Correction to: Health effects of nutrients and environmental pollutants in Baltic herring and salmon: a quantitative benefit-risk assessment.

It was highlighted that the original article [1] contained a formatting error in the equations.

Health effects of nutrients and environmental pollutants in Baltic herring and salmon: a quantitative benefit-risk assessment.

BACKGROUND: Health risks linked with dioxin in fish remain a complex policy issue. Fatty Baltic fish contain persistent pollutants, but they are otherwise healthy food. We studied the health benefits and risks associated with Baltic herring and salmon in four countries to identify critical uncertainties and to facilitate an evidence-based discussion. METHODS: We performed an online survey investigating consumers' fish consumption and its motivation in Denmark, Estonia, Finland, and Sweden. Dioxin and methylmercury concentrations were estimated based on Finnish studies. Exposure-response functions for several health endpoints were evaluated and quantified based on the scientific literature. We also quantified the infertility risk of men based on a recent European risk assessment estimating childhood dioxin exposure and its effect on sperm concentration later in life. RESULTS: Baltic herring and salmon contain omega-3 fatty acids and vitamin D, and the beneficial impact of these fishes on cardiovascular diseases, mortality, and the risk of depression and cancer clearly outweighs risks of dioxins and methylmercury in people older than 45 years of age and in young men. Young women may expose their children to pollutants during pregnancy and breast feeding. This study suggests that even in this critical subgroup, the risks are small and the health benefits are greater than or at least similar to the health risks. Value of information analysis demonstrated that the remaining scientific uncertainties are not large. In contrast, there are several critical uncertainties that are inherently value judgements, such as whether exceeding the tolerable weekly intake is an adverse outcome as such; and whether or not subgroup-specific restrictions are problematic. CONCLUSIONS: The potential health risks attributable to dioxins in Baltic fish have more than halved in the past 10 years. The new risk assessment issued by the European Food Safety Authority clearly increases the fraction of the population exceeding the tolerable dioxin intake, but nonetheless, quantitative estimates of net health impacts change only marginally. Increased use of small herring (which have less pollutants) is a no-regret option. A more relevant value-based policy discussion rather than research is needed to clarify official recommendations related to dioxins in fish.

Premature Deaths, Statistical Lives, and Years of Life Lost: Identification, Quantification, and Valuation of Mortality Risks.

Mortality effects of exposure to air pollution and other environmental hazards are often described by the estimated number of "premature" or "attributable" deaths and the economic value of a reduction in exposure as the product of an estimate of "statistical lives saved" and a "value per statistical life." These terms can be misleading because the number of deaths advanced by exposure cannot be determined from mortality data alone, whether from epidemiology or randomized trials (it is not statistically identified). The fraction of deaths "attributed" to exposure is conventionally derived as the hazard fraction (R - 1)/R, where R is the relative risk of mortality between high and low exposure levels. The fraction of deaths advanced by exposure (the "etiologic" fraction) can be substantially larger or smaller: it can be as large as one and as small as 1/e (≈0.37) times the hazard fraction (if the association is causal and zero otherwise). Recent literature reveals misunderstanding about these concepts. Total life years lost in a population due to exposure can be estimated but cannot be disaggregated by age or cause of death. Economic valuation of a change in exposure-related mortality risk to a population is not affected by inability to know the fraction of deaths that are etiologic. When individuals facing larger or smaller changes in mortality risk cannot be identified, the mean change in population hazard is sufficient for valuation; otherwise, the economic value can depend on the distribution of risk reductions.

From insight network to open policy practice: practical experiences.

