In situ generated active substances
Active substances generated in situ are substances formed from so-called precursors on the site of use. They are chemical substances which may have a biocidal effect themselves. In other words, in situ generated active substances as such are not placed on the market, merely their precursors. This is an issue that has raised many questions. In 2002 a guidance document was published to clarify questions relating to their notification (see Infobox.)
It was agreed that data must be provided on the active substance generated in situ as well as on the precursor substance. If the precursor substance itself has a biocidal effect, it has to be notified as active substance as well. Examples include formaldehyde releasers (active substances intended to release formaldehyde under conditions of use). If the precursors themselves exert no effect, but if the in situ generated active substances are very unstable or difficult to handle, their notification has to include data on both substances. Examples are chlorine dioxide generated from sodium chlorite or metal ions generated through electrolysis from metal electrodes.
Further examples are Copper Chrome Arsenic (CCA) and Copper Chrome Boron (CCB); zinc, magnesium, calcium and aluminium phosphides; sodium cyanide; formaldehyde releasers; chlorine and bromine generators; Open Air Factor (in-situ ozone plus terpene); peracetic acid (PAA) generated from tetra-acetylethylene-diamine (TAED).
In the case of precursors which are no active substances in their own right, the Annex I entry (in Directive 98/8/EC) should include the substance generated in situ together with an indication of the releasing precursor(s): “substance (released from precursor I [precursor II, …])”.
In September 2010 the EU Commission and the Competent Authorities for biocidal products released a revised and extended guidance document for a consultation period of stakeholders running until 15 April 2011.
In this revised guidance document, a substance generated in situ is defined as active substance that is not directly placed on the market. It is generated intentionally via a chemical reaction or other means. It is released from one or several other chemicals (precursor active substances) as a result of direct manipulation on the site of use prior or during its intended application, where a biocidal effect is desired. In situ generated substances are to be distinguished from degradation products and metabolites.
Further details relating to the in situ generation of active substances and the relevant entry in Annex I to Directive 98/8/EC can be found in the draft guidance document 2010 (see Infobox).