Genetic engineering work with producers of highly potent toxins

The hazard potential of an organism is often based on the production and interaction of various pathogenicity factors, which can include toxins. If toxin genes are transferred to a recipient organism (e.g. from risk group 1) during genetic engineering work and the production of the active toxin cannot be ruled out in the resulting genetically modified organism (GMO), this work is usually assigned to safety level 2. The same generally applies if toxin producers from risk group 2 are used as recipient organisms for genetic engineering work. However, the situation is different for producers of highly potent toxins. According to Section 3 No. 5 of the GenTSV, highly potent toxins are very toxic metabolites that can cause extremely serious acute or chronic health damage or death if inhaled, swallowed or absorbed through the skin. The classification as a highly potent toxin is based on animal experiments with rats or rabbits, in which the mean lethal concentration or the LC50 value of the substances was determined. Section 12, paragraph 1 of the Genetic Engineering Ordinance states that genetic engineering work aimed at highly effective toxins to produce the Security level 3 are to be assigned. Section 12, Paragraph 2 of the GenTSV further states that the Central Commission for Biological Safety (ZKBS) issues recommendations on the necessary technical and biological safety measures that take into account the mode of action of these highly potent toxins. It should be noted here that this legal regulation also covers genetic engineering work in which only very small amounts of the highly potent toxins are produced by the GMOs during laboratory work.

A list of toxins classified as highly potent does not currently exist. Therefore, operators and project managers must consider in their safety classification of genetic engineering work, as part of notification, registration, or approval procedures, whether the recipient or donor organisms or GMOs used are producers of toxic molecules or highly potent toxins (based on the relevant ZKBS statements and/or published findings from animal experiments). In this context, reference should be made to a statement by the ZKBS from 2021 ( ref. 6790-10-57 ), in which the enterohemorrhagic E. coli Shiga toxins produced by strains are classified as highly effective.