A Terrestrial Biotic Ligand Model (TBLM) was developed using noncalcareous soils from Europe based on Cu and Ni speciation and barley (Hordeum vulgare cv. Regina) root elongation bioassays. Free metal ion (M2+) activity was computed by the WHAM VI model using inputs of soil metal, soil organic matter, and alkali and alkaline earth metals concentrations, and pH in soil solution. The TBLM assumes that metal in soil and in the solution are in equilibrium. Metal ions react with the biotic ligand, the receptor site, and inhibit root elongation. Other ions, principally H+, Ca2+ and Mg2+, compete with M2+ and, therefore, affect its toxicity. Toxicity is correlated only to the fraction of the total biotic ligand sites occupied by M2+. Compared to other models using either the soil metal concentration or M2+ activity as the toxic dose, the TBLM provides a more consistent method to normalize and compare Cu and Ni toxicities to root elongation among different soils. The TBLM was able to predictthe EC50 soil Cu and Ni concentrations generally within a factor of 2 of the observed values, a level of precision similar to that for the aquatic Biotic Ligand Model, indicating its potential utility in metals risk assessment in soils.

The Terrestrial Biotic Ligand Model (TBLM) is applied to a number of noncalcareous soils of the European Union for Cu and Ni toxicities using organisms and endpoints representing three levels of terrestrial organisms: higher plants, invertebrates, and microbes. A comparison of the TBLM predictions to soil metal concentration or free metal ion activity in the soil solution shows that the TBLM is able to achieve a better normalization of the wide variation in toxicological endpoints among soils of disparate properties considered in this study. The TBLM predictions of the EC50s were generally within a factor of 2 of the observed values. To our knowledge, this is the first study that incorporates Cu and Ni toxicities to multiple endpoints associated with higher plants, invertebrates, and microbes for up to eleven noncalcareous soils of disparate properties, into a single theoretical framework. The results of this study clearly demonstrate that the TBLM can provide a general framework for modeling metals ecotoxicity in soils.

The inhalation of nickel-containing dust has been associated with an increased risk of respiratory cancer in workplaces that process and refine sulfidic nickel mattes, where workers are exposed to mixtures of sulfidic, oxidic, water-soluble, and metallic forms of nickel. Because there is great complexity in the physical and chemical properties of nickel species, it is of interest which specific nickel forms are associated with carcinogenic risk. A bioavailability model for tumor induction by nickel has been proposed, based on the results of animal inhalation bioassays conducted on four nickel-containing substances. The nickel ion bioavailability model holds that a nickel-containing substance must release nickel ions that become bioavailable at the nucleus of epithelial respiratory cells for the substance to be carcinogenic, and that the carcinogenic potency of the substance is proportional to the degree to which the nickel ions are bioavailable at that site. This hypothesis updates the nickel ion theory, which holds that exposure to any nickel-containing substance leads to an increased cancer risk. The bioavailability of nickel ions from nickel-containing substances depends on their respiratory toxicity, clearance, intracellular uptake, and both extracellular and intracellular dissolution. Although some data gaps were identified, a weight-of-evidence evaluation indicates that the nickel ion bioavailability model may explain the existing animal and in vitro data better than the nickel ion theory. Epidemiological data are not sufficiently robust for determining which model is most appropriate, but are consistent with the nickel ion bioavailability model. Information on nickel bioavailability should be incorporated into future risk assessments.

IARC is reassessing the human carcinogenicity of nickel compounds in 2009. To address the inconsistencies among results from studies of water-soluble nickel compounds, we conducted a weight-of-evidence analysis of the relevant epidemiological, toxicological, and carcinogenic mode-of-action data. We found the epidemiological evidence to be limited, in that some, but not all, data suggest that exposure to soluble nickel compounds leads to increased cancer risk in the presence of certain forms of insoluble nickel. Although there is no evidence that soluble nickel acts as a complete carcinogen in animals, there is limited evidence that suggests it may act as a tumor promoter. The mode-of-action data suggest that soluble nickel compounds will not be able to cause genotoxic effects in vivo because they cannot deliver sufficient nickel ions to nuclear sites of target cells. Although the mode-of-action data suggest several possible non-genotoxic effects of the nickel ion, it is unclear whether soluble nickel compounds can elicit these effects in vivo or whether these effects, if elicited, would result in tumor promotion. The mode-of-action data equally support soluble nickel as a promoter or as not being a causal factor in carcinogenesis at all. The weight of evidence does not indicate that soluble nickel compounds are complete carcinogens, and there is only limited evidence that they could act as tumor promoters.

