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NTP Makes News with Report on Hexavalent Chromium

By Eddy Ball and Robin Mackar
June 2007

Michelle Hooth
Sodium Dichromate Dihydrate Study Scientist Michelle Hooth (Photo courtesy of Steve McCaw)

Ron Herbert
Sodium Dichromate Dihydrate Study Pathologist Ron Herbert (Photo courtesy of Steve McCaw)

NTP Interim Associate Director Allen Dearry, Ph.D., Subcommittee Chair Nancy Kerkvliet, Ph.D., NIEHS Deputy Director Sam Wilson, M.D., and Chief, Toxicology Operations Branch,
Seated at the head of the Subcommittee table were, left to right, NTP Interim Associate Director Allen Dearry, Ph.D., Subcommittee Chair Nancy Kerkvliet, Ph.D., NIEHS Deputy Director Sam Wilson, M.D., and Chief, Toxicology Operations Branch, John Bucher, Ph.D. (Photo courtesy of Steve McCaw)

Harish Sikka
Principal Reviewer Harish Sikka, Ph.D., of the State University of New York College at Buffalo, was impressed by evidence that sufficient Cr (VI) escaped breakdown in the stomach to cause neoplasms in the small intestines of test animals. (Photo courtesy of Steve McCaw)

Richard Irwin
Following each of their presentations, NTP investigators answered questions from their places at the table. Shown here are Formamide Study Scientist Richard Irwin, Ph.D. (Center), and David Malarkey, D.V.M., Ph.D. Malarkey was filling in for Study Pathologist Susan Elmore, D.V.M. (Photo courtesy of Steve McCaw)

On May 16 and 17, a subcommittee of the Board of Scientific Counselors for the National Toxicology Program (NTP) met in Rodbell Auditorium to provide public peer review of several recently completed NTP study findings and conclusions. At the meeting, the Technical Reports Review Subcommittee approved reports on sodium dichromate dihydrate, which sparked interest in the national press, and six other compounds that have undergone two-year toxicology and carcinogenesis testing in rats and mice.

The report on sodium dichromate dihydrate in drinking water drew nationwide attention because the compound contains hexavalent chromium, which is also known as Cr (VI). USA Today, Bloomberg News and Reuters printed reports about the study after the NIEHS news release was distributed on May 16.

The dangers of Cr (VI) were brought to the public's attention by the $330 million settlement in 1996 of a high-profile lawsuit on behalf of the people of Hinkley, Calif. against the Pacific Gas and Electric Company. The company had stored improperly waste water containing Cr (VI) that leached into ground water used a source of drinking water for the town's residents. In 2000, the film "Erin Brockovich," starring Julia Roberts, made the provocative crusader a household name and further raised public awareness of Cr (VI).

Sodium dichromate dihydrate is an inorganic compound containing Cr (VI) used in various industrial processes including electroplating operations, leather tanning and textile manufacturing. It is one of several compounds containing Cr (VI) that enter drinking water as a result of poor storage or improper disposal practices.

Although Cr (VI) is a known carcinogen when inhaled, there was little known about its effects when ingested orally. In a 1998 report, the Environmental Protection Agency determined that "No data were located in the available literature that suggested that it is carcinogenic by the oral route of exposure."

Eleven members of the California Congressional Delegation sent a letter to the NTP Director requesting that the NTP conduct the studies. Nominations for studying this compound also came from the California Environmental Protection Agency and the California Department of Health Services. The NTP began work on the compound after gaining input from the public and a panel of scientific experts about the study design.

Defenders of the safety of Cr (VI)-containing compounds had pointed to evidence that ingested Cr (VI) is reduced by a number of molecules, including ascorbate, glutathione and cysteine, in the acidic environment of the stomach and converted to Cr (III). Cr (III) is a harmless form of the element and an essential nutrient linked to healthy glucose metabolism. In addition to finding evidence of carcinogenic activity in the oral mucosa, however, the NTP investigators discovered increased incidences of neoplasms of the small intestine, indicating that the compound is not completely reduced in the stomach.

NTP toxicologist Michelle Hooth, Ph.D., was study scientist for the technical report and Ron Herbert, D.V.M., Ph.D., served as study pathologist. "Previous studies have shown that hexavalent chromium causes lung cancer in humans in certain occupational settings as a result of inhalation exposure," Hooth explained. "We now know that it can also cause cancer in animals when administered orally."

The Technical Reports Review Subcommittee voted unanimously to accept the conclusions of the draft NTP Technical Report 546 on sodium dichromate dihydrate with editorial amendment. All of the reports reviewed will now go to the full committee of the NTP Board of Scientific Counselors for approval at its June 22 meeting.

Technical Reports Reviewed

Although Cr (VI) received the most attention, the subcommittee approved with editorial changes Technical Reports on six other compounds that have shown toxicity and carcinogenesis in two-year studies.

  • Formamide (TR 541) - Exposure by gavage, or forced feeding. Formamide was nominated for reproductive and genetic toxicity evaluation by the Environmental Defense Fund and for carcinogenicity evaluation by the National Cancer Institute because of the potential for human exposure associated with its widespread industrial use.
  • Ethinyl Estradiol - Multigenerational Study (TR 547) - Exposure in feed. Ethinyl estradiol is a potent synthetic estrogen widely used in pharmaceutical preparations. It was selected by the NTP for inclusion in studies to examine endocrine disrupting compounds with estrogenic activity.
  • Ethinyl Estradiol - Bioassay (TR 548) - Exposure in feed. Ethinyl estradiol was selected because of potential human developmental exposures resulting from unintentional continuation of the use of oral contraceptives containing ethinyl estradiol during early pregnancy.
  • Cumene (TR 542) - Exposure by inhalation. Cumene occurs naturally in petroleum and in a variety of foodstuffs, as well as by a process utilizing acidic catalysts. Cumene was nominated for study by the NIEHS because of its high production volume, presence in gasoline and other fuels, potential for human exposure and the lack of existing carcinogenicity test data.
  • Cresols (TR 550) - Exposure in feed. Cresols are high volume chemicals used in a wide variety of industrial and consumer products, including cleaners, petroleum additives and synthetic food flavors. They were nominated for study because of the potential for occupational and consumer exposure and the lack of chronic toxicity data.
  • Propargyl Alcohol (TR 552) - Exposure by inhalation. Propargyl alcohol is used in the manufacture of chemicals and pharmaceuticals and in corrosion inhibition and solvent stabilization. It was nominated by the National Cancer Institute for study because of the potential for human exposure in occupational settings.

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