Benchmark dose analysis framework for developing wildlife toxicity reference values

Abstract

The effects characterization phase of ecological risk assessments (ERAs) often includes the selection or development of toxicity reference values (TRVs) for chemicals under investigation. In wildlife risk assessments, TRVs are thresholds represented by a dose or concentration associated with a specified adverse response. Traditionally, a TRV may be derived from an estimate of the no-observed-adverse effect level or lowest-observed-adverse-effect level, identified from a controlled toxicity study. Because of the limitations of this approach, risk assessors are increasingly developing TRVs using alternative methods. Benchmark dose (BMD) analysis is widely recognized as one approach for developing TRVs. A BMD is derived using the full dose-response relationship from all experimental doses and may represent a user-specified response level (e.g., 5, 10, 20, or 50%). Although many regulatory programs consider the use of BMD-derived wildlife TRVs, there is limited guidance available for implementing the BMD approach, particularly for ERA. The present study provides a framework for ecological risk assessors to identify appropriate data, examine dose-response relationships, estimate BMDs, and document the results for use in risk analysis. This framework demonstrates the process of developing a TRV using BMD analysis and identifies applications for which this approach may enhance ERAs (e.g., site assessment, chemical or pesticide registration programs). Environ Toxicol Chem 2018;37:1496-1508. © 2018 SETAC.

A Simplified Population-Level Landscape Model Identifying Ecological Risk Drivers of Pesticide Applications, Part One: Case Study for Large Herbivorous Mammals

“…While standard risk assessment approaches focus on setting thresholds, our proposal for population modelling is to use the full dose-response curve and to integrate the time component, selecting for each pesticide the relevant duration of effects associated with chronic exposure according to the information extracted from the different studies. This is in line with the use in ecotoxicology of novel dose-response tools such as the benchmark dose approach [31]; it also considers that at the population level, the pesticide exposure will vary both over time and among individuals, and consequently the effect on mortality and reproduction rates is better modelled by a continuous rather than a binary response. Extracting information from the toxicity studies and constructing the dose-time-response models requires expert knowledge and has an associated level of uncertainty.…”

“…This situation requires the reanalysis of the daily data from each test to identify the time required for observing the effects. The comparison of the NOAELs and LOAELs from studies with different duration may offer relevant information [31]. For glyphosate and bromoxynil, the lowest LOAELs were observed already at short exposure durations, suggesting the use of exposure time windows of 12 and 5 days for glyphosate and bromoxynil, respectively.…”

“…For glyphosate and bromoxynil, the lowest LOAELs were observed already at short exposure durations, suggesting the use of exposure time windows of 12 and 5 days for glyphosate and bromoxynil, respectively. Achieving the maximum toxicity level within a relatively short time period is a frequent feature in chronic toxicity testing, observed for about 50% of pesticides [32] as well as chemicals in general [33], being more frequent for chemicals with high toxicity [31]. Based on this information, substance and endpoint specific values are required regarding the number of days to be used for estimating the time-weighted average exposure.…”

Transcriptomic effects of tributyltin (TBT) in zebrafish eleutheroembryos. A functional benchmark dose analysis

“…This is so because the effects of a pollutant on functional pathways are generally more robust than their effects on the expression of specific genes, whatever useful may they be for exposure and effect assessment studies. In addition, the application of benchmark dose approach in toxicology, chemical effects and risk assessment are nowadays preferred to other more conventional parameters as NOECs or LOECs (Altenburger et al, 2012;Escher et al, 2014;Mayfield and Skall, 2018) and allow us to compare different datasets at different doses, as previously reported (Tu et al, 2019). Finally, applying the BMD concept at the functional level J o u r n a l P r e -p r o o f allowed us to separate the initially affected pathways (steroid biosynthesis, in our case) from the ones disrupted at higher concentrations (cell viability, general development or lipid-related pathways, among others).…”

Cadmium levels in human breast tissue and estradiol serum levels: Is there a connection?

“…This value depends not only on the selected dose range used in the experiment, but also on the ability to detect adverse effects in the experiment. The advantages of the BMD approach are that, in addition to threshold effects, it also includes non-threshold effects, gives better usability of experimental data, and the obtained results do not depend on the dose range used in the experiment (17,18). The European Food Safety Authority (EFSA) considers this approach to be more advanced than the NOAEL approach (17).…”