September 8, 2003
Mr. Jerry A. Cook
Chemical Products Corporation
Cartersville, Georgia 30120
Re: Request for Reconsideration submitted March 27, 2003
Dear Mr. Cook:
On behalf of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), I am responding to your March 27, 2002, Request for Reconsideration submitted for the Chemical Products Corporation (CPC) under the NIH's "Guidelines for Ensuring the Quality of Information Disseminated to the Public" (NIH Guidelines). Your Reconsideration Request appealed the NIH's March 19, 2003, decision regarding the CPC's November 15, 2003, Request for Correction contained in the Abstract for Draft National Toxicology Program (NTP) Technical Report # TR-494. A summary of the background information on the study that culminated in draft TR-494, the process I used to consider the appeal, and my conclusions are provided as follows:
Background: The NTP conducted a 2-year carcinogenicity study in rodents on a batch of anthraquinone obtained commercially that was shown to be 99.9% pure; results of this study eventually led to a draft report termed TR-494. Once it was peer reviewed, the abstract of draft TR-494 was posted on the NTP website. On July 25, 2000, you sent a letter to Dr. Kenneth Olden, Director of the NTP, stating that the sample of anthraquinone tested contained a 0.1% contamination by 9-nitroanthracene, a mutagenic compound, and noting that the presence of this contaminant called the study interpretations into question. The NTP followed up on your letter, confirming that a contaminant in the anthraquinone sample at about the 0.1% level was indeed 9-nitroanthracene. The NTP then initiated the process, in September 2000, to assess the metabolism of the parent compound, anthraquinone, in rodents, and to assess the relative mutagenicity in an Ames test of anthraquinone, its two major urinary metabolites, the contaminant 9-nitroanthracene, and two isomers of 9-nitroanthracene. You subsequently filed an Information Quality Request for Correction on November 15, 2002, asking that the abstract be immediately removed from the NTP's website in view of errors or misleading statements in the material presented. On March 19, 2003, NIH sent you a response to your Request for Correction stating that additional information would be incorporated into the NTP web site to clarify the material in the abstract of draft TR-494 and informing you about ongoing follow-up studies of anthraquinone. The NTP amended the abstract of draft TR-494 on April 1, 2003, on its website to include reference to the 9-nitroanthracene contaminant, and the NTP also made mention of ongoing studies to resolve whether or not this contaminant might have affected the 2-year study results. On March 27, 2003, you submitted a Request for Reconsideration to NIH.
Process: In the course of my review, I have reviewed the HHS and NIH Guidelines for Ensuring the Quality of Information Disseminated to the Public, read draft TR-494, and read Chemical Products Corporation's letters and the NTP's responses to those letters. I have consulted with NIH and HHS staff familiar with the Information Quality process. I also have reviewed data and ongoing tests with the staff of NIEHS' Environmental Toxicology Program who were responsible for the NTP studies and draft report. I have been assisted in these efforts by staff from the NIEHS Office of Policy, Planning and Evaluation.
Conclusions: Following the process outlined above and after careful review of the information that I have described, I have reached the following conclusions:
1. The sample of anthraquinone used in the NTP 2-year study was contaminated with 9-nitroanthracene at a level of about 0.1%.
2. The presence of this contaminant raises doubt as to the effect(s) of anthraquinone itself, or its metabolites, and confounds interpretation of the NTP studies referenced in draft TR-494. In addition, in view of imprecise statements in the text presented on the website, this abstract needs to have greater specificity than it presently has.
3. The abstract of draft TR-494 will immediately be removed from the NTP website.
Further studies are underway on the metabolism of anthraquinone in rodents and on the relative mutagenic potency of this compound, its major metabolites, the contaminant 9-nitroanthracene, and two isomers of 9-nitroanthracene. Additional information from this work will eventually be incorporated into a revised abstract and technical report which will be submitted for peer review and subsequent publication.
I appreciate your comments and hope that the actions that I have taken address your concerns.
Samuel H. Wilson, M.D.
cc: Mary Wolfe, Ph.D.
Director, NTP Liaison and Scientific Review Office
Last Revised: April, 2004