The first principal comes from green chemistry. Green chemists design against hazard . The earlier in the design process that hazard can be discovered, the more likely it is that downstream problems will be minimized, if not avoided entirely. This can have material benefits for the chemist and his/her company.
The second principle, on current scientific understanding, contrasts our protocol with standardized approaches used in regulatory toxicology. As noted above, the standardized assays upon which traditional toxicological approaches are based are often decades old. They rarely reflect the quality and modernity of assay tools used in scientific research funded by the National Institutes of Health, including the National Institute of Environmental Health Sciences. The old approaches are insensitive and largely incapable of dealing with EDCs. Ignoring current science would result in chemists producing yet another generation of hazardous chemicals.
That said, the assays we recommend have been chosen because multiple laboratories have successfully used them. They can require specialized knowledge and skills, but are not so arcane that only a single, or small number of, laboratories, would be capable of implementing them. The second half of the principle acknowledges the fast pace of scientific discoveries in the field of endocrine disruption. New modes of action requiring new assays will certainly be discovered. Incorporating this evolving knowledge into the protocol is essential.
The third principle, a comprehensive range of EDC mechanisms, reflects the need to look for more than one or two EDC modes of action. This is because single chemicals can act through multiple mechanisms. The absence of action through one mechanism cannot be taken as evidence of no action through another mechanism. A case in point is BPA. It is an estrogen via both genomic and non-genomic pathways, an anti-androgen, a thyroid hormone antagonist, and a peroxisome proliferater-activated receptor (PPAR) agonist.
The fourth principle acknowledges that the current state of in silico and in vitro assays do not sufficiently incorporate the complexity of an endocrine system functioning in a living organism, and especially that of a developing organism.