Identification of Research Needs to Resolve the Carcinogenicity of High-priority IARC Carcinogens. Views and Expert Opinions of an IARC/NORA Expert Group Meeting, Lyon, France, 30 June - 2 July 2009. IARC Technical Publication No. 42. Lyon, France: International Agency for Research on Cancer, 2010 Jul; 42:79-86
The animal data consist of oral, inhalation and subcutaneous studies in three strains of rats and two strains of mice. Propylene oxide caused tumors at or near the site of administration in rodents, causing nasal tumors after inhalation exposure (NTP, 1985). One of the major limitations in cancer epidemiological studies is that records of exposure are often incomplete or lacking (Kolman et al., 2002). Measuring hemoglobin adducts, an extremely sensitive effect biomarker, which does not undergo repair as DNA-adducts, may overcome this problem. In addition, low background level of OHPrVal shows that contributions from non-occupational sources are minor. The levels of OHPrVal of the smokers were similar to those of the nonsmokers, indicating that tobacco smoking is not the major contributing factor to the found background levels. Therefore, a future prospective study exploring cytogenetic effect would be feasible even though PO exposures are low because: 1) the great difference in means between exposed and controls seen in the pilot study will require few participants in the two groups (exposed and unexposed workers) and 2) the OHPrVal is a sensitive and specific biomarker to PO exposures (even detected in controls with unknown exposures). The OHPrVal adduct represents cumulative exposures over a 3-month time period. The number of workers recruited to such a study would only be about 11 assuming equal variances in the two groups; however, other possible confounders should be included in the study such as gender, age, ethnicity, years of education, smoking, and possibly polymorphisms in the GST metabolizing pathway of PO. In addition, loss of follow-up and errors in power calculations would benefit from a larger study (~ 100 exposed and 100 controls in a balanced design). Various exposure-selective cross sectional epidemiological studies that look at OHPrVal adducts and cytogenetic effects would be useful. Possible sources of future cohorts for such a study might be the already established cohorts in PO manufacturing workers (USA) (Olsen et al., 1997), which did not show an increased mortality rate due to cancer by duration with or without latency or cancer risk by process (PO versus EO); or the manufacturing cohorts in France and the Netherlands (Jones et al., 2005), and China (Czene et al., 2008). PO production is being expanded, and workers at these new PO manufacturing sites should be recruited for a future study. Other possible cohorts for propylene oxide biomarker epidemiological studies are: processing workers where PO is used as a starting material in polyurethane polyols (NTP 11th RoC), surfactants for textiles (Schettgen et al., 2002) and glycol/glycol ether manufacturing (Boogaard et al., 1999), and manufacturing of polyethylene (PE), which metabolizes to PO. Women should be included in the study as PO might be mammary carcinogen (Rudel et al., 2007). Workers' exposures to PO in paint and automotive fluids have not been adequately characterized. If these workers have exposures to PO then these could potentially be included in a future biomarker epidemiological study. Therefore recruiting sufficient workers to a future prospective study should be feasible.
Identification of Research Needs to Resolve the Carcinogenicity of High-priority IARC Carcinogens. Views and Expert Opinions of an IARC/NORA Expert Group Meeting, Lyon, France, 30 June - 2 July 2009, IARC Technical Publication No. 42