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Advances in the biological sciences have led to an ongoing paradigm shift in toxicity testing based on expanded application of high-throughput in vitro screening and in silico methods to assess potential health risks of environmental agents. This review examines progress on the vision for toxicity testing elaborated by the US National Research Council (NRC) during the decade that has passed since the 2007 NRC report on Toxicity Testing in the 21st Century (TT21C). Concomitant advances in exposure assessment, including computational approaches and high-throughput exposomics, are also documented. A vision for the next generation of risk science, incorporating risk assessment methodologies suitable for the analysis of new toxicological and exposure data, resulting in human exposure guidelines is described. Case study prototypes indicating how these new approaches to toxicity testing, exposure measurement, and risk assessment are beginning to be applied in practice are presented. Overall, progress on the 20-year transition plan laid out by the US NRC in 2007 has been substantial. Importantly, government agencies within the United States and internationally are beginning to incorporate the new approach methodologies envisaged in the original TT21C vision into regulatory practice. Future perspectives on the continued evolution of toxicity testing to strengthen regulatory risk assessment are provided. [ABSTRACT FROM AUTHOR]

A preface for the February 2007 issue of "Journal of Toxicology and Environmental Health" is presented.

An international colloquium, “Strategies for Clean Air and Health,” was organized by the Network of Environmental Risk Assessment and Management (NERAM) and the AIRNET European Network on Air Pollution and Health to identify directions for air quality policy development and research priorities to improve public health. A conference statement was prepared to provide guidance from the perspective of an international group of scientists, regulators, industries, and interest groups on a path forward to improve the interface between science and clean air policy strategies to protect public health. The statement represents the main findings of two breakout group discussion sessions, supported by perspectives of keynote speakers from North America and Europe on science–policy integration and views of the delegates expressed in plenary discussions. NERAM undertook a carefully considered process to try to ensure that the statement would accurately reflect the conference discussions, including documentation of supporting comments from the proceedings and inviting delegates' comments on two draft versions of the statement. [ABSTRACT FROM AUTHOR]

Because the results of the Harvard Six Cities Study played a critical role in the establishment of the current U.S. ambient air quality objective for fine particles (PM 2.5 ), the U.S. Environmental Protection Agency, industry, and nongovernmental organizations called for an independent reanalysis of this study to validate the original findings reported by Dockery and colleagues in the New England Journal of Medicine (vol. 329, pp. 1753–1759) in 1993. Validation of the original findings was accomplished by a detailed statistical audit and replication of original results. With the exception of occupational exposure to dust (14 discrepancies of 249 questionnaires located for evaluation) and fumes (15/249), date of death (2/250), and cause of death (2/250), the audit identified no discrepancies between the original questionnaires and death certificates in the audit sample and the analytic file used by the original investigators. The data quality audit identified a computer programming problem that had resulted in early censorship in 5 of the 6 cities, which resulted in the loss of approximately 1% of the reported person-years of follow-up; the reanalysis team updated the Six Cities cohort to include the missing person-years of observation, resulting in the addition of 928 person-years of observation and 14 deaths. The reanalysis team was able to reproduce virtually all of the original numerical results, including the 26% increase in all-cause mortality in the most polluted city (Stubenville, OH) as compared to the least polluted city (Portage, WI). The audit and validation of the Harvard Six Cities Study conducted by the reanalysis team generally confirmed the quality of the data and the numerical results reported by the original investigators. The discrepancies noted during the audit were not of epidemiologic importance, and did not substantively alter the original risk estimates associated with particulate air pollution, nor the main conclusions reached by the original investigators. [ABSTRACT FROM AUTHOR]

Following the validation and replication of the Harvard Six Cities Study (Krewski et al., this issue), we conducted a wide range of sensitivity analyses to explore the observed associations between long-term exposure to fine particle or sulfate air pollution and mortality. We examined the impact of alternative risk models on estimates of risk, taking into account covariates not included in the original analyses. These risk models provided a basis for identifying covariates that may confound or modify the association between fine particle or sulfate air pollution and mortality, and for identifying sensitive population subgroups. The possibility of confounding due to occupational exposures was also investigated. Residence histories were coded for the study subjects and were used to examine temporal patterns of exposure and risk. Our sensitivity analyses showed the mortality risk estimates for fine particle and sulfate air pollution to be highly robust against alternative risk models of the Cox proportional hazards family, including models with additional covariates from the original questionnaires not included in the original published analyses. There was limited evidence of departures from the proportional hazards assumption. Flexible exposure-response models provided some evidence of departures from linearity at both low and high sulfate concentrations. Incorporating information on changes over time in cigarette smoking and body mass index had little effect on the association between fine particles and mortality. There was limited evidence of variation in risk with attained age, gender, smoking status, occupational exposure to dust and fumes, marital status, heart or lung diseases, or lung function. However, air pollution risk did appear to decreasing with increasing educational attainment. Extensive adjustment for occupation using aggregate indices of occupational “dirtiness” and occupational exposure to known lung carcinogens had little impact on the mortality risks associated with particulate air pollution. Our evaluation of population mobility indicated that relatively few subjects moved from their original city of residence. Attempts to identify critical exposure time windows were limited by the lack of marked interindividual variation in temporal exposure patterns throughout the study period. Overall, this extensive sensitivity analysis both supported the conclusions reached by the original investigators and demonstrated the robustness of these conclusions to alternative analytic approaches. [ABSTRACT FROM AUTHOR]

