THE EFFECTS OF IODIDES, 1-THIOSORBITOL, AND TWENTY-FIVE OTHER COMPOUNDS ON ALPHANAPHTHYLTHIOUREA (ANTU) TOXICITY IN RATS

¹ Toxicology Section, Medical Division, Army Chemical Center, Maryland

(1) Of twenty-five compounds tested only potassium iodide and 1-thiosorbitol were unequivocally successful in preventing the lethal pulmonary edema and pleural effusion caused by the administration of ANTU to albino rats of the Wistar strain. Cysteine caused a delay in the onset of symptoms and in the appearance of edema and effusion fluid but did not significantly decrease mortality. Negative results were obtained with other sulfhydryl and labile sulfur compounds (BAL, BAL glucoside, sodium thiosulfate, diphenyl sulfide, and diphenyl disulfide), reducing substances (dextrose and n-heptaldehyde), aliphatic and aromatic acids (glycine, paraminobenzoic acid, and nicotinic acid), anti-histamine drugs (benadryl and pyribenzamine), vasomotor and respiratory stimulants (ephedrine and coramine), a melanin precursor (tyrosine), a prophylactic against phosgene pulmonary edema (hexamethylenetetramine), a hexanehexol (sorbitol), organic iodides (diiodotyrosine, cetyl iodide, n-decyl iodide, amyl iodide, and iodoacetic acid) and iodine.

(2) Potassium iodide protected only when given prophylactically. Complete protection was obtained by the intraperitoneal injection of a single 250 mg./kg. dose 48 hours prior to the administration of 2 LD₅₀'s of ANTU. Decreasing or increasing this period between iodide and ANTU injection resulted in decreasing degrees of protection; animals receiving the iodide at six hours or ten days before the administration of the ANTU were afforded no protection at all. Reduction of the dose of iodide to 100 mg./kg. resulted in complete loss of protection, regardless of the time of administration. The 250 mg./kg. dose was more effective when administered by a single injection 48 hours before the ANTU than when given in divided doses or in drinking water during the 48 hour period.

(3) The addition of free iodine, bromine, iodoacetic acid, or sodium iodoacetate to the ANTU solution immediately prior to injection completely destroyed the toxicity of the rodenticide, while the addition of potassium iodide or potassium bromide alone had no effect. However, iodine, iodoacetic acid, and sodium iodoacetate were found to be ineffective in vivo.

(4) Thiosorbitol was effective therapeutically, consistently reducing mortality when given in a dose of 1.5 gm./kg. simultaneously with the administration of 2 LD₅₀'s of ANTU.

(5) Position was shown to have no influence on the response of rats to ANTU.

(6) Sustained nembutal anesthesia was shown to have no influence on the response of rats to ANTU, a finding which suggests that there is no neurogenic factor involved in the development of the acute pulmonary edema shown by ANTU poisoned rats.

(7) Data on the rate and extent of pulmonary edema and pleural transuclate formation in response to various doses of ANTU, and on the effect of concomitantly administered cysteine on such formation, are presented.