US agencies collaborate to test 10,000 chemicals

A high-speed robotic screening system jointly initiated by three key US health agencies began testing more than 10,000 chemical compounds for potential toxicity on 7 December. The National Institutes of Health (NIH), the Environmental Protection Agency (EPA) and the Food and Drug Administration (FDA) aim to improve how chemicals, including many consumer products, food additives and pharmaceuticals, are tested for safety. 

The project will develop, validate and translate innovative, high-throughput chemical testing methods to characterise key steps in toxicity pathways. The testing will take place in the Tox21 robotic screening system at the NIH Chemical Genomics Center in Rockville, Maryland, US, which is part of the agency’s National Human Genome Research Institute. The three participating agencies are hopeful that the high-throughput screening programme will determine whether these chemicals pose a risk to human health. 

Compounds to be screened include boric acid, an antiseptic ingredient, insecticides, flame retardants, calcium chloride and tributylamine, a solvent used as an intermediate in pharmaceutical production. 

The chemical library took two years to assemble and contains over 8100 unique compounds. It also includes 135 failed drugs that pharmaceutical firms provided to the EPA under material transfer agreements, according to Ray Tice, chief of the biomolecular screening branch at the NIH’s National Institute of Environmental Health Sciences (NIEHS). 

’That is significant because it’s the first time that pharma has ever provided something like that,’ Tice tells Chemistry World. This information is valuable because the compounds in question failed in human clinical trials due to toxicity, and the interagency National Toxicology Program doesn’t have human data, only animal toxicology data. This information on failed drugs could help the programme link in vitro results to human disease. 

Individuals and mixtures 

’There has never been a compound library like this before,’ said NIEHS’ director, Linda Birnbaum. ’All of us are exposed to many different chemicals at the same time, not just one chemical at a time. These new technologies allow us to more rapidly advance our understanding of not only individual chemicals, but mixtures of chemicals as well.’ 

One area that will benefit from the data being generated on Tox21 is the effort to reform the Toxic Substances Control Act (TSCA), which controls chemicals sold on the US market. Under that law, the EPA has broad authority to issue information collection regulations that require the submission of health and safety studies which are known or available to those who manufacture, process or distribute specified chemicals. 

Beyond TSCA in the US, there are also repositories of toxicology data on consumer chemicals in Europe as a result of Reach - the EU’s principal chemical legislation. Enacted in 2007, Reach aims to improve the protection of human health and the environment through the earlier and better identification of the intrinsic properties of chemical substances. 

However, Tice said a lot of the REACH data is proprietary and therefore not publicly accessible. In contrast, all of the information in Tox21 is being made public and can be downloaded. 

’It would be really wonderful to know to what extent the data being submitted to Reach is being made publicly available so that it can be integrated into other databases and we can have a better understanding of the interaction between chemical structure and other kinds of activities,’ Tice says. 

Rebecca Trager