In an article published on September 6, 2019, in the peer-reviewed journal Food and Chemical Toxicology, Adejoke Ogungbesan and colleagues from the Office of Food Additive Safety (OFAS) in the Center for Food Safety and Nutrition (CFSAN) of the U.S. Food and Drug Administration (FDA) reviewed the currently available assays for studying developmental immunotoxicity and discussed how such tests “might be used to contribute to the safety assessment of food contact substances.”

The authors explain that their focus on developmental immunotoxicity is justified by the higher susceptibility of the neonatal immune system to chemical perturbations, compared to adults. Indeed, previous studies have shown that “there are different critical windows of susceptibility to immunotoxicants” and therefore “the effects of immunotoxicants during development may not be fully detected in toxicity studies performed on adult animals.” In addition, the 2019 FDA guidance for the premarket assessment of food contact materials intended for use with infant formula or human milk requests evaluation of the migrants’ potential “to elicit effects on the developing immune, nervous, reproductive, endocrine, or skeletal systems”  (FPF reported). Therefore, the authors set out to review the state of developmental immunotoxicity testing for food contact substances (FCSs) and discussed the FDA’s current approach to evaluating the potential for FCSs to have adverse impacts on the developing immune system.

The review showed that “the current immune assays have been generally characterized and validated in the mature immune system of adult animals” and often “may not fully detect adverse effects of a toxicant on the immune system of developing animals.” This suggests that the assessment of developmental immunotoxicity “is an important aspect to be considered in the evaluation of multiple critical windows or stages during immune system development in juvenile and other immature animals utilized in a toxicity study.” Both cellular and humoral immunity appear to be important and, therefore, developmental immunotoxicity assessment “should involve a multi-parameter approach (including a robust measure of cell mediated immunity via multiple immunotoxicity assays) to evaluate the point of departure for risk assessment of FCSs.” The authors concluded that, despite some developmental differences evident among species such as rats and humans, and pending the necessary optimization, some of the available techniques “may […] enable translation of animal toxicity findings to human risk assessment of potential immunotoxicants.”


Ogungbesan, A., et al. (2019). “Exploring the use of current immunological assays for the developmental immunotoxicity assessment of food contact materials.Food and Chemical Toxicology 133: 110801.