Panel peer reviews and approves seven NTP technical reports
By Robin Mackar
A panel of external scientific experts convened by the National Toxicology Program (NTP) peer reviewed and approved the conclusions of seven draft technical reports (http://ntp.niehs.nih.gov/?objectid=152479D1-B06B-5CB3-2D013DB07876F313) . The two-year studies outlined in the NTP technical reports covered a broad spectrum of substances ranging from a popular herbal supplement and industrial solvents to HIV treatment approaches. The meeting Feb. 8-9 was webcast and included presentations and comments from the public.
After brief welcoming remarks by NIEHS/NTP Director Linda Birnbaum, Ph.D., and NTP Associate Director John Bucher, Ph.D., and accolades to NTP’s Michelle Hooth, Ph.D., and David Malarkey, D.V.M., Ph.D., for overseeing the reports, the meeting began with a short presentation by Hooth outlining the panel’s charge.
Hooth discussed how NTP technical reports describe the methods, results, and NTP conclusions. She said NTP conclusions are presented as levels of evidence under the specific conditions of each study, and that both the clear and some-evidence conclusions indicate positive responses for carcinogenic activity in the rodent studies. It was the panel’s role to determine whether the study’s experimental design, conduct, and findings support the NTP’s conclusions.
Presentations on Ginkgo and DMPT
June Dunnick, Ph.D., of NTP kicked off the first studies to be reviewed, which were on N,N-Dimethyl-p-toluidine (DMPT), a high-production chemical used in dental materials and bone cements. Dunnick presented data showing that both rats and mice developed tumors after being given DMPT for up to two years. The NTP also found anemia-like symptoms in rats and mice. All three primary reviewers, as well as the panel, concurred with the clear -evidence call made by the NTP.
The second report on Ginkgo biloba extract was presented by NTP’s Cynthia Rider, Ph.D. Ginkgo is among the top five herbal supplements on the market, with an estimated 7.7 million Americans taking it in 2002. Ginkgo extract was given orally to mice and rats for up to 105 weeks. The NTP found an increase in liver cancer in male and female mice, and in cancer of the thyroid gland in male and female rats and male mice.
Written and oral comments from the American Herbal Products Association and from Intertek Cantox were presented to the panel. The comments largely focused on the Ginkgo biloba extract used in the NTP studies, claiming that it was not representative of ginkgo products in the U.S.
With citations in hand, Rider said, “The range of constituents in the ginkgo extract used in our NTP studies is within the ranges found in the U.S. market.” After a brief discussion around this topic, Birnbaum commented on the importance of putting human-use doses into context for people, so they can better understand, appreciate, and use the NTP findings.
NTP pathologist Mark Hoenerhoff, D.V.M, Ph.D., also added to the discussion by presenting molecular work conducted by NTP on ginkgo, which begins to unravel the underlying mechanisms for the tumors in the rodent studies. “We really applaud this extra effort by the NTP. It is very helpful in interpreting the data,” said Paul Howard, Ph.D., of the National Center for Toxicological Research (NCTR) at the U.S. Food and Drug Administration. Hoenerhoff’s findings are being submitted to a peer-reviewed journal.
Remaining technical reports approved
After hearing the study overview and conclusions put forward by NTP study scientist Michael Wyde, Ph.D., on beta-picoline, a solvent used to make pharmaceuticals, resins, dyes, rubber accelerators, and insecticides, the panel voted to accept the NTP conclusions as written.
The reviewers also heard presentations on two dermal studies that were conducted by NTP. The panel approved of the studies and conclusions presented by NTP’s Minerva Mercado-Feliciano, Ph.D., on pyrogallol, a byproduct of plant tannins used to make consumer products, such as some hair dyes and photography developers. After hearing the discussion on trimethylolpropane triacrylate from NTP’s In Ok Surh, Ph.D., and a few public comments, the panel recommended minor revisions to the NTP conclusions on this industrial compound. The NTP will consider the input from the panel in finalizing the technical reports.
On the second day of the meeting, the panel also approved the two final reports on AIDS therapeutics. After a brief introduction from Howard, Julian Leakey, Ph.D., also of NCTR, thoughtfully walked the panel through the details of the two reports on 3′-azido-3′-deoxythymidine (AZT) and its combined mixtures with lamivudine or nevirapine. AZT is widely used worldwide, as part of combination drug therapy, to stop mother-to-child transmission of HIV. However, the long-term or lifetime consequences of perinatal exposure to these therapies are unknown. The studies were conducted in genetically modified mice.
(Robin Mackar is the news director in the NIEHS Office of Communications and Public Liaison.)