How Does Rodent Development Affect Toxicity Assessments?

Toxicity testing data from rodents are often used to inform potential developmental risks to humans, but rodents have much shorter gestation periods, and they are born considerably less mature than human infants. As a result, near-term rodent fetuses often exhibit immature structures that may reflect normal developmental stages rather than toxic effects. In "Perinatal Development: Misunderstood Biology That Can Lead Hazard Assessment Astray," Exponent's John DeSesso, Ph.D., synthesizes information gleaned from more than 90 scientific papers and chapters to describe how developmental toxicity assessments can be misleading if they fail to account for major developmental differences between rodents and humans. 

Some of these differences include skeletal findings like delayed ossification, enlarged fontanelles, "missing" bones, wavy ribs, and bent bones that may simply reflect incomplete mineralization at the time fetuses are examined. Dr. DeSesso also points to some heart defects like open foramen ovale and other immature cardiac structures that continue to grow and mature after birth, as well significant differences in both the development of pulmonary surfactant production and the mechanism of intestinal absorption in very young rodents compared to humans.

Given these and other important differences, Dr. DeSesso emphasizes the importance of grounding developmental and reproductive toxicity (DART) assessments in comparative developmental biology. Scientists can evaluate whether observed findings represent:

• Temporary developmental delays
• Normal species-specific developmental stages
• Genuine adverse effects that are relevant to humans

Failure to account for these differences can lead to incorrect hazard classifications and inappropriate extrapolation of rodent findings to human health risks, Dr. DeSesso writes. Read the full paper in the journal Birth Defects Research.

From the publication: "Due to the compressed development schedule of rodents compared with humans, delays in rodent development may be misinterpreted as malformations."