Application of the “threshold of toxicological concern” to derive tolerable concentrations of “non-relevant metabolites” formed from plant protection products in ground and drinking water

Limits for tolerable concentrations of ground water metabolites (“non-relevant metabolites” without targeted toxicities and specific classification and labeling) derived from active ingredients (AI) of plant protection products (PPPs) are discussed in the European Union. Risk assessments for “non-relevant metabolites” need to be performed when concentrations are above 0.75 μg/L. Since oral uptake is the only relevant exposure pathway for “non-relevant metabolites”, risk assessment approaches as used for other chemicals with predominantly oral exposure in humans are applicable. The concept of “thresholds of toxicological concern” (TTC) defines tolerable dietary intakes for chemicals without toxicity data and is widely applied to chemicals present in food in low concentrations such as flavorings. Based on a statistical evaluation of the results of many toxicity studies and considerations of chemical structures, the TTC concept derives a maximum daily oral intake without concern of 90 μg/person/day for non-genotoxic chemicals, even for those with appreciable toxicity. When using the typical exposure assessment for drinking water contaminants (consumption of 2 L of drinking water/person/day, allocation of 10% of the tolerable daily intake to drinking water), a TTC-based upper concentration limit of 4.5 μg/L for “non-relevant metabolites” in ground/drinking water is delineated. In the present publication it has been evaluated, whether this value would cover all relevant toxicities (repeated dose, reproductive and developmental, and immune effects). Taking into account, that after evaluation of specific reproduction toxicity data from chemicals and pharmaceuticals, a value of 1 μg/kg bw/day has been assessed as to cover developmental and reproduction toxicity, a TTC value of 60 μg/person/day was assessed as to represent a safe value. Based on these reasonable worst case assumptions, a TTC-derived threshold of 3 μg/L in drinking water is derived. When a non-relevant metabolite is present in concentration below 3 μg/L, animal testing for toxicity is not considered necessary for a compound-specific risk assessment since the application of the TTC covers all relevant toxicities to be considered in such assessment and any health risk resulting from these exposures is very low.