TP14 Internal Exposure
Tuesday, 15 November 2005: 8:00 AM - 6:30 PM in Exhibit Hall

(JAG-1117-748360) Relating internal concentrations to chronic endpoints in life-cycle studies.

Jager, T¹, Alda Alvarez, O², Kammenga, J², Kooijman, SALM¹, ¹ Vrije Universiteit, Dept. Theoretical Biology, Amsterdam, The Netherlands² Wageningen University, Dept. Nematology, Wageningen, The Netherlands

ABSTRACT- For mortality, internal concentrations can be directly related to toxicity because mortality is a quantal response (dead or alive). For continuous endpoints such as growth and reproduction, such a comparison is more difficult to make. At the EC50 for reproduction, it is not 50% of the animals that is responding; it is more likely that the response of all animals is approximately 50% of the control. Furthermore, the concentration-response curves (and thereby ECx estimates) will differ between endpoints (e.g. growth and reproduction) for the same chemical, and will change in time in curious ways. Clearly, the relationship between internal exposure and chronic effects requires more detailed ideas about resource allocation. It is still likely that the internal concentration causes the effects, but in a much more continuous fashion, and depending on the mode of action of the toxicants. We link internal concentrations to effects on growth and reproduction using the theory of Dynamic Energy Budgets (DEB). This theory aims to quantify individual growth, development and reproduction on the basis of a set of simple rules for metabolic organisation. The effects of toxicants can be understood as a change in energetic parameters, such as an increase in maintenance costs, or the costs for egg production, or a decrease of the assimilation of energy from food. This leads to (at least) five different energetics-based modes of action, that all have a very specific effect on the growth and reproduction patterns, and especially affect the extrapolation from individuals to populations. We demonstrate our approach using several life-cycle data sets for nematodes. This analysis shows that internal concentrations do dictate effects on growth and reproduction, not in a direct fashion, but indirectly by affecting resource allocation.

Key words: life-cycle toxicity, dynamic energy budgets, dose-effect modelling, chronic toxicity