Carcinogenicity Research

There is no conclusive evidence indicating that styrene is a human carcinogen.

Human Epidemiology Studies

When evaluated together, the most recent collective cohort mortality studies - involving more than 55,000 workers in styrene-related industries in the United States and Europe over a 45-year period - show that styrene exposure does not cause cancer (or any other disease). The styrene levels to which some workers in the past were exposed were much higher than those encountered by workers today. Since workplace exposures to styrene are as much as 10,000 fold higher than environmental levels, a lack of effect in workers is an indicator that general public exposure to current environmental levels of styrene should not cause adverse health effects.

Prior to 1992, there were eight published epidemiology studies covering a total of 50,000 potentially exposed workers in styrene-related industries. Seven of these studies examined workers in industries that had low styrene exposures and equal or greater exposures to other chemicals. One study of workers in the reinforced plastics industry primarily involved styrene exposures, but was limited by a short follow-up period.

This situation led to a SIRC-sponsored update of a study of nearly 16,000 workers in the American reinforced plastics industry, with the results published in 1994 by Wong et al in Occupational and Environmental Medicine. In providing an average worker follow-up period of over 19 years (adding 12 years to an earlier study of the same cohort), this report provides comprehensive information for a longer latency period. The study found no styrene-related increase in cancer or other long-term diseases, or deaths.

A similar study of 40,000 workers in the European reinforced plastics industry was published by Kogevinas et al in the Scandinavian Journal of Work Environment and Health, also in 1994. It provides an average worker follow-up of 13 years. This study likewise reported no styrene-related increase in cancer or other long-term diseases, or deaths.

Animal Studies

Twelve existing long-term animal studies using styrene or a styrene ß-nitrostyrene mixture were reported in a review by McConnell and Swenberg published by the International Agency for Research on Cancer (IARC) in 1993. Each published study was reviewed and evaluated for adequacy of design and reported data, appropriateness of interpretation, and whether it had been peer-reviewed. The purpose of the review was to determine the weight of evidence for carcinogenic activity in animals, and to judge whether the data are adequate for drawing conclusions about carcinogenic activity. Based on the available data the authors concluded that:

• There was no convincing evidence for carcinogenic action of styrene in animals, even though it has been studied in several species and by several routes of exposure (inhalation, gavage, in drinking water, and by intraperitoneal and subcutaneous injection).
• None of the studies reviewed was well suited for extrapolating potential carcinogenic activity in humans; all had deficiencies in design, conduct, or interpretation. An up-to-date chronic inhalation study was concluded to be necessary in order to evaluate this aspect of hazard assessment.

To address this significant data gap, SIRC, the EPA's Office of Research and Development (ORD) and National Toxicology Program (NTP) discussed and agreed upon the need to clarify the toxicology data on styrene through state-of-the-art chronic animal bioassays. Working in consultation with ORD and NTP on protocols, SIRC sponsored 24-month inhalation studies in both the rat and mouse. Both studies were conducted according to internationally recognized Good Laboratory Practice (GLP) standards, and the agencies were periodically updated on the progress of the studies.

A final report on the rat study was released in 1996. The animals had been exposed to styrene at levels of 50, 200, 500 and 1000 parts per million (ppm). The results showed that styrene is not carcinogenic in rats.

A final report on a two-year mouse study was issued in mid-1998. The mice were exposed at levels of 20, 40, 80, and 160 ppm. As can be anticipated due to the sensitivity of the species, some lung tumor effects were noted. However, malignancy occurred only in the high-dose females, there was no obvious dose response pattern, and tumors were not noted during interim sacrifices at 12 and 18 months.

Given an absence of carcinogenic effect in both human epidemiology and rat chronic study data, SIRC has conducted additional research to better define the nature of the mouse lung effects. Results of this work to date suggest that the effects seen in mice are unique to the species, and are not relevant for extrapolation to potential human effects. Additional information can be found under Styrene Metabolism and Mode of Action.