Toxic effects on reproduction

Dr. D. T. Jager, Prof. Dr. S. A. L. M. Kooijman ,

Chemical risk assessment attempts to protect the environment from the potential adverse effects of chemicals. However, the only information that is generally available are laboratory tests with single species. The methods that are currently used to analyse data from toxicity tests do not allow useful extrapolations to the population level, because they focus on a single endpoint only (e.g. body size in the standard fish growth test), and do not explicitly deal with exposure time.

About DEBtox

The software protocol DEBtox was developed to provide a process-based alternative for the analysis of toxicity tests. Basic idea is the following:
  1. A chemical first needs to be taken up by the organism to exert a toxic effect. The first step in the model chain is thus a one-compartment accumulation model.
  2. Once inside the chemical influences the energy allocation of the organism. Several modes of action are currently implemented.

Extending DEBtox

DEBtox focuses on the analysis of standard short-term tests. For a proper understanding of the toxic mechanism of a compound, as well as a translation to populations, life-cycle tests are required. In these tests, the organisms are followed for a significant part of their life cycle, scoring survival, growth and reproduction. This requires several adaptations to DEBtox:
  1. The endpoints share common parameters (e.g. growth affects reproduction). Therefore, the different endpoints must be analysed together.
  2. Life-cycle tests run longer than standard test. Therefore, we need to account for the effects of old age (senescence).
  3. The combined results for all endpoints can be used to calculate population consequences. Because food limitation has predictable effects within DEB context, effects at low food levels can be explored.

Testing the extensions

This project implements these adaptations, and tests them with life-cycle experiments for nematodes (performed by the Dept. of Nematology at the Wageningen University ). Nematodes are small roundworms, with a relatively short life cycle. A further advantage of this group is that it comprises species with diverse reproductive and feeding strategies.

An example of a life-cycle analysis is shown below, for the nematode Caenorhabditis elegans, exposed to the fungicide carbendazim. Green points are the controls, red points are the results for the highest exposure concentration. Carbendazim is assumed to work on the assimilation of energy from food. All endpoints have been fitted simultaneously.

The intrinsic rate of population increase (according to the Euler-Lotka equation) is shown in the other plot, with the predicted effects at limiting food levels (as percentage of the maximum). Clearly, the severity of the effects of carbendazim increases with decreasing food availability.

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