Copper partitioning at moisture content of 1.2-fold the field moisture capacity (corresponding to a soil water potential of 7.84 J/kg; pF = 1.9) was studied in 11 soils with pH 3.4 to 6.8 and an organic matter content of 4.1 to 233 g C/kg. Soil solutions were separated with the centrifuge method and analyzed to determine pH, Cu2+ activity, dissolved organic carbon, and Cu, Ca, Mg, and Na concentrations. Soil organic matter content, total Cu content, and soil pH were the main variables explaining variation in Cu activity in soil solutions. Based on total Cu, soil organic matter content, and soil solution pH, the Windermere Humic Aqueous Model (WHAM) VI assemblage model provided estimates of Cu2+ activity, {Cu2}, with a root mean square error of the predicted pCu (i.e., -log{Cu2+}) of 0.77.

The effects of 0.1 to 0.6 ppm nitrogen dioxide (NO2) on airway hyper-responsiveness (AHR) to airway challenges in asthmatics have been evaluated in several controlled exposure studies. The authors conducted meta-analyses and meta-regressions of these studies using several effect measures for AHR: a change (in NO2 versus air) in (1) the provocative dose of a challenge agent necessary to cause a specified change in lung function (PD), (2) the change in FEV1 after an airway challenge, and (3) the fraction of subjects with increased AHR. Although several effect estimates from the meta-analyses are statistically significant, they are all so small that they are not likely to be clinically relevant. More importantly, there are no exposure-response associations for any effect estimates based on linear meta-regressions or analyses of effect estimates for exposure groups (0.1 to <0.2 ppm, 0.2 to <0.3 ppm, etc.). This is also generally the case for analyses stratified by airway challenge (specific/nonspecific), exposure method (mouthpiece/whole chamber), and activity during exposure (rest/exercise). The results of these analyses indicate that, to the extent the effects observed are associated with NO2 exposure, they are sufficiently small such that they do not provide evidence that NO2 has a significant adverse effect on AHR at concentrations up to 0.6 ppm.

a b s t r a c tToxicity data for microorganism in soil or in soil less cultures have been described with ion competition models, however these models disregard electrostatic and osmotic effects which are known to affect ion sorption and toxicity. Using European soils with diverse characteristics, the factors that influence the toxicity of soil Cu or Ni to potential nitrification rate (PNR) and glucose-induced respiration (GIR) were evaluated based on the electrical potential (j 0 ) and ion activities ({M 2þ } 0 ) at the outer surfaces of bacterial cell membranes (CMs). The zeta potentials (z) of bacterial (Escherichia coli) protoplasts, as affected by the ionic composition of the solution, were measured and used to estimate the parameters of a GouyeChapmaneStern (GCS) model which was then used to compute j 0 values. The j 0 values varied widely with soil type and increased markedly (became less negative) as metal salts were added.Computed j 0 was then used to predict the surface ion activities from the soil solution composition. The toxicity data (both PNR and GIR) were statistically related to (i) surface activities of free metal ions ({M 2þ } 0 ), (ii) the ameliorative effect of surface H þ activity ({H þ } 0 ), (iii) the j 0 -influenced electrical driving force for cation uptake across CMs, and (iv) osmotic effects. This electrostatic model predicted the observed GIR and PNR with R 2 adj > 0:816 for observed vs. predicted PNR and R 2 adj > 0:861 for observed vs. predicted GIR. These predictions were generally better than those by previous models. The suggestion that metal toxicity in spiked soils is partly related to a spike-induced osmotic increase is corroborated by fitting the model to spiked soils that were or were not leached and aged to reduce the osmotic increase. The predicted soil EC50 values (in mg metal/kg soil) were within a factor of 2.5 for up to nineteen European soils with a wide range of properties.

Despite the evolution over the last half century of regulatory programs and frameworks developed for the evaluation of safety and management of risks associated with chemicals and materials, new and emerging contaminant issues continue to be identified. These recurring issues suggest a need for review and reflection on current approaches and strategies for ensuring the safety of chemicals and materials. Twelve existing frameworks relating to the evaluation and management of chemical or material risk were reviewed to identify potential process improvements for facilitating early identification of potentially problematic substances and better inform risk management strategies (e.g., prohibition, restricted use, or selection of safer alternatives). The frameworks were selected to represent a broad spectrum of regional, national, and international authorities and purposes, including preproduction evaluation of new substances, classification and hazard communication, identification of persistent pollutants, and identification of safer alternatives. Elements common to the frameworks were identified, as well as features unique to select frameworks. A comparative evaluation was performed, and potential new strategies and approaches were identified to inform process improvement recommendations. These recommendations include requiring validated analytical procedures to enable measurement in environmental media, improved data transparency and accessibility, flexibility to incorporate advances into the state of the practice (e.g., new approach methodologies and high‐throughput assessment tools), and incorporation of monitoring and adaptive management strategies to enable more timely intervention. Process improvement recommendations are discussed and summarized in a conceptual risk management framework. Integr Environ Assess Manag 2022;00:1–16. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.