JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table I. Lethal dose of sodium pyridinethione in rabbits with and without assisted respiration Group Mean lethal dose Condition of rabbits size (mg kg -•) Anaesthetized and artificially ventilated 5 Anaesthetized and breathing spontaneously 5 Conscious 5 1608 •230 1041 &196 1159 &228 The mean lethal dose for rabbits with assisted respiration was significantly greater than the other LD values (P= 0.05), i.e. assisted respiration aided the rabbit's tolerance for sodium pyridinethione. Further respiration studies on anaesthetized rabbits breathing spon- taneously (Fig. 2) indicated a 20•o increase in respiration rate during the 'øø I +ve - ve 6O 4O 2d 2O 4O 6O 8O IOC I I I I l 200 400 600 800 1000 1200 Dose (mg kg -I) Figure 2. The mean effects upon respiration, blood pressure and heart rate of infusing sodium pyridinethione intravenously into the marginal ear vein of five anaesthetized rabbits. [•, Respiration rate ¸, heart rate A, blood pressure O, control.

EVALUATION OF SODIUM PYRIDINETHIONE infusion of 50 mg kg -• sodium pyridinethione, which remained elevated until 700 mg kg -• was infused. At this point respiration rate diminished dramatically as did the blood pressure and heart rate. The respiration rhythm was impaired at doses of 500 mg kg -• and eventual collapse was climaxed by anoxic convulsions. It would appear from Fig. 2 that infusion of sodium pyridinethione had a primary effect on blood pressure rather than heart rate, a hypotensive effect being recorded at the 50 mg kg -• dose level. Results from the control group of rabbits indicated no gross changes in respiration, blood pressure or heart rate arising from the infusion, surgery or the anaesthetic during the time taken to infuse the lethal dose in the test group of rabbits. These studies showed that systemic levels of 50 mg kg -• precipitated functional changes in the respiratory and cardio- vascular systems of the anaesthetized rabbit. Percutaneous absorption Percutaneous absorption studies were carried out using 35S-labelled sodium pyridinethione as described above. A dermal dose in excess of the threshold systemic toxic dose, namely 0.11 g kg -•, was applied to intact and 35 • 30 x x I I I I 120 180 240 Time (rain) Figure 3. Serum levels of sodium pyridinethione for rabbits with (O) intact and (X) abraded skin.