From nature to threat: Natural toxins as emerging dual-use agents in chemical security

Natural toxins represent structurally diverse class of bioactive compounds that pose underrecognized risks extending beyond traditional food safety concerns into chemical security applications. Recent high-profile incidents have highlighted critical gaps in detection capabilities, clinical management, and regulatory frameworks governing these substances. This review discusses the diversity, potency profiles and security implications of natural toxins with a focus on compounds with outstanding acute toxicity, such as batrachotoxin from Phyllobates poison dart frogs (LD50 2-3 μg/kg intravenously), amatoxins from Amanita species (LD50 100-300 μg/kg) and conotoxins from cone snails (LD50 10-100 μg/kg), comparable to synthetic chemical warfare agents. Critical vulnerabilities include the absence of specific antidotes, analytical challenges related to structural diversity and incomplete coverage by routine toxicological screens. Historical examples of intentional intoxications (e.g., ricin assassination of Georgi Markov in 1978 and bioterrorism by mail between 2003 and 2013) illustrate the general availability but also the limitations of this modus operandi. Developments in high-resolution mass spectrometry and computational toxicology offer promising improvements in detection. International regulations under the Chemical Weapons Convention need further improvement to address the growing threat posed by these natural but potentially weaponizable compounds.