Approaching a closer surrogate for the biologically effective dose with subcellular partitioning-based toxicokinetic models

Abstract

A general concept in risk assessment is that a threshold of exposure exists above which adverse effects are initiated. Toxicity is related to the target-site concentration or the biologically active dose. Although it is often a huge challenge to measure the specific dose metric of metal toxicity, significant progress has been obtained to approach closer to the target-site concentration. Such developments are reviewed in the present study. In addition, a general framework to simulate the subcellular metal partitioning, which is supposed to account for the internal metal sequestration, is developed and applied to various metals. The framework allows for delineating mechanisms of internal metal sequestration. Moreover, the specificity in these mechanisms, which varies among metals, species, and exposure conditions, might explain the complicated relationship between the internal concentration and metal toxicity. Attention should be paid to the data requirements as the high number of unknown parameters might be accompanied by potential uncertainties. In addition, future efforts should focus on linking the concentration of metals in sensitive fractions and toxicological effects.

Association between heavy metal uptake and growth and reproduction in the anecic earthworm, Alma nilotica (Grube 1855)

“…Toxicity is related to the target-site concentration or the biologically active dose (Le et al, 2023) and whole-body internal concentration are better approximations of the concentrations at the target site (Escher and Hermens, 2004) as well as being a more promising approach for risk assessment (Lobo et al, 2021). Therefore, the internal earthworm metal concentrations are used in analysis of growth and reproduction effects and the resulting internal effect concentrations (IECs) are reported.…”

Some Facts and Questions about Nanoparticles and Nanomaterials Research

“…Works on the biological responses (i.e. oxidative stress, modifi cation of photosynthesis, metabolism) and onto the consequences from a genetic point of view (transcriptomics and proteomics) are regularly published [9][10][11][12]. Indeed, concentrations, at which biological modifi cations due to additive, cocktail or synergistic and antagonistic eff ects appear at levels much lower than those mentioned by the manufacturers', users' or mandatory tests (REACH regulation in Europe for example [13]).…”