Toxicokinetics‐based survival analysis in bioassays using nonpersistent chemicals

Abstract

Present statistical analysis of survivorship data obtained from bioassays using nonpersistent toxicants does not explicitly take into account that exposure decreases with time due to degradation of the toxicant. Such a situation typically occurs in static aquatic toxicity tests and in soil tests. We develop a model for the analysis of survival data obtained in such experiments and show how estimates for the initial LC50, the degradation rate constant, and the elimination rate constant may be obtained from observations on time‐dependent survival rates. The model assumes linear one‐compartment toxicokinetics with exponentially decreasing input. The probability of dying is assumed to be directly proportional to the internal concentration. An explicit expression for time‐ and concentration‐dependent survival is obtained. The model predicts that, with increasing exposure time, survival will approach a nonzero baseline value for certain initial concentrations. Application of the model is illustrated by curve‐fitting to experimental observations, made over 6 weeks, for the effect of diazinon on the terrestrial isopod Porcellio scaber. The fit to data is fairly good, but the parameter estimates tend to have a high coefficient of variation. A considerable increase of precision may be obtained if the degradation rate constant is given a fixed value (for example, following from chemical residue analysis of the medium). The approach is applicable to all situations where, due to loss of the toxicant during the test, mortality shows no further increase after a certain exposure period.

Toxicokinetics of Polycyclic Aromatic Hydrocarbons in Eisenia Andrei (Oligochaeta) Using Spiked Soil

“…The same model formulation was applied by Widianarko and Van Straalen [19], although in their case, the factor k dis did not reflect a change in bioavailability but a change in total concentration of a pesticide in soil.…”

“…Chem. 19,2000 T. Jager et al able, given the lag phase observed in the degradation), an additional estimate for k 2 is obtained. Especially for PHE, this results in a higher value than found in the depuration phase (Table 2), which compares better to the literature data and reveals a relationship between k 2 and K ow (Fig.…”

INVESTIGATION OF THE TOXICOKINETICS OF PETROLEUM HYDROCARBON DISTILLATES WITH THE EARTHWORM EISENIA ANDREI

“…However, in the present study, no decrease in lipid levels in earthworms was observed. Induced metabolism may also result in peak accumulation curves [29,31]. However, earthworm cytochrome P450 monooxygenase enzyme activities are considerably lower than those found in many other organisms [32], with only 1% or less of pyrene metabolized by E. andrei in one study [20], so metabolism is not thought to be an important elimination route for aromatics such as PAHs in earthworms [20,22].…”

Toxicokinetics and Toxicity of Zinc Under Time-Varying Exposure in the Guppy (Poecilia Reticulata)

“…Conventional toxicological approaches and concepts based on the premise of constant exposure to chemicals may no longer be adequate to deal with time-variable exposure. Analysis of variable exposures appears to be an area of increasing attention, both in experimental [2][3][4][5] and modeling studies [1,[6][7][8][9][10][11]. Most of the proposed models that deal with timevariable exposure are based on the concept of critical body residues (i.e., the internal concentration above which toxicity manifests) [1,12].…”

“…Objectives of the present study were to determine the toxicokinetics of zinc in P. reticulata, to analyze the effect of time-varying exposure on the survival of guppies, and to evaluate the applicability of a toxicokinetics-based survival model [11] to the present data.…”