Utilizing relative potency factors (RPF) and threshold of toxicological concern (TTC) concepts to assess hazard and human risk assessment profiles of environmental metabolites: A case study

Thresholds of Toxicological Concern – Setting a threshold for testing below which there is little concern

“…Terry et al (2015) used relative potency factors and TTC to assess hazard and human risk assessment It is feasible that within REACH the TTC concept may be of use for the chemical safety assessment at tonnage levels triggering limited information on repeated dose toxicity and/or reproduction: REACH clearly indicates the need for non-testing methods and provides the opportunity of waiving testing based on exposure considerations. When clearly documented and justified the following options could apply.…”

Managing Risk in Nanotechnology

“…Groundwater was identifi ed as a natural resource which should be protected using a 'limit value' for active substances and their relevant metabolites (provided in Annex VI of Directive 91/414/EC (and Directive 98/83/EC)). The guidance document describes a scheme to determine whether a metabolite is relevant or not relevant using criteria of biological activity, genotoxicity and toxicological hazard (Terry et al, 2015 ). Relevant metabolites are subject to the 0.1 μg/L limit value in groundwater.…”

“…TTCs are analogous to chemical-specifi c reference doses, such as an Acceptable Daily Intakes, but as generic reference values, a TTC can be used to assess the risk from estimated exposures for chemicals with limited toxicity data (EFSA, 2012 ;Terry et al, 2015 ).…”

“…A recent development of the TTC concept was to introduce the approach of comparative toxicity, which was used to determine the environmental metabolites of a new chemical, sulfoxafl or (X11422208) (Terry et al, 2015 ). The ultimate aim was to address the human safety of the metabolites with the minimum number of in vivo studies, while at the same time, ensuring that human safety would be considered addressed on a global regulatory scale (Terry et al, 2015 ).…”

“…The ultimate aim was to address the human safety of the metabolites with the minimum number of in vivo studies, while at the same time, ensuring that human safety would be considered addressed on a global regulatory scale (Terry et al, 2015 ). The comparative toxicity component was designed to determine whether the metabolites had the same or similar toxicity profi les to their parent molecule, and also to one another, with the ultimate goal of establishing whether the metabolites had the potential to cause key effects-such as cancer and developmental toxicity, based on mode-of-action (MoA) studies-and to develop a relative potency factor (RPF) compared to the parent molecule (Terry et al, 2015 ).…”