Assessments of the biological activity of various nanomaterials and chemicals in the context of primary human cell biology were presented at the annual meeting of the Society of Toxicology by scientists from the U.S. Environmental Protection Agency and BioSeek, LLC.
The presented findings further demonstrate the value of BioMAP® human primary cell assay systems for both identifying critical bioactivities and potentially adverse effects of drugs, new materials and other compounds in a high-throughput format.
“Through our work with EPA, BioMAP is yielding a rich harvest of biological information on a wide variety of environmental and other chemicals and their potential effects on human health,” said Ellen Berg, Ph.D., General Manager of BioSeek.
Berg continued, “In addition to helping meet the goals of the ToxCast Program, which are aimed at developing high-throughput screening methods capable of predicting chemical toxicities, this information is continuing to enrich our BioMAP database. We view that resource as an increasingly valuable tool that can be mined to better understand the activities and potential safety of our pharmaceutical partners’ compounds in the context of human biology, prior to undertaking costly human clinical trials.”
In an oral presentation by EPA, various nanomaterials with varying cores and their ion and micro counterparts were tested for cytotoxicity in various cell types, for transcription factor activation in HepG2cells, and for protein bioactive profiling in eight BioMAP human primary cell systems at concentrations equivalent to human exposures of 24 hours to 45 years.
Analysis showed that nanomaterial cores are critical to bioactivities and their effects are often similar to those of related ions.
Comparing test results on nanomaterials to reference profiles of other compounds in the BioMAP database suggested further molecular targets and pathways affected by the tested nanomaterials that weren’t directly measured by the assays performed.
A poster presented by EPA and BioSeek collaborators discussed the biological profiling of the ToxCast Phase II Chemical Library in BioSeek’s primary human cell co-culture systems.
The Phase II library contains 1060 unique compounds including failed pharmaceuticals donated by industry partners, reference compounds known to be endocrine disrupters, carcinogens or reproductive/developmental toxicants, and other widely used chemicals, food and cosmetic additives, and proposed alternatives to current industrially used chemicals.
The chemicals were tested in a panel of BioMAP co-culture systems and classified based on their ability to cause overt cytotoxicity in various cells types and on their bioactivity profiles when compared to reference compounds.