The possible association of specific fatty acid (FA) intake and pancreatic cancer risk was investigated in a population-based case-control study of 462 histologically confirmed cases and 4721 frequency-matched controls in eight Canadian provinces between 1994 and 1997. Dietary intake was assessed by means of a self-administered food frequency questionnaire. Unconditional logistic regression was used to assess associations between dietary FAs and pancreatic cancer risk. After adjustment for age, province, body mass index, smoking, educational attainment, fat and total energy intake, statistically significant inverse associations were observed between pancreatic cancer risk and palmitate (odds ratios (ORs)=0.73; 95% confidence intervals (CIs) 0.56-0.96; P-trend=0.02), stearate (OR=0.70; 95% CI 0.51-0.94; P-trend=0.04), oleate (OR=0.75; 95% CI 0.55-1.02; P-trend=0.04), saturated FAs (OR=0.67; 95% CI 0.50-0.91; P-trend=0.01), and monounsaturated FAs (OR=0.72; 95% CI 0.53-0.98; P-trend=0.02), when comparing the highest quartile of intake to the lowest. Significant interactions were detected between body mass index and both saturated and monounsaturated FAs, with a markedly reduced risk associated with intake of stearate (OR=0.36; 95% CI 0.18-0.70; P-trend=0.001), oleate (OR=0.36; 95% CI 0.19-0.72; P-trend=0.002), saturated FAs (OR=0.35; 95% CI 0.18-0.67; P-trend=0.002), and monounsaturated FAs (OR=0.32; 95% CI 0.16-0.63; P-trend<0.0001) among subjects who are obese. The results suggest that substituting polyunsaturated FAs with saturated or monounsaturated FAs may reduce pancreatic cancer risk, independently of total energy intake, particularly among obese subjects. [ABSTRACT FROM AUTHOR]

Deliberations over chemical safety rely heavily upon the interpretation of toxicological and epidemiological evidence. Dose-response modeling plays an important role, allowing true effects to be more effectively discerned from background processes (qualitative determinations) and playing an even more instrumental role in quantitative judgments (e.g., the estimation of potency or acceptable dose). We survey five relatively distinct topic areas (ranging from the assessment of genotoxicity, to epidemiological studies of respirable particles) where dose-response models have been applied, and explore the varying degrees of complexity used in modeling. We choose a descriptive approach, presenting each topic area as a case study. The survey reveals a wide spectrum of complexity both within and between topic areas. The question of 'what level of model detail is appropriate?' is widely debated in various disciplines. Notably, the policy context of dose-response assessment (with its attendant real-world stakes) involves some added considerations. We therefore try to emphasize the role of each modeling application's outcome in affecting a decision process. The case studies provide a first step in identifying issues related to model parsimony that are unique to the dose-response, and policy realm. [ABSTRACT FROM AUTHOR]

Highlights the Benzene-State-of-the Science Workshop on the physiological effects of chronic exposure to benzene. Correlation between leukemia and benzene exposure; Details on the metabolism and pharmacokinetics of benzene; Types of mercapturic acids derived from benzene.

Blood and urine are historically the most frequent matrices used for measuring chemical levels in human biomonitoring studies. As biomonitoring programs are refreshed, consideration of specific priority substances and specific population targets provide opportunities for inclusion of alternative non- or minimally invasive matrices. This review describes methods used in health risk assessment to characterize exposure and risk based upon biomarkers from noninvasive matrices other than urine or blood, including human milk, hair, fingernails, toenails, exhaled breath, deciduous teeth, sweat, semen, meconium, and feces. Illustrative examples of these methods relevant to chemical management are provided. This review suggests that, although these alternative noninvasive biomarkers are not frequently used in human health risk assessment at present, these biomarkers may prove useful in (1) characterizing exposure and health risk in vulnerable populations, (2) cumulative risk assessments, and (3) community-based risk assessments, depending upon the substance of concern. To incorporate alternative noninvasive biomarkers into human health risk assessments with confidence, more research is needed to improve our knowledge of the relationships between external dose, internal dose, and biologic consequent effects in matrices other than blood and urine. [ABSTRACT FROM AUTHOR]

ABSTRACT Tests for trend in tumour response rates with increasing dose in long-term laboratory studies of carcinogenicity that take into account historical control information are discussed. The theoretical basis for these tests is described, and their small-sample properties evaluated using computer simulation. The performance of these tests is also evaluated using data from carcinogenicity experiments conducted under the U.S. National Toxicology Program. Based on these results, recommendations are made as to the most appropriate tests in practice. When the assumptions underlying these tests are satisfied, the use of historical control information is shown to result in an increase in power relative to the classical Cochran-Armitage test that is widely used without historical controls. [ABSTRACT FROM AUTHOR]

An introduction to articles published within the issue is presented, incuding one on a simulation study designed to evaluate the performance of statistical methods for the analysis of time series of longitudinal count data subject to extra-Poisson variation, another on the regression parameters on Poisson regression, and another on the relationship between hospital admissions and air pollution.

The article discusses a study which used a linear-exponential model that has an initial linear component describing mutational effects and an exponentially decreasing model for toxic effects. The downturn at high doses was characterized by introducing a toxicity-curvature parameter. The mutational (IPCS) study showed the variation in the mutagenic potency of complex mixtures as expressed in the assay by B. N. Ames.

