β-Cyclodextrin Attenuates Perfluorooctanoic Acid Toxicity in the Zebrafish Embryo Model.

Abstract

Perfluorooctanoic acid (PFOA) has been linked to negative health outcomes including cancer, thyroid disease, infertility, and developmental delays. β-Cyclodextrin (β-CD), a cyclic sugar, has been previously shown to form strong host–guest complexes with PFOA, and is proposed as a means of environmental remediation with respect to this widespread contaminant. In the present study, β-CD was directly examined with regards to possible attenuation of the toxicity of PFOA specifically employing the zebrafish (Danio rerio) embryo model. Zebrafish embryos were exposed to various concentrations of PFOA without β-CD, and with equimolar (1:1) and excess (2:1) molar ratios of β-CD to PFOA, and assessed for lethality and developmental toxicity through seven days post-fertilization (dpf). Rapid onset of lethality with limited morphological abnormalities was observed at relatively low concentrations of PFOA (LC50 ≈ 50 ppm), along with effects on morphometric and neurobehavioral parameters in surviving embryos. A highly significant difference (p < 0.0001) was observed between the 2:1 treatment, and both 1:1 and PFOA only treatments, with respect to lethal concentration and apparent neurobehavioral effects, suggesting an effectively reduced toxicity of the fully complexed PFOA. In contrast, however, neither β-CD treatment reduced developmental toxicity with respect to the morphometric endpoint (i.e., interocular distance). Whereas LC50 of PFOA alone did not change over 7 dpf, the 1:1 and 2:1 values decreased slightly over time, suggesting either delayed or alternative toxic effects on later developmental stages at presumptively lowered levels. This study, therefore, indicates β-CD may be an effective agent to reduce toxicity of and mitigate environmental health concerns associated with PFOA, but that further study is required to elucidate the mechanism of complexation as it relates to the attenuation of toxicity.