NTP board moves initiatives forward
By Ernie Hood
The NTP Board of Scientific Counselors (BSC) accomplished quite a bit in its Dec. 15, 2011, session at NIEHS. Highlights of the meeting included updates by the NTP director and associate director, three chemical nominations, a hair dye workshop proposal, a report on the NTP diabetes and obesity workshop, and presentation of a proposed review process for the Report on Carcinogens (see text box).
Before moving into its packed agenda of reports and proposals, the BSC heard from NIEHS/NTP Director Linda Birnbaum, Ph.D., who thanked three departing members for their contributions. Birnbaum presented certificates and letters of appreciation to Mitzi Nagarkatti, Ph.D., Ruthann Rudel, and Gina Solomon, M.D., whose terms expired Dec. 27, 2011.
Chemical nominations evaluated
The BSC approved NTP research and testing concepts for three chemicals, moving each of them to the next step in the process of being developed into an NTP research program. Two are high production volume (HPV) compounds, while the third is used mainly in laboratory settings and has been implicated in the deaths of two workers.
Sulfolane is a solvent used mainly in natural gas and petroleum refining, with U.S. production in 2006 estimated at 10-50 million pounds. Nominated to the NTP by several agencies and officials from the state of Alaska and the Agency for Toxic Substances and Disease Registry, sulfolane has been detected in nearly 300 drinking water wells within the town of North Pole, Alaska, possibly as a result of activities at a nearby petroleum refinery. It is also present at other sites within Canada. Sulfolane has not been tested for chronic toxicity or carcinogenic activity, and BSC member Elaine Faustman, Ph.D., from the University of Washington, expressed a high level of support for going forward with further evaluation by NTP. Fellow concept reviewer Melissa McDiarmid, M.D., of the University of Maryland School of Medicine, agreed, noting, “This is precisely the situation that the NTP is supposed to serve.”
The HPV class of chemicals called phenolic benzotriazoles (PBZTs) was nominated to the NTP by NIEHS. Used as UV stabilizers within products to increase stability to light, there are 10 HPV PBZTs among the 29 compounds in the class, some of which are used in food contact polymers and adhesives, cosmetics, sunscreens, and fragrances. With high production and high potential for human exposure, the challenge will be to prioritize which of the chemicals to evaluate for potential health hazards, and which tests will eventually yield a class evaluation. BSC concept reviewers recommended that the NTP start its program on PBZTs with ADME (absorption, distribution, metabolism, excretion) and toxicokinetics tests to determine whether the active agent is a parent compound or a metabolite, and then move on with a testing funnel strategy similar to that used in the pharmaceutical industry for drug discovery.
The third proposed compound, trimethylsilyldiazomethane (TMSD), was nominated by the Occupational Safety and Health Administration (OSHA), due largely to the recent deaths of two chemists exposed to the agent in the laboratory workplace. TMSD is a synthetic methylating reagent used for organic synthesis and in analytical methods, such as gas chromatography. Originally developed as a less toxic and more stable substitute for the highly explosive compound diazomethane, there is currently very little toxicity data on TMSD, but dermal and inhalation exposures are likely in occupational settings. The BSC recommended moving forward with the proposed NTP testing program, but urged that extreme caution be exercised, including the use of appropriate personal protective equipment by testing personnel, due to the presumed acute toxicity of the compound.
Hair dye workshop supported
The BSC favored a proposed workshop on permanent hair dyes. According to NTP presenter Ruth Lunn, Dr.P.H., the conference would advance the state of the science related to potential human health hazards associated with the widely used products, by focusing discussions on data gaps, research strategies, and testing methods. Potential carcinogenicity is a major concern, but studies to date have been unclear. Because there are so many different chemicals involved, and the dyes are all mixtures, determining safety of the products presents quite a challenge. Several BSC members noted that there are many scientific questions to be addressed, and the needed studies will be complex. Despite that cautionary note, the BSC supported moving forward with organizing the workshop. A representative from the Personal Care Products Council, in attendance, commended the NTP for tackling this issue, and said the industry looks forward to working with NTP to address this important subject.
The next BSC meeting is scheduled for June 21-22.
(Ernie Hood is a contract writer for the NIEHS Office of Communications and Public Liaison.)
Proposed RoC review process
The BSC also spent time listening to comments from the public and receiving an update from the NTP on proposed changes on how the congressionally mandated Report on Carcinogens (RoC) would be developed.
The proposed changes to the RoC are intended to increase the transparency and openness of how the NTP reviews substances. Numerous opportunities for public input are built into the process.
NTP Associate Director John Bucher, Ph.D., walked the BSC through a number of changes that the NTP has made since the original proposed review process(202KB) was released for public comment Oct. 31, 2011. Since then, the NTP has held a public listening session, (353KB) which brought 19 speakers, and a public comment period, allowing the NTP an opportunity to revise the process to accommodate some of the issues raised by the public.
As he thanked everyone for input, Bucher said all input has been considered and some revisions have been made. Bucher illustrated changes to the process, which is comprised of four parts: nomination and selection of candidate substances; scientific evaluation of candidate substances; public release of the draft RoC monograph and peer review; and HHS approval and release of the latest edition of the RoC.
BSC chair David Eastmond, Ph.D., from the University of California, Riverside, told the NTP, “The BSC supports what you are trying to do, and supports you going forward.”