Botulinum neurotoxins inhalation

Adler, M. 2006. Inhalation toxicology of botulinum neurotoxin. In Inhalation Toxicology, 2nd edition, eds. 

The seven serotypes of botulinum toxin produced by Clostridium botulinum are the most toxic substances known. They are associated with lethal food poisoning after the consumption of canned foods. This family of toxins was evaluated by the United States as a potential biological weapon in the 1960s and is believed to be an agent that could be used against our troops. Unlike other threat toxins, botulinum neurotoxin appears to cause the same disease after inhalation, oral ingestion, or injection. Death results from skeletal muscle paralysis and resultant ventilatory failure. Because of its extreme toxicity, the toxin typically cannot be identified in body fluids, other than nasal... 

Botulinum neurotoxins (BoNTs) are produced by the anaerobic Clostridium botulinum species of bacteria and are the cause of botulism, a life-threatening neuroparalytic disease. They are extremely potent food poisons, with a mouse LD50 of 0.1 ng/kg for type A [1,2]. Aerosol exposure of BoNTs does not occur naturally, but could be attempted by bioterrorists to achieve a widespread effect. It has been estimated that a single gram of crystalline toxin, evenly dispersed and inhaled, could kill more than one million people [2]. 

Although inhalational botulinum intoxication was investigated in other animal species, these studies have not provided specific data on toxin absorption. The behavior of BoNTs in the respiratory tract was only recently investigated. Park and Simpson (2003) studied the properties of pure BoNT/A neurotoxin both in vivo and in vitro using mice and pulmonary cell culture models, respectively. Mean survival times were compared in mice receiving various doses of pure BoNT/A either IN or IP. Pure BoNT/A was found to be a potent intranasal poison, although the toxicity (as determined by mean survival time) associated with IP administration was somewhat higher. Mean survival times in mice were less than 100 (IP) or 600 min (IN) after administration of 0.1 pg pure toxin 75 (IP) or 400 min (IN) for 1 pg toxin and 120 min (IN) for 10 pg toxin (Park and... 

Chemical Abstracts Service Registry Number CAS 93384-43-1. Botulinum toxins comprise a series of seven related protein neurotoxins that prevent fusion of synaptic vesicles with the presynaptic membrane and thus prevent release of acetylcholine. Exposure in a battlefield or terrorist setting would most likely be to inhaled aerosolized toxin. The clinical presentation is that of classical botulism, with descending skeletal muscle weakness (with an intact sensorium) progressing to respiratory paralysis. A toxoid vaccine is available for prophylaxis, and a pentavalent toxoid can be used following exposure its effectiveness wanes rapidly, however, after the end of the clinically asymptomatic latent period. Because treatment is supportive and intensive (involving long-term ventilatory support), the use of botulinum toxin has the potential to overwhelm medical resources especially at forward echelons of care. 

Data sources (1) Holzer E. Botulism caused by inhalation. Med Klin. 1962 41 1735-1740. (2) Franz DR, Pitt LM, Clayton MA, Hanes MA, Rose KJ. Efficacy of prophylactic and therapeutic administration of antitoxin for inhalation botulism. In Das Gupta B, ed. Botulinum and Tetanus Neurotoxins and Biomedical Aspects. New York, NY Plenum Press 1993 473-476. 

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