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.
OBJECTIVE: To assess the safety and health-related quality of life (HRQOL) of continuous combined hormone replacement therapy (ccHRT) with estradiol valerate/medroxyprogesterone acetate (E(2)V/MPA) over nine years and at follow-up one year after discontinuation. Study design: A total of 419 women were randomized to one of four treatments: once-daily 1 mg E2V/2.5 mg MPA (1 + 2.5 group); 1 mg E2V/5 mg MPA daily (1 + 5 group); 2 mg E2V/2.5 mg MPA daily (2 + 2.5 group); 2 mg E2V/5 mg MPA daily (2 + 5 group) (Indivina, Orion Pharma). For the last six months, all received the 1 + 2.5 dosage. The 2 + 2.5 dosage was discontinued at the end of year 7. A total of 198 women continued after year 7. RESULTS: Annualized percentage rates for cardiovascular events [corrected] and endometrial cancers [corrected] were below national rates for Finland and those reported for the Women's Health Initiative. There were no serious events with the 1 + 2.5 dosage or after ccHRT discontinuation. Climacteric symptoms remained significantly below baseline values after dosage reduction; some symptoms recurred after discontinuation of ccHRT. HRQOL ratings improved with ccHRT, irrespective of dosage, including depressed mood, anxiety, health perception and sexual interest. Scores on a scale assessing daily functioning and enjoyment (Q-LES-Q) improved from year 7 to year 9. They deteriorated during follow-up in women not continuing ccHRT. CONCLUSIONS: Lower dosages of HRT were as effective as higher doses in improving climacteric symptoms and HRQOL ratings and had fewer safety concerns. Following discontinuation of ccHRT, patient satisfaction was variable, with 15% electing to continue or restart HRT and 7% resuming at follow-up. This supports the need for an individualized approach to therapy recommendations.
A consistent methodology for assessing the accumulating effects of natural and manmade change on riverine systems has not been developed for a whole host of reasons including a lack of data, disagreement over core elements to consider, and complexity. Accumulated state assessments of aquatic systems is an integral component of watershed cumulative effects assessment. The Yukon River is the largest free flowing river in the world and is the fourth largest drainage basin in North America, draining 855,000 km(2) in Canada and the United States. Because of its remote location, it is considered pristine but little is known about its cumulative state. This review identified 7 "hot spot" areas in the Yukon River Basin including Lake Laberge, Yukon River at Dawson City, the Charley and Yukon River confluence, Porcupine and Yukon River confluence, Yukon River at the Dalton Highway Bridge, Tolovana River near Tolovana, and Tanana River at Fairbanks. Climate change, natural stressors, and anthropogenic stresses have resulted in accumulating changes including measurable levels of contaminants in surface waters and fish tissues, fish and human disease, changes in surface hydrology, as well as shifts in biogeochemical loads. This article is the first integrated accumulated state assessment for the Yukon River basin based on a literature review. It is the first part of a 2-part series. The second article (Dubé et al. 2013a, this issue) is a quantitative accumulated state assessment of the Yukon River Basin where hot spots and hot moments are assessed outside of a "normal" range of variability.
More than one-third of the calories consumed by U.S. and European populations contain acrylamide, a substance classified as a "probable human carcinogen" based on laboratory data. Thus, it is a public health concern to evaluate whether intake of acrylamide at levels found in the food supply is an important cancer risk factor. Mean dietary intake of acrylamide in adults averages 0.5 microg/kg of body weight per day, whereas intake is higher among children. Several epidemiological studies examining the relationship between dietary intake of acrylamide and cancers of the colon, rectum, kidney, bladder, and breast have been undertaken. These studies found no association between intake of specific foods containing acrylamide and risk of these cancers. Moreover, there was no relationship between estimated acrylamide intake in the diet and cancer risk. Results of this research are compared with other epidemiological studies, and the findings are examined in the context of data from animal models. The importance of epidemiological studies to establish the public health risk associated with acrylamide in food is discussed, as are the limitations and future directions of such studies.
Surveillance & Risk Assessment, Centre for Chronic Disease Prevention and Control, Population and Public Health Branch, Health Canada, Tunney's Pasture AL0601C1, Ottawa, Ontario K1A 0L2, Canada. Yang_Mao@hc-sc.gc.ca
This study assessed the influence of active and passive smoking on the risk of stomach cancer by subsite. Mailed questionnaires were used to obtain information on 1171 newly diagnosed histologically confirmed stomach cancer cases and 2207 population controls between 1994 and 1997 in eight Canadian provinces. Data were collected on socio-economic status, lifestyle and passive smoking status. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived by logistic regression. Compared with those who had never smoked, there was strongly increased risk for ex- and current smokers among subjects with cardial stomach cancer. For men with cardial cancer, the adjusted ORs were 1.9 (95% CI 1.2-3.0) and 2.6 (95% CI 1.6-4.3) for ex-smokers and current smokers, respectively, with a similar pattern among women. Among men, the adjusted ORs were lower for subsites of stomach cancer other than cardia. These findings suggest that active and passive smoking may play an important role in the development of cardial stomach cancer.
