Toxicity, mechanisms overview

This section presents a brief overview of any known mechanisms of metabolism, absorption, distribution, and excretion including substance reactions or physiological processes that lead to or comprise the mechanism(s) of toxic effect. 

While there is no standard assay design for teratogenicity or developmental toxicity screening, there are many similarities in the types of assays that have been described in the literature (4-9, 22-25). One version of these (4) is described here, and an overview of the assay design is shown in Fig. 3. Variations on this assay (alone or in combination with other techniques) can also be used for more descriptive characterization of the effects of a test substance or evaluation of the mechanisms of developmental toxicity. 

Bishop JB Kimmel CA (1997) Molecular and cellular mechanisms of early mammalian development an overview Of NIEHS/EPA developmental toxicity workshops. Reprod Toxicol, 11 285-291. 

The metabolism of halogenated organic compounds is related directly to their environmental impact and toxicology. Accordingly, there has been extensive research into metabolic mechanisms, some of which detoxify and remove environmental pollutants, others which are responsible for in vivo toxicity. A brief overview in this subject will be given in this section. 

In this chapter, we outline the issues and principles that are relevant to toxicity assessments of combined exposures. The scope of this overview is limited to combinations of chemicals, but excludes the topic of nonchemical stressors acting in concert with chemicals. Because the issues are of a generic nature, we draw on examples from human, environmental, and ecological toxicology. Section 3.2 briefly outlines approaches to mixture effects assessment (Chapter 4 elaborates these approaches in more detail), Section 3.3 discusses mixture effects in relation to modes and mechanisms of action, and Section 3.4 addresses the problems and possibilities of predicting mixture effects. In Sections 3.5 and 3.6, emphasis is on the predictability of synergism and on effects at low concentration or dose levels of chemicals in mixtures. Section 3.7 provides an overview of scarcely available data on mixture effects in real-world exposure scenarios. This chapter ends with an outlook to the future. 

Polycyclic aromatic hydrocarbons exert their toxicity in the central nervous system through various mechanisms. The following is a brief overview of the pathways involved. 

What are the molecular events involved in the development of asbestos-induced respiratory and pleural effects and how are they influenced by fiber dimensions and mineral type Identification of the molecular and cellular events of asbestos-induced disease has been the subject of extensive research within the past two decades (see Mechanisms of Asbestos Toxicity Overview section). However, much remains unknown, and the precise steps in pathogenic pathways are not frilly established. 

Overviews of QSAR studies for aquatic toxicity of chemicals which show narcosis are extensively discussed in several publications [93,94]. At first sight, it is quite remarkable that QSAR equations for all kinds of different species are so similar. On the other hand, the explanation is rather simple. It is generally accepted that the mechanism of narcosis is not a very specific process and each compoimd has the same intrinsic activity. In other words the external concentration of a compound at a fixed effect (e.g. narcosis or death) is only a fimction of the probability of a compound to reach its site of action. For many chemicals for which bioaccumulation is not influenced by biotransformation reactions, this probability is correlated to the octanol-water partition coefficient (K ) and this explains directly the correlation between and the external effect concentrations. 

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