Toxicological testing frameworks

Toxicological Testing Frameworks and Screening Strategies for Nanomaterials... 

TOXICOLOGICAL TESTING FRAMEWORKS AND SCREENING STRATEGIES FOR NANOMATERIALS... 

Acute tests typically do not extensively evaluate the toxicity associated with a chemical, but focus on identifying if the chemical can kill or directly affect a target species from short-term exposure. Acute tests do not attempt to identify how toxicity occurs, but only measure if it does occur. Acute tests are included in the overall toxicology testing battery required under some of the acts discussed earlier (the Regulatory Framework section at the beginning of this chapter). Table 5.2 lists a sample of the required components of the acute testing protocols. 

New biomarkers will be useful in hepatotoxicity risk assessment if the data quality and validity can be established. The FDA defines a valid biomarker as one that can be measured in an analytical test system with well-established performance characteristics and has an established scientific framework or body of evidence that elucidates the significance of the test results [160]. Although there is no formerly agreed upon path, biomarker validation should include appropriate end-points for study (i.e., toxicology, histopathology, bioanalytical chemistry, etc.) and dose- and time-dependent measurements. An assessment of species, sex and strain susceptibility is also important to evaluate across species differences. More specific considerations for validation of gene and protein expression technologies are reviewed by Corvi et al. and Rifai et al. [144, 147]. 

The Developmental and Reproductive Toxicology (DART) Technical Committee at HESI has been continually active in the development of alternative tests by providing a forum to exchange information and data and by its organizational framework to pool resources for collaborative efforts. 

Assessments of environmental impacts from herbicides are usually done at the single-species level. These assessments use toxicological data from laboratory bioassay tests and estimates of exposure from laboratory or field studies of environmental chemistry. Few tests have assessed the impacts of herbicides on organisms in the field and few, if any, at the ecosystem level. There are two main reasons why there have been so few field or ecosystem tests They are exceedingly difficult and costly, and the current philosophies of risk assessment have evolved from classical toxicology and the federal regulatory framework that covers pharmaceuticals, food additives, and pesticides. 

The expectation of combined effects from mixture exposure is most often founded in the basic principles of toxicology and pharmacology (Loewe and Muischnek 1926a Bliss 1939 Plackett and Hewlett 1952). The first strictly pharmacological ideas formulated (Loewe and Muischnek 1926a) were supplemented by biometrical considerations. Later, Bliss (1939), a biologist and a biometrician, provided the first consistent framework, as depicted in Table 5.2 (Plackett and Hewlett 1952). In this framework, the main ideas focused on the presence or absence of interactions (commonly referred to as interactive and noninteractive joint action) with respect to responses observed in test organisms, and the presence of the same or a different mode of action. 

In order to answer those needs specified above, a collaborative effort (BIOSAFEPAPER) was undertaken in the fifth EU framework programme. In this project, coordinated by the University of Kuopio, Finland, nine European research institutes and 16 industrial partners aimed at establishing a test battery with relevant toxicological endpoints and allowing a decision-tree approach to ensure consumer safety. An important aspect of the undertaking was also the development of extraction procedures compatible with the tests and reflecting real-life conditions. 

Chapter 2, A Framework for Environmental Toxicology, provides an overview of the field of environmental toxicology and introduces the progression from the initial introduction of the toxicant to the environment, its effect upon the site of action, and finally the impacts upon an ecosystem. Many of the terms used throughout this book are introduced in this section. After an introduction to toxicity testing, the remainder of the book is organized from the molecular chemistry of receptors to the ecological effects seen at the system level. 

From this brief overview of toxicity tests, their uses and methods of assessing their responses to toxic substances, it can be seen that this is a very complex topic with many unknowns and no single best way of addressing the problem of bioavailable toxicant estimation. In this chapter, an attempt will be made to describe some applications of toxicological data, how they could be analysed and how toxicity results could be integrated in ecological risk assessment frameworks. 

Data derived from comprehensive toxicity testing may be integrated in risk assessment frameworks for a more reliable estimation of the probability that the contaminated site poses environmental harm. Moreover, toxicity tests may be used as screening tools in order to identify polluted soil or water samples, and to reduce the number of samples that require full chemical and/or toxicological analysis. 

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