Developmental exposure to mixtures of persistent environmental pllutants with focus on bone and retinoid system modulations

• Main Author: Elabbas, Lubna E
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: Institutet för miljömedicin / Institute of Environmental Medicine 2011
• Subjects: Arctic; inuit
• Online Access: http://hdl.handle.net/10616/40808

Environmental pollution of Arctic regions has evoked a scientific as well as public concern. Arctic Inuit inhabitants consume large amounts of fatty fish and marine mammals and are therefore exposed to levels of environmental toxicants that are suspected to cause adverse health effects. Exposure to mixtures of environmental pollutants affects a wide range of clinical and biochemical parameters. Developing fetuses and infants are the most vulnerable groups to environmental contaminants. Experimental studies demonstrate that alterations of bone tissue and modulations in the retinoid system are considered as sensitive toxicological end-points. The present thesis is based on a one-generation toxicity study performed according to standard guidelines with enhancement to accommodate bone and retinoid system endpoints. Rats were exposed during gestation and lactation to two chemical mixtures: the Northern Contaminants Mixture (NCM) or the commercial mixture Aroclor 1254. The overall aim of the current work was to generate new experimental data, which will contribute new knowledge to improve the health risk assessment associated with the exposure to chemical mixtures with a focus on the postnatal consequences of the exposure during fetal life, using the situation of the Canadian Arctic populations as an example. The body and organ weights, as well as serum levels of thyroid hormones and cholesterol were altered in young offspring at post-natal day (PND) 35 by perinatal exposure to the NCM or Aroclor 1254. In addition, levels of hepatic retinoids were decreased in the dams, as well as in their offspring at all post-natal follow-up time points following perinatal exposure to NCM or Aroclor 1254. Based on these findings, it was decided to perform both bone studies and more detailed retinoid studies. Multiple bone parameters, including geometrical and biomechanical parameters, were clearly affected in the offspring at PND35 and partly affected at PND77, while no bone changes were detected at PND350 following perinatal ...