The uninary hippuric acid (H.A.) of workers in an automobile factory, a plastic toy factory, and a gravure painting factory, where toluene is used, was determined, and the urinary hippuric acid and the methyl hippuric acid (M.H.A.) of the worker using thinner containing toluene and xylene were also measured. The concentration of toluene or xylene in the air was determined by gas chromatography with FID and by a Kitagawa's detector, and the average concentration inhaled by workers was calculated with a chart showing the relationship between the toluene or xylene density in the air of an artificial exposure chamber and the excretion per minute or the concentration of H.A. or M.H.A. of volunteers as reported previously. The results obtained were as follows. 1. Seasonal measurements of urinary H.A. and M.H.A. in workers, who were using thinner containing toluene and xylene, were conducted six times in two years. Both urinary excretions per mimute of H.A. and M.H.A. increased during the working time. As daily urinary H.A. and M.H.A. excretions varied according to the concentration of toluene or xylene due to the kind and velocity of the spraying work; in fact, the amount of excretion of worker's urinary H.A. and M.H.A. during work varied every time when the survey was made. Therefore, it was found necessary to check the excretion of H.A. and M.H.A. in worker's urine at least once a month. 2. Molar ratio of toluene to m-and p-xylene in the thinner was similar to that of urinary H.A. and to M.H.A. in the worker who was using that thinner. 3. We can screen out a worker exposed to toluene plus xylene at 200 p.p.m. from the excretion perminute by the following equation. (H.A. excretion per minute in working time (mg/min))/(H.A. excretion exposed to 200 p.p.m. of toluene (3.77 mg/min))+(M.H.A. excretion per minute (mg/min))/(M.H.A. excretion exposed to 200 p.p.m. of xylene (4.10 mg/min)) ⪌ 1…(1) or simply by (H.A. + M.H.A. excretion mg per minute (mg/min))/(3.95 mg/min) ⪌ 1…(2) When the value of equation (1) or (2) is over 1, the average concentration of the sum of toluene and xylene in the worker who has inhaled both, is judged to be over the threshold limit value (T.L.V.). Equation (2) was found useful in the case in which the sum of H.A. and M.H.A. exretions per minute was measured by the simple paper chromatograph with buthanol-acetic acid-water as a developing solvent. 4. The worker working in the atmosphere higher in the density of toluene excreted so much higher concentration of urinary hippuric acid. And also, the higher the densities of toluene and xylene in the environmental air, the higher was the concentration of glycine conjugates (H.A. + M.H.A.). 5. In evaluating the results of the medical examination of workers who were using thinner containing toluene and xylene, results of measurements of urinary H.A. and M.H.A. of workers, indicating the amount of toluene and xylene inhaled by the workers, should be taken into account in addition to counting erythrocytes and leucocytes, because toluene and xylene have relatively higher narcotic actions.

View full abstract

Effects of methanol, ethanol, n-propanol, carbon disulfide and o-phthalodinitrile on the electrical activities of the central nervous system of cats and rabbits were studied. Also, from the results of the present investigation and of the pervious one dealing with the effect of nitroglycol, the use of the electroencephalographic technique to the study of industrial toxicology was discussed. 1. Methanol, ethanol and n-propanol: Oral administration of 1-3ml-kg of n-propanol to curarized rabbits induced slow waves with high amplitude in EEG of the neo-cortex. In the hippocampal lead, there were two types of changes, one with persisting appearance of regular slow waves and the other with appearance of irregular slow waves. In the latter cases, the waves were accompanied with synchronization in the cortical lead. Change of EEG was similar in the case of noncurarized, unanesthetized rabbits. The above-mentioned effects were quite similar to those observed after the administration of methanol or ethanol. 2. Carbon disulfide: The intravenous injection of 0.1-0.2ml/kg of carbon disulfide to curarized cats revealed an appearance of slow waves and a decrease of amplitude in the cortical tracing. According to the changes of frequency and voltage of the electrical activity and of time from the administration to the beginning of flattening, the EEG patterns after administration were classified into four types; (I) rapid decrease of amplitude of the electrical activity in the neo-cortex followed by flattening in each lead without delay, (II) some delay in the appearance of flattening, after the decrease of amplitude in the neo-cortex, (III) a transitory arousal pattern in the neo-cortex, the amygdaloid nucleus and the hippocampus just after the injection, then appearance of slow waves in the neo-cortex about five minutes after the injection, and finally flattening of EEG, and (IV) no particular change. These types were dependent on whether the intravenous injection had been performed quickly or slowly. Type I or II was seen in cases when animals were injected quickly. Type III or IV was seen in cases when injections were performed slowly. In curarized rabbits, injected intravenously with doses at 0.1-0.3ml/kg, the resulst were similar. In the case of intraperioneal injection, type III or IV was observed. 3. O-Phthalodinitrile: Oral administration of doses ranging from 50 to 300mg/kg revealed the appearance of the slow wave burst or the spike and wave complex in the electrical activity of the neo-cortex in both curarized and non-curarized rabbits. When slow wave burst or spike and wave complex was found in EEG, none of excitatory symptoms was observed in the behaviour of non-curarized, unanesthetized rabbits. Seizure discharge in EEG was observed in all the rabbits except a case which had been given a single dose at 50mg/kg. Seizure discharge in EEG of non-curarized animals was accompanied with motor seizures. It is thought to be possible to classify the action of chemicals on the electrical activities of the central nervous system according to the change of frequency, voltage and shape of waves. As far as the present investigation is concerned, changes of the electrical activities after the administration of chemicals were classified into three patterns, namely appearance of slow waves, flattening and appearance of spike waves. It appears that observation of changes of EEG after the administration of chemicals are useful for the classification of toxicity of chemicals and for the comparison of effective doses of them under a definite experimental condition as in the case of this study.

View full abstract