Mode of action and aquatic exposure thresholds of no concern

Abstract

Threshold concepts of toxicological concern are based on the possibility of establishing an exposure threshold value for chemicals below which no significant risk is to be expected. The objective of the present study is to address environmental thresholds of no toxicological concern for freshwater systems (ETNCaq) for organic chemicals. We analyzed environmental toxicological databases (acute and chronic endpoints) and substance hazard assessments. Lowest numbers and 95th‐percentile values were derived using data stratification based on mode of action (MOA; 1 = inert chemicals; 2 = less inert chemicals; 3 = reactive chemicals; 4 = specifically acting chemicals). The ETNCaq values were derived by multiplying the lowest 95th percentile values with appropriate application factors; ETNCaq,MOA1–3 is approximately 0.1 μg/L. A preliminary analysis with complete MOA stratification of the databases shows that in the case of MOA1 or MOA2, the ETNCaq value could be even higher than 0.1 μg/L. A significantly lower ETNCaqMOA4 value was observed based on the long‐term toxicity information in the European Centre for the Ecotoxicology and Toxicology of Chemicals database. Application of the ETNCaq value in a tiered risk‐assessment scheme may help chemical producers to set data‐generation priorities and to refine or reduce animal use. It also may help to inform downstream users concerning the relative risk associated with their specific uses and be of value in putting environmental monitoring data into a risk‐assessment perspective.

Derivation of an Aquatic Predicted No-Effect Concentration for the Synthetic Hormone, 17α-Ethinyl Estradiol

“…In the case of EE2, ACRs based upon reproductive effects can be calculated for a range of taxa, some with and some without the estrogen receptor (31,32). Fish are the only taxa in the aquatic toxicity baseset that have estrogen receptors.…”

A decision tree for assessing effects from exposures to multiple substances

“…This approach is a reasonable example of using an existing tool to identify exposures of low concern based only on the chemicals' structure and has been shown to be protective for mixtures [15]. It must be noted that, while several researchers have proposed to establish a TTC for ecological effects [12,16], there is currently no widely accepted equivalent of the TTC in ecotoxicology and methods for setting levels of minimal concern for ecological effects need further development. In the human health area, the applicability range of the TTC will benefit from modifications and extensions of the tool that address inhalation and dermal routes of exposure, see for example the work of Escher et al, [17].…”

Peer Reviewed: Meeting the Scientific Needs of Ecological Risk Assessment in a Regulatory Context

“…Components of an intelligent testing strategy include the use of exposure information (27,34), thresholds of toxicological concern (TTCs) (35,36), QSARs, read-across methods, and in vitro testing methodologies. TTC is an exposure threshold value for chemicals, below which no significant risk is expected.…”

“…TTC is an exposure threshold value for chemicals, below which no significant risk is expected. ic end points) and substance hazard assessments, lowest numbers and 95th percentile values were derived with data stratification based on mode of action (MOA 1, inert chemicals; MOA 2, less-inert chemicals; MOA 3, reactive chemicals; and MOA 4, specifically acting chemicals) (36). The authors derived TTC values by multiplying these values by appropriate application factors (10, 100, or 1000).…”