According to the REACH Regulation, for all substances manufactured or imported in amounts of 10 or more tons per year, that are not exempted from the registration requirement, a Chemical Safety Assessment (CSA) must be conducted. According to CSA criteria, for these substances persistent, bioaccumulative and toxic (PBT), and very persistent and very bioaccumulative (vPvB) assessment is requested. In order to reduce the number of applications of the expensive bioaccumulation test it seems useful to search thresholds for other related parameters above which no bioaccumulation is observed.
View Article and Find Full Text PDFSubstances of unknown or variable composition, complex reaction products, and biological materials (UVCBs) comprise approximately 40% of all registered substances submitted to the European Chemicals Agency. One of the main characteristics of UVCBs is that they have no unique representation. Industry scientists who are part of the scientific community have been working with academics and consultants to address the problem of a lack of a defined structural description.
View Article and Find Full Text PDFSubstances of unknown or variable composition, complex reaction products, or biological materials (UVCBs) have been conventionally described in generic terms. Commonly used substance identifiers are generic names of chemical classes, generic structural formulas, reaction steps, physical-chemical properties, or spectral data. Lack of well-defined structural information has significantly restricted in silico fate and hazard assessment of UVCB substances.
View Article and Find Full Text PDFCarcinogenicity is a complex endpoint of high concern yet the rodent bioassay still used is costly to run in terms of time, money and animals. Therefore carcinogenicity has been the subject of many different efforts to both develop short-term tests and non-testing approaches capable of predicting genotoxic carcinogenic potential. In our previous publication (Mekenyan et al.
View Article and Find Full Text PDFBackground: It is widely accepted that there is a molecular weight (MW) cut-off of 500, such that single chemicals with MWs higher than 500 cannot be skin sensitizers. If true, this could serve as a useful principle for designing non-sensitizing chemicals.
Objectives: To assess whether the 500 MW cut-off is a myth or a reality.
Chem Res Toxicol
February 2012
Strategic testing as part of an integrated testing strategy (ITS) to maximize information and avoid the use of animals where possible is fast becoming the norm with the advent of new legislation such as REACH. Genotoxicity is an area where regulatory testing is clearly defined as part of ITS schemes. Under REACH, the specific information requirements depend on the tonnage manufactured or imported.
View Article and Find Full Text PDFMandated efforts to assess chemicals for their potential to bioaccumulate within the environment are increasingly moving into the realm of data inadequacy. Consequently, there is an increasing reliance on predictive tools to complete regulatory requirements in a timely and cost-effective manner. The kinetic processes of absorption, distribution, metabolism, and elimination (ADME) determine the extent to which chemicals accumulate in fish and other biota.
View Article and Find Full Text PDFThe TImes MEtabolism Simulator platform used for predicting skin sensitization (TIMES-SS) is a hybrid expert system that was developed at Bourgas University using funding and data from a consortium comprised of industry and regulators. TIMES-SS encodes structure-toxicity and structure-skin metabolism relationships through a number of transformations, some of which are underpinned by mechanistic three-dimensional quantitative structure-activity relationships. Here, we describe an external validation exercise that was recently carried out.
View Article and Find Full Text PDFThe TImes MEtabolism Simulator platform used for predicting Skin Sensitization (TIMES-SS) is a hybrid expert system that was developed at Bourgas University using funding and data from a Consortium comprising industry and regulators. The model was developed with the aim of minimizing animal testing and to be scientifically valid in accordance with the OECD principles for (Q)SAR validation. TIMES-SS encodes structure-toxicity and structure-skin metabolism relationships through a number of transformations, some of which are underpinned by mechanistic 3D QSARs.
View Article and Find Full Text PDFA quantitative structure-activity relationship (QSAR) system for estimating skin sensitization potency has been developed that incorporates skin metabolism and considers the potential of parent chemicals and/or their activated metabolites to react with skin proteins. A training set of diverse chemicals was compiled and their skin sensitization potency assigned to one of three classes. These three classes were, significant, weak, or nonsensitizing.
View Article and Find Full Text PDFDesigning biologically active chemicals and managing their risks requires a holistic perspective on the chemical-biological interactions that form the basis of selective toxicity. The balance of therapeutic and adverse outcomes for new drugs and pesticides is managed by shaping the probabilities for transport, metabolism, and molecular initiating events. For chemicals activated as well as detoxified by metabolism, selective toxicity may be considered in terms of relative probabilities, which shift dramatically across species as well as within a population, depending on many factors.
View Article and Find Full Text PDF