Amid growing attention on environmental exposures involving mixtures, National Toxicology Program (NTP) projects are increasingly focused on learning more about how exposure to multiple chemicals affects human health. In past years, much of NTP research was geared toward single-chemical toxicology.
At its June 29 meeting, the NTP Board of Scientific Counselors (BSC) enthusiastically supported the substantial NTP progress in mixtures research.
Cynthia Rider, Ph.D., from the NTP Toxicology Branch, outlined the complex challenges involved in studying exposures to multiple chemicals and described research approaches (see sidebar). “We are tackling big mixtures questions using the latest toxicology tools,” she said.
Thumbs up from the panel
"Relative to what we once knew, we actually know quite a bit and we're making great progress," said Norman Barlow, D.V.M., Ph.D., from Johnson and Johnson. "The NTP is rising to this challenging area and needs to continue to push."
BSC Chair Kenneth McMartin, Ph.D., from Louisiana State University, agreed. "The board was very excited and very impressed with the [mixtures] presentation," he said. "NTP is addressing the key questions in this area."
An external science advisory board for the mixtures research program was recommended by Kenneth Ramos, M.D., Ph.D., from the Arizona Health Sciences Center. "I think you need some outside perspective on this to enrich what you’re trying to do," he noted.
Where the rubber meets the road
Crumb rubber, used with artificial turf, is one of the newest NTP mixtures projects. Georgia Roberts, Ph.D., from the NTP Program Operations Branch (POB), updated the BSC on progress since the program was introduced to the board in June 2016.
An estimated 11,000 sports fields in the U.S. are made of artificial turf containing crumb rubber, so widespread exposure is possible. This led to concern about potential public health effects, particularly because young people are the main users of the fields.
Working with other federal agencies, NTP research follows three tracks — chemical analysis of crumb rubber, cell-based studies, and animal model experiments. Important factors that affect exposures to either crumb rubber or its components include conditions, such as new or weathered turf, and exposure routes, such as dermal, ingestion, and inhalation. That information helps to inform potential toxicity evaluations through cell-based assays and in vivo studies.
Roberts reported that the chemistry- and cell-based experiments are completed. Exposure feasibility studies are still in progress. The project team plans to release data from completed studies in late 2017 or early 2018. Board members approved of the project’s progress and said they were eager to learn the final results.
Scrutiny of children's products proposed
Scott Masten, Ph.D., director of the NTP Office of Nominations and Selection, asked for input on a possible new NTP project to screen for biological activities of concern posed by mixtures of chemicals that may be released from children’s products – a research effort that would involve many thousands of mixtures.
The BSC was cautious in its evaluation of the project. Several members suggested that a workshop would be the best way to evaluate whether and how to move forward.
Reaching across generations?
Vickie Walker, from the NTP Office of Health Assessment and Translation, reported results of a systematic review regarding the nature and quality of the scientific literature available on transgenerational inheritance of health effects — the idea that an exposure in one generation can have negative consequences three or more generations later.
The state-of-the-science review found few studies with good quality data that could be used to assess whether the phenomenon occurs.
"The analysis has shown that although there has been lots of talk about transgenerational exposure, the data is just not that strong when you look at it carefully," said Linda Birnbaum, Ph.D., NIEHS and NTP director.
(Ernie Hood is a contract writer for the NIEHS Office of Communications and Public Liaison.)
Beth Bowden, from POB, described upcoming improvements to the NTP website. (Photo courtesy of Steve McCaw) 
Donald Stump, Ph.D., from WIL Research, right, seated by Cynthia Afshari, Ph.D., from Amgen, praised the systematic review of transgenerational research. (Photo courtesy of Steve McCaw) 
Warren Casey, Ph.D., director of the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods, described new approaches in chemical safety testing. (Photo courtesy of Steve McCaw) 
Myrtle Davis, D.V.M., Ph.D., from the National Cancer Institute, asked technical questions about methods used in crumb rubber research. (Photo courtesy of Steve McCaw) 
Jennifer Sass, Ph.D., from the Natural Resources Defense Council, left, seated by Daniel Kass, from Vital Strategies, cautioned against too much research focus on mechanism of action in mixtures. (Photo courtesy of Steve McCaw) 
Ramos endorsed the systems biology approach to mixtures research. "A lot of bang for the buck can come from that," he observed. (Photo courtesy of Steve McCaw) 
Birnbaum, center front, BSC members, and NTP leadership took advantage of nice weather. Members serve overlapping 4-year terms. (Photo courtesy of Steve McCaw) 
