Previous research updated the mortality experience of North American synthetic rubber industry workers during the period 1944-1998, determined if leukemia and other cancers were associated with several employment factors and carried out Poisson regression analysis to examine exposure-response associations between estimated exposure to 1,3-butadiene (BD) or other chemicals and cancer. The present study used Cox regression procedures to examine further the exposure-response relationship between several unlagged and lagged, continuous, time-dependent BD exposure indices (BD parts per million (ppm)-years, the total number of exposures to BD concentrations >100 ppm ("peaks") and average intensity of BD) and leukemia, lymphoid neoplasms and myeloid neoplasms. All three BD exposure indices were associated positively with leukemia. Using continuous, untransformed BD ppm-years the regression coefficient (beta) from an analysis that controlled only for age was 2.9 x 10(-4) (p
1,3-Butadiene has been assessed as a Priority Substance under the Canadian Environmental Protection Act. The general population in Canada is exposed to 1,3-butadiene primarily through ambient air. Inhaled 1,3-butadiene is carcinogenic in both mice and rats, inducing tumors at multiple sites at all concentrations tested in all identified studies. In addition, 1,3-butadiene is genotoxic in both somatic and germ cells of rodents. It also induces adverse effects in the reproductive organs of female mice at relatively low concentrations. The greater sensitivity in mice than in rats to induction of these effects by 1,3-butadiene is likely related to species differences in metabolism to active epoxide metabolites. Exposure to 1,3-butadiene in the occupational environment has been associated with the induction of leukemia; there is also some limited evidence that 1,3-butadiene is genotoxic in exposed workers. Therefore, in view of the weight of evidence of available epidemiological and toxicological data, 1,3-butadiene is considered highly likely to be carcinogenic, and likely to be genotoxic, in humans. Estimates of the potency of butadiene to induce cancer have been derived on the basis of both epidemiological investigation and bioassays in mice and rats. Potencies to induce ovarian effects have been estimated on the basis of studies in mice. Uncertainties have been delineated, and, while there are clear species differences in metabolism, estimates of potency to induce effects are considered justifiably conservative in view of the likely variability in metabolism across the population related to genetic polymorphism for enzymes for the critical metabolic pathway.
We have studied the role of ATP binding cassette (ABC) transporters in fetal exposure to carcinogens using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) a known substrate for ABC transporters as a model compound. In perfusion of human term placenta, transfer of (14)C-PhIP (2 microM) through the placenta resulted in fetal-to-maternal concentration ratio (FM ratio) of 0.72+/-0.09 at 6 h. The specific ABCG2 inhibitor KO143 increased the transfer of (14)C-PhIP from maternal to fetal circulation (FM ratio 0.90+/-0.08 at 6 h, p
Acrylamide in baked and toasted wheat and rye bread was studied in relation to levels of asparagine in flour, dough, bread and toasts. Asparagine was consumed during bread preparation resulting in reduced acrylamide content in the products. In wheat bread, 12% of the asparagine initially present in the flour (0.14 g kg(-1)) remained after yeast fermentation and baking; for rye bread, 82% of asparagine remained after sourdough fermentation and baking. Asparagine present in untoasted wheat bread had totally reacted after hard toasting. Toasted wheat and rye bread slices contained 11-161 and 27-205 microg kg(-1) acrylamide, respectively, compared to untoasted wheat and rye bread with
Four authoritative reviews of active smoking and breast cancer have been published since 2000, but only one considered data after 2002 and conclusions varied. Three reviews of secondhand smoke (SHS) and breast cancer (2004-2006) each came to different conclusions. With 30 new studies since 2002, further review was deemed desirable. An Expert Panel was convened by four Canadian agencies, the Ontario Tobacco Research Unit, the Public Health Agency of Canada, Physicians for a Smoke-Free Canada and the Canadian Partnership Against Cancer to comprehensively examine the weight of evidence from epidemiological and toxicological studies and understanding of biological mechanisms regarding the relationship between tobacco smoke and breast cancer. This article summarises the panel's full report (http://www.otru.org/pdf/special/expert_panel_tobacco_breast_cancer.pdf). There are 20 known or suspected mammary carcinogens in tobacco smoke, and recognised biological mechanisms that explain how exposure to these carcinogens could lead to breast cancer. Results from the nine cohort studies reporting exposure metrics more detailed than ever/never and ex/current smoker show that early age of smoking commencement, higher pack-years and longer duration of smoking increase breast cancer risk 15% to 40%. Three meta-analyses report 35% to 50% increases in breast cancer risk for long-term smokers with N-acetyltransferase 2 gene (NAT2) slow acetylation genotypes. The active smoking evidence bolsters support for three meta-analyses that each reported about a 65% increase in premenopausal breast cancer risk among never smokers exposed to SHS. The Panel concluded that: 1) the association between active smoking and breast cancer is consistent with causality and 2) the association between SHS and breast cancer among younger, primarily premenopausal women who have never smoked is consistent with causality.