TY - JOUR
T1 - Metal and pharmaceutical mixtures
T2 - Is ion loss the mechanism underlying acute toxicity and widespread additive toxicity in zebrafish?
AU - Alsop, Derek
AU - Wood, Chris M.
N1 - Funding Information:
Thanks to Dr. Joanna Wilson (McMaster University) for providing a number of the pharmaceutical compounds and Dr. Warren Norwood (Environment Canada) for helpful discussions on modeling mixture toxicities. This study was funded by an NSERC (Canada) Discovery grant to CMW, who is supported by the Canada Research Chair Program. DA was supported by an NSERC Postdoctoral fellowship .
PY - 2013/9/15
Y1 - 2013/9/15
N2 - The acute toxicities and mechanisms of action of a variety of environmental contaminants were examined using zebrafish larvae (Danio rerio; 4-8 days post fertilization). Toxic interactions were observed between metals. For example, the addition of a sublethal level of nickel (15% of the LC50, one third of the LC01) to all copper treatments decreased the copper 96h LC50 by 58%, while sublethal copper exposure (6% of the copper LC50, 13% of the LC01) decreased the cadmium 96h LC50 by 47%. Two predictive models were assessed, the concentration addition (CA) model, which assumes similar mechanisms of action, and the independent action (IA) model, which assumes different mechanisms of action. Quantitative comparisons indicated the CA model performed better than the IA model; the latter tended to underestimate combined toxicity to a greater extent. The effects of mixtures with nickel or ammonia were typically additive, while mixtures with copper or cadmium were typically greater than additive. Larvae exposed to cadmium, copper or nickel experienced whole body ion loss. Decreases were greatest for Na+ followed by K+ (as high as 19% and 9%, respectively, in 24h). Additive toxicity between copper and other pharmaceutical compounds such as fluoxetine (Prozac™), β-naphthoflavone, estrogen and 17α-ethinylestradiol were also observed. Similar to metals, acutely toxic concentrations of fluoxetine, β-naphthoflavone and ammonia all decreased whole body Na+ and K+. Overall, whole body Na+ loss showed the greatest correlation with mortality across a variety of toxicants. We theorize that a disruption of ion homeostasis may be a common mechanism underlying the acute additive toxicity of many contaminants in fish.
AB - The acute toxicities and mechanisms of action of a variety of environmental contaminants were examined using zebrafish larvae (Danio rerio; 4-8 days post fertilization). Toxic interactions were observed between metals. For example, the addition of a sublethal level of nickel (15% of the LC50, one third of the LC01) to all copper treatments decreased the copper 96h LC50 by 58%, while sublethal copper exposure (6% of the copper LC50, 13% of the LC01) decreased the cadmium 96h LC50 by 47%. Two predictive models were assessed, the concentration addition (CA) model, which assumes similar mechanisms of action, and the independent action (IA) model, which assumes different mechanisms of action. Quantitative comparisons indicated the CA model performed better than the IA model; the latter tended to underestimate combined toxicity to a greater extent. The effects of mixtures with nickel or ammonia were typically additive, while mixtures with copper or cadmium were typically greater than additive. Larvae exposed to cadmium, copper or nickel experienced whole body ion loss. Decreases were greatest for Na+ followed by K+ (as high as 19% and 9%, respectively, in 24h). Additive toxicity between copper and other pharmaceutical compounds such as fluoxetine (Prozac™), β-naphthoflavone, estrogen and 17α-ethinylestradiol were also observed. Similar to metals, acutely toxic concentrations of fluoxetine, β-naphthoflavone and ammonia all decreased whole body Na+ and K+. Overall, whole body Na+ loss showed the greatest correlation with mortality across a variety of toxicants. We theorize that a disruption of ion homeostasis may be a common mechanism underlying the acute additive toxicity of many contaminants in fish.
KW - Concentration addition
KW - Copper
KW - Danio rerio
KW - Fluoxetine
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U2 - 10.1016/j.aquatox.2013.05.021
DO - 10.1016/j.aquatox.2013.05.021
M3 - Article
C2 - 23831971
AN - SCOPUS:84880031432
VL - 140-141
SP - 257
EP - 267
JO - Aquatic Toxicology
JF - Aquatic Toxicology
SN - 0166-445X
ER -