Use of the threshold of toxicological concern (TTC) approach as an alternative tool for regulatory purposes: A case study with an inert ingredient used in pesticide products.

This study investigates the potential of the Threshold of Toxicological Concern (TTC) as an alternative to traditional animal testing in pesticide regulatory risk assessments. The TTC is a principle that establishes exposure threshold values for chemicals with certain structural features, below which there is no appreciable risk to human health. A case study was conducted with α-terpineol, an inert ingredient proposed to be used at low concentrations in pesticide products, to compare a conventional risk assessment using animal data with one using the TTC method. For the conventional risk assessment, animal data showed that there was no toxicity endpoint of concern, which resulted in a qualitative assessment and no risks of concern identified. For the risk assessment using the TTC method, a 5th percentile no-observed-effect level (NOEL) selected based on α-terpineol's Cramer classification was used as a point of departure (POD) for a quantitative risk assessment that resulted in no risks of concern identified. Therefore, the same conclusion was reached with both approaches and α-terpineol is considered safe for use in pesticide products at low concentrations. A comparative analysis was also performed to determine the applicability of the TTC method in calculating potential dietary risk from common pesticide use patterns for chemicals that fall within different Cramer classes. Results showed that use of the TTC method may be feasible for inert ingredient risk assessments when chemicals are used in a pesticide product at concentrations below 1%. This research underscores the TTC as a valuable and robust tool for assessing the potential hazards from inert ingredient use in pesticide formulations, considering factors such as chemical properties and the concentrations at which a chemical may be used in pesticide products. These findings contribute to the ongoing efforts by the United States Environmental Protection Agency (US EPA) to reduce animal testing in chemical safety assessments. The TTC method presents a viable alternative for risk evaluations of chemicals used at low concentrations, with anticipated low exposure, and with a predicted low toxicity potential.