BACKGROUND: Evidence-informed decision-making and better use of scientific information in societal decisions has been an area of development for decades but is still topical. Decision support work can be viewed from the perspective of information collection, synthesis and flow between decision-makers, experts and stakeholders. Open policy practice is a coherent set of methods for such work. It has been developed and utilised mostly in Finnish and European contexts. METHODS: An overview of open policy practice is given, and theoretical and practical properties are evaluated based on properties of good policy support. The evaluation is based on information from several assessments and research projects developing and applying open policy practice and the authors' practical experiences. The methods are evaluated against their capability of producing quality of content, applicability and efficiency in policy support as well as how well they support close interaction among participants and understanding of each other's views. RESULTS: The evaluation revealed that methods and online tools work as expected, as demonstrated by the assessments and policy support processes conducted. The approach improves the availability of information and especially of relevant details. Experts are ambivalent about the acceptability of openness - it is an important scientific principle, but it goes against many current research and decision-making practices. However, co-creation and openness are megatrends that are changing science, decision-making and the society at large. Against many experts' fears, open participation has not caused problems in performing high-quality assessments. On the contrary, a key challenge is to motivate and help more experts, decision-makers and citizens to participate and share their views. Many methods within open policy practice have also been widely used in other contexts. CONCLUSIONS: Open policy practice proved to be a useful and coherent set of methods. It guided policy processes toward a more collaborative approach, whose purpose was wider understanding rather than winning a debate. There is potential for merging open policy practice with other open science and open decision process tools. Active facilitation, community building and improving the user-friendliness of the tools were identified as key solutions for improving the usability of the method in the future.

Health impact assessment of transport policies in Rotterdam: Decrease of total traffic and increase of electric car use.

BACKGROUND: Green house gas (GHG) mitigation policies can be evaluated by showing their co-benefits to health. METHOD: Health Impact Assessment (HIA) was used to quantify co-benefits of GHG mitigation policies in Rotterdam. The effects of two separate interventions (10% reduction of private vehicle kilometers and a share of 50% electric-powered private vehicle kilometers) on particulate matter (PM2.5), elemental carbon (EC) and noise (engine noise and tyre noise) were assessed using Years of Life Lost (YLL) and Years Lived with Disability (YLD). The baseline was 2010 and the end of the assessment 2020. RESULTS: The intervention aimed at reducing traffic is associated with a decreased exposure to noise resulting in a reduction of 21 (confidence interval (CI): 11-129) YLDs due to annoyance and 35 (CI: 20-51) YLDs due to sleep disturbance for the population per year. The effects of 50% electric-powered car use are slightly higher with a reduction of 26 (CI: 13-116) and 41 (CI: 24-60) YLDs, respectively. The two interventions have marginal effects on air pollution, because already implemented traffic policies will reduce PM2.5 and EC by around 40% and 60% respectively, from 2010 to 2020. DISCUSSION: The evaluation of planned interventions, related to climate change policies, targeting only the transport sector can result in small co-benefits for health, if the analysis is limited to air pollution and noise. This urges to expand the analysis by including other impacts, e.g. physical activity and well-being, as a necessary step to better understanding consequences of interventions and carefully orienting resources useful to build knowledge to improve public health.

Public health impacts of city policies to reduce climate change: findings from the URGENCHE EU-China project.

BACKGROUND: Climate change is a global threat to health and wellbeing. Here we provide findings of an international research project investigating the health and wellbeing impacts of policies to reduce greenhouse gas emissions in urban environments. METHODS: Five European and two Chinese city authorities and partner academic organisations formed the project consortium. The methodology involved modelling the impact of adopted urban climate-change mitigation transport, buildings and energy policy scenarios, usually for the year 2020 and comparing them with business as usual (BAU) scenarios (where policies had not been adopted). Carbon dioxide emissions, health impacting exposures (air pollution, noise and physical activity), health (cardiovascular, respiratory, cancer and leukaemia) and wellbeing (including noise related wellbeing, overall wellbeing, economic wellbeing and inequalities) were modelled. The scenarios were developed from corresponding known levels in 2010 and pre-existing exposure response functions. Additionally there were literature reviews, three longitudinal observational studies and two cross sectional surveys. RESULTS: There are four key findings. Firstly introduction of electric cars may confer some small health benefits but it would be unwise for a city to invest in electric vehicles unless their power generation fuel mix generates fewer emissions than petrol and diesel. Second, adopting policies to reduce private car use may have benefits for carbon dioxide reduction and positive health impacts through reduced noise and increased physical activity. Third, the benefits of carbon dioxide reduction from increasing housing efficiency are likely to be minor and co-benefits for health and wellbeing are dependent on good air exchange. Fourthly, although heating dwellings by in-home biomass burning may reduce carbon dioxide emissions, consequences for health and wellbeing were negative with the technology in use in the cities studied. CONCLUSIONS: The climate-change reduction policies reduced CO2 emissions (the most common greenhouse gas) from cities but impact on global emissions of CO2 would be more limited due to some displacement of emissions. The health and wellbeing impacts varied and were often limited reflecting existing relatively high quality of life and environmental standards in most of the participating cities; the greatest potential for future health benefit occurs in less developed or developing countries.

