BIOLOGICAL SPIN-TRAPPING .2. TOXICITY OF NITRONE SPIN TRAPS - DOSE-RANGING IN THE RAT

To obtain the strongest possible free radical spin adduct signal using the electron paramagnetic resonance spectroscopy-spin trapping techni que, it is desirable to load an animal with the highest dose of spin t rap possible. One hundred and twenty six male Sprague-Dawley rats were used to establish the toxic dose range for PEN (alpha-phenyl N-tert b utyl nitrone) and 18 other similar spin traps. The lethal dose of PEN was found to be approximately 100 mg/100 g EW (0.564 mmol/100 g). The 18 other compounds were then tested, and their toxicities were gauged in terms of molar equivalents to PEN. Of these spin traps, DMPO (5,5-d imethyl-1-pyrroline-N-oxide) was found to be the least toxic (no toxic signs at twice the lethal dose for PEN) while 2,6-difluoro-PBN and M( 4)PO (3,3,5,5-tetramethyl-1-pyrroline-N-oxide) were the most toxic, bo th causing death at one eighth the PEN-equivalent lethal dose. Nine of the 18 nitrones appeared non-toxic at the 0.25 PEN-equivalent lethal dose level.