There have been relatively few epidemiological studies to verify the information obtained from study participants on the use of menopausal hormone replacement therapy. We conducted this study as part of a case-control study of diet, hormone use, and endometrial cancer in Toronto, Ontario, Canada, 1994-1998. We compared records from 653 subjects, 30-79 years of age, with reports from their physicians on ever/never use of hormone replacement therapy and duration, type, and dose of hormone replacement therapy. A total of 88% of the interview records were in agreement with physician reports for ever/never use of hormone replacement therapy. The overall kappa value for ever/never use agreement was 0.76 (range = 0.71-0.81), and the intraclass correlation coefficient was 0.64 (range = 0.57-0.70) for duration of hormone replacement therapy use, indicating good agreement; similar correlations were seen among cases and controls for overall use, as well as estrogen- or progestogen-alone use. Concordance for brand codes was observed for about 43% of the subjects. This study suggests that information obtained by interview in case-control studies provides a reasonable measure of ever use of hormone replacement therapy and duration of use. Interviews, however, do not represent a reliable source of information on brands and dosage of hormone replacement therapy preparations.
A population-based case-control study of soft-tissue sarcoma (STS), Hodgkin's disease (HD), and non-Hodgkin's lymphoma (NHL) in Kansas found farm herbicide use to be associated with NHL (odds ratio [OR], 1.6; 95% confidence interval [CI], 0.9, 2.6). Relative risk of NHL increased significantly with number of days of herbicide exposure per year and latency. Men exposed to herbicides more than 20 days per year had a sixfold increased risk of NHL (OR, 6.0; 95% CI, 1.9, 19.5) relative to nonfarmers. Frequent users who mixed or applied the herbicides themselves had an OR of 8.0 (95% CI, 2.3, 27.9) for NHL. Excesses were associated with use of phenoxyacetic acid herbicides, specifically 2,4-dichlorophenoxyacetic acid. Neither STS nor HD was associated with pesticide exposure. This study confirms the reports from Sweden and several US states that NHL is associated with farm herbicide use, especially phenoxyacetic acids. It does not confirm the case-control studies or the cohort studies of pesticide manufacturers and Vietnam veterans linking herbicides to STS or HD.
In the Pacific Basin, the hepatitis B virus is closely associated with hepatocellular carcinoma in its geographic distribution and familial clustering, and its presence in liver tissues. The contribution of aflatoxin to the development of hepatocellular carcinoma in different regions varies from negligible to probably major. Neither the hepatitis B virus nor aflatoxin can account for the varied epidemiology of hepatocarcinogenesis in the Pacific Basin. Many potential carcinogens for the liver have been identified in food, drugs, industrial chemicals, and in the general environment, but their importance in hepatocarcinogenesis remains to be defined.
Coumarin derivatives and anticonvulsants administered during pregnancy enter the fetal circulation, interfering with the action of vitamin K. Vitamin K plays a crucial part in the gamma-carboxylation of glutamic acid residues of the vitamin K-dependent coagulation factors prothrombin, FVII, FIX, and FX. Other vitamin K-dependent proteins in the coagulation cascade are protein C and protein S. Vitamin K-dependent bone proteins are osteocalcin and gamma-carboxyglutamate matrix protein. Administration of coumarol derivatives results in under carboxylation of the vitamin K-dependent proteins. Anticoagulation therapy with warfarin is followed by an increased risk of embryopathy, which has been shown to be greatest between gestational weeks 6 and 12. Administration of warfarin is also followed by an increased risk both of fetal intraventricular hemorrhage, and of cerebral microbleedings, which may result in microencephaly and mental retardation. Treatment with coumarol derivatives should therefore be avoided during pregnancy, even in pregnant women with artificial heart valves, and replaced by heparin. Hemorrhage in the newborn related to the use of anticonvulsant drugs during pregnancy occurs very early within the first 24 hours, probably due to increased degradation of vitamin K. Transplacental administration of vitamin K has been shown to prevent neonatal hemorrhage induced by maternal anticonvulsant therapy. Prophylactic administration of vitamin K, especially by intramuscular injection, has been reported to be associated with an increased risk of childhood cancer. However, subsequent extensive studies have yielded no evidence of any relationship between prophylactic vitamin K administration and the occurrence of childhood cancer.