Abstract

Contemporary translational biomedical research strives to move from discoveries in models (in silico, in vitro and in vivo) into human clinical trials to expeditiously develop specific therapeutics. Translational toxicology must similarly strive to identify applicable therapeutics that can safely and effectively mitigate potential harm from exposures. Since human exposures to chemicals, physical agents and social factors are inevitable, the human fetus is subject to effects that can have lifelong consequences. In order to apply the translational concept to developmental toxicology, we are guided by the modest number of established and accepted obstetrical therapeutics used primarily for fetal benefit. These established or potential therapeutic obstetrical interventions suggest that early steps into testing or implementing developmental translational toxicology therapies during the in utero and early neonatal period will likely derive from Generally-Recognized-As-Safe (GRAS) options. If we are to translate environmental health discoveries into safe and effective interventions, we must assert and characterize valid, applicable therapies such as GRAS treatments and eventually “ethical pharmaceuticals” for the protective care of these highly vulnerable young patients. We can create a safe and efficacious environmental health portfolio of interventional options to improve human health that include both reduction/avoidance of exposure and specific preventative/mitigative/restorative therapeutics.

Highlights

  • We have recently asserted that the relatively new term of “translational toxicology” should encompass both the existing principles of toxicology and epidemiology but be driven by the aim of developing safe and effective interventions to include prevention, mitigation or reversion of adverse human health effects of exposures

  • The results suggest that the adverse effects of benzo[a]pyrene on follicle growth, steroidogenesis and Anti-Müllerian hormone (AMH) output are mediated through activation of the Aryl hydrocarbon Receptor (AhR)

  • Sørensen et al [34] studied whether lower maternal serum concentrations of 25-hydroxy-vitamin D (25-OH D) during pregnancy were associated with an increased risk of childhood-onset type 1 diabetes

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Summary

Introduction

We have recently asserted that the relatively new term of “translational toxicology” should encompass both the existing principles of toxicology and epidemiology but be driven by the aim of developing safe and effective interventions to include prevention, mitigation or reversion of adverse human health effects of exposures. The research and development aims within translational toxicology should be the creation of a safe and effective portfolio of interventional options to improve human health that goes beyond mere reduction and/or avoidance of exposure(s) so that practitioners have specific preventative/mitigative/ restorative therapeutics for human clinical use. Short of directly measuring clinical endpoints, surrogate endpoints can be measured, but at a minimum, biomarkers must be explicitly validated as predictors of surrogate endpoints to be plausibly interpreted as indicators of clinical endpoints. Pge 2 of 8 between exposure and effect plus development and validation of safe and efficacious preventative/mitigative/restorative therapeutics in humans, we assert that the following clinical study design elements must be included in translational developmental toxicology research and development projects: 1. Pge 2 of 8 between exposure and effect plus development and validation of safe and efficacious preventative/mitigative/restorative therapeutics in humans, we assert that the following clinical study design elements must be included in translational developmental toxicology research and development projects: 1. Indicator(s) of timing of exposure

Findings
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