Paralytic shellfish toxins (PSTs) are a family of neurotoxins that can block neuronal transmission by binding to voltage-gated sodium channels, resulting in severe poisoning to animals and humans that ingest PST-contaminated diets. C2 toxin (C2) and its derivatives gonyautoxin 2/3 (GTX2/3) are relatively prevalent PSTs found in the coastal waters of Southern China and Hong Kong. They are likely involved in the paralytic shellfish poisoning (PSP) cases in this region. The present study was conducted to gain more understanding of the toxicology of these toxins in mammalian systems to better assess their health hazard. Sufficient amount of C2, GTX2/3, and ¹⁴C-C2 were produced and purified to allow five specific studies using mice or rats as animal models: 1) in vitro and in vivo biotransfo...[ Read more ]

Paralytic shellfish toxins (PSTs) are a family of neurotoxins that can block neuronal transmission by binding to voltage-gated sodium channels, resulting in severe poisoning to animals and humans that ingest PST-contaminated diets. C2 toxin (C2) and its derivatives gonyautoxin 2/3 (GTX2/3) are relatively prevalent PSTs found in the coastal waters of Southern China and Hong Kong. They are likely involved in the paralytic shellfish poisoning (PSP) cases in this region. The present study was conducted to gain more understanding of the toxicology of these toxins in mammalian systems to better assess their health hazard. Sufficient amount of C2, GTX2/3, and ¹⁴C-C2 were produced and purified to allow five specific studies using mice or rats as animal models: 1) in vitro and in vivo biotransformation, 2) effects of PSTs on enzyme activities in vivo, 3) toxicokinetics, 4) acute oral toxicity determination and 5 ) health risk assessment. The results indicated that C2 and GTX2/3 were not metabolized by liver preparations or by the whole animals. In addition to being neurotoxic, the toxins caused reduction of the activity of some essential metabolizing and antioxidant enzymes and the gain of weight in animals at sublethal doses. Experiments using orally administered unlabeled and ¹⁴C-labled toxins revealed that C2 and GTX2/3 have comparable kinetic patterns, but GTX2/3 had higher absorption efficiency than C2. Using the established health risk assessment protocol, the recommended acceptable levels calculated for C2 and GTX3 were significantly lower than the regulatory limits currently promulgated by many countries. A re-evaluation of these regulatory limits for better protection of public health seems justifiable.