Toxicological Properties Of Chemicals Research Articles

The importance of evaluating the physicochemical and toxicological properties of a contaminant for remediating environments affected by chemical incidents

In the event of a major chemical incident or accident, appropriate tools and technical guidance need to be available to ensure that a robust approach can be adopted for developing a remediation strategy. Remediation and restoration strategies implemented in the aftermath of a chemical incident are a particular concern for public health. As a result an innovative methodology has been developed to help design an effective recovery strategy in the aftermath of a chemical incident that has been developed; the UK Recovery Handbook for Chemical Incidents (UKRHCI). The handbook consists of a six-step decision framework and the use of decision trees specifically designed for three different environments: food production systems, inhabited areas and water environments. It also provides a compendium of evidence-based recovery options (techniques or methods for remediation) that should be selected in relation to their efficacy for removing contaminants from the environment. Selection of effective recovery options in this decision framework involves evaluating the physicochemical and toxicological properties of the chemical(s) involved. Thus, the chemical handbook includes a series of tables with relevant physicochemical and toxicological properties that should be assessed in function of the environment affected. It is essential that the physicochemical properties of a chemical are evaluated and interpreted correctly during the development of a remedial plan in the aftermath of a chemical incident to ensure an effective remedial response. This paper presents a general overview of the key physicochemical and toxicological properties of chemicals that should be evaluated when developing a recovery strategy. Information on how physicochemical properties have impacted on previous remedial responses reported in the literature is also discussed and a number of challenges for remediation are highlighted to include the need to develop novel approaches to remediate sites contaminated by mixtures of chemicals as well as methods for interpreting chemical reactions in different environmental matrices to include how climate change may affect the speciation and mobility of chemicals in the environment.

REACH and reproductive and developmental toxicology: still questions

Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) is a new chemicals regulation law in the European Union (EU). The law is supplemented by tens of thousands of pages of guidance documents, and the implementation of REACH is still a work in progress. Requirements for chemical testing are based on the annual volume of a chemical or ‘substance’ that is produced or imported into the EU. These requirements include reproductive and developmental toxicity testing in experimental animals for an annual volume of 10 metric tonnes or more. However, under REACH, the testing in vertebrate animals may not be performed without permission, and the law encourages the use of alternative methods of filling data gaps on the toxicological properties of chemicals. These alternatives might include in vitro and structure-activity relationship studies, but the REACH technical guidance indicates that these kinds of studies are not adequate to replace reproductive and developmental toxicity testing in whole animals. The most practical opportunity for the avoidance of whole animal testing may be ‘read-across,’ a process in which gaps are filled using data from related compounds. A method called ‘weight of evidence’ under REACH may also be used to avoid whole animal reproductive and developmental toxicity testing based on existing data in regulation and non-regulation studies and based on factors such as chemical structure and anticipated exposure. It is also possible that thresholds of toxicological concerns will be accepted under REACH as a method to avoid vertebrate animal testing.

Counter propagation artificial neural network categorical models for prediction of carcinogenicity for non-congeneric chemicals

One of the main goals of the new chemical regulation REACH (Registration, Evaluation and Authorization of Chemicals) is to fill the gaps on the toxicological properties of chemicals that affect human health. Carcinogenicity is one of the endpoints under consideration. The information obtained from (quantitative) structure–activity relationship ((Q)SAR) models is accepted as an alternative solution to avoid expensive and time-consuming animal tests. The reported results were obtained within the framework of the European project ‘Computer Assisted Evaluation of industrial chemical Substances According to Regulations (CAESAR)’. In this article, we demonstrate intermediate results for counter propagation artificial neural network (CP ANN) models for the prediction category of the carcinogenic potency using two-dimensional (2D) descriptors from different software programs. A total of 805 non-congeneric chemicals were extracted from the Carcinogenic Potency Database (CPDBAS). The resulting models had prediction accuracies for internal (training) and external (test) sets as high as 91–93% and 68–70%, respectively. The sensitivity and specificity of the test set were 69–73 and 63–72% correspondingly. High specificity is critical in models for regulatory use that are aimed at ensuring public safety. Thus, the errors that give rise to false negatives are much more relevant. We discuss how we can increase the number of correctly predicted carcinogens using the correlation between the threshold and the values of the sensitivity and specificity.

The ECITTS integrated toxicity testing scheme: The application of in vitro test systems to the hazard assessment of chemicals

A multicentre project has been designed, with the purpose of developing the concept of integrated in vitro testing. The aim is to use non-animal methods to assess the toxicological properties of chemicals, and to improve this assessment through the use of knowledge of mechanisms of toxic action. A number of tests or test batteries were selected within eight areas: basal cytotoxicity, irritancy, developmental toxicology, hepatotoxicity, nephrotoxicity, immunotoxicity, neurotoxicity and biokinetics. For each area, a number of calibration chemicals were selected. In an initial pilot study, the neurotoxic properties of five chemicals will be studied in combination with a biokinetic analysis, in which blood and brain concentrations will be predicted from biokinetic modelling.

Reversed-phase thin-layer chromatography of polynuclear aromatic hydrocarbons and chlorinated biphenyls : Relationship with hydrophobicity as measured by aqueous solubility and octanol-water partition coefficient

Reversed-phase thin-layer chromatography with methanol-water as eluent was used to study relationships between retention and hydrophobicity of non-polar aromatic compounds. For polynuclear aromatic hydrocarbons, n-alkyl- and chloro-substituted benzenes, good correlation was observed between R m values and log P octanol . Significantly different correlations were obtained for polychlorinated biphenyls (PCBs) containing chlorine atoms in the positions ortho to the phenyl-phenyl bond. This effect could not be explained by the measured lower π octanol values for ortho chlorine in PCBs. Estimation of hydrophobicity from aqueous solubility, S, combined with melting point data is restricted to S values higher than 1 μg/l. A group-contribution approach, including a retention index scale, will be very useful for correlation and prediction of reversed-phase retention, hydrophobicity and environmental and toxicological properties of chemicals.