Nanosafety
There is increasing concern that a given nanoparticle may expose people to unknown toxicologies due to the extremely small size relative to cellular structure. These exposures may occur in the manufacturing process or environmental releases and may be persistent. The chemical entities must be proven safe in cellular and animal models prior to introduction to the marketplace. This will involve the use of the facility to expose the most appropriate animal model to the nanomaterials as an aerosol (lung deposition) or other forms (skin exposure, ingestion, or intravenous injection). Appropriate end points of testing will be defined and measured to gain a full understanding of the effects in the human systems.
As nanoparticles are developed, the biological activity of the particle must be understood and appropriate testing performed. Testing will include immunological assays, pathological evaluation of tissues from the relevant organs, carcinogenic assays, and other biological or toxicological end points. Since particles may pass through the cell membrane, many questions are being asked about the reactivity with organelles and reactivity with the DNA causing concern of cytotoxicity. In addition, cell culture assays will be performed to evaluate whether a given nanomaterial enters cells or induces apoptosis or other forms of cell death or intracellular carcinogenic transformation. Primary human cell lines will be the culture of choice for these studies. Differentiated air/liquid interface human lung epithelium will be the culture system of choice for lung damage assessment. On occasion, microarray studies may be performed to assess the effect of the materials on gene function. Frequently, commercial or government entities will want to utilize these in vitro assays prior to moving into the more extensive and expensive animal model testing. Wherever possible the nanomaterials will be labeled with radioisotopes or fluorescent probes or other labeling techniques to allow for the study of the uptake and clearance of the materials in animal models and or cultured systems.
Once the biological activity is defined, then safety evaluations will be performed to support environmental, workplace, or pharmaceutical safety claims. The safety evaluations include both in vitro and in vivo evaluation of the formulations in short-term and long-term testing that must meet standards set by international organizations such as ISO, the OECD, and the U.S. FDA or EPA. This will be especially critical for those materials that are designed to be used in therapeutic protocols. ADME/PK protocols are included in the GLP pre-clinical facility operation.
Animal models for surrogate human health assessment will include the mouse, rat, rabbit, canine, and nonhuman primate models. Studies will use fully international GLP and international environmental testing standards. Basing on nanomaterials toxicity tests on animals recommendations for clinical trials will be given.
