STUDIES ON THE TOXICITY AND PHARMACOLOGICAL ACTION OF SODIUM N-p-CHLOROPHENYLDIAZOTHIOUREA (PROMURIT)

¹ University of Chicago Toxicity Laboratory, Chicago, Illinois
² Department of Pharmacology, University of Chicago, Chicago, Illinois

1. The acute, intraperitoneal toxicity of Promurit in mgm./kgm. to several species was as follows: 200-gm. female albino rats, 0.2; 200-gm. male rats, 0.4; 300-gm. male rats, 0.2; mice, 1.35; guinea pigs, 1.9; and rabbits, 1.75-1.9. The acute, oral toxicity of Promurit in mgm./kgm. was as follows: 200-gm. female rats, 0.28; 200-gm. male rats, 0.89; 300-gm. male rats, 0.27; and female guinea pigs, 3.1. Death appears to be due to massive pleural effusion and pulmonary edema.

2. Concentrations of Promurit from 0.05 to 1.0 per cent, mixed with ground dog blocks, were acceptable and uniformly fatal to all the animals tested when offered to rats overnight while a concentration of 0.025 per cent Promurit in the diet resulted in 75 per cent mortality.

3. Acute poisoning by Promurit caused hyperglycemia, reduction in liver glycogen and prevented the deposition of liver glycogen.

4. Rats made tolerant to 100 mgm./kgm. of ANTU can withstand 2 but not 3 mgm./kgm. of Promurit. For female rats consuming 3.03 gm. of iodide per kgm. of body weight (an amount which would raise the LD₅₀ of ANTU to about 100 mgm./kgm.) over a ten-day period, the LD₅₀ was between 0.3 and 0.4 mgm./kgm. of Promurit.

5. Treatment with l-thiosorbitol protected rats from one but not two times the LD₅₀ of Promurit. Pretreatment with 500 mgm./kgm. of thiourea increased the LD₅₀ to over 5 mgm./kgm. of Promurit, but thiourea given two hours after Promurit failed to protect rats against 1 mgm./kgm.

6. Adrenal demedullation and thyroidectomy failed to alter the acute toxicity of Promurit to rats.

7. Promurit (10^-4 M) inhibited tyrosinase and peroxidase but not carbonic anhydrase or catalase.