An introduction is presented in which the editor discusses various reports within the issue on statistical issues in acid rain.

Objective: Asthma is an important determinant of hospitalization. The study aims to examine the modifying effects of demographic and socioeconomic factors on the relationship between asthma and the overall number of hospitalizations.Methods: We examined the data on 17,601 Canadians who were > or = 12 years of age to explore the combined effects of asthma and other factors on hospitalization within the context of a publicly funded health-care system. Asthma was determined by an affirmative response to the question: "Do you have asthma diagnosed by a health professional?" The subjects also were asked whether they had been an overnight patient in a hospital during the past 12 months.Results: Asthma as a risk factor explained 3.7% of all hospitalizations of men and 2.4% of all hospitalizations of women. Overall, hospitalization was positively associated with female gender, old age, and low household income. The odds ratio for asthma as a risk factor for overall hospitalization (ie, hospitalization for any reason and all causes, not only for asthma) was greater for younger men than for older men, for less-educated women than for well-educated women, and for men with middle or high incomes than for men with low incomes.Conclusions: These results suggest that demographic and socioeconomic factors play a role in the relationship between asthma and the overall number of hospitalizations, with certain population subgroups being at greater risk of hospitalization in relation to asthma. [ABSTRACT FROM AUTHOR]

Highlights the satellite workshop on Hematotoxicity Modeling held on December 15, 1998. Effects of benzene on hematopoietic system; Comparison between the biologically based risk assessment model and the empirical risk assessment model; Role of mutation and cell proliferation on normal stem cells neoplastic transformation.

Objective To compare infant outcomes between mothers with hypertension treated by beta-blockers alone and by methyldopa alone during pregnancy. Design Historical cohort study. Setting Saskatchewan, Canada. Population Women who delivered a singleton birth in Saskatchewan during the periods from 1 January 1980 to 30 June 1987 or from 1 January 1990 to 31 December 2005 (women who delivered between 1 July 1987 and 31 December 1989 were excluded because the information recorded on maternal drug use during pregnancy is incomplete) with a diagnosis of a hypertensive disorder during pregnancy, and who were dispensed only beta-blockers ( n = 416) or only methyldopa ( n = 1000). Methods Occurrences of adverse infant outcomes were compared between women who received beta-blockers only and women who received methyldopa only during pregnancy, first in all eligible women, and then in women with chronic hypertension and in women with gestational hypertension or pre-eclampsia/eclampsia, separately. Multiple logistic regression analyses were performed to adjust for potential confounding. Main outcome measures Small for gestational age ( SGA) < 10th percentile, SGA < 3rd percentile, preterm birth, stillbirth, institutionalisation for respiratory distress syndrome ( RDS), sepsis, seizure during infancy, and infant death. Results Adjusted odds ratios ( aORs) and 95% confidence intervals (95% CIs) for infants born to mothers with chronic hypertension who were dispensed beta-blockers only, as compared with infants born to mothers who were dispensed methyldopa only, during pregnancy were: 1.95 (1.21-3.15), 2.17 (1.06-4.44), and 2.17 (1.09-4.34), respectively, for SGA < 10th percentile, SGA < 3rd percentile, and being institutionalised during infancy. Conclusions For infants born to mothers with chronic hypertension, compared with those treated by methyldopa alone, those treated by beta-blockers appear to be at increased rates of SGA and hospitalisation during infancy. [ABSTRACT FROM AUTHOR]

Objective:To examine prescription Food and Drug Administration (FDA) C, D and X drugs in general obstetric population.Study Design:Historical cohort study.Result:A total of 18 575 women who gave a birth in Saskatchewan between January 1997 and December 2000 were included. Among them, 3604 (19.4%) received FDA C, D or X drugs at least once during pregnancy. The pregnancy exposure rates were 15.8, 5.2 and 3.9%, respectively, for category C, D and X drugs, and were 11.2, 7.3 and 8.2%, respectively, in the first, second and third trimesters. Salbutamol (albuterol), trimethoprim/sulfamethoxazole (co-trimoxazole), ibuprofen, naproxen and oral contraceptives were the most common C, D, X drugs used during pregnancy.Conclusion:About one in every five women uses FDA C, D and X drugs at least once during pregnancy, and the most common prescription drugs in pregnancy are antiasthmatic, antibiotics, nonsteroid anti-inflammation drugs, antianxiety or antidepressants and oral contraceptives.Journal of Perinatology (2008) 28, 324–329; doi:10.1038/jp.2008.6; published online 21 February 2008 [ABSTRACT FROM AUTHOR]

Introduction: The incidence of pancreatic cancer worldwide appears to correlate with increasing age, and it is slightly more common among men and Jewish people. There is evidence that the incidence rate is higher among blacks than among whites. Methods: The published literature was reviewed for preparation of an overview on epidemiology of pancreatic cancer. Results: A possible role of diabetes in the etiology of pancreatic cancer has been suggested by different epidemiological studies. Several investigations indicate that a history of pancreatitis may increase the risk of pancreas cancer, and it appears that people with a history of pernicious anemia or partial gastrectomy for ulcer as well as cholecystectomy may be at higher risk. Individuals with familial adenomatous polyposis (FAP) also have a high risk of developing this cancer. Pancreatic cancer is seen in some breast cancer families with BRCA1 and BRCA2 mutations. Epidemiological studies have confirmed that relatives of individuals with pancreatic cancer have an increased risk of this malignancy. Affected family members of the familial atypical multiple-mole melanoma (FAMMM) as well as those with a positive family history of ataxia-telangiectasia (AT) have much higher risk of developing pancreatic cancer, compared with the general population. A positive association has been reported between pancreatic cancer risk and dietary intake such as fat and oil, meat, and dairy products, as well as with high intake of energy, fried foods, carbohydrates, cholesterol, and salt. The risk is found to decrease with increased consumption of fresh fruits and vegetables, fiber, natural foods, and Vitamin C. Cigarette smoking has shown the strongest positive association with risk of pancreatic cancer. Conclusion: Some diseases and medical conditions such as diabetes, chronic pancreatitis, AP, family aggregation of pancreatic cancer, FAMMM, AT, as well as nutrition and lifestyle factors, like smoking may play important role in the etiology of pancreatic cancer. [Copyright &y& Elsevier]

