TY - JOUR
T1 - Factors Affecting the Binding of Diltiazem to Rainbow Trout Plasma
T2 - Implications for the Risk Assessment of Pharmaceuticals in Aquatic Systems
AU - Glover, Chris N.
AU - Klaczek, Chantelle E.
AU - Goss, Greg G.
AU - Saari, Gavin N.
N1 - Publisher Copyright:
© 2022 SETAC.
PY - 2022/12
Y1 - 2022/12
N2 - The accumulation of organic toxicants in fish plasma, and how they partition between the bound and unbound fraction once absorbed, are important metrics in models that seek to predict the risk of such contaminants in aquatic settings. Rapid equilibrium dialysis of diltiazem, an ionizable weak base and important human pharmaceutical contaminant of freshwaters, was conducted with rainbow trout (Oncorhynchus mykiss) plasma. The effect of fed state, fish sex, fish strain/size, and dialysis buffer pH on the binding of radiolabeled diltiazem (9 ng ml−1) was assessed. In fed fish, 24.6%–29.5% of diltiazem was free, unbound to plasma proteins. Although starvation of fish resulted in a decrease in plasma protein, the bound fraction of diltiazem remained relatively constant. Consequently, the protein-bound concentration of diltiazem increased with length of starvation. In general, rainbow trout strain was a significant factor affecting plasma binding, although the two strains tested also differed markedly in size. Dialysis buffer pH significantly influenced plasma binding, with a higher unbound diltiazem fraction at pH 6.8 than pH 8.0. These data indicate that empirical measures of plasma binding in fish are important for accurate risk assessment and that the physiological status of a fish is likely to impact its sensitivity to toxicants such as diltiazem. Environ Toxicol Chem 2022;41:3125–3133.
AB - The accumulation of organic toxicants in fish plasma, and how they partition between the bound and unbound fraction once absorbed, are important metrics in models that seek to predict the risk of such contaminants in aquatic settings. Rapid equilibrium dialysis of diltiazem, an ionizable weak base and important human pharmaceutical contaminant of freshwaters, was conducted with rainbow trout (Oncorhynchus mykiss) plasma. The effect of fed state, fish sex, fish strain/size, and dialysis buffer pH on the binding of radiolabeled diltiazem (9 ng ml−1) was assessed. In fed fish, 24.6%–29.5% of diltiazem was free, unbound to plasma proteins. Although starvation of fish resulted in a decrease in plasma protein, the bound fraction of diltiazem remained relatively constant. Consequently, the protein-bound concentration of diltiazem increased with length of starvation. In general, rainbow trout strain was a significant factor affecting plasma binding, although the two strains tested also differed markedly in size. Dialysis buffer pH significantly influenced plasma binding, with a higher unbound diltiazem fraction at pH 6.8 than pH 8.0. These data indicate that empirical measures of plasma binding in fish are important for accurate risk assessment and that the physiological status of a fish is likely to impact its sensitivity to toxicants such as diltiazem. Environ Toxicol Chem 2022;41:3125–3133.
KW - Diltiazem
KW - fish plasma model
KW - fraction unbound
KW - ionizable organic compound
KW - plasma binding
UR - http://www.scopus.com/inward/record.url?scp=85141345096&partnerID=8YFLogxK
U2 - 10.1002/etc.5493
DO - 10.1002/etc.5493
M3 - Journal Article
C2 - 36177769
AN - SCOPUS:85141345096
SN - 0730-7268
VL - 41
SP - 3125
EP - 3133
JO - Environmental Toxicology and Chemistry
JF - Environmental Toxicology and Chemistry
IS - 12
ER -