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Bushnell, P. AND L. Driscoll. Cognitive Function. Chapter 13, Biomedical Sciences. Elsevier Online, New York, NY, , N/A, (2015).
The fact that exposure to chemicals can result in adverse effects on the structure and function of the central and peripheral nervous system of humans has been documented in numerous review papers (Anger, 1990; Anger and Johnson, 1985; Grandjean and Landrigan, 2006; 2014), and books (Chang, 1995; Gupta, 2006; Harry and Tilson, 2010), and federal guidelines for risk assessment (U.S. Environmental Protection Agency, 1998). Anger and Johnson (1985) reviewed the toxicity of 750 chemicals that affect the nervous system, and identified some 120 different effects related to functions of the nervous system associated with exposure to those chemicals. Manifestation of neurotoxicity in humans may be categorized as chemical-induced alterations in motor, sensory, affective, personality, and cognitive function. Of these effects, alterations in cognitive function appear to be the most diverse and include changes in learning, mathematical abilities, categorization, coding, concept shifting, distractibility, memory, pattern recognition, reading, spatial relations, sustained and selective attention, vocabulary, and intelligence. The nature and extent of alterations can depend on the timing and type of exposure, but effects have been found following exposure to many environmentally relevant chemicals such as lead, mercury, carbon disulfide, styrene, solvent mixtures, and pesticides (reviewed by Anger (2003)). Moreover, it has become clear that the incidence of neurodevelopmental disabilities is rising, affecting approximately one in six children under the age of 18, or more than 10 million children in the United States alone (Boyle et al., 2011). Recent reviews identified a dozen chemicals with clear developmental neurotoxicity and some 200 more with adverse clinical consequences in adults (Grandjean and Landrigan, 2006; 2014). The societal cost of these developmental effects can be enormous: chemical exposure during childhood has been estimated to lead to a population-based loss of cognitive capacity, indexed by a reduction in IQ scores, on par with pre-term birth and attention-deficit disorders (Bellinger, 2012).
Because chemicals can adversely affect cognitive function in humans, considerable effort has been made to characterize their effects using animal models. Information from such models will be necessary to: evaluate whether chemicals identified as potentially neurotoxic by screening methods actually do affect cognitive function; identify and characterize the mechanisms or pathways by which effects at these targets lead to cognitive dysfunction; address issues of susceptibility and variability, which require understanding the compensations and interactions that only a whole organism can engage; and improve our understanding of the neurobiological underpinnings of cognitive function.This chapter has several purposes. First, it provides working definitions of cognitive functions, such as learning, memory and attention, in terms frequently used by behavioral toxicologists. It is important to have a common vocabulary to assess methods used in this area of research. Second, it presents an overview of some of the procedures commonly used in behavioral toxicology to assess the effects of chemicals on cognitive function in animals. It should be noted that this overview is not intended to be comprehensive or complete, but is intended to illustrate specific points by discussing examples. Finally, this chapter discusses some critical experimental and conceptual variables that are important for studies on chemical-induced cognitive dysfunction, and touches on the potential problems and opportunities for analysis of cognitive function in whole animals in the context of current efforts to implement simple high throughput tests to screen chemicals for toxicity.Due to space limitations, this chapter reviews methods only for mammalian models, primarily in rodents.
Record Details:Record Type: DOCUMENT (BOOK CHAPTER)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
TOXICOLOGY ASSESSMENT DIVISION