Does Styrene Pose a Lung Cancer Risk in Occupational Settings?

Styrene occupational exposures originate from manufacture of styrene-based products, and substantially lower-level general population exposures are secondary to residual emissions from a broad-spectrum of styrene-based consumer wares. Importantly, reports of styrene-induced mouse lung cancer raise the obvious question of whether such human exposures present lung cancer risks of concern.

In their publication, "Styrene lung cancer risk assessment: an alternative evaluation of human lung cancer risk assuming mouse lung tumors are potentially human relevant and operating by a threshold-based non-genotoxic mode of action," Exponent authors James Bus and Steave Su, along with co-authors, conduct a cancer risk assessment by performing benchmark dose (BMD) modeling of mouse lung tumor dose response data to derive occupational and general population inhalation reference concentrations (RfCs) generally protective of lung cancer concerns. The RfC-based approach was implemented as a conservative risk assessment alternative to comprehensive mode of action analyses that had previously indicated styrene mouse lung tumors were more likely not qualitatively relevant to human cancer risks.

Styrene uses include polystyrene in building construction and food packaging applications; styrene-butadiene synthetic rubber (SBR) for tires and automotive parts; unsaturated polyester resins for boat and tub/shower stall manufacture; styrene-butadiene latexes in carpet backings and paper coatings; and styrene-butadiene-acrylonitrile or styrene-acrylonitrile plastics in household appliances, housewares and battery casings as well as various additive manufacturing processes including 3-D printers, binder jetting machines and directed energy deposition.

Using an overall weight-of-evidence (WoE) examination of styrene-initiated genotoxicity and mode of action information, the authors found that styrene and its primary rodent and human metabolite styrene oxide (SO) appear unlikely to be genotoxic in vivo. These key conclusions justified use of threshold-based RfC risk assessments as plausible alternatives to evaluate human carcinogenicity risk.

The integrated data analyses lead the authors to conclude that, even if mouse lung tumors are conservatively considered as human relevant, "typical occupational and general population exposures are a low-priority concern for human lung risk. This conclusion is consistent with an [included] updated analysis of lung cancer risk in workers who produce styrene products that did not support an association between styrene and lung cancer occurrence."

From the publication: "The overall objectives and rationale of this review are to conduct an alternative and conservative cancer risk assessment by deriving occupational and general population inhalation reference concentrations (RfCs) by assuming that styrene-induced mouse lung tumors are potentially human relevant but are attributable to a non-genotoxic (threshold) MOA."