SIRC is the primary group spearheading the new work with modified mice, notes Cruzan. “We worked with a researcher at New York-based University of Albany to genetically modify a mouse in which the CYP2F2 gene was made inactive, so that the enzyme is not produced,” Cruzan explains. These genetically modified mice are now more like humans, since they lack the mouse-specific enzyme. “We found that when those modified mice are exposed to styrene, there is no toxicity – it completely eliminates the lung toxicity. We are quite certain that the CYP2F2 is causing the toxicity, so we are pursing that now.”
Pathology slides of mouse lungs under high magnification are quite remarkable. “Lung sections from the normal, unmodified mice are full of abnormal growth following styrene exposure,” says Cruzan. “But the lungs of the genetically modified mice look completely normal following styrene exposure. Not like it’s a 50 percent reduction; it’s a 100 percent reduction in toxicity. So it’s pretty exciting for scientists,” he adds.
According to ACMA’s Schweitzer, the preliminary data from that study supports the hypothesis that styrene-induced mouse lung tumors are a species-specific effect and do not indicate a potential risk to humans. He notes that the research currently underway involves adding a different gene that will cause mice to metabolize styrene like humans. He points to the latest findings in support of the ACMA’s position that the government does not have a sound basis to proceed with a cancer listing for styrene.
“The preponderance of styrene-exposure data supports a conclusion of no concern. That was the recent decision in a European Union risk assessment report on styrene which looked at all the data and concluded that there is no evidence for a causal link between cancer and exposure to styrene,” Schweitzer reports. He adds that under the EU REACH program, no further risk management activity is required relating to carcinogenicity.
Schweitzer met with Kathleen Sebelius, Secretary of the U.S. Department of Health & Human Services, in December. “The NTP’s proposal to list styrene as a reasonably anticipated carcinogen had just arrived on her desk for her review and approval,” recounts Schweitzer. He was there to make the ACMA’s case against the proposal. He maintained that NTP styrene reviews and listings should be based on a full consideration of all the available science.
“Secretary Sebelius said that she would look into it carefully. I think that they understand the scientific issues and the impact on jobs that this would have, so they are proceeding carefully,” Schweitzer says. “Apart from immediate OSHA labeling requirements, the listing would have only limited direct regulatory consequences, but it may lead to increased regulatory or legal burdens at the state and local level,” he adds. “More importantly, the listing is likely to result in widespread, unnecessary concern among composites industry workers and plant neighbors. We hope that can be avoided.”