Purpose: We used Poisson regression methods to examine the relation between temporal changes in the levels of fine particulate air pollution (PM(2.5)) and the risk of mortality among participants of the Harvard Six Cities longitudinal study.Methods: Our analyses were based on 1430 deaths that occurred between 1974 and 1991 in a cohort that accumulated 105,714 person-years of follow-up. For each city, indices of PM(2.5) were derived using daily samples. Individual level data were collected on several risk factors including: smoking, education, body mass index (BMI), and occupational exposure to dusts. Time-dependent indices of PM(2.5) were created across 13 calendar periods (< 1979, 1979, 1980, em leader, 1989, >/= 1990) to explore whether recent or chronic exposures were more important predictors of mortality.Results: The relative risk (RR) of mortality calculated using Poisson regression based on average city-specific exposures that remained constant during follow-up was 1.31 [95% confidence interval (CI) = 1.12-1.52] per 18.6 microg/m(3) of PM(2.5). This result was similar to the risk calculated using the Cox model (RR = 1.26, 95% CI = 1.08-1.46). The RR of mortality was attenuated when the Poisson regression model included a time-dependent estimate of exposure (RR = 1.19, 95% CI = 1.04-1.36). There was little variation in RR across time-dependent indices of PM(2.5).Conclusions: The attenuated risk of mortality that was observed with a time-dependent index of PM(2.5) is due to the combined influence of city-specific variations in mortality rates and decreasing levels of air pollution that occurred during follow-up. The RR of mortality associated with PM(2.5) did not depend on when exposure occurred in relation to death, possibly because of little variation between the time-dependent city-specific exposure indices. [ABSTRACT FROM AUTHOR]

The Scoring and Ranking Assessment Model (SCRAM) was developed to serve as an analytical tool in chemical scoring and ranking of Great Lakes contaminants. The model provides an initial screening evaluation, based on minimal amount of data, of large numbers of chemicals to identify those chemicals that have the greatest potential to cause adverse effects. The SCRAM model is different from most screening systems in that it assesses uncertainty. The SCRAM model was used to score a list of contaminants existing or potentially present in the Great Lakes. Data on environmental fate properties, such as persistence and bioaccumulation potential and toxicity were compiled on selected chemicals. Uncertainty scores were also assigned based on incompleteness of the database. A score was calculated for each chemical and given a relative rank based on its persistence, bioaccumulation, toxicity, and uncertainty. The relative rankings of chemicals can be used as a decision-making tool to determine which chemicals need immediate research or monitoring based on their SCRAM score and the chemical's use and environmental loading. [ABSTRACT FROM AUTHOR]

L'information recueillie sur les unités expérimentales sacrifiées ou sur les causes de décès des unités a décès non provoqué est systématiquement utilisée dans les analyses statistiques sur les expériences cancérogéniques impliquant les tumeurs cachées. Les auteurs décrivent un modèle simple semi-paramétrique qui ne requiert pas cette information. Les morts naturelles d'unités expérimentales ainsi que les sacrifices systématiques d'unités fournissent suffisamment d'information pour s'assurer que les taux de fréquence de tumeurs, qui sont d'intéiêt majeur dans les études de tumeurs cachées, puissent être estimés non paramétriquement. Les avantages de cette approche semi-paramétrique pour l'analyse des expériences de survie/sacrifice sont illustrés en utilisant des données d'une etude sur l'acétate de benzyle menée dans le cadre du programme de toxicologie national des États-Unis. Les résultats obtenus se comparent favorablement avec ceux d'une étude publiée précédemment qui utilise une approche sur l'analyse de données tumorigéniques. [ABSTRACT FROM AUTHOR]

We undertook a re-analysis of the Canadian data from the 13-country case-control Interphone Study (2001-2004), in which researchers evaluated the associations of mobile phone use with the risks of brain, acoustic neuroma, and parotid gland tumors. In the main publication of the multinational Interphone Study, investigators concluded that biases and errors prevented a causal interpretation. We applied a probabilistic multiple-bias model to address possible biases simultaneously, using validation data from billing records and nonparticipant questionnaires as information on recall error and selective participation. In our modeling, we sought to adjust for these sources of uncertainty and to facilitate interpretation. For glioma, when comparing those in the highest quartile of use (>558 lifetime hours) to those who were not regular users, the odds ratio was 2.0 (95% confidence interval: 1.2, 3.4). After adjustment for selection and recall biases, the odds ratio was 2.2 (95% limits: 1.3, 4.1). There was little evidence of an increase in the risk of meningioma, acoustic neuroma, or parotid gland tumors in relation to mobile phone use. Adjustments for selection and recall biases did not materially affect interpretation in our results from Canadian data. [ABSTRACT FROM AUTHOR]

