Abstract
It has been demonstrated that T-1220, a derivative of aminobenzylpenicillin, had a broad antibacterial spectrum against gram positive and negative microorganisms and was especially effective against Pseudomonas aeruginosa.
The acute toxicity test of T-1220, therefore, was carried out in mice, rats, dogs and monkeys in this experiment. The results are as follows.
1) The acute intravenous LD50 was 5 g/kg in mice, 2.7 g/kg in rats, more than 6 g/kg in beagle dogs and more than 4 g/kg in monkeys. These values indicated that intravenous LD50 varied depending upon the species, and T-1220 was more toxic to rats than the others.
2) When the possible maximum dose, 10 g/kg, was administered orally and subcutaneously to mice and rats, they only showed the transient depression of spontaneous movement. Mice and rats died following the administration revealed a large amount of bloody exudate in the abdominal and thoracic cavities in intraperitoneal administration and massive hemorrhage of the lung in intravenous administration. Such changes were thought to be the cause s of death.
3) In beagle dogs treated intravenously with T-1220 at 6 g/kg, the toxic signs of vomiting, diarrhea, salivation, watery eye, blepharoptosis and borgorygmus were observed during and immediately after the administration. GOT and GPT increased moderately on a day after the administration. Any abnormalities, however, were not seen in autopsy and histological examination. In beagle dogs treated intravenously with T-1220 at 2 and 4 g/kg respectively, values of GOT, GPT, LDH and ALP did not change, while in 1 out of 3 and all 3 dogs treated intravenously with ABPC and CBPC at 2 g/kg respectively, levels of GOT, GPT and LDH increased.
The LD50 value of T-1220 in dogs administered into the cisterna magna was about 10 mg/kg, and the maximum nontoxic dose was 1 mg/kg.
4) In monkeys treated intravenously with T-1220 at 4 g/kg, any abnormalities were not observed, except for the slight and moderate increases of GOT, GPT and LDH values.
