Timescales of Developmental Toxicity Impacting on Research and Needs for Intervention

Basic Clin Pharmacol Toxicol. 2019 Aug;125 Suppl 3(Suppl 3):70-80. doi: 10.1111/bcpt.13162. Epub 2018 Dec 10.

Abstract

Much progress has happened in understanding developmental vulnerability to preventable environmental hazards. Along with the improved insight, the perspective has widened, and developmental toxicity now involves latent effects that can result in delayed adverse effects in adults or at old age and additional effects that can be transgenerationally transferred to future generations. Although epidemiology and toxicology to an increasing degree are exploring the adverse effects from developmental exposures in human beings, the improved documentation has resulted in little progress in protection, and few environmental chemicals are currently regulated to protect against developmental toxicity, whether it be neurotoxicity, endocrine disruption or other adverse outcome. The desire to obtain a high degree of certainty and verification of the evidence used for decision-making must be weighed against the costs and necessary duration of research, as well as the long-term costs to human health because of delayed protection of vulnerable early-life stages of human development and, possibly, future generations. Although two-generation toxicology tests may be useful for initial test purposes, other rapidly emerging tools need to be seriously considered from computational chemistry and metabolomics to CLARITY-BPA-type designs, big data and population record linkage approaches that will allow efficient generation of new insight; epigenetic mechanisms may necessitate a set of additional regulatory tests to reveal such effects. As reflected by the Prenatal Programming and Toxicity (PPTOX) VI conference, the current scientific understanding and the timescales involved require an intensified approach to protect against preventable adverse health effects that can harm the next generation and generations to come. While further research is needed, the main emphasis should be on research translation and timely public health intervention to avoid serious, irreversible and perhaps transgenerational harm.

Publication types

  • Review

MeSH terms

  • Animals
  • Big Data
  • Computational Chemistry / methods
  • Congresses as Topic
  • Disease Models, Animal
  • Ecotoxicology / methods*
  • Endocrine Disruptors / adverse effects*
  • Environmental Exposure / adverse effects*
  • Environmental Medicine / methods*
  • Epigenesis, Genetic / drug effects
  • Epigenomics / methods
  • Female
  • Fetal Development / drug effects
  • Fetal Development / genetics
  • Humans
  • Metabolomics / methods
  • Pregnancy
  • Prenatal Exposure Delayed Effects / diagnosis*
  • Prenatal Exposure Delayed Effects / etiology
  • Prenatal Exposure Delayed Effects / prevention & control
  • Research Design
  • Risk Assessment / methods
  • Time Factors

Substances

  • Endocrine Disruptors