Intestinal absorption of botulinum toxins of different molecular sizes in rats.

During a period of 10 to 12 h after injection of type B 16S (L) toxin into the ligated duodenum of rats, 0.01 to 0.1% of the total toxicity administered was found in the lymph drawn by cannulation of the thoracic duct. The recovery was 50 to 100 times higher than that of the rat given type B 12S (M) or 7S (S) toxin. During the same period, 0.6 to 1.5% of the specific antigens were recovered, regardless of the molecular size of the toxin that had been administered. In lymph of the B-L or B-M toxin recipient, the toxic and nontoxic components were detected in comparable quantities, indicating that the undissociated progenitor toxin molecule is absorbed through the intestinal wall. Although the toxic component had lost its toxic activity, the two components of B-M toxin appearing in lymph reassembled to reconstruct the 12S molecule, whereas those of B-L toxin did not, although the toxic component was still active. Type B-L, B-M, and B-S toxins showed similar stabilities to in vitro exposure to rat lymph (pH 8.2), but B-L toxin showed a considerably higher stability to intestinal juice (pH 7.0) than did B-M toxin. Thus, the toxicity of lymph of rats administered botulinum toxin intraduodenally depends not upon the rate of absorption, but largely upon the stability in the intestine.