Neurological conditions are among the leading causes of disability in the Canadian population and are associated with a large public health burden. An increase in life expectancy and a declining birth rate has resulted in an aging Canadian population, and the proportion of age-adjusted mortality due to non-communicable diseases has been steadily increasing. These conditions are frequently associated with chronic disability and an increasing burden of care for patients, their families and caregivers. The National Population Health Study of Neurological Conditions (NPHSNC) aims to improve knowledge about neurological conditions and their impacts on individuals, their families, caregivers and health care system. The Systematic Review of Determinants of Neurological Conditions, a specific objective within the NPHSNC, is a compendium of systematic reviews on risk factors affecting onset and progression of the following 14 priority neurological conditions: Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), brain tumours (BT), cerebral palsy (CP), dystonia, epilepsy, Huntington’s disease (HD), hydrocephalus, multiple sclerosis (MS), muscular dystrophies (MD), neurotrauma, Parkinson’s disease (PD), spina bifida (SB), and Tourette’s syndrome (TS). The burden of neurological disease is expected to increase as the population ages, and this trend is presented in greater detail for Alzheimer’s and Parkinson’s disease because the incidence of these two common neurological diseases increases significantly with age over 65 years. This article provides an overview of burden of neurological diseases in Canada to set the stage for the in-depth systematic reviews of the 14 priority neurological conditions presented in subsequent articles in this issue. [ABSTRACT FROM AUTHOR]

The application of a recently developed mathematical model for predicting the spread of chronic wasting disease (CWD) in wild deer was assessed under different scenarios where harvesting is employed in disease management. A process-based mathematical model for CWD transmission in wild deer populations was recently developed and parameterized by Al-arydah et al. (2011) to provide a scientific basis for understanding the factors that affect spread of CWD and evaluate concomitant disease-control strategies. The impact of gender on CWD transmission was shown to have a significant influence on the spread of the disease in the wild. Our model demonstrates a range of harvesting rates in which CWD is controlled and deer populations survive. However, if harvesting rates are too low, the disease remains endemic for decades. Conversely, the Canadian deer population is eradicated if harvesting rates are excessive. Future investigation includes building the model to assess the spread of CWD under different disease-management scenarios. [ABSTRACT FROM AUTHOR]

Introduction : Le syndrome métabolique (SMét) est un ensemble de marqueurs de risques qui semble favoriser l'apparition de maladies chroniques. Nous avons examiné le fardeau lié au SMét au Canada et son association actuelle et projetée avec les maladies chroniques. Méthodologie : Nous avons utilisé les données de l'Enquête canadienne sur les mesures de la santé 2007-2009 pour déterminer la prévalence du SMét chez les adultes canadiens et pour examiner les associations entre divers facteurs sociodémographiques et les principales maladies chroniques. Nous avons estimé l'incidence cumulative projetée du diabète et le risque, en pourcentage, d'événements cardiovasculaires mortels en utilisant l'algorithme DPoRT (Diabètes Population Risk Tool) et l'algorithme de Framingham. Résultats : Après ajustement en fonction de l'âge, nous avons pu déterminer que 14,9 % des adultes canadiens présentaient un SMét. Les taux étaient similaires pour les deux sexes, mais ils étaient plus élevés chez les non-Blancs et chez les personnes présentant un embonpoint ou obèses (p < 0,001 dans les trois cas). L'importance du SMét sur le plan de la santé publique découle du fait qu'il est associé de manière statistiquement significative avec des maladies chroniques, en particulier avec le diabète de type 2 diagnostiqué (11,2 % contre 3,4 %) et non diagnostiqué (6,0 % contre 1,1 %). Létaux estimé d'incidence sur 10 ans associé au diabète et le risque moyen en pourcentage d'événements cardiovasculaires mortels étaient plus élevés chez les personnes atteintes de SMét que chez celles qui ne l'étaient pas (18,0 % contre 7,1 % pour le diabète et 4,1 % contre 0,8 % pour les maladies cardiovasculaires). Conclusion : Le SMét est répandu chez les adultes canadiens, et une forte proportion de personnes souffrant d'un SMét ont également des affections chroniques, diagnostiquées ou non. Les estimations projetées du taux d'incidence de maladies chroniques associées à un SMét sont plus élevées chez les personnes aux prises avec ce syndrome. Par conséquent, le SMét pourrait être un facteur de risque pertinent dans l'apparition de maladies chroniques. [ABSTRACT FROM AUTHOR]

Information regarding the consensus conference by the Alliance of Blood Operators on the creation of a framework that will cover risk-based decision-making for blood safety. Topics that were discussed includes blood transfusion, blood safety, and decision-making on blood safety application. It also mentions that well-being of the recipients of blood should be the center of risk management strategy.

