Building on National Initiatives for New Chemicals Screening
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Non-technical overview:
 
 
 
 Understanding how exposure to chemicals in the environment may raise the risk of breast cancer could offer clues to preventing the disease. Currently, the vast majority of chemicals found in homes, consumer products, and the environment have not been safety-tested. For those chemicals that are tested, most of the methods used are not designed to detect chemical effects specific to breast cancer, and they are typically too slow and expensive to screen the tens of thousands of chemicals on the market. As chemicals in the environment are increasingly suspected to contribute --directly or indirectly-- to breast cancer risk, improving these tests has become a top research priority for many breast cancer organizations. The proposed project addresses these concerns by developing innovative methods to rapidly screen chemicals using methods that are directly relevant to breast cancer. The project also responds to the findings of the CBCRP-funded Breast Cancer and Chemicals Policy project, which recommended development of novel breast cancer-relevant cell-based chemical tests (assays) that can be incorporated into regulatory testing programs and initiatives to design safer chemicals (green chemistry). Finally, it builds on, and will provide information for, major new initiatives at the US Environmental Protection Agency (EPA’s ToxCast program) and the National Toxicology Program (NTP’s Tox21 program) that are developing rapid chemical screening methods to fill current gaps in chemical safety evaluation. Data from the EPA ToxCast and NTP Tox21 screening programs will be used to prioritize chemicals for further evaluation and regulation, so it is important that they use breast-cancer relevant tests.
 
 
 
 
 
 Research questions:
 
 
 
 We anticipate that cell-based (in vitro) chemical tests can be adapted and used to quickly and cost-effectively identify chemicals that may play a role in breast cancer. The EPA ToxCast assays evaluate many different mechanisms of action, or ways that chemicals can affect cells and tissues. However, these tests were not specifically designed to detect mechanisms relevant to breast cancer. We will adapt the cell-based tests used by EPA to make them relevant for breast cancer by transferring the methods into breast cells. We will also develop new tests to fill gaps in current testing methods, for example tests that measure changes in mammary cell specific enzymes involved in estrogen production. By comparing the effects of chemicals that we know cause tumors in animal studies (carcinogens) to those chemicals that do not (non-carcinogens), we will be able to identify a set of tests that can help predict which chemicals might raise the risk of the disease. These chemicals could then be targeted for further testing or for regulation. By identifying the cell changes that occur frequently with exposure to chemicals known to cause breast cancer in laboratory animals, we furthermore expect to be able to create a profile of a possible breast carcinogen.
 
 
 
 
 
 General methodology:
 
 
 
 First we will select from chemical tests already validated by ToxCast, choosing the assays that are most relevant to breast cancer. We will transfer these tests into a variety of breast cell models that range in their complexity. We will also develop two new assays that are not part of the ToxCast program but that represent mechanisms likely to be important in breast cancer. Second, we will run these assays on approximately 60 chemicals and compare the results of assays performed on chemicals not associated with breast cancer to the results of assays performed on known carcinogens. Several of the chemicals we have selected for testing are associated with breast cancer risk in humans, but because there is more data available from laboratory animal studies, our analysis will focus on animal carcinogens. Our goal is to identify the assays that help predict whether a chemical will cause mammary gland tumors in animals, allowing researchers to screen many chemicals and flag the most hazardous ones or others that need further study.
 
 
 
 
 
 Innovative elements:
 
 
 
 ToxCast assays are going to be used to improve chemical testing, so it is important to develop new, breast cancer-relevant assays, as we propose in this project. The new assays will include tests for the kinds of changes in estrogen metabolism that occur in breast tissue, and the particular type DNA-damage specific to breast carcinogens. In addition, we will transfer approximately 100 ToxCast assays into breast cell systems and identify those that produce significantly different results in these sell systems. The project’s focus on rapid cell-based tests extends current innovation in chemical testing and will improve our ability to identify chemicals that might contribute to breast cancer. These assays can also be used to test mixtures, such as consumer products, house dust, drinking water, and even air samples. By testing many chemicals that cause mammary gland tumors in animal studies, we will also identify the specific mechanisms that cause some chemicals to affect breast cancer risk, helping understand how the disease occurs.
 
 
 
 
 
 Advocacy involvement and relevance to the human issues associated with breast cancer:
 
 
 
 The project arises directly from advocates’ concerns that chemical exposures represent a preventable cause of breast cancer, and that improved screening and evaluation of chemicals is a priority. We will work with the advocacy community through our Advisory Council and partnerships with non-profit organizations dedicated to promoting research on breast cancer and the environment. This will enable us to provide advocacy organizations with the information and materials to disseminate these research findings to their constituencies. Silent Spring Institute, a partner in the project, is a research organization founded by activists and experienced in community-based research and proactive dialogue with activists and policy-makers.
 
 
 
 
 
 
 
 Publications: 
 
 
 
 BCScreen: A gene panel to test for breast carcinogenesis in chemical safety screening