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Anatoxin-a: formulation and stability in support of rodent studies
Citation:
Ruto, B., S. Waidyanatha, J. Blake, R. Fernando, AND D. Jenkins-Hill. Anatoxin-a: formulation and stability in support of rodent studies. Society of Toxicology, Salt Lake City, UT, March 11 - 14, 2024.
Impact/Purpose:
A collaboration with NIEHS-NTP funded a contract at RTI International to evaluate the stability of a purified natural toxin, anatoxin-a, being used in mouse studies at US EPA. Anatoxin-a degrades quickly in light and higher pH. This study verified that the dosing formulations used for the mouse studies at EPA were stable at the conditions used by the investigator. The dosing formulation concentrations were also verified.
Description:
Anatoxin-a (ATX) is a cyanobacterial neurotoxin produced in freshwater lakes, streams, and reservoirs both in planktonic and benthic blooms. It is a potent and irreversible nicotinic acetylcholine receptor (nAChR) agonist that causes central and peripheral effects while it is the prolonged contraction of muscles leading to the common signs of toxicity: weakness, paralysis and sometimes death. ATX occurs globally and has caused illness and death in pets, livestock, and wildlife. The World Health Organization (WHO) has provisional human health guidelines for ATX in drinking and recreational water, but ATX is not regulated in the US. The US Environmental Protection Agency (US EPA) currently has health advisories for two other cyanotoxins, cylindrospermopsin and microcystin, but not for ATX. A multi-faceted in vivo study for orally exposed mice with ATX is underway in the Office of Research and Development (ORD) at EPA to provide data that may be used by the Office of Water (OW) for establishing human health guidance for ATX. ATX is known for being unstable in light and pH > 5. The purpose of this work was to investigate the accuracy of formulation preparation and evaluate the stability of ATX in formulation under the conditions to be used in the study.