Predicting the Bioconcentration of Fragrance Ingredients by Rainbow Trout Using Measured Rates ofin VitroIntrinsic Clearance

Abstract

Bioaccumulation in aquatic species is a critical end point in the regulatory assessment of chemicals. Few measured fish bioconcentration factors (BCFs) are available for fragrance ingredients. Thus, predictive models are often used to estimate their BCFs. Because biotransformation can reduce chemical accumulation in fish, models using QSAR-estimated biotransformation rates have been developed. Alternatively, biotransformation can be measured by in vitro methods. In this study, biotransformation rates for nine fragrance ingredients were measured using trout liver S9 fractions and used as inputs to a recently refined in vitro-in vivo extrapolation (IVIVE) model. BCFs predicted by the model were then compared to (i) in vivo BCFs, (ii) BCFs predicted using QSAR-derived biotransformation rates, (iii) BCFs predicted without biotransformation, and (iv) BCFs predicted by a well-known regression model. For fragrance ingredients with relatively low (<4.7) log K(OW) values, all models predicted BCFs below a bioaccumulation threshold of 1000. For chemicals with higher (4.7-5.8) log K(OW) values, the model incorporating measured in vitro biotransformation rates and assuming no correction for potential binding effects on hepatic clearance provided the most accurate predictions of measured BCFs. This study demonstrates the value of integrating measured biotransformation rates for prediction of chemical bioaccumulation in fish.

Concentration dependence of in vitro biotransformation rates of hydrophobic organic sunscreen agents in rainbow trout S9 fractions: Implications for bioaccumulation assessment

“…The apparent in vitro concentration dependence of modeled BCFs may also help explain the tendency of IVIVE methods to overestimate BCFs relative to empirical data (Han et al ; Laue et al ). The past use of substrate concentrations ranging from 1 to 10 µM (Han et al ; Cowan‐Ellsberry et al ; Johanning et al ) may have saturated biotransformation enzymes, resulting in underestimates of k MET and overestimates of the BCF.…”

“…In the present study, the setting of f U = 1.0 resulted in BCFs that fell within or slightly below the range of empirical values for most of the modeled conditions. Several authors have reported that BCFs calculated using in vitro biotransformation data exhibited improved agreement with empirical data when f U was set to 1.0 (Escher et al ; Laue et al ). One explanation for these findings is that bound chemicals rapidly dissociate from molecular binding sites in plasma, making them available for metabolism in the time available for this activity to occur (i.e., the residence time of blood in the liver; Escher et al ; Nichols et al ).…”

Benzo(a)pyrene Metabolism and EROD and GST Biotransformation Activity in the Liver of Red- and White-Blooded Antarctic Fish

“…The actual biotransformation rates in Antarctic fish are completely unknown so far. Here, we used a substrate-depletion approach in hepatic S9 fractions as a proxy for the metabolism capacity of the intact fish, as demonstrated by Johanning et al 32 and Laue et al, 70 with BaP as a model substrate.…”

Concentration dependence of biotransformation in fish liver S9: Optimizing substrate concentrations to estimate hepatic clearance for bioaccumulation assessment

“…An alternative method measures the rate of loss (or depletion) of the chemical in the incubation medium as a result of biotransformation . Here, the first‐order depletion rate constant, k dep (min –1 ), is measured as the slope of the relationship between the natural logarithm of the remaining substrate concentration in the incubation medium ( C I ) at incubation time ( t ) where C I,t=0 is the initial substrate concentration in the incubation medium.…”