Application
of Mass Balance Models and the Chemical
Activity Concept To Facilitate the Use of in Vitro Toxicity Data for
Risk Assessment
- Publication date
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Abstract
Practical,
financial, and ethical considerations related to conducting
extensive animal testing have resulted in various initiatives to promote
and expand the use of in vitro testing data for chemical evaluations.
Nominal concentrations in the aqueous phase corresponding to an effect
(or biological activity) are commonly reported and used to characterize
toxicity (or biological response). However, the true concentration
in the aqueous phase can be substantially different from the nominal.
To support in vitro test design and aid the interpretation of in vitro
toxicity data, we developed a mass balance model that can be parametrized
and applied to represent typical in vitro test systems. The model
calculates the mass distribution, freely dissolved concentrations,
and cell/tissue concentrations corresponding to the initial nominal
concentration and experimental conditions specified by the user. Chemical
activity, a metric which can be used to assess the potential for baseline
toxicity to occur, is also calculated. The model is first applied
to a set of hypothetical chemicals to illustrate the degree to which
test conditions (e.g., presence or absence of serum) influence the
distribution of the chemical in the test system. The model is then
applied to set of 1194 real substances (predominantly from the ToxCast
chemical database) to calculate the potential range of concentrations
and chemical activities under assumed test conditions. The model demonstrates
how both concentrations and chemical activities can vary by orders
of magnitude for the same nominal concentration