In this report we review the health effects of three short-lived greenhouse pollutants-black carbon, ozone, and sulphates. We undertook new meta-analyses of existing time-series studies and an analysis of a cohort of 352,000 people in 66 US cities during 18 years of follow-up. This cohort study provides estimates of mortality effects from long-term exposure to elemental carbon, an indicator of black carbon mass, and evidence that ozone exerts an independent risk of mortality. Associations among these pollutants make drawing conclusions about their individual health effects difficult at present, but sulphate seems to have the most robust effects in multiple-pollutant models. Generally, the toxicology of the pure compounds and their epidemiology diverge because atmospheric black carbon, ozone, and sulphate are associated and could interact with related toxic species. Although sulphate is a cooling agent, black carbon and ozone could together exert nearly half as much global warming as carbon dioxide. The complexity of these health and climate effects needs to be recognised in mitigation policies. [ABSTRACT FROM AUTHOR]

The public is increasingly concerned about risks associated with food. Food-borne diseases can easily mobilize public concerns and create strong emotional, behavioral, and political reactions with significant negative economic and psychosocial outcomes. This was observed in various countries globally experiencing the presence of prion disease bovine spongiform encephalopathy (BSE). This study highlights case-study material from various countries for key psychosocial impacts such as the public's worry and fear vis-a-vis beef consumption and the loss of confidence and trust in authorities stemming from the occurrence and management of the BSE crisis. These psychosocial impacts and resultant public behavioral responses are presented at a number of levels including individual, family, community, and societal for several European countries, with special emphasis on the UK case study. Given failures to identify the scope of individual concern about prion diseases, and to address these concerns in decision-making processes and risk communication strategies, there remains a need for further systematic research and psychosocial monitoring of the ripple effects of BSE. [ABSTRACT FROM AUTHOR]

A national public survey on public perceptions of prion disease risk in Canada was conducted from October to December 2007. The survey aimed at documenting the public's perceptions of prion diseases, within the broader context of food safety, in establishing parameters of risk acceptability. It also documented the public's perceptions of prion diseases in delineating social values and ethics that can guide Canada's future policies on prion disease risk management. In addition, the survey served to establish baseline data against which to monitor the evolution of the public's views on and understanding of this important risk issue. In total, 1517 Canadians were randomly selected to be representative of the adult population by region, age, and gender, as per the 2001 Census. This study presents descriptive findings from the survey regarding perceived risk, perceived control, uncertainty, sources of information, trust and knowledge, and beliefs pertaining to bovine spongiform encephalopathy (BSE). The survey data reveal that Canadians do not perceive mad cow disease as a salient risk but consider it more of an economic, political, social, and foreign trade issue than a public health one. Canadians are somewhat prepared to pay a premium to have a safer food supply, but not to the same extent that they desire extra measures pertaining to BSE risk management. In the context of increasing accountability in risk management decisions about food safety and population health issues, it is important to understand the way Canadians perceive such matters and identify their information needs and the factors that influence the acceptability of risks and of risk management policies. [ABSTRACT FROM AUTHOR]

An investigation was conducted to identify high-risk industries for histological subtypes of lung cancer based on a large population-based case-control study in British Columbia, Canada. Occupational histories and information on smoking and relevant covariates were collected from 14,755 male incident cancer cases. Industrial risk factors for 2998 lung cancer cases, including histological subtypes were assessed by logistic regression using other cancer cases, excluding smoking-related cancers, as controls. An excess risk of lung cancer was found among workers in mining, metal manufacturing, and electric power systems for all histological-subtypes, and construction, water transport, health services for specific histological subtypes. Industrial associations that are unique to histological subtypes of lung cancer were identified. Future research needs to focus on confirming these histological associations, and identifying the risk from key exposures found within these industries (e.g. medical radiation, electromagnetic fields, and cooking fumes). [ABSTRACT FROM AUTHOR]

Assessing the long-term benefits of marginal improvements in air quality from regulatory intervention is methodologically challenging. In this study, we explore how the relative risks (RRs) of mortality from air pollution exposure change over time and whether patterns in the RRs can be attributed to air quality improvements. We employed two-stage multilevel Cox models to describe the association between air pollution and mortality for 51 cities with data from the American Cancer Society (ACS) cohort ( N = 264,299, deaths = 69,819). New pollution data were computed through models that predict yearly average fine particle (PM2.5) concentrations throughout the follow-up (1982–2000). Average PM2.5 concentrations from 1999 to 2000 and sulfate concentrations from 1980 were also examined. We estimated the RRs of mortality associated with air pollution separately for five time periods (1982–1986, 1987–1990, 1991–1994, 1995–1998, and 1999–2000). Mobility models were implemented with a sub-sample of 100,557 subjects to assist with interpreting the RR estimates. Sulfate RRs exhibit a large decline from the 1980s to the 1990s. In contrast, PM2.5 RRs follow the opposite pattern, with larger RRs later in the 1990s. The reduction in sulfate RR may have resulted from air quality improvements that occurred through the 1980s and 1990s in response to the acid rain control program. PM2.5 concentrations also declined in many places, but toxic mobile sources are now the largest contributors to PM in urban areas. This may account for the heightened RR of mortality associated with PM2.5 in the 1990s. The paper concludes with a three alternative explanations for the temporal pattern of RRs, each emphasizing the uncertainty in ascribing health benefits to air quality improvements. [ABSTRACT FROM AUTHOR]

