A Toxicokinetic Framework and Analysis Tool for Interpreting Organisation for Economic Co-operation and Development Guideline 305 Dietary Bioaccumulation Tests.

The Organisation for Economic Co-operation and Development guideline 305 for bioaccumulation testing in fish includes the option to conduct a dietary test for assessing a chemical's bioaccumulation behavior. However, the one-compartment toxicokinetic model that is used in the guidelines to analyze the results from dietary bioaccumulation tests is not consistent with the current state of the science, experimental practices, and information needs for bioaccumulation and risk assessment. The present study presents 1) a 2-compartment toxicokinetic modeling framework for describing the bioaccumulation of neutral hydrophobic organic chemicals in fish and 2) an associated toxicokinetic analysis tool (absorption, distribution, metabolism, and excretion [ADME] B calculator) for the analysis and interpretation of dietary bioaccumulation test data from OECD-305 dietary tests.

In vitro to in vivo extrapolation of biotransformation rates for assessing bioaccumulation of hydrophobic organic chemicals in mammals.

Incorporating biotransformation in bioaccumulation assessments of hydrophobic chemicals in both aquatic and terrestrial organisms in a simple, rapid, and cost-effective manner is urgently needed to improve bioaccumulation assessments of potentially bioaccumulative substances. One approach to estimate whole-animal biotransformation rate constants is to combine in vitro measurements of hepatic biotransformation kinetics with in vitro to in vivo extrapolation (IVIVE) and bioaccumulation modeling. An established IVIVE modeling approach exists for pharmaceuticals (referred to in the present study as IVIVE-Ph) and has recently been adapted for chemical bioaccumulation assessments in fish.

In Vivo Biotransformation Rates of Organic Chemicals in Fish: Relationship with Bioconcentration and Biomagnification Factors.

In vivo dietary bioaccumulation experiments for 85 hydrophobic organic substances were conducted to derive the in vivo gastrointestinal biotransformation rates, somatic biotransformation rates, bioconcentration factors (BCF), and biomagnification factors (BMF) for improving methods for bioaccumulation assessment and to develop an in vivo biotransformation rate database for QSAR development and in vitro to in vivo biotransformation rate extrapolation. The capacity of chemicals to be biotransformed in fish was found to be highly dependent on the route of exposure. Somatic biotransformation was the dominant pathway for most chemicals absorbed via the respiratory route.

Deriving bioconcentration factors and somatic biotransformation rates from dietary bioaccumulation and depuration tests.

The present study develops, applies, and tests a method for deriving empirical bioconcentration factors and somatic biotransformation rate constants from dietary bioaccumulation tests and simplified bioaccumulation experiments that measure depuration rates. In this approach, measurement of the chemical concentration in the water is not required. The method aims to improve bioaccumulation assessment, reduce cost and animal use, and shorten experiments.

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

In vitro bioassays to estimate biotransformation rate constants of contaminants in fish are currently being investigated to improve bioaccumulation assessments of hydrophobic contaminants. The present study investigates the relationship between chemical substrate concentration and in vitro biotransformation rate of 4 environmental contaminants (9-methylanthracene, pyrene, chrysene, and benzo[a]pyrene) in rainbow trout (Oncorhynchus mykiss) liver S9 fractions and methods to determine maximum first-order biotransformation rate constants. Substrate depletion experiments using a series of initial substrate concentrations showed that in vitro biotransformation rates exhibit strong concentration dependence, consistent with a Michaelis-Menten kinetic model.

Somatic and gastrointestinal in vivo biotransformation rates of hydrophobic chemicals in fish.

To improve current bioaccumulation assessment methods, a methodology is developed, applied, and investigated for measuring in vivo biotransformation rates of hydrophobic organic substances in the body (soma) and gastrointestinal tract of the fish. The method resembles the Organisation for Economic Co-operation and Development (OECD) 305 dietary bioaccumulation test but includes reference chemicals to determine both somatic and gastrointestinal biotransformation rates of test chemicals. Somatic biotransformation rate constants for the test chemicals ranged between 0 d(-1) and 0.