Human Health Effects Research
Nanomaterials have become widely used in products ranging from clothing (which incorporates bacteria-fighting nano Silver) to sunscreen. Nanomaterials are very useful, but there is little research about how nanomaterials affect human health. Since nanomaterials are much smaller than normal (about 100,000 times smaller than the width of a human hair), they are absorbed more easily by people’s lungs and skin. EPA is in the process of researching how nanomaterials interact with biological processes important to human health. To accomplish this, EPA researchers are identifying the unique make up (properties) of nanomaterials that regulate their reactivity, interactions with important biological processes and toxicity.
EPA researchers are developing methods, models and guidelines to:
- Assess, rank and predict with greater certainty the acute and chronic nanomaterial health effects using rapid, automated chemical screening called high-throughput and high-content testing methods.
- Inform green nano-chemistry/engineering and identify alternative, “greener” nanomaterials.
- Identify adverse outcome pathways (AOPs), their key events and dose concentrations for specific nanomaterial health effects.
- Identify susceptibility factors influencing nanomaterial deposition, fate and toxicity.
The rapid and diverse growth of engineered nanomaterials presents a challenge for regulators and risk assessors in understanding potential for adverse effects and whether methods used for assessing conventional chemicals can be applied for these novel materials.
EPA scientists recently evaluated the use of high-throughput screening assays (from the ToxCast chemical prioritization program) to understand the compatibility of the assays with nanomaterials and the types of endpoints responsive to nanomaterial bioactivity.
A collection of 61 samples consisting of nanomaterials along with ion and micro versions of the core material was assembled with a focus on materials that fall under EPA regulatory authority or are of program office interest. Materials were screened in mammalian cellular assays and a zebrafish development assay with 262 assay endpoints measured.
Results fell in to two general categories. The first consisted of metal nanoparticles that showed strong cellular stress responses, in particular oxidative stress, and cytotoxicity across many different cell types in a range of 0.5-100 g/ml. Ionic, nano and, in some cases, micro versions of the same core material had very similar patterns of activity. Assay endpoints provided some discrimination between the core materials. Most other materials were not significantly cytotoxic.
The second category of activity was a broad collection of endpoints grouped loosely together as inflammatory responses. Nano forms of Ce, TiO2, SiO2 and CNT were all active in various primary human cell systems for a variety of specific endpoints, generally at concentrations above 1 g /ml.
A nanomaterial designed to be environmentally benign method for delivery of silver (Ag) as a biocide, indulin AT (IAT), was tested with and without Ag. The material displayed activity similar to Ag ion in the cellular stress and cytotoxicity category and the IAT also produced responses in the inflammatory category.
The methods used here demonstrate the feasibility of use of high-throughput screening assays to evaluate a broad range of engineered nanomaterials. However, much refinement is needed before using it to build property-activity relationships or define doses capable of causing adverse events in vivo.