related the differential change of the consciousness level (w) per time (between t1 and t2); delta w/delta t to one of the regression coefficients (Bi) of eq. (1) expressing the elimination of toluene from the body. A set of Bi whose scale parameter Ai is positive and whose absolute value is the minimum in the individual eq. (1) has the highest correlation coefficient with the value of delta w/delta t (r = -.870, p less than .05). We calculated the toluene elimination equivalent (X) from the brain by applying this Bi to the equation; X = exp(-Bit) on the respective time point, t1, t2 and t3, and related this X to W by simulating a logistic eq.; W = 3.0/[1 + exp[alpha(X - beta]].....(2), as to each respective case. The calculated values by eq. (2) for the occupationally toluene exposed cases revealed that the scale parameter (alpha) and the location parameter (beta) correlated well with the integral HA excretion value for 48 hours computed by eq. (1), and the elimination rate equivalent (Bi), respectively. But the calculated data of the solvent addict using eq. (2) indicated that there is a tolerance mechanism against toluene exposure; the scale parameter is larger and the location parameter is smaller than the respective ones from the painters and the plasterers.