Considering the cumulative risk of mixtures of chemicals – A challenge for policy makers

<p>Abstract</p> <p>Background</p> <p>The current paradigm for the assessment of the health risk of chemical substances focuses primarily on the effects of individual substances for determining the doses of toxicological concern in order to inform appropriately the regulatory process. These policy instruments place varying requirements on health and safety data of chemicals in the environment. REACH focuses on safety of individual substances; yet all the other facets of public health policy that relate to chemical stressors put emphasis on the effects of combined exposure to mixtures of chemical and physical agents. This emphasis brings about methodological problems linked to the complexity of the respective exposure pathways; the effect (more complex than simple additivity) of mixtures (the so-called 'cocktail effect'); dose extrapolation, i.e. the extrapolation of the validity of dose-response data to dose ranges that extend beyond the levels used for the derivation of the original dose-response relationship; the integrated use of toxicity data across species (including human clinical, epidemiological and biomonitoring data); and variation in inter-individual susceptibility associated with both genetic and environmental factors.</p> <p>Methods</p> <p>In this paper we give an overview of the main methodologies available today to estimate the human health risk of environmental chemical mixtures, ranging from dose addition to independent action, and from ignoring interactions among the mixture constituents to modelling their biological fate taking into account the biochemical interactions affecting both internal exposure and the toxic potency of the mixture.</p> <p>Results</p> <p>We discuss their applicability, possible options available to policy makers and the difficulties and potential pitfalls in implementing these methodologies in the frame of the currently existing policy framework in the European Union. Finally, we suggest a pragmatic solution for policy/regulatory action that would facilitate the evaluation of the health effects of chemical mixtures in the environment and consumer products.</p> <p>Conclusions</p> <p>One universally applicable methodology does not yet exist. Therefore, a pragmatic, tiered approach to regulatory risk assessment of chemical mixtures is suggested, encompassing (a) the use of dose addition to calculate a hazard index that takes into account interactions among mixture components; and (b) the use of the connectivity approach in data-rich situations to integrate mechanistic knowledge at different scales of biological organization.</p

Development of a quantitative methodology to assess the impacts of urban transport interventions and related noise on well-being

Well-being impact assessments of urban interventions are a difficult challenge, as there is no agreed methodology and scarce evidence on the relationship between environmental conditions and well-being. The European Union (EU) project “Urban Reduction of Greenhouse Gas Emissions in China and Europe” (URGENCHE) explored a methodological approach to assess traffic noise-related well-being impacts of transport interventions in three European cities (Basel, Rotterdam and Thessaloniki) linking modeled traffic noise reduction effects with survey data indicating noise-well-being associations. Local noise models showed a reduction of high traffic noise levels in all cities as a result of different urban interventions. Survey data indicated that perception of high noise levels was associated with lower probability of well-being. Connecting the local noise exposure profiles with the noise-well-being associations suggests that the urban transport interventions may have a marginal but positive effect on population well-being. This paper also provides insight into the methodological challenges of well-being assessments and highlights the range of limitations arising from the current lack of reliable evidence on environmental conditions and well-being. Due to these limitations, the results should be interpreted with caution.</p

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.</p

Scoping Review-The Association between Asthma and Environmental Chemicals

Asthma is one of the most common chronic diseases worldwide affecting all age groups from children to the elderly. In addition to other factors such as smoking, air pollution and atopy, some environmental chemicals are shown or suspected to increase the risk of asthma, exacerbate asthma symptoms and cause other respiratory symptoms. In this scoping review, we report environmental chemicals, prioritized for investigation in the European Human Biomonitoring Initiative (HBM4EU), which are associated or possibly associated with asthma. The substance groups considered to cause asthma through specific sensitization include: diisocyanates, hexavalent chromium Cr(VI) and possibly p-phenylenediamine (p-PDA). In epidemiological studies, polyaromatic hydrocarbons (PAHs) and organophosphate insecticides are associated with asthma, and phthalates, per- and polyfluoroalkyl substances (PFASs), pyrethroid insecticides, mercury, cadmium, arsenic and lead are only potentially associated with asthma. As a conclusion, exposure to PAHs and some pesticides are associated with increased risk of asthma. Diisocyanates and Cr(VI) cause asthma with specific sensitization. For many environmental chemicals, current studies have provided contradicting results in relation to increased risk of asthma. Therefore, more research about exposure to environmental chemicals and risk of asthma is needed.Peer reviewe

Development of a quantitative methodology to assess the impacts of urban transport interventions and related noise on well-being

Well-being impact assessments of urban interventions are a difficult challenge, as there is no agreed methodology and scarce evidence on the relationship between environmental conditions and well-being. The European Union (EU) project "Urban Reduction of Greenhouse Gas Emissions in China and Europe" (URGENCHE) explored a methodological approach to assess traffic noise-related well-being impacts of transport interventions in three European cities (Basel, Rotterdam and Thessaloniki) linking modeled traffic noise reduction effects with survey data indicating noise-well-being associations. Local noise models showed a reduction of high traffic noise levels in all cities as a result of different urban interventions. Survey data indicated that perception of high noise levels was associated with lower probability of well-being. Connecting the local noise exposure profiles with the noise-well-being associations suggests that the urban transport interventions may have a marginal but positive effect on population well-being. This paper also provides insight into the methodological challenges of well-being assessments and highlights the range of limitations arising from the current lack of reliable evidence on environmental conditions and well-being. Due to these limitations, the results should be interpreted with caution

Passive exposures of children to volatile trihalomethanes during domestic cleaning activities of their parents

Domestic cleaning has been proposed as a determinant of trihalomethanes (THMs) exposure in adult females. We hypothesized that parental housekeeping activities could influence children's passive exposures to THMs from their mere physical presence during domestic cleaning. In a recent cross-sectional study (n=382) in Cyprus [41 children (<18y) and 341 adults (≥18y)], we identified 29 children who met the study's inclusion criteria. Linear regression models were applied to understand the association between children sociodemographic variables, their individual practices influencing ingestion and noningestion exposures to ΣTHMs, and their urinary THMs levels. Among the children-specific variables, age alone showed a statistically significant inverse association with their creatinine-adjusted urinary ΣTHMs (rS=−0.59, p<0.001). A positive correlation was observed between urinary ΣTHMs (ng g−1) of children and matched-mothers (rS=0.52, p=0.014), but this was not the case for their matched-fathers (rS=0.39, p=0.112). Time spent daily by the matched-mothers for domestic mopping, toilet and other cleaning activities using chlorine-based cleaning products was associated with their children's urinary THMs levels (rS=0.56, p=0.007). This trend was not observed between children and their matched-fathers urinary ΣTHMs levels, because of minimum amount of time spent by the latter in performing domestic cleaning. The proportion of variance of creatinine-unadjusted and adjusted urinary ΣTHMs levels in children that was explained by the matched-mothers covariates was 76% and 74% (p<0.001), respectively. A physiologically-based pharmacokinetic model adequately predicted urinary chloroform excretion estimates, being consistent with the corresponding measured levels. Our findings highlighted the influence of mothers' domestic cleaning activities towards enhancing passive THMs exposures of their children. The duration of such activities could be further tested as a valid indicator of children's THMs body burden

A NOVEL APPLICATION OF THE NEWCOMB-BENFORD LAW TO EXPOSURE DATA

The Newcomb-Benford Law (NBL) is a powerful mathematical concept that describes the distribution frequency of the significant digits for in large data sets (Judge and Schechter 2009). NBL suggests that the probability