The Evaluation of Neurodevelopmental and Behavioural Correlates of Acute Postnatal Exposure to di(2-ethylhexyl) phthalate in Rats

Phthalates are synthetically derived chemicals used as plasticizers in a variety of common household products. They are not chemically bound to plastic polymers and over time easily migrate out of these products and into the environment. Experimental investigations evaluating the biological impact of phthalate exposure on developing organisms are critical given that that estimates of phthalate exposure are considerably higher in infants and children compared to adults. Extensive growth and re-organization of neurocircuitry occurs during development leaving the brain highly susceptible to environmental insults. The primary goals of this dissertation were to evaluate the effects of early developmental phthalate exposure on brain structure and function, and to explore what changes in neurobiology were associated with changes in performance using behavioural measures of cognitive function. Widespread disruptions in hippocampal and dopaminergic neurocircuitry were reported in DEHP-treated male rats while only minimal changes in neurobiology were observed in DEHP-treated female rats. The cognitive effects of postnatal DEHP exposure were marginal and were only evident in female rats. The biological contributors underlying DEHP-induced changes in neurodevelopment and behaviour are not fully understood, but it is likely that the effects of DEHP are mediated by different mechanisms in male and female rats. Decreased BDNF expression may be a potential candidate for the near-selective detrimental effect of DEHP exposure on neurodevelopment in male rats. The up-regulation of hippocampal lipids may serve a neuroprotective role in DEHP-treated female rats. Comprehensive investigations which simultaneously assess the neurodevelopmental and behavioural correlates of DEHP exposure are needed and will provide an opportunity to thoroughly evaluate the toxic potential of DEHP.