This tier involves testing in mammalian models, primarily rodents. It is not designed to replace regulatory testing but to be a focused assessment of endpoints/tissues/diseases/pathways that may have been missed by earlier tiers because they lack the complexity of mammalian development. It can also be used to shed additional light on endocrine disrupting actions identified by earlier tiers.
The mammalian models are unique in their capacity to study in utero exposures that involve interactions between endocrine responses in the mother, placenta and embryo/fetus. Furthermore, certain behavioral repertoires can be studied in mammals that have greater biomedical relevance, such as mating and maternal behaviors, lactation, weaning, and complex adult socio-sexual behaviors.
We assume here that the chemist employing TiPED has run his/her molecule through the other 4 tiers without detecting EDC activity. To be confident the chemical has no endocrine activity or to assess a specific endocrine system in more detail it is essential to consider mammalian whole animal assessment. These are the assays of ‘last resort,’ which would only be used if work in prior tiers revealed no EDC activity.