Building-related health impacts in European and Chinese cities: a scalable assessment method.

BACKGROUND: Public health is often affected by societal decisions that are not primarily about health. Climate change mitigation requires intensive actions to minimise greenhouse gas emissions in the future. Many of these actions take place in cities due to their traffic, buildings, and energy consumption. Active climate mitigation policies will also, aside of their long term global impacts, have short term local impacts, both positive and negative, on public health. Our main objective was to develop a generic open impact model to estimate health impacts of emissions due to heat and power consumption of buildings. In addition, the model should be usable for policy comparisons by non-health experts on city level with city-specific data, it should give guidance on the particular climate mitigation questions but at the same time increase understanding on the related health impacts and the model should follow the building stock in time, make comparisons between scenarios, propagate uncertainties, and scale to different levels of detail. We tested The functionalities of the model in two case cities, namely Kuopio and Basel. We estimated the health and climate impacts of two actual policies planned or implemented in the cities. The assessed policies were replacement of peat with wood chips in co-generation of district heat and power, and improved energy efficiency of buildings achieved by renovations. RESULTS: Health impacts were not large in the two cities, but also clear differences in implementation and predictability between the two tested policies were seen. Renovation policies can improve the energy efficiency of buildings and reduce greenhouse gas emissions significantly, but this requires systematic policy sustained for decades. In contrast, fuel changes in large district heating facilities may have rapid and large impacts on emissions. However, the life cycle impacts of different fuels is somewhat an open question. CONCLUSIONS: In conclusion, we were able to develop a practical model for city-level assessments promoting evidence-based policy in general and health aspects in particular. Although all data and code is freely available, implementation of the current model version in a new city requires some modelling skills.

[Big data in the promotion of public health]. / Massadata kansanterveyden edistämisessä.

Big data (very large data sets) are increasing in an accelerating speed. More and more data is also becoming freely available. This article is an overview of this progress and data sources related to molecular biology and public health especially from the Finnish perspective. Finland has several excellent data sources that are currently not used effectively. Big data has already produced major benefits especially in molecular biology, but benefits in public health and individual choice are only now being materialised. The paradigm in research may change dramatically, if the effort switches from article production to the production of knowledge crystals, i.e. collaborative data-based answers to research questions. Also the role of a clinician is becoming more like that of a coach.

Openness in participation, assessment, and policy making upon issues of environment and environmental health: a review of literature and recent project results.

Issues of environment and environmental health involve multiple interests regarding e.g. political, societal, economical, and public concerns represented by different kinds of organizations and individuals. Not surprisingly, stakeholder and public participation has become a major issue in environmental and environmental health policy and assessment. The need for participation has been discussed and reasoned by many, including environmental legislators around the world. In principle, participation is generally considered as desirable and the focus of most scholars and practitioners is on carrying out participation, and making participation more effective. In practice also doubts regarding the effectiveness and importance of participation exist among policy makers, assessors, and public, leading even to undermining participatory practices in policy making and assessment.There are many possible purposes for participation, and different possible models of interaction between assessment and policy. A solid conceptual understanding of the interrelations between participation, assessment, and policy making is necessary in order to design and implement effective participatory practices. In this paper we ask, do current common conceptions of assessment, policy making and participation provide a sufficient framework for achieving effective participation? This question is addresses by reviewing the range of approaches to participation in assessment and policy making upon issues of environment and environmental health and some related insights from recent research projects, INTARESE and BENERIS.Openness, considered e.g. in terms of a) scope of participation, b) access to information, c) scope of contribution, d) timing of openness, and e) impact of contribution, provides a new perspective to the relationships between participation, assessment and policy making. Participation, assessment, and policy making form an inherently intertwined complex with interrelated objectives and outcomes. Based on experiences from implementing openness, we suggest complete openness as the new default, deviation from which should be explicitly argued, in assessment and policy making upon issues of environment and environmental health. Openness does not undermine the existing participatory models and techniques, but provides conceptual means for their more effective application, and opens up avenues for developing new kinds of effective participatory practices that aim for societal development through collaborative creation of knowledge.

