Human Health

1. How well are the effects of PBO on human and animal health understood? Can you explain with some examples? 

   Safety comes first, this has always been the commitment of Endura together with several other companies that have been supporting PBO over the last 45 years in a dedicated industry task force. The first comprehensive data generation program was initiated in the 1990s following a data call in by the US agency EPA. PBO was demonstrated to be of low mammalian toxicity, not genotoxic, not toxic for reproduction and not carcinogenic. PBO is quickly metabolized in mammalian organisms and does not bioaccumulate. 

   Subsequently and gradually, additional testing was carried out because regulatory requirements increase. Older studies are re-assessed and new endpoints must be tested according to new guidelines (e.g. neurotoxicity). 

   The legal classification of PBO in Europe for human health refers to the possibility of respiratory reversible irritation after chronic inhalation exposure and to skin irritation – the letter based on a study with PBO from an unknown source, which may have contained relevant impurities. 

2. Can you offer evidence to support PBO as non-carcinogenic, genotoxic, or toxic for reproduction? 

   A comprehensive series of mechanistic studies showed that tumour formation observed in individual male mice at very high doses was due to a mechanism not relevant for humans. Here it has to be noted that chemicals, which are of low general toxicity, must be tested at extremely high doses in long-term studies. Any tumour formation at such high doses has no practical relevance, but understanding the mode of action becomes increasingly relevant. 
   
   From the carcinogenicity studies it can be confirmed that PBO is not a genotoxic carcinogen. In addition, the available data show overall, that PBO exerts also no other genotoxic effects. 
   
   The mechanistic work, as well as the studies on reproductive toxicity, have been evaluated in recent years by independent experts and have been published in peer reviewed journals, confirming the safety of PBO.  

3. Can you offer evidence to support PBO as not having Endocrine Disrupting properties? 

   In 2009, US EPA requested a total of 10 studies to be generated with PBO on a number of mammalian and on-mammalian endocrine disruption endpoints. This work was completed and submitted in 2011 and 2012. The authorities found no convincing evidence of potential interaction with estrogen, androgen or thyroid pathways.  
   
   

Environment

1. How well are the environmental effects of PBO understood? Can you explain them? 

   Piperonyl butoxide is not toxic to mammals and birds, but is relatively toxic to aquatic organisms. This area has been extensively investigated, also with a focus on a potential synergism towards these sensitive species. It was demonstrated that at typical concentrations, only a marginal synergism could be observed and the benefit of PBO – reduced application rate of the co-applied active substance – can be expected to outweigh this effect. 

   Bioconcentration in fish is also relatively low, but PBO is not readily biodegradable and can be stable in water and soil. In order to protect the environment, emissions to the environment must be adequately assessed. 

2. PBO is not classified as PBT or vPvB (persistent, bioaccumulative, toxic), how does this influence the formulation choices for pest control product manufacturers? 

   Piperonyl Butoxide meets the classification criterion for being very persistent according to EU regulations, but did not meet the criteria for being bioaccumulative or toxic. These classification criteria take into account that environmental health concerns arise predominantly from chemicals that meet not only 1, but that meet 2 or 3 of these criteria at the same time. Instead, PBO can be considered to have an overall favourable environmental profile. 

   Endura continues to investigate the environmental conditions under which PBO is stable or is degraded quickly. A certain inherent stability, however, is an important property of PBO from the point of view of efficacy and allows to develop products with long lasting effects.