Toxicological evaluation of microbial secondary metabolites in the context of European active substance approval for plant protection products.

Risk assessment (RA) of microbial secondary metabolites (SM) is part of the EU approval process for microbial active substances (AS) used in plant protection products (PPP). As the number of potentially produced microbial SM may be high for a certain microbial strain and existing information on the metabolites often are low, data gaps are frequently identified during the RA. Often, RA cannot conclusively clarify the toxicological relevance of the individual substances. This work presents data and RA conclusions on four metabolites, Beauvericin, 2,3-deepoxy-2,3-didehydro-rhizoxin (DDR), Leucinostatin A and Swainsonin in detail as examples for the challenging process of RA. To overcome the problem of incomplete assessment reports, RA of microbial AS for PPP is in need of new approaches. In view of the Next Generation Risk Assessment (NGRA), the combination of literature data, omic-methods, in vitro and in silico methods combined in adverse outcome pathways (AOPs) can be used for an efficient and targeted identification and assessment of metabolites of concern (MoC).

Toxoplasma gondii and the blood-brain barrier.

Infection with the protozoan parasite Toxoplasma gondii is characterized by asymptomatic latent infection in the central nervous system and skeletal muscle tissue in the majority of immunocompentent individuals. Life-threatening reactivation of the infection in immunocompromized patients originates from rupture of Toxoplasma cysts in the brain. While major progress has been made in our understanding of the immunopathogenesis of infection the mechanism(s) of neuroinvasion of the parasite remains poorly understood. The present review presents the current understanding of blood-brain barrier (patho)physiology and the interaction of Toxoplasma gondii with cells of the blood-brain barrier.