A recent analysis showed that the excess odds ratio (EOR) for lung cancer due to smoking can be modeled by a function which is linear in total pack-years and exponential in the logarithm of smoking intensity and its square. Below 15-20 cigarettes per day, the EOR/pack-year increased with intensity (direct exposure rate or enhanced potency effect), suggesting greater risk for a total exposure delivered at higher intensity (for a shorter duration) than for an equivalent exposure delivered at lower intensity. Above 20 cigarettes per day, the EOR/pack-year decreased with increasing intensity (inverse exposure rate or reduced potency effect), suggesting greater risk for a total exposure delivered at lower intensity (for a longer duration) than for an equivalent exposure delivered at higher intensity. The authors applied this model to data from 10 case-control studies of cancer, including cancers of the lung, bladder, oral cavity, pancreas, and esophagus. At lower intensities, there was enhanced potency for several cancer sites, but narrow ranges for pack-years increased uncertainty, precluding definitive conclusions. At higher intensities, there was a consistent reduced potency effect across studies. The intensity effects were statistically homogeneous, indicating that after accounting for risk from total pack-years, intensity patterns were comparable across the diverse cancer sites. [ABSTRACT FROM AUTHOR]

Objective:To assess the risk of neonatal mortality and morbidity in vertex-vertex second twins according to mode of delivery and birth weight.Study design:Data from a historical cohort study based on a twin registry in the US (1995-1997) were used. Multivariate logistic regression was used to control for maternal age, race, marital status, cigarette smoking during pregnancy, parity, medical complications, gestational age, and other confounders.Results:A total of 86 041 vertex-vertex second twins were classified into two groups: second twins delivered by cesarean section after cesarean delivery of first twin (C-C) (43.0%), second twins whose co-twins delivered vaginally (V-X) (57.0%). In infants of birth weight 2500 g group, the risks of noncongenital anomaly-related death (adjusted odds ratio (aOR): 4.64, 95% confidence interval (95% CI): 1.90, 13.92), low Apgar score (aOR: 2.39, 95% CI: 1.43, 4.14), and ventilation use (aOR: 1.31, 95% CI: 1.18, 1.47) were higher in the V-X group compared with the C-C group. No asphyxia-related neonatal deaths occurred in C-C group, whereas the incidence of this death was 0.04% in the V-X group.Conclusion:The risks of neonatal mortality and morbidity are increased in vertex-vertex second twins with birth weight 2500 g whose co-twins delivered vaginally compared with second twins delivered by cesarean section after cesarean delivery of first twin.Journal of Perinatology (2006) 26, 3-10. doi:10.1038/sj.jp.7211408; published online 24 November 2005 [ABSTRACT FROM AUTHOR]

Objective:To assess the risk of neonatal mortality and morbidity in vertex–vertex second twins according to mode of delivery and birth weight.Study design:Data from a historical cohort study based on a twin registry in the US (1995–1997) were used. Multivariate logistic regression was used to control for maternal age, race, marital status, cigarette smoking during pregnancy, parity, medical complications, gestational age, and other confounders.Results:A total of 86 041 vertex–vertex second twins were classified into two groups: second twins delivered by cesarean section after cesarean delivery of first twin (C–C) (43.0%), second twins whose co-twins delivered vaginally (V–X) (57.0%). In infants of birth weight 2500 g group, the risks of noncongenital anomaly-related death (adjusted odds ratio (aOR): 4.64, 95% confidence interval (95% CI): 1.90, 13.92), low Apgar score (aOR: 2.39, 95% CI: 1.43, 4.14), and ventilation use (aOR: 1.31, 95% CI: 1.18, 1.47) were higher in the V–X group compared with the C–C group. No asphyxia-related neonatal deaths occurred in C–C group, whereas the incidence of this death was 0.04% in the V–X group.Conclusion:The risks of neonatal mortality and morbidity are increased in vertex–vertex second twins with birth weight 2500 g whose co-twins delivered vaginally compared with second twins delivered by cesarean section after cesarean delivery of first twin.Journal of Perinatology (2006) 26, 3–10. doi:10.1038/sj.jp.7211408; published online 24 November 2005 [ABSTRACT FROM AUTHOR]

Chlorination disinfection by-products (CDBPs) are produced during the treatment of water with chlorine to remove bacterial contamination. CDBPs have been associated with an increased risk of bladder cancer. There is also some evidence that they may increase the risk of pancreatic cancer. We report results from a population-based case-control study of 486 incident cases of pancreatic cancer and 3,596 age- and sex-matched controls. Exposure to chlorination by-products was estimated by linking lifetime residential histories to two different databases containing information on CDBP levels in municipal water supplies. Logistic regression analysis found no evidence of increased pancreatic cancer risk at higher CDBP concentrations (all odds ratios < 1.3). Null findings were also obtained assuming a latency period for pancreatic cancer induction of 3, 8, or 13 years. [ABSTRACT FROM AUTHOR]

Although some consensus has emerged among the scientific and regulatory communities that the urban ambient atmospheric mix of combustion related pollutants is a determinant of population health, the relative toxicity of the chemical and physical components of this complex mixture remains unclear. Daily mortality rates and concurrent data on sizefractionated particulate mass and gaseous pollutants were obtained in eight of Canada's largest cities from 1986 to 1996 inclusive in order to examine the relative toxicity of the components of the mixture of ambient air pollutants to which Canadians are exposed. Positive and statistically significant associations were observed between daily variations in both gas- and particulate-phase pollution and daily fluctuations in mortality rates. The association between air pollution and mortality could not be explained by temporalvariation in either mortality rates or weather factors. Fine particulate mass (less than 2.5 µm in average aerometric diameter) was a stronger predictor of mortality than coarse mass (between 2.5 and 10 µm). Size-fractionated particulate mass explained 28% of the total health effect of the mixture, with the remaining effects accounted for by the gases. Forty-seven elemental concentrations were obtained for the fine and coarse fraction using nondestructive x-ray fluorescence techniques. Sulfate concentrations were obtained by ion chromatography. Sulfate ion, iron, nickel, and zinc from the fine fraction were most strongly associated with mortality. The total effect of these four components was greater than that for fine mass alone, suggesting that the characteristics of the complex chemical mixture in the fine fraction maybe a better predictor of mortality than mass alone. However,the variation in the effects of the constituents of the fine fraction between cities was greater than the variation in the mass effect, implying that there are additional toxic components of fine particulate matter not examined in this study whose concentrations and effects vary between locations. One of these components, carbon, represents half the mass of fine particulate matter. We recommend that measurements of elemental and organiccarbon be undertaken in Canadian urban environments to examine their potential effects on human health. [ABSTRACT FROM AUTHOR]

