Single dose acute toxicity testing for N,N-bis(2-mercaptoethyl)-N′,N′ diethylethylenediamine in beagles

- Beagles were exposed to BMEDA using intravenous administration to conduct a single dose 14-day acute toxicity study.
- No lethality was observed in beagles during this 14-day acute toxicity study.
- BMEDA was not associated with any adverse effects in beagles at doses of up to 2 mg/kg.

N,N-Bis(2-mercaptoethyl)-N′,N′-diethylenediamine (BMEDA) is used in the preparation of the 188Re-BMEDA-liposome as a chelator to deliver rhenium 188 into liposomes. Although the safety of the 188Re-BMEDA-liposome had been established, the use of BMEDA in preparing the liposome is of interest; however, an assessment of its safety is warranted. In this present work, we report on the acute toxicity study of BMEDA in beagles to identify doses causing no adverse effect and doses causing life-threatening toxicity. In a single dose 14-day systemic toxicity study conducted in beagles, BMEDA was without compound-related adverse effects at doses of up to 2 mg/kg in a series of clinical observations and clinical pathology examinations. The results of these studies could aid in choosing doses for repeat-dose studies and in the selection of starting doses for Phase 1 human studies.