TTC Towards a universal acute fish THRESHOLD OF TOXICOLOGICAL CONCERN (TTC).

Threshold of Toxicological Concern (TTC) is a concept that has been around for decades in human health sciences. Ecotoxicology recently adopted a variant of this concept as eco-TTC. Adoption of the concept of TTC considerably reduces the amount of animal testing required for regulatory purposes. Here we provide an application of a universal TTC for the entirety of acute fish toxicity data, i.e. establishment of an exposure level below which there would be minimal probability of acute fish toxicity for any chemical, without consideration of Mechanism of Action. We calculated TTC values for a number of subgroups using various approaches. These approaches were evaluated using data from a cohort of 69,999 acute fish toxicological assays. This database was normalized/curated for units, exposure duration, QA/QC and duplicates which reduced it to 47,694 assays. Data were not normally but log-normally distributed making geometric means the most appropriate statistical parameter. Thus we developed descriptive statistics using geometric means with 95, 99, and 99.9 % confidence intervals. Various assessment factors (akin to PNEC derivation) were applied to the geometric means to derive TTC's. Other approaches employed were the calculations of y=0 intercepts as well as development of 95 and 99.75% cutoffs of cumulative data as well as MUST (Modular Uncertainty Scoring Tool) analysis. All the methodologies derived highly congruent TTC's ranging from to 2-8 ug/L except for the 99.75th percentile cutoff of 0.3ug/L. The data described here would be most useful in making a binary testing/no testing required decision. For acute fish toxicity, a TTC value of 2 ug/L was most appropriate, based on 95th (99.75%) percentile of data distribution without any assessment factor. This article is protected by copyright. All rights reserved.