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Prenatal Origins of Endocrine Disruption

Critical Windows of Development

How We Created the Timeline

How we created the Critical Windows of Development

In order to create the Critical Windows of Development we conducted extensive scientific literature searches on both normal human development and the health effects of environmental chemicals. Then we designed a database where we recorded the experimental details of the relevant studies. From this, we developed a web page that displayed the information in a concise and readily accessible format. It is important to note that we did not interpret the research, we simply cataloged the information to present it to the public.

An important feature of the Critical Windows of Development is that it can be updated as often as necessary. We add new studies to the display when they appear in the published literature. We strive to stay as current as possible.

How we search the literature

In conducting literature searches, we use two primary databases:

  • PubMed is a service of the U.S. National Library of Medicine that includes over 18 million citations for biomedical articles.
  • The Web of Science provides access to approximately 8,700 of the most prestigious research journals in the world.

How we decide what studies to include

Normal Human development: While we would prefer to cite only original research on normal human development, such studies are often difficult to obtain. This is either because the findings have become so well accepted they are not cited, or the study was conducted so long ago that we could not obtain the original articles. For these reasons, much of the information on basic human development is obtained from textbooks and secondary sources, such as peer-reviewed articles that cite older studies. Note that we choose only those textbooks that are highly regarded by experts in the field. Wherever possible, results of original experimental research are presented.

Chemical studies: Chemical studies are chosen based on the following criteria. The authors must report the methods and results of an experimental study (no reviews, summaries, or commentaries). Studies must be conducted on rodents or human cells/tissue. Chemicals must be administered during the time period comparable to human prenatal development (which includes approximately three weeks of rodent postnatal development). The authors must report statistically significant results when the chemical is administered at or below the low-dose cut-off. Cut-off doses, which vary by chemical, represent exposures that humans might encounter in the environment.

How we determine the correspondence between rodent and human development

There are approximately 38 weeks in human gestation, from fertilization to birth. The corresponding period among rats and mice is approximately 41 days, although this encompasses gestation, birth (typically on day 19 for mice and day 23 for rats) and post-natal lactation. Bayer, et al (1993)1 confirmed and refined this correspondence in a detailed study of human and rat brain development. The Critical Windows of Development relies on the Bayer study for weeks 3–19 of human development and extrapolates from this research for the earlier and later time periods.

We recognize that mapping of rodent to human brain development may not translate exactly to development of other components of the body (for example, the thyroid, testes, or heart). However, the brain plays a major role in all endocrine functions and has been thoroughly studied with regards to the correspondence between human and rodent development. It was simply not within the scope of this project to map rodent to human development separately for every system or organ.

1Bayer SA, Altman J, Russo RJ, Zhang X. 1993. Timetables of neurogenesis in the human brain based on experimentally determined patterns in the rat. Neurotoxicology 14(1):83–144.

How we conduct peer-review of the Critical Windows of Development

In addition to the scientific peer-review that each cited paper undergoes prior to publication, we developed an additional peer-review process for the Critical Windows of Development.

Prior to making the timeline public, formal peer-review sessions were conducted with over 40 scientists, including many whose work is cited in the timeline. We made a point of selecting reviewers from a range of research fields (for example, biochemistry, endocrinology, toxicology, and reproductive health). We also selected reviewers to ensure that all the systems (for example, the central nervous system and the endocrine system) were reviewed.

Review sessions were typically conducted by phone, with the scientist carefully evaluating the Critical Windows of Development and providing direct and immediate feedback which was documented by our research staff. Reviewers also spent time outside the interviews critiquing the fine details of the research relevant to their field.

This peer-review process will continue as we add chemicals to the timeline and update the website with the latest breaking research.