Friday, December 19, 2008

Speculating on Mode of Action for Styrene Carcinogenicity - Is Houdini in the Wings?

BrooklynDodger(s) comment: Styrene is one of those old, huge-use carcinogens which has gotten lost in the regulatory forest. Styrene is used in open-to-the-workroom air processes making fiberglass reinforced articles like boats and bathtubs. It's sprayed. The OSHA PEL is 100 ppm, and is not on very many lists for an update from 1968. The TLV is 20 ppm, obviously better but not set based on a disciplined process. The EPA reference concentration is 1 mg/m^3 (not ppm) based on CNS effects, set in 1993.

The classification of styrene as a 2A carcinogen in 2002 is explained in an IARC monograph, now available in full text.

What's up with styrene in the risk assessment "community" is the mouse Clara cell hypothesis. Clara cells (the Dodger(s) think) are the lung's version of the Kuppfer cell - a resident phagocytic cell in the parenchema of the tissue. [It's more complicated than this.]

Several lower molecular weight vapors cause lung tumors in mice, but not rats. Of these, several cause liver tumors in both species. So one approach to making the risk estimate lower is to parallogramate mouse, rat and human clara cell properties. This study finds increased levels of a protein the Dodger(s) never heard of before, and messinger RNA for that protein (a technique unknown in the Dodger(s) youth), following a single dose. We can expect a similar study in rats, and then an argument that for styrene, people are rats, not mice. So don't worry, be happy.

[Remember, this ain't the NAS, it's just blogging. The Dodger(s) disclaimer on being wrong and flippant.]

Toxicology Letters Volume 183, Issues 1-3, 15 December 2008, Pages 28-35

CC10 mRNA and protein expression in Clara cells of CD-1 mice following exposure to styrene or its metabolites styrene oxide or 4-vinylphenol

Jill A. Harvilchucka, Rebekah J. Zurbrugga and Gary P. Carlson, a,
aSchool of Health Sciences, Purdue University, 550 Stadium Mall Drive, West Lafayette, IN 47907-2051, United States

"Styrene, widely used in manufacturing, has both acute and chronic effects in humans. In mice, styrene is both hepato- and pneumo-toxic and causes lung tumors. The primary site for styrene metabolism and its effects in mouse lung is the Clara cell, ...The mode of action for styrene-induced lung tumor formation has yet to be elicited, yet one possibility relates to oxidative stress ...

[single dose intraperitoneal injection]...

[lots of changes in biochemical markers] ...

These studies demonstrate that acute changes in lung CC10 protein and mRNA expression do occur following in vivo treatment with styrene and its metabolites. These changes may be early indicators for a potential mechanism for lung tumor formation in mice as it relates to oxidative stress and the possibility deserves further study.

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