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Environmental Factor

Environmental Factor

Your Online Source for NIEHS News

August 2017

Experts concur with three draft NTP reports

An NTP scientific panel reviewed and accepted draft technical reports on the carcinogenicity and toxicity of three substances.

An expert scientific panel reviewed new National Toxicology Program (NTP) draft technical reports on the carcinogenicity and toxicity of three substances — a chemical used to flavor microwave popcorn and other foods, an industrial solvent, and dietary zinc. Russell Cattley, V.M.D., Ph.D., from Auburn University chaired the July 13 peer review session.

Based on their assessments of the draft reports and the meeting presentations by NTP study scientists, the panelists voted to accept NTP's conclusions for all three draft reports as written.


The compound that gives butter its characteristic flavor, 2,3-butanedione, is naturally present in butter, coffee beans, honey, and some fruits, according to Daniel Morgan, Ph.D., the project’s lead scientist at NTP. However, he and others are mainly concerned about its occupational exposure.

"The potential toxicity of 2,3-butanedione was first reported in a cluster of workers in a microwave popcorn packaging plant that were diagnosed with an unusual lung disease called bronchiolitis obliterans," Morgan said.

The National Institute for Occupational Safety and Health found a strong correlation between exposure to butter flavor vapors and occurrence of bronchiolitis obliterans, a rare, irreversible and progressive disease characterized by tissue scarring that blocks airways.

Rodent studies with 2,3-butanedione showed some evidence of carcinogenic activity, along with non-neoplastic lesions of the nose, larynx, trachea, lung, and eyes of rats and mice. The scientists did not observe bronchiolitis obliterans, but as panel member Noel Dybdal, D.V.M., Ph.D., from Genentech, noted, there was clear respiratory tract damage.

"I think there is a smoking gun in this data that supports that this compound could well be problematic for the workers," Dybdal said.


p-Chloro-alpha,alpha,alpha-trifluorotoluene (PCTFT) is a solvent used to make paints, coatings for automobiles, and other chemicals. Because PCTFT does not deplete the ozone layer and is compliant with the Clean Air Act, more companies may be including it in their production methods.

NTP conducted 3-month and 2-year PCTFT rodent inhalation studies to determine if the chemical had any health effects. NTP researchers found clear evidence of carcinogenic activity in male and female mice, as well as increases in non-neoplastic lesions, or noncancerous tissue alterations.

Dietary zinc

Zinc is an essential trace element with several critical biological functions. Responding to two different nominations, NTP studied the effects of both zinc deficiency and excess zinc in the diet.

Zinc's popularity as a dietary supplement has meant that many people consume excess zinc, which may interfere with absorption of other important metals, such as copper and iron. Nevertheless, epidemiologic data have shown that zinc intake for Americans is below the estimated threshold for good health. The research suggests men older than 18 years and women older than 14 years need more zinc in their diets.

The only evidence of carcinogenesis in the draft report was equivocal evidence in zinc-deficient diets in rats. Non-neoplastic lesions were seen in rats with both excess and deficient diets. Genotoxicity tests also revealed some DNA damage in male and female rats.

Study design was critical, particularly the strict oversight of zinc exposure levels in the laboratory, where zinc hardware coatings are common. "I was impressed with the efforts that were made to manage the environmental zinc exposure issues," said Dybdal.

NTP staff will now incorporate the panel's suggestions into final versions of the technical reports.

(Ernie Hood is a contract writer for the NIEHS Office of Communications and Public Liaison.)

Chad Blystone, Ph.D. NTP toxicologist Chad Blystone, Ph.D., briefed the panelists on the format of the meeting. (Photo courtesy of Steve McCaw)
Michael Conner, D.V.M. Michael Conner, D.V.M., from Global Blood Therapeutics, Inc., pointed out that there is a substantial body of literature about zinc deficiency in animals. (Photo courtesy of Steve McCaw)
Noel Dybdal Dybdal said she was concerned that the rodent model may not be appropriate for looking at bronchiolitis obliterans. (Photo courtesy of Steve McCaw)
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