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ACMA/SIRC CA Workshop

ACMA/SIRC CA Workshop. October 28, 2009. Styrene PEL Issues. Cancer – SIRC believes styrene does not cause cancer Reproductive Toxicity – SIRC does not believe styrene is a reproductive toxicant, EU considering OEL based on this.

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ACMA/SIRC CA Workshop

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  1. ACMA/SIRC CA Workshop October 28, 2009

  2. Styrene PEL Issues • Cancer – SIRC believes styrene does not cause cancer • Reproductive Toxicity – SIRC does not believe styrene is a reproductive toxicant, EU considering OEL based on this. • Human Neurotoxicity – These effects occur if exposures are high enough.

  3. Current SIRC Cancer Research • Updating Wong (US RPC) cohort study – add at least 15 years of follow-up. Increase “years-at-risk” from ~350,000 to ~500,000. • Comparable size (years-at-risk) to Kogevinas • Comparable years of follow-up to Ruder (2004) • Work to be done by Dow, $182,000, completed by end of 2010.

  4. Current SIRC Cancer Research • Mouse Lung Tumors • Manuscript published on mode of action, indicates not relevant for humans • Includes EB, naphthalene, divinylbenzene

  5. Current SIRC Cancer Research • Mouse Lung Tumor MOA • MOA proposes styrene metabolized in mouse lung by CYP2F2, leading to different toxic metabolites, and tumors. Much less in rat lung; no effect. Even less in human lung • Developing CYP2F2-KO mice • Confirm no toxicity in absence of 2F2 • Identify toxic metabolites – they should still be toxic in KO mice

  6. Reproductive Issues • SIRC sponsored 2 generation study – reduction in growth at 500 ppm during exposure of F1 offspring; slight reduction in growth of F2 offspring – not directly exposed, very slight (<1 day) retardation in several developmental landmarks. SIRC – effects related to reduced BW in dams. • UK proposes OEL of 4 ppm based on effect.

  7. Neurotoxicity • Vision • Smell • Hearing • Response

  8. Potential Effects on Vision • Color Discrimination • Many studies; some show difference from control population; differences are very small. • Triebig Study – no differences related to styrene exposure • Effects not expected with exposures less than 40 ppm • Visual Contrast Sensitivity • Triebig Study – no differences related to styrene exposure

  9. Smell • Styrene smells • Workers exposed to styrene over several years had decreased sensitivity to styrene odor • Workers exposed to styrene over several years had NO decreased sensitivity to standard odor (essence of rose) • No effect on identification of standard odors

  10. Hearing • A few worker studies report deficit in hearing by audiometry • Mostly high frequency • Animal studies also demonstrate (NOAEL = 400 ppm for 4 weeks) • A couple of studies report effect exacerbated by noise • Noise in “noise only” and “styrene plus noise” groups were not the same

  11. Hearing • Triebig study • Workers exposed for more than 15 years at 30 ppm or greater had reduced hearing at low frequencies by audiometry • Based on Transient Evoked OtoacouticEmssions (TEOAE) – no styrene effect • NOAEL – 30 ppm?

  12. Neurobehavioral • Effect on Symptoms >100 ppm • Effect on Mood >100 ppm • Effect on Memory and Association >100 ppm

  13. Neurobehavioral • Reaction Time • Mutti 1984 – NOAEL 25 ppm (average duration 8 years) • Lindstrom 1992 – No effect at 30 ppm average • Triebig, 1989 –No effect from exposures averaged at 18 ppm (range 3-251) • Cherry, 1980 – NOAEL 92 ppm • Seeber (Triebig), 2009 – No effects up to average of 40 ppm.

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