Suchergebnisse

AbstractWe propose benchmark dose estimation for event‐time data, using a two‐step approach. This approach avoids estimation of complex models and has been previously shown to give robust results for summarizing relevant parameters for risk assessment. In the first step, the probability of the event of interest to occur (in a certain time interval) is described as a function of time, resulting in an event‐time model; such a model is fitted allowing an individual curve for each dose, and relevant estimates are extracted. In the second step, a dose–response model is fitted to the estimates of t50 obtained from the event‐time model in the first step. Given a predefined benchmark response, the benchmark dose is then estimated from the resulting model. This novel approach is demonstrated in two examples. Our application of the time‐to‐event model showed a gain in power compared to the traditional analysis of end‐of‐study summary data.

Abstract
Background
Many plants contain phytotoxic alkaloids to deter herbivorous pests and grazing animals. Alkaloids include quinolizidine and indole alkaloids found in the lupin (Lupinus spp.), an ornamental flower and emerging protein crop, as well as pyrrolizidine alkaloids in the ragwort (Senecio jacobaea), an invasive, weed-like flower. When lupins and ragworts are present in large densities in fields, there is a concern that alkaloids may leach into freshwater environments in amounts that may affect non-target organisms, such as Daphnia magna. This study aimed to investigate (i) the acute toxicity of alkaloids (gramine, heliotrine, lupanine, lupinine, monocrotaline, monocrotaline N-oxide, senecionine and sparteine) in D. magna, (ii) the contribution of these individual alkaloids to lupin plant extract toxicity, (iii) the longer term reproductive effects of a representative alkaloid, sparteine, and conclude with (iv) a tentative risk assessment for the sum of alkaloids measured in soil and surface waters.

Results
The alkaloids exhibited toxicity, with 48 h EC50 values in the range of 5.6 to > 100 mg/L. The 48 h EC50 of the Lupinus angustifolius plant extract was 1.38 mg/L, which was far more toxic than the simulated extract where lethality was < 10% at 10 mg/L after 48 h. Hence, non-measured compounds may have contributed to the joint toxicity. Daphnid mothers exposed to > 2.5 mg/L sparteine produced significantly fewer and smaller offspring during the 21-day exposure, making chronic effects occur at concentrations approximately 10-fold lower than the 48 h EC50 for sparteine. The risk assessment of cumulated alkaloids measured in drain, running and pond waters showed a potential risk, particularly for stagnant pond water, where concentrations were severalfold higher than in the drain and running waters.

Conclusions
The results highlight that natural toxins may contribute to poor chemical quality of natural waters, and that natural toxins from upcoming crops or invasive weeds should be considered in aquatic risk assessments.