[Display omitted] • Increasing use of mobile technologies by young people is a topic of public health concern. • MOBI-Kids studied brain tumour risk and wireless phone use (and EMF) in 14 countries. • The study includes 899 brain tumour cases aged 10–24 years old and 1,910 controls. • We have no evidence of a causal association between wireless phone use and brain tumours. • Because of likely biases we cannot rule out a small increased risk. In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20–24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15–19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk. [ABSTRACT FROM AUTHOR]

Biomonitoring equivalents (BEs) have been increasingly applied for biomonitoring purposes by regulatory bodies worldwide. The present report describes the development of a BE for titanium based on a 4-step process: (i) identification of a critical study/point of departure (PoD) supporting an established oral exposure guidance value (OEGV);, (ii) review the available oral PK data and application of a pharmacokinetic model for titanium; (iii) selection of the most appropriate biomarker of exposure in a specific tissue and calculation of steady-state tissue levels corresponding to the PoD in the critical study; and (iv) derivation of BE value adjusting for the uncertainties considered in the original OEGV assessment. Using the above 4-step approach, a blood BE value of 32.5 μg titanium/L was derived. Key components of the analysis included a pharmacokinetic model developed by investigators at the Netherlands National Institute of Public Health (RIVM) and a two-year rodent bioassay of titanium conducted by the US National Cancer Institute. The most sensitive pharmacokinetic parameter involved in the current BE derivation is the oral absorption factor of 0.02%. The provisional BE proposed in this article may be updated as new information on the pharmacokinetics of titanium becomes available. • Titanium (Ti), as titanium dioxide, is widely permitted by regulatory authorities for use as a food color additive. • Food represents the main source of titanium intake in the general population. • Food-grade titanium particles occur primarily in non-nano form and exist as aggregates. • Absorption of orally ingested titanium is very low, and more than 97% of ingested titanium is eliminated through feces. • Biomonitoring equivalent (BE) values derived here are useful screening tools for evaluation of biomonitoring data on Ti. [ABSTRACT FROM AUTHOR]

Lithium salts have numerous industrial uses and are also used in the treatment of bipolar disorders. The main source of lithium exposure to the general population is drinking water and foods. Lithium is nephrotoxic at higher doses. Thus, oral exposure guidelines for lithium have been derived, including ICH's permitted daily exposure (PDE = 0.008 mg lithium/kg-bw/day) adopted by Health Canada and the United States Environmental Protection Agency's (U.S. EPA) provisional peer reviewed toxicity value (PPRTV = 0.002 mg lithium/kg-bw/day), both based on human data. To derive whole blood biomonitoring equivalents (BEs) associated with PDE and PPRTV to interpret population-level biomonitoring data in health risk context. A simple kinetic relationship based on plasma clearance value (0.5 L/kg-bw/day) and the oral absorption fraction (100%) was used to derive blood BEs for PDE and PPRTV. This analysis resulted in BE values in plasma and whole blood of 16 and 10 μg/L, respectively, based on the PDE values developed by the Health Canada and of 4.2 and 2.7 μg/L, respectively, based on the PPRTV developed by U.S. EPA. The derived BE values can be used to interpret population-level biomonitoring data. • Drinking water and foods represent the main source of lithium intake in the general population. • Lithium may have beneficial neurological and anti-aging effects in humans; at higher doses, it causes nephrotoxicity. • The present publication describes derivation of biomonitoring equivalent (BE) values for lithium in plasma and whole blood. • BE values derived here can be used as screening tools for evaluation of population biomonitoring data for lithium. [ABSTRACT FROM AUTHOR]

Occupational exposure limits (OELs) serve as health-based benchmarks against which measured or estimated workplace exposures can be compared. In the years since the introduction of OELs to public health practice, both developed and developing countries have established processes for deriving, setting, and using OELs to protect workers exposed to hazardous chemicals. These processes vary widely, however, and have thus resulted in a confusing international landscape for identifying and applying such limits in workplaces. The occupational hygienist will encounter significant overlap in coverage among organizations for many chemicals, while other important chemicals have OELs developed by few, if any, organizations. Where multiple organizations have published an OEL, the derived value often varies considerably—reflecting differences in both risk policy and risk assessment methodology as well as access to available pertinent data. This article explores the underlying reasons for variability in OELs, and recommends the harmonization of risk-based methods used by OEL-deriving organizations. A framework is also proposed for the identification and systematic evaluation of OEL resources, which occupational hygienists can use to support risk characterization and risk management decisions in situations where multiple potentially relevant OELs exist. [ABSTRACT FROM PUBLISHER]