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National Toxicology Program

National Toxicology Program

UPDATE NewsletterUPDATE NewsletterMarch 2016

Expert panel agrees with draft NTP reports

By Ernie Hood
Reprinted from Environmental Factor

An expert scientific panel reviewed draft National Toxicology Program (NTP) technical reports on the carcinogenicity and toxicity of the flame retardant antimony trioxide and the metalworking fluid TRIM VX. Jon Mirsalis, Ph.D., from SRI International in Menlo Park, California, chaired the meeting.

NTP conducts mainly rodent studies on agents of public health concern, to identify potential human health hazards. The technical reports describe the methods, results, and NTP conclusions regarding levels of evidence for carcinogenic activity under the specific conditions of each study.

Antimony trioxide

Antimony trioxide is the most commercially significant form of the metal antimony. It is used as a flame retardant in canvas, textiles, paper, and plastics, and as a catalyst in plastics manufacturing. The major source of human exposure is by inhalation during metal ore mining and smelting operations. Antimony trioxide dust and fumes have been shown to cause irritation of the respiratory tract and mucous membranes. It was nominated for NTP study by the Consumer Product Safety Commission and NIEHS, due to substantial human exposure in occupational settings.

NTP conducted two-week and two-year studies in male and female rats and mice. The peer reviewers agreed with the draft NTP conclusion of clear evidence of carcinogenic activity based on lung neoplasms, which are abnormal growths on or in the lung, in both male and female mice, and malignant lymphoma in female mice. There was also some evidence of carcinogenic activity in male and female rats related to lung neoplasms and tumors of the adrenal medulla.

The panel also agreed that skin tumors in male mice were related to exposure. In addition, carcinogenic effects in the lung of female rats and skin of female mice may have been related to exposure.


TRIM VX is a metalworking fluid used as a lubricant and coolant, and for cleaning tools and parts during metal cutting, drilling, milling, and grinding. The National Institute for Occupational Safety and Health nominated such fluids for NTP study because of their high production volume, the large number of occupationally exposed workers, and the lack of carcinogenicity and toxicology data.

Water-soluble metalworking fluids are produced and used more than oil-based compounds. This is the second water-soluble metalworking fluid NTP has evaluated. The first, CIMSTAR 3800, was reviewed in 2014. 

NTP researchers conducted three-month and two-year whole body inhalation studies of TRIM VX in both male and female rats and mice. The peer review panel agreed with the draft NTP conclusion of clear evidence of carcinogenic activity in male and female mice, and equivocal evidence in rats, based on lung neoplasms. Equivocal evidence means there was a marginal increase in neoplasms, which may be related to the chemical exposure.

NTP Associate Director John Bucher, Ph.D., praised the panel’s work, as the meeting came to a close. “We certainly enjoyed the depth and the seriousness with which you took these reviews, and these reports always get much better after the peer review process,” he said.

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

Ron Herbert TRIM VX study pathologist Ron Herbert, D.V.M., Ph.D., explained technical details to the panel members. (Photo courtesy of Steve McCaw)
Madhuri Singal Panel member Madhuri Singal, Ph.D., is a senior product safety advisor at Reckitt Benckiser in Montvale, New Jersey. (Photo courtesy of Steve McCaw)
Gordan Flake Gordon Flake, Ph.D., study pathologist for antimony trioxide, was on hand to answer questions from the peer reviewers. (Photo courtesy of Steve McCaw)
Kent Pinkerton and Michael Pino Panel member Kent Pinkerton, Ph.D., from the University of California, Davis, left, commented, as Michael Pino, D.V.M., Ph.D., veterinary toxicology consultant from Albuquerque, New Mexico, looked on. (Photo courtesy of Steve McCaw)
William Brock Consulting toxicologist William Brock, Ph.D., from Montgomery Village, Maryland, was another panel member who shared his expertise during the proceedings. (Photo courtesy of Steve McCaw)

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Director of Office of Policy, Review, and Outreach and Editor-in-Chief: Mary Wolfe | Managing Editor: Anna Lee Mosley