NTP Peer Reviewers Back Listing of Cumene, 1-Bromopropane in Report on Carcinogens

By Pat Rizzuto  


A peer-review panel convened by the National Toxicology Program unanimously recommended that two widely used industrial chemicals, cumene and 1-bromopropane, be classified as reasonably anticipated human carcinogens.

A panel of nine--epidemiologists, genetic toxicologists, consultants, and other experts--met March 21 and 22 to review the draft summaries, called “monographs,” for cumene (CAS No. 98-82-8) and 1-bromopropane (CAS No. 106-94-5) as well as draft substance profiles.

When completed and approved by the secretary of health and human services, the substance profiles will be published in the congressionally mandated Report on Carcinogens, which lists known and reasonably anticipated human carcinogens. The report is not a regulatory document, although inclusion in the report triggers hazard communication requirements and can lead to state regulations.

Cumene and 1-bromopropane are both produced in high volumes, according to draft monographs that NTP released for comment in January (37 CRR 102, 1/28/13).

Cumene, 1-Bromopropane Components

Cumene, a component of petroleum and a chemical used to make plastics, nylon, and other chemicals, was produced in the United States for industrial and commercial purposes in quantities of 1 billion pounds or more in 2006 and imported in volumes of more than 2 billion pounds in 2011, NTP's draft monograph said.

Cumene's primary use is to make phenol and acetone, which in turn are used to make bisphenol A and other chemicals.

The chemical 1-bromopropane is a brominated hydrocarbon used as a solvent in industrial and commercial applications such as dry cleaning and to degrease electronics, precision optics, and metals.

Since 1998, 1-bromopropane's U.S. production volume has ranged from 1 million pounds to 15.3 million pounds in 2012, NTP scientist Diane Spencer told the panel.

“In recent years, occupational exposures to 1-bromopropane have increased due to new industrial and commercial applications … involving its use as a substitute for ozone-depleting chemicals or suspect carcinogens,” the draft monograph said.

Change in Use Patterns?

Open, dispersive uses of the solvent, which raise particular concern, may have peaked, said Kevin Hanley, a technical adviser serving the committee who works with the National Institute for Occupational Safety and Health.

In 2007, the Environmental Protection Agency proposed to limit certain open uses of the solvent, Hanley said. EPA cited neurological and other concerns about workers.

In 2008, NIOSH said 1-bromopropane may have caused neurotoxic, reproductive, developmental, and other health problems in workers who use or make it. The chemical may, therefore, “represent an unrecognized occupational health risk,” NIOSH said.

The American Conference of Governmental Industrial Hygienists is considering lowering its threshold limit value of 10 parts per million for the chemical, several panel members said.

Hanley said manufacturers are aware of concerns and are trying to reduce worker exposure.

Exposure Said to Exceed Levels Harming Mice

Nevertheless, during a public comment portion of the meeting, Adam Finkel, who teaches at the University of Pennsylvania and formerly served as director of health standards programs for the Occupational Safety and Health Administration, supported the recommendation that 1-bromopropane be classified as a reasonably anticipated human carcinogen.

The tests NTP conducted clearly showed 1-bromopropane caused tumors in laboratory animals, Finkel said.

He said he nominated 1-bromopropane for NTP analysis 14 years ago when he realized its workplace use was increasing.

NTP's peer-review panel found that the rodent tumors may be caused by biological changes that make them relevant to human cancer.

Lung tissue developed neoplasms (abnormal growth) in female mice at exposure levels lower than those some workers experienced, Finkel said.

Evidence Called Unconvincing

The peer reviewers discussed but were not convinced by scientific evidence chemical manufacturers submitted prior to the meeting. The companies argued against either cumene or 1-bromopropane being classified as human carcinogens (37 CRR 308, 3/18/13).

The deliberations by the peer-review panel will be posted on the toxicology program's website in about two weeks, Lori White, NTP's designated federal official said.

NTP's Office of the Report on Carcinogens will then consider the experts' recommendations, prepare the program's response to the peer-review report, post the response on the website, and revise the draft monographs.

NTP's Board of Scientific Counselors must review the revised draft monographs at a public meeting where comments can be submitted.

Following the board's meeting, the office, together with NTP's director, will complete the monograph and a much shorter, substance profile, which will be provided to the program's executive committee for consultation. The HHS secretary makes final listing decisions.

By Pat Rizzuto  

Information about the cumene and 1-bromopropane peer-review meeting, including draft monographs and public comments, is available at http://ntp.niehs.nih.gov/?objectid=98DAF3E2-E316-D8D9-A4F834B80E0EE1C4, where slides from presentations made during the meeting will be posted in early April.