Spatial aspects of the dioxin risk formation in the Baltic Sea: A systematic review.

Dioxins have been an inconvenience to the Baltic Sea ecosystem for decades. Although the concentrations in the environment and biota have continuously decreased, dioxins still pose a risk to human health. The risk and its formation vary in different parts of the Baltic Sea, due to variability in the environmental and societal factors affecting it. This paper presents a systematic literature review and knowledge synthesis about the regional dioxin risk formation in four sub-areas of the Baltic Sea and evaluates, whether systemic approach changes our thinking about the risk and its effective management. We studied the dioxin flux from atmospheric deposition to the Baltic Sea food webs, accumulation to two commercially and culturally important fish species, Baltic herring (Clupea harengus membras) and Baltic salmon (Salmo salar), and further to risk group members of four Baltic countries. Based on 46 studies, we identified 20 quantifiable variables and indexed them for commensurable regional comparison. Spatial differences in dioxin pollution, environmental conditions, food web dynamics, and the following dioxin concentrations in herring and salmon, together with fishing and fish consumption, affect how the final health risk builds up. In the southern Baltic Sea, atmospheric pollution levels are relatively high and environmental processes to decrease bioavailability of dioxins unfavorable, but the growth is fast, which curb the bioaccumulation of dioxins in the biota. In the North, long-range atmospheric pollution is minor compared to South, but the local pollution and slower growth leads to higher bioaccumulation rates. However, based on our results, the most remarkable differences in the dioxin risk formation between the areas arise from the social sphere: the emissions, origin of national catches, and cultural differences in fish consumption. The article suggests that acknowledging spatial characteristics of socio-ecological systems that generate environmental risks may aid to direct local focus in risk management.

Quantitative and statistical analysis of differences in sensitivity between Long-Evans and Han/Wistar rats following long-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

In this study, differences in sensitivity between Long-Evans (L-E; dioxin sensitive) and Han/Wistar (H/W; dioxin resistant) rats following long-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were statistically and quantitatively investigated. Sensitivity differences were analyzed by comparing benchmark doses (BMDs) for the two strains considering a number of toxicological endpoints including data on body and organ weights, hepatic foci, hepatic CYP1A1 induction, as well as tissue retinoid levels. Dose-response relationships for L-E and H/W rats, described by the Hill function, were assumed to be parallel, which was supported according to statistical analysis. It was concluded that L-E and H/W rats differed statistically in their response to TCDD treatment for most of the parameters investigated. Differences between the strains were most pronounced for hepatic foci; L-E rats were approximately 20-40 times more sensitive than H/W rats. For body and organ weight parameters, L-E rats were approximately 10-20 times more sensitive than H/W rats. For retinoid parameters and hepatic CYP1A1 induction, estimated differences between the strains were generally about 5-fold, and associated with a low uncertainty. In conclusion, the present study employs a dose-response modeling approach suitable for statistical evaluation of strain and species differences in sensitivity to chemical exposure. The study demonstrates quantitatively the differences in sensitivity between the L-E and H/W rat strains following long-term TCDD exposure.

Estimated PCDD/F TEQ and total TEQ concentrations in the serum of 7-10 year old Finnish children.

Polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are persistent organic pollutants that have detrimental health effects. As people are exposed to them mainly through the diet, EU has set maximum food dioxin and PCBs levels. EFSA CONTAM Panel made new risk assessment in 2018 that lowered the tolerable weekly intake (TWI) from 14 pg-TEQ/kg bw/week to 2 pg-TEQ/kg bw/week. Critical effect was decreased semen count at the age of 18-19 years if serum total TEQ at the age of 9 years exceeded the No Observed Adverse Effect Level (NOAEL) of 7 pg/g lipid. However, it is largely unknown to what extent NOAEL is exceed in European boys currently. We thus measured PCBs from small volume of serum in 184 Finnish children 7-10 years of age. To estimate the TEQ levels of children from measured PCB levels, we used our existing human milk PCDD/F and PCB concentrations to create a hierarchical Bayesian regression model that was used to estimate TEQs from measured PCBs. For quality control (QC), three pooled blood samples from 18 to 20 year old males were measured for PCDD/Fs and PCBs, and estimated for TEQs. In QC samples measured and estimated TEQs agreed within 84%-106%. In our estimate for 7-10 year old children, PCDD/F TEQ exceeded NOAEL only in 0.5% and total TEQ in 2.7% of subjects. Risk management following the decreased TWI proposed by the CONTAM Panel should be carefully considered if total TEQ in children is already largely below the NOAEL.

