Fish bioaccumulation and biomarkers in environmental risk assessment: a review

The recent REACH Policy of the European Union has led to scientists and regulators to focus their attention on establishing general validation principles for QSAR models in the context of chemical regulation (previously known as the Setubal, nowadays, the OECD principles). This paper gives a brief analysis of some principles: unambiguous algorithm, Applicability Domain (AD), and statistical validation. Some concerns related to QSAR algorithm reproducibility and an example of a fast check of the applicability domain for MLR models are presented. Common myths and misconceptions related to popular techniques for verifying internal predictivity, particularly for MLR models (for instance crossvalidation, bootstrap), are commented on and compared with commonly used statistical techniques for external validation. The differences in the two validating approaches are highlighted, and evidence is presented that only models that have been validated externally, after their internal validation, can be considered reliable and applicable for both external prediction and regulatory purposes. (“Validation is one of those words...that is constantly used and seldom defined” as stated by A. R. Feinstein in the book Multivariate Analysis: An Introduction, Yale University Press, New Haven, 1996).

Principles of QSAR models validation: internal and external

Veterinary pharmaceuticals (VPs) are used in large amounts in modern husbandry. Due to their use pattern, they possess a potential for reaching the soil environment. To assess their mobility in soil, the literature on sorption of chemicals used as VPs is reviewed and put into perspective of their physicochemical properties. The compilation of sorption coefficients to soil solids (Kd,solid) demonstrates that these chemicals display a wide range of mobility (0.2 < Kd,solid < 6,000 L/kg). Partition coefficients for association of tetracycline and quinolone carboxylic acid VPs to dissolved organic matter (Kd,DOM) vary between 100 and 50,000 L/kg. The variation in Kd,solid for a given compound in different soils can be significant. For most of the compounds, the variation is not considerably lower for the organic carbon-normalized sorption coefficient Koc. In addition, prediction of log Koc by log Kow leads to significant underestimation of log Koc and log Kd,DOM values. This suggests that mechanisms other than hydrophobic partitioning play a significant role in sorption of VPs. A number of hydrophobicity-independent mechanisms such as cation exchange, cation bridging at clay surfaces, surface complexation, and hydrogen bonding appear to be involved. These processes are not accounted for by organic carbon normalization, suggesting that this data treatment is conceptually inappropriate and fails to describe the sorption behavior. Moreover, prediction of log Koc based on the hydrophobicity parameter log Kow is not successful.

Sorption of veterinary pharmaceuticals in soils: a review.

Silver nanoparticles: behaviour and effects in the aquatic environment.

This article provides an overview of methods for reliability assessment of quantitative structure-activity relationship (QSAR) models in the context of regulatory acceptance of human health and environmental QSARs. Useful diagnostic tools and data analytical approaches are highlighted and exemplified. Particular emphasis is given to the question of how to define the applicability borders of a QSAR and how to estimate parameter and prediction uncertainty. The article ends with a discussion regarding QSAR acceptability criteria. This discussion contains a list of recommended acceptability criteria, and we give reference values for important QSAR performance statistics. Finally, we emphasize that rigorous and independent validation of QSARs is an essential step toward their regulatory acceptance and implementation.

Methods for reliability and uncertainty assessment and for applicability evaluations of classification- and regression-based QSARs.

General Introduction- Emissions of Chemicals to The Environment- Transport, Accumulation and Transformation Processes- Environmental Exposure Assessment- Human Exposure Assessement- Toxicity Testing for Human Health Risk Assessment- Ecotoxicological Effects- Data:Needs, Availability, Sources and Evaluation- Predicting Fate-Related Physicochemical Properties- Predicting Toxicological and Ecotoxicological Endpoints- Intelligent Testing Strategies- The Management of Industrial Chemicals in the Eu- The Management of Industrial Chemicals in the USA- The Management of Industrial Chemicals in Japan- The Assessment and Management of Industrial Chemicals in Canada- The Oecd Chemicals Programme

Risk assessment of chemicals : an introduction

Cities play a prominent role in our economic development as more than 80 % of the gross world product (GWP) comes from cities. Only 600 urban areas with just 20 % of the world population generate 60 % of the GWP. Rapid urbanization, climate change, inadequate maintenance of water and wastewater infrastructures and poor solid waste management may lead to flooding, water scarcity, water pollution, adverse health effects and rehabilitation costs that may overwhelm the resilience of cities. These megatrends pose urgent challenges in cities as the cost of inaction is high. We present an overview about population growth, urbanization, water, waste, climate change, water governance and transitions. Against this background, we discuss the categorization of cities based on our baseline assessments, i.e. our City Blueprint research on 45 municipalities and regions predominantly in Europe. With this bias towards Europe in mind, the challenges can be discussed globally by clustering cities into distinct categories of sustainability and by providing additional data and information from global regions. We distinguish five categories of sustainability: (1) cities lacking basic water services, (2) wasteful cities, (3) water-efficient cities, (4) resource-efficient and adaptive cities and (5) water-wise cities. Many cities in Western Europe belong to categories 3 and 4. Some cities in Eastern Europe and the few cities we have assessed in Latin America, Asia and Africa can be categorized as cities lacking basic water services. Lack of water infrastructures or obsolete infrastructures, solid waste management and climate adaptation are priorities. It is concluded that cities require a long-term framing of their sectoral challenges into a proactive and coherent Urban Agenda to maximize the co-benefits of adaptation and to minimize the cost. Furthermore, regional platforms of cities are needed to enhance city-to-city learning and to improve governance capacities necessary to accelerate effective and efficient transitions towards water-wise cities. These learning alliances are needed as the time window to solve the global water governance crisis is narrow and rapidly closing. The water sector can play an important role but needs to reframe and refocus radically.

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The challenges of water, waste and climate change in cities

Combined effects of metals; an ecotoxicological evaluation

The "Workshop on Regulatory Use of (Q)SARs for Human Health and Environmental Endpoints," organized by the European Chemical Industry Council and the International Council of Chemical Associations, gathered more than 60 human health and environmental experts from industry, academia, and regulatory agencies from around the world. They agreed, especially industry and regulatory authorities, that the workshop initiated great potential for the further development and use of predictive models, that is, quantitative structure-activity relationships [(Q)SARs], for chemicals management in a much broader scope than is currently the case. To increase confidence in (Q)SAR predictions and minimization of their misuse, the workshop aimed to develop proposals for guidance and acceptability criteria. The workshop also described the broad outline of a system that would apply that guidance and acceptability criteria to a (Q)SAR when used for chemical management purposes, including priority setting, risk assessment, and classification and labeling.

C.J. Van Leeuwen

Papers

Risk assessment of chemicals : an introduction

The challenges of water, waste and climate change in cities

Combined effects of metals; an ecotoxicological evaluation

Summary of a workshop on regulatory acceptance of (Q)SARs for human health and environmental endpoints.

The use of cohorts and populations in chronic toxicity studies with Daphnia magna: a cadmium example.