Exposure-driven risk assessment: Applying exposure-based waiving of toxicity tests under REACH

Thresholds of Toxicological Concern – Setting a threshold for testing below which there is little concern

“…This promising strategy enables the assessment of what "no relevant exposure" is and safeguards an appropriate level of protection of the general population demonstrated for reproductive toxicity endpoints. Similar arguments in favor of TTC in REACH were made by Rowbotham and Gibson (2011).…”

Mixture Genotoxicity of 2,4-Dichlorophenoxyacetic Acid, Acrylamide, and Maleic Hydrazide on Human Caco-2 Cells Assessed with Comet Assay

“…Remor et al (2009) found significant genotoxic effects in peripheral blood leukocytes from workers exposed to a mixture of genotoxic pesticides, illustrating that mixture genotoxicity is relevant at realistic exposure concentrations, and not only in regard to the high exposure concentrations used in our rapid in vitro study. Our data together with the previous findings described in the preceding illustrate that it might be problematic to apply thresholds for individual chemicals in regulation of genotoxic chemicals as done for determination of "thresholds of toxicological concern" (TTC) (Rowbotham and Gibson, 2011;European Food Safety Authority [EFSA], 2012).…”

The threshold of toxicological concern for prenatal developmental toxicity in rabbits and a comparison to TTC values in rats

“…The establishment of a wider TTC concept, consisting of different end point-specific values rather than an overall TTC value based on chronic and carcinogenicity studies would benefit consumers, industry as well as regulators and last but not least animal welfare. Examples of how such an exposure driven risk assessment, with waiving of animal studies, can be applied have been discussed by Rowbotham and Gibson (2011). In precluding extensive toxicity testing and safety evaluations when human intakes are below such a threshold, it would focus limited resources of time, cost and expertise on the testing and evaluation of substances with greater potential to pose risks to human health and contribute to a reduction in the use of animals (Barlow et al, 2001).…”