Corrigendum to "City scale climate change policies: Do they matter for wellbeing?" [Prev. Med. Rep. 6 (2017) 265-270].

[This corrects the article DOI: 10.1016/j.pmedr.2017.03.019.].

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on heme oxygenase-1, biliverdin IXalpha reductase and delta-aminolevulinic acid synthetase 1 in rats with wild-type or variant AH receptor.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes hepatic accumulation of biliverdin and its monoglucuronide in moderately TCDD-resistant line B rats, but not in highly TCDD-resistant line A rats. In the mammalian heme degradation process, heme is cleaved to biliverdin by the rate-limiting enzyme heme oxygenase-1 (HO-1). Subsequently, biliverdin IXalpha reductase (BVRA) catalyzes the reduction of biliverdin to bilirubin. In heme biosynthesis, the rate-limiting enzyme is delta-aminolevulinic acid synthetase 1 (ALAS1). The effect of TCDD on HO-1, BVRA and ALAS1 was studied at the levels of mRNA (all three enzymes), protein expression (HO-1), and enzymatic activity (BVRA, liver only) in order to determine whether the accumulation of biliverdin could be due to their altered expression. In both lines A and B, 300 microg/kg TCDD transiently repressed hepatic HO-1 mRNA on day 2 but induced HO-1 protein expression at later time-points; however, the impact emerged earlier (day 14 vs. day 35) in line B rats. In spleen, TCDD repressed HO-1 mRNA and protein expression in lines A and B through days 2-35, but did not affect its mRNA levels in TCDD-sensitive L-E rats (10 days after 100 microg/kg). In all rat strains/lines, there was a strong repression of ALAS1 and a moderate induction of BVRA mRNA in liver, but mostly not in spleen. Hepatic BVRA activity was increased in lines A and B on day 14. At 5 weeks, it was still elevated in line A but reduced to 51% of control in line B. The results suggest that hepatic heme degradation is induced by TCDD in rats; however, this does not alone explain the accumulation of biliverdin in line B rats. Other factors such as the late repression of BVRA found here and possibly oxidative stress may be important contributors to biliverdin accumulation in these rats.

Patterns of dioxin-altered mRNA expression in livers of dioxin-sensitive versus dioxin-resistant rats.

Dioxins exert their major toxicologic effects by binding to the aryl hydrocarbon receptor (AHR) and altering gene transcription. Numerous dioxin-responsive genes previously were identified both by conventional biochemical and molecular techniques and by recent mRNA expression microarray studies. However, of the large set of dioxin-responsive genes the specific genes whose dysregulation leads to death remain unknown. To identify specific genes that may be involved in dioxin lethality we compared changes in liver mRNA levels following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in three strains/lines of dioxin-sensitive rats with changes in three dioxin-resistant rat strains/lines. The three dioxin-resistant strains/lines all harbor a large deletion in the transactivation domain of the aryl hydrocarbon receptor (AHR). Despite this deletion, many genes exhibited a "Type-I" response-that is, their responses were similar in dioxin-sensitive and dioxin-resistant rats. Several genes that previously were well established as being dioxin-responsive or under AHR regulation emerged as Type-I responses (e.g. CYP1A1, CYP1A2, CYP1B1 and Gsta3). In contrast, a relatively small number of genes exhibited a Type-II response-defined as a difference in responsiveness between dioxin-sensitive and dioxin-resistant rat strains. Type-II genes include: malic enzyme 1, ubiquitin C, cathepsin L, S-adenosylhomocysteine hydrolase and ferritin light chain 1. In silico searches revealed that AH response elements are conserved in the 5'-flanking regions of several genes that respond to TCDD in both the Type-I and Type-II categories. The vast majority of changes in mRNA levels in response to 100 microg/kg TCDD were strain-specific; over 75% of the dioxin-responsive clones were affected in only one of the six strains/lines. Selected genes were assessed by quantitative RT-PCR in dose-response and time-course experiments and responses of some genes were assessed in Ahr-null mice to determine if their response was AHR-dependent. Type-II genes may lie in pathways that are central to the difference in susceptibility to TCDD lethality in this animal model.

