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The Endocrine Disruption Exchange
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Critical Windows of Development Timeline

methods 

How did we create the Critical Windows of Development timeline?

TEDX scientists conducted extensive literature searches on both normal human development and the health effects of environmental chemicals. Our primary sources were PubMedWeb of Science, and medical textbooks. Then we designed a database where we recorded the experimental details of relevant studies. From this, we developed a web page that displayed the information in a concise and readily accessible format, translated directly from published studies without interpretation. 

How did we decide what studies to include?

Chemical studies were chosen based on the following criteria. The authors must have reported the methods and results of an experimental study (no reviews, summaries, or commentaries). Studies must have been conducted on rodents or human cells/tissue. Chemicals must have been administered during the time period comparable to human prenatal development (which includes approximately three weeks of rodent postnatal development). The authors must have reported statistically significant results when the chemical was administered at or below the low-dose cut-off, which was determined on a chemical-by-chemical basis.

How did 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) 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 glands and organs (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 not within the scope of this project to map rodent to human development separately for every system or organ.

Why did we use animal studies to understand humans?

For decades scientists have relied on animal research to understand adverse health effects in situations where it would be dangerous to test a substance directly on humans. For decades scientists have relied on animal research to understand adverse health effects in situations where it would be dangerous to test a substance directly on humans. Further, human experimental studies evaluating the link between prenatal exposures and adult disease are impractical and time intensive. Epidemiological studies designed to determine correlations between adult disease and prenatal exposure are challenged by several factors including the inability of subjects to know or recall whether they were exposed in the womb. Thus, the major governing bodies in the U.S. that create regulations to protect our health, including the FDA and EPA, have routinely used animals to test for chemical effects. Although alternative non-animal methods (in cells and on computers) are rapidly being developed for such purposes, this project relies on studies in which the time period of exposure and outcomes in animals can be extrapolated to humans.  

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

In addition to the scientific peer-review that each cited paper received prior to publication, we developed an additional peer-review process for the Critical Windows of Development timeline. Prior to making the timeline public, formal peer-review sessions were conducted with over 40 scientists, from a range of research fields (for example, biochemistry, endocrinology, toxicology, and reproductive health), including many whose work was cited in the timeline.