Carcinogenicity of trichloromethine hydrochloride (TS-160 Spofa) and morphological damage after its intraamniotic injection.

The cytostatic TS-160 (trichloromethine hydrochloride, tris-/2-chloroethyl/amine hydrochloride) was injected subcutaneously into SPF Wistar rats of both sexes. After all doses used, spindle-cell or even polymorphocellular sarcomas developes at the injection sites in both sexes: after the dose of 0.1 mg/kg daily for 6 months, in 70%; after 0.25 mg/kg, in 79%; and after 1.0 mg/kg weekly for 6 months, in 45% of the rats. Besides, in 21% of the rats receiving the dosage of 0.25 mg/kg mucus-secreting intestinal adenocarcinomas were found. A relationship was apparent between the incidence figures of subcutaneous tumors on the one hand and the daily injection of the low dose versus the intermittent injection of the dose higher by a decimal order on the other hand. In a concurrent test, TS-160 was given to rats in intraamniotic injection on day 18 of pregnancy in doses of 1, 2.5, and 5 micrograms per embryo. On the first postnatal days, in the affected young rats there were observed morphogenetic disturbances: splanchnocrania and juvenile hair alopecia. These changes became repaired in the further course of postnatal development.