Comparative risk analysis of dioxins in fish and fine particles from heavy-duty vehicles.

Dioxins and airborne fine particles are both environmental health problems that have been the subject of active public debate. Knowledge on fine particles has increased substantially during the last 10 years, and even the current, lowered levels in the Europe and in the United States appear to be a major public health problem. On the other hand, dioxins are ubiquitous persistent contaminants, some being carcinogens at high doses, and therefore of great concern. Our aim was to (a) quantitatively analyze the two pollutant health risks and (b) study the changes in risk in view of the current and forthcoming EU legislations on pollutants. We performed a comparative risk assessment for both pollutants in the Helsinki metropolitan area (Finland) and estimated the health effects with several scenarios. For primary fine particles: a comparison between the present emission situation for heavy-duty vehicles and the new fine particle emission standards set by the EU. For dioxins: an EU directive that regulates commercial fishing of Baltic salmon and herring that exceed the dioxin concentration limit set for fish meat, and a derogation (= exemption) from the directive for these two species. Both of these two decisions are very topical issues and this study estimates the expected changes in health effects due to these regulations. It was found that the estimated fine particle risk clearly outweighed the estimated dioxin risk. A substantial improvement to public health could be achieved by initiating reductions in emission standards; about 30 avoided premature deaths annually in the study area. In addition, the benefits of fish consumption due to omega-3 exposure were notably higher than the potential dioxin cancer risk. Both regulations were instigated as ways of promoting public health.

How scientists perceive the evolutionary origin of human traits: Results of a survey study.

Various hypotheses have been proposed for why the traits distinguishing humans from other primates originally evolved, and any given trait may have been explained both as an adaptation to different environments and as a result of demands from social organization or sexual selection. To find out how popular the different explanations are among scientists, we carried out an online survey among authors of recent scientific papers in journals covering relevant fields of science (paleoanthropology, paleontology, ecology, evolution, human biology). Some of the hypotheses were clearly more popular among the 1,266 respondents than others, but none was universally accepted or rejected. Even the most popular of the hypotheses were assessed "very likely" by <50% of the respondents, but many traits had 1-3 hypotheses that were found at least moderately likely by >70% of the respondents. An ordination of the hypotheses identified two strong gradients. Along one gradient, the hypotheses were sorted by their popularity, measured by the average credibility score given by the respondents. The second gradient separated all hypotheses postulating adaptation to swimming or diving into their own group. The average credibility scores given for different subgroups of the hypotheses were not related to respondent's age or number of publications authored. However, (paleo)anthropologists were more critical of all hypotheses, and much more critical of the water-related ones, than were respondents representing other fields of expertise. Although most respondents did not find the water-related hypotheses likely, only a small minority found them unscientific. The most popular hypotheses were based on inherent drivers; that is, they assumed the evolution of a trait to have been triggered by the prior emergence of another human-specific behavioral or morphological trait, but opinions differed as to which of the traits came first.

Flame retardants in placenta and breast milk and cryptorchidism in newborn boys.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are widely used in Western countries. OBJECTIVES: Because the prevalence of cryptorchidism appears to be increasing, we investigated whether exposure to PBDEs was associated with testicular maldescent. METHODS: In a prospective Danish-Finnish study, 1997-2001, all boys were examined for cryptorchidism. We analyzed whole placentas (for 95 cryptorchid/185 healthy boys) and individual breast milk samples (62/68) for 14 PBDEs and infant serum samples for gonadotropins, sex-hormone binding globulin, testosterone, and inhibin B. RESULTS: In 86 placenta-milk pairs, placenta PBDE concentrations in fat were lower than in breast milk, and a larger number of congeners were nondetectable. There was no significant difference between boys with and without cryptorchidism for individual congeners, the sum of 5 most prevalent, or all 14 congeners. The concentration of PBDEs in breast milk was significantly higher in boys with cryptorchidism than in controls (sum of BDEs 47, 153, 99, 100, 28, 66, and 154: median, 4.16 vs. 3.16 ng/g fat; p < 0.007). There was a positive correlation between the sum of PBDEs and serum luteinizing hormone (p < 0.033). The sum of PBDEs in breast milk did not differ between Denmark and Finland (median, 3.52 vs. 3.44 ng/g fat), but significant differences in some individual congeners were found. CONCLUSIONS: Two different proxies were used for prenatal PBDE exposure, and levels in breast milk, but not in placenta, showed an association with congenital cryptorchidism. Other environmental factors may contribute to cryptorchidism. Our observations are of concern because human exposure to PBDEs is high in some geographic areas.

