The rationale is that, as gene expression is a sensitive end-point, alterations in microarray expression profiles may act as useful biomarkers to define more precisely the nature and level of exposure to hazardous chemicals.
Depending on the end point (e.g., endocrine alterations, tumor cell proliferation, organ proliferation, and immune alterations), a hormetic response may be considered beneficial, neutral, or adverse (Calabrese 2004).
The primary end points were the alterations in parameters of cellular and humoral immunity.
Overall survival (OS) is the primary end point and will be correlated with metabolic parameters and (epi genetic alterations assessed from tumour and serial blood samples.
Important potential confounding factors for the primary end point that were considered included improvements in glycemic control and alterations in blood pressure or renal function during the 24 weeks of treatment in either group.
Of all indicators of disrupted sexual development, alterations in retained nipples were the most sensitive end point, with effects becoming noticeable at the lowest doses.
Revision was defined as the end point.
Alterations (elimination or reduction) of sexually dimorphic behaviors are a particularly sensitive end point for BPA exposure [reviewed by National Toxicology Program (2008)].
Prenatal exposure to BPA in mice led to alterations in brain structure and corresponding changes in behavior, with the latter being a notable end point for low dose exposure (reviewed by Chapin et al. 2008; Palanza et al. 2008).
For mixtures containing a relatively small number of interacting substances, commonly affected end points and/or commonly affected alterations in gene or protein expression could be detected by means of the CTD and alterations postulated in this way could be verified experimentally for the specific mixture.
Secondary end points included mortality, treatment alteration and change in weight, NYHA functional class or quality of life (QoL).
