Comparative toxicity of the cyanobacterial toxin cylindrospermopsin between mice and cattle: human implications

Abstract

The cyanobacterial toxin cylindrospermopsin is produced by Cylindrospermopsis raciborskii and Aphanizomenon ovalisporum in many parts of the world. A human poisoning incident occurring at Palm Island, Queensland, Australia in 1979 was subsequently ascribed to cylindrospermopsin. The structure of cylindrospermopsin, a tricyclic guanidinium moiety bridged to hydroxymethyluracil, was deduced in 1992. A number of studies have investigated the acute toxicity of cylindrospermopsin in mice. It is primarily a hepatotoxin with a 24-hour acute intraperitoneal (IP) LD50 of 2 mg/kg, a 5-day acute i.p. LD50 of 0.2 mg/kg and a 5-day acute oral LD50 of approximately 6 mg/kg. A human health risk assessment using data from longer-term oral dosing studies suggests a guideline value for cylindrospermopsin in drinking water of approximately 10 姯L.We have recently studied cattle poisonings by cylindrospermopsin and detected the toxin in a number of tissues after necropsy. Concentrations of 1 mg/L or above in drinking water (dose is approximately 50 姯kg/day) were shown to result in cattle death after short-term exposure (less than 10 days). Oral dosing of mice at levels up to 5 mg/L with cylindrospermopsin in drinking water for 90 days did not produce any significant toxicity. Human health risk assessment based on cattle however, which are much more sensitive to cylindrospermopsin than rodents, would produce a guideline for human drinking water of approximately 0.05 姯L. A consideration of reported human poisoning incidents that implicate cylindrospermopsin suggests that humans may also be more sensitive than rodents to this toxin.