Differences in acute toxicity syndromes of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin in rats.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent congener of polychlorinated dibenzo-p-dioxins. The potency of 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (HxCDD) is only 10% of that of TCDD for typical aryl hydrocarbon receptor (AHR)-mediated effects. Acute lethality, macroscopic effects, and liver toxicity of TCDD and HxCDD were compared in male rats of the strain Han/Wistar (Kuopio; H/W), and of the lines A and B. The latter two rat lines originate from crossbreeding of H/W and Long-Evans (Turku/AB) rats. H/W and line A rats are highly resistant to acute toxicity of TCDD due to an altered AHR, while line B rats are moderately resistant due to H/W-type alleles of another, yet unidentified gene contributing to TCDD resistance ("gene B"). The rats received 200-10,000 microg/kg of either TCDD or HxCDD intragastrically and were monitored for 46 days. In all rats, the highest dose of HxCDD (10,000 microg/kg) reduced body weight more effectively than an identical dose of TCDD. Only HxCDD (10,000 microg/kg) caused gastrointestinal hemorrhage, pale (fatty) livers and death by day 15 in H/W and line A rats. In line B rats, HxCDD caused pronounced hepatic fatty degeneration, whereas TCDD induced hepatic accumulation of biliverdin and its derivatives. Both congeners induced sinusoidal distension in liver. In H/W and line A rats, the estimated LD(50) values were >10,000 microg/kg and 2000-10,000 microg/kg for TCDD and HxCDD, respectively; for line B rats they were 480 microg/kg and 1000-2000 microg/kg, respectively. Thus, HxCDD was more potent than TCDD in inducing acute mortality in H/W and line A rats, contrary to what is predicted by toxic equivalency factor (TEF) values. In line B, the expected rank order of potencies prevailed. These findings suggest that in addition to the canonical AHR-mediated toxic pathways, HxCDD possesses an AHR-independent mechanism of toxicity, whose main manifestations are rapid body weight loss, mortality, fatty liver and gastrointestinal hemorrhage.

Parameter and model uncertainty in a life-table model for fine particles (PM2.5): a statistical modeling study.

BACKGROUND: The estimation of health impacts involves often uncertain input variables and assumptions which have to be incorporated into the model structure. These uncertainties may have significant effects on the results obtained with model, and, thus, on decision making. Fine particles (PM2.5) are believed to cause major health impacts, and, consequently, uncertainties in their health impact assessment have clear relevance to policy-making. We studied the effects of various uncertain input variables by building a life-table model for fine particles. METHODS: Life-expectancy of the Helsinki metropolitan area population and the change in life-expectancy due to fine particle exposures were predicted using a life-table model. A number of parameter and model uncertainties were estimated. Sensitivity analysis for input variables was performed by calculating rank-order correlations between input and output variables. The studied model uncertainties were (i) plausibility of mortality outcomes and (ii) lag, and parameter uncertainties (iii) exposure-response coefficients for different mortality outcomes, and (iv) exposure estimates for different age groups. The monetary value of the years-of-life-lost and the relative importance of the uncertainties related to monetary valuation were predicted to compare the relative importance of the monetary valuation on the health effect uncertainties. RESULTS: The magnitude of the health effects costs depended mostly on discount rate, exposure-response coefficient, and plausibility of the cardiopulmonary mortality. Other mortality outcomes (lung cancer, other non-accidental and infant mortality) and lag had only minor impact on the output. The results highlight the importance of the uncertainties associated with cardiopulmonary mortality in the fine particle impact assessment when compared with other uncertainties. CONCLUSION: When estimating life-expectancy, the estimates used for cardiopulmonary exposure-response coefficient, discount rate, and plausibility require careful assessment, while complicated lag estimates can be omitted without this having any major effect on the results.