Risk assessment of toxins derived from Bacillus thuringiensis ”” synergism, efficacy, and selectivity
Christoph Then
Environ Sci Pollut Res
Received: 12 March 2009 / Accepted: 28 May 2009 / Published online: 26 June 2009
DOI 10.1007/s11356-009-0208-3
http://www.springerlink.com/content/a42th8677132802g/

Key points extracted by GMWatch

Background, aim, and scope
This review deals with publications concerning the mode of action of Bt proteins and their potential synergism with extrinsic factors. The aim was to assess the impact of those factors especially regarding selectivity and efficacy of Bt toxins and to discuss possible gaps in current risk assessment of genetically engineered plants expressing Bt toxins.

So-called Bt plants are one of the dominant genetically engineered crops grown on a large scale and in many regions of the world (ISAAA 2009). There is a wide range of issues being discussed in the context of the risk assessment of these Bt plants. This review deals with specific aspects of risk assessment of the insecticidal Bt toxins, which are produced in the genetically engineered plants. It is important to understand its mode of action and possible interference with elements from its environment, to be sure that the Bt plants and their toxins do not show unexpected or even hazardous effects under changing environmental conditions. This is especially relevant since Bt Plants are being grown under various regional and climatic conditions; the Bt toxins are produced throughout the growing season and get in contact with the environment above and below the ground as well as being used in feed and food. This issue was elaborated by a review of the current literature; in addition, a questionnaire was developed for consulting experts to improve the coverage. To identify contributions that might be difficult to access otherwise, it was agreed (with the experts) to keep their input anonymous.

One crucial issue identified is that published scientific literature not only shows some open questions concerning the general mode of action of Bt toxins (Gilliland et al. 2002; Crickmore 2005; Hilbeck and Schmidt 2006) but also gives some indications that the toxicity of Bt toxins is influenced by several factors. On the one hand, it is known that, in general, the toxicity of Bt toxins in target organisms depends on factors such as certain pH, proteases, and receptors (Oppert 1999; de Maagd et al. 2001). On the other hand and more specifically, extrinsic factors and specific cofactors can also influence the efficacy of Bt toxins in resistant target organisms and/or might also impact on selectivity and toxicity in non-target organisms (see for example Schnepf et al. 1998; Sharma et al. 2004). While the issue of efficacy of Bt toxins in resistant target organisms is also of economical relevance and quite well investigated by several authors, the potential change of toxicity for nontarget organisms so far is hardly reflected in literature. The aim of this review was to identify publications dealing with relevant factors and their synergisms with Bt toxins and to discuss their specific relevance

Main features
The review shows that several extrinsic factors are able to influence the selectivity and efficacy of Bt toxins. The findings are seen as being relevant for risk assessment in Bt plants. This conclusion is derived by discussing current state of knowledge about the mode of action of Bt proteins, unexpected effects on non-target organism, and the way how modified Bt toxins are expressed in genetically engineered plants.

Results
Several publications have been identified that show that certain factors and synergism can impact efficacy and selectivity of Bt toxins. These extrinsic factors are various and include other Bt toxins or parts from the spore of Bacillus thuringiensis as well as certain enzymes, environmental stress, non-pathogenic microorganisms, and infectious diseases.

Discussion
Research on the underlying mechanism of observed synergism might help to explain some of the effects found in non-target organisms. In general, possible synergism of Bt toxins with extrinsic factors can be relevant for risk assessment of genetically engineered Bt plants since they expose a modified Bt toxin to the environment under various conditions and over a long period of time.

Conclusions
Risk assessment of genetically engineered plants should put into question the general assumption of a high selectivity and a linear dose response relationship in the toxicity of Bt proteins. Both selectivity and efficacy can be influenced by synergism, which can provoke unexpected and undesired effects in non-target organisms.

Perspectives
It is suggested that systematic research be promoted on synergism between Bt toxins and potential extrinsic factors that could impact the spectrum of susceptible organisms. This research should become a prerequisite for risk assessment of Bt plants.