Biological monitoring of exposure to botulinum neurotoxins

Abstract

Biological monitoring is an important method of assessing human exposure to toxic chemicals and biological toxins. To provide a means of assessing exposure, we have developed methods to measure protein toxins in human clinical samples. These methods include the Endopep-MS method, which can detect and differentiate botulinum neurotoxins (BoNTs) in food and clinical samples. The Endopep-MS method has three levels of selectivity that include extracting the toxin with high-affinity antibodies that are selective for only one of the BoNT serotypes; cleavage of synthetic peptides according to the specific enzymatic activity for each of the BoNT serotypes; and selectively detecting the toxin-dependent peptides by using high resolution matrix-assisted laser-desorption ionization time-of-flight mass spectrometry. The Endopep-MS method is specific for detecting each of the BoNT serotypes. Since botulism in humans is generally caused by BoNT A, B, E, or F, these serotypes are the focus of this report. The method is very sensitive, detecting less than 0.5 mouse LD50 of BoNT A in serum and 0.1 mouse LD50 of BoNT B, E, and F in human serum samples. The method has been applied to selected food matrices and serum and stool samples from individuals diagnosed with botulism. Biological monitoring (or biomonitoring) is an important tool used to assess exposure to toxic chemicals. 1 , 2 , 3