Metal and pharmaceutical mixtures

Is ion loss the mechanism underlying acute toxicity and widespread additive toxicity in zebrafish?

Derek Alsop, Chris M. Wood

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)257-267
Number of pages11
JournalAquatic Toxicology
Volume140-141
DOIs
StatePublished - Sep 15 2013

Fingerprint

Zebrafish
acute toxicity
Danio rerio
Copper
drug
copper
Metals
metals
Ions
ions
toxicity
drugs
ion
metal
lethal concentration 50
Fluoxetine
Pharmaceutical Preparations
Nickel
nickel
Cadmium

Keywords

  • Concentration addition
  • Copper
  • Danio rerio
  • Fluoxetine

ASJC Scopus subject areas

  • Aquatic Science
  • Health, Toxicology and Mutagenesis

Cite this

Metal and pharmaceutical mixtures : Is ion loss the mechanism underlying acute toxicity and widespread additive toxicity in zebrafish? / Alsop, Derek; Wood, Chris M.

In: Aquatic Toxicology, Vol. 140-141, 15.09.2013, p. 257-267.

Research output: Contribution to journalArticle

@article{a8af920c07734b2b9464abf0d0d178da,
title = "Metal and pharmaceutical mixtures: Is ion loss the mechanism underlying acute toxicity and widespread additive toxicity in zebrafish?",
abstract = "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.",
keywords = "Concentration addition, Copper, Danio rerio, Fluoxetine",
author = "Derek Alsop and Wood, {Chris M.}",
year = "2013",
month = "9",
day = "15",
doi = "10.1016/j.aquatox.2013.05.021",
language = "English",
volume = "140-141",
pages = "257--267",
journal = "Aquatic Toxicology",
issn = "0166-445X",
publisher = "Elsevier",

}

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.

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

UR - http://www.scopus.com/inward/record.url?scp=84880031432&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880031432&partnerID=8YFLogxK

U2 - 10.1016/j.aquatox.2013.05.021

DO - 10.1016/j.aquatox.2013.05.021

M3 - Article

VL - 140-141

SP - 257

EP - 267

JO - Aquatic Toxicology

JF - Aquatic Toxicology

SN - 0166-445X

ER -