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.
During the past 15 years there has been an exponential increase in the number of prescriptions for lipid-lowering drugs. Uncertainties remain about the long-term impact of these medications on cancer, which is particularly bothersome given that the duration of these treatments may extend for several decades.
To explore the association between 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and cancer incidence.
Using the administrative health databases of the Régie de l'Assurance-Maladie du Québec we performed a nested case-control study. We selected a cohort of 6721 beneficiaries of the health care plan of Quebec who were free of cancer for at least 1 year at cohort entry, 65 years and older, and treated with lipid-modifying agents. Cohort members were selected between 1988 and 1994 and were followed up for a median period of 2.7 years. From the cohort, 542 cases of first malignant neoplasm were identified, and 5420 controls were randomly selected. Users of HMG-CoA reductase inhibitors were compared with users of bile acid-binding resins as to their risk of cancer. Specific cancer sites were also considered.
Users of HMG-CoA reductase inhibitors were found to be 28% less likely than users of bile acid-binding resins to be diagnosed as having any cancer (rate ratio, 0.72; 95% confidence interval, 0.57-0.92). All specific cancer sites under study were found to be not or inversely associated with the use of HMG-CoA reductase inhibitors.
The results of our study provide some degree of reassurance about the safety of HMG-CoA reductase inhibitors.
Comment In: Arch Intern Med. 2001 Jun 11;161(11):146011386902
Ten cases of angiosarcoma of the liver among vinyl chloride workers from a plant in Shawinigan, Québec, are reported. The author insist mostly on the occupational history of these workers and on the morphologic description of the lesions. A pathogenic hypothesis is submitted.
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.
It has been a matter of controversy whether there is an increased risk of lung cancer among asbestos-exposed workers without radiographic asbestosis. A previous study of lung cancer risk among asbestos-cement workers has been updated with an additional 12 years of follow-up.
Subjects had received radiographic examination at 20 and 25 years from first exposure to asbestos. Radiographs were interpreted by a single National Institute of Safety and Health (NIOSH)-certified B-reader using the 1971 International Labor Office (ILO) Classification of the pneumoconioses as reference standard. Asbestosis was defined as an ILO coding of 1/0 or higher. Standardized Mortality Ratios (SMRs) were calculated using the general population of Ontario as reference.
Among asbestos-cement workers without radiographic asbestosis at 20 years latency the lung cancer SMR was 3.84 (2.24-6.14). Among workers without asbestosis when examined at 25 years latency the SMR was 3.69 (1.59-7.26).
Workers from an Ontario asbestos-cement factory who did not have radiographic asbestosis at 20 or 25 years from first exposure to asbestos continued to have an increased risk of death from lung cancer during an additional 12 years of follow-up.
Comment In: Am J Ind Med. 2011 Jun;54(6):495-6; author reply 497-821328422
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.
Accumulations of polycyclic aromatic hydrocarbons in a snowpack were studied in an industrial urban area with numerous anthropogenic sources of PAHs. Average PAH loadings stored in the snowpack were determined, plotted on a map of the study area, and arenal distribution approximated by isoloading contours. The loading contours exhibited a marked elongation in the direction of prevailing winds. The unit-area deposition rates observed in the study area exceeded the typical rates reported for other urban areas, and were the highest immediately downwind of a steel plant. PAH levels in snowmelt were well below the freshwater aquatic life toxicity criteria, but exceeded both the WHO drinking water standard and the U.S. EPA carcinogenic criteria at the 10(-5) risk level.
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.