We just finished two manuscripts that are online now:
Silva, E., Rajapakse, N., Scholze, M., Backhaus, T., Ermler, S., Kortenkamp A. Joint effects of heterogeneous estrogenic chemicals in the E-Screen – exploring the applicability of concentration addition. Tox Sciences, in press doi:10.1093/toxsci/kfr103
Backhaus, T., Porsbring, T., Arrhenius, A., Brosche, S., Johansson, P., Blanck, H. Single substance and mixture toxicity of 5 pharmaceuticals and personal care products to marine periphyton communities, Env. Tox. Chem, in press doi:10.1002/etc.586
The first one provides details on the predictability of the joint action of various mixtures of endocrine disrupters in the well-known E-Screen. Usually, Concentration Addition works rather well, but we found some interesting patterns. To simply summarize from the paper:
[...] we identified estrogen mixtures that followed CA, but statistically significant deviations from additivity occurred with mixtures that contained both steroidal estrogens
665 and synthetic estrogenic chemicals. There are some indications that the observed weak antagonisms are related to differential expression of CYP 1B1, although it is likely that additional factors are also at play.
The second one also goes for the investigations of mixture effects (surprise, surprise…). But this time on a completely different level. Switching the scenery from a proliferation assay with an isolated breast cancer cell line to a study analysing the impact of pharmaceutical mixtures on ecological succession in microbial communties. However, a (sort of) similar result: in principle the mixtures were ”well behaved”, but on the fringes it became obvious that we are only dealing with coarse models of reality. In the case of the biofilm communities, we saw strong stimulatory effects (hormesis) – but only in the mixture, not in the single substances. To be frank, currently we can only speculate on the reasons for this pattern. Our current hypothesis revolves around indirect effects caused by one of the compounds in the mixture.
When talking about hormesis, I would like to provide another quote from the paper:
It should finally be pointed out that hormetic effects of a chemical or chemical mixture certainly cannot be considered the opposite of harmful, adverse ecological effects. Similarly to an inhibition of growth, they indicate a disturbance of the network and interactions within an ecological community. An assessment of their implications for risk assessment, however, is not possible without further detailed knowledge on the underlying causes.
This paragraph was introduced following a comment from one of the reviewers of that manuscript. So, thanks for that suggestion!
Actually, I was really impressed with the quality of both reviews that we received for this manuscript – they certainly added a lot of critical reflection to the manuscript. And provided some food for thought (and follow-up studies). Sometimes peer-review still works nicely…
And my sincere apologies to the editoral staff of ET&C who had to suffer through my not always optimum response times – and an initially missing figure in the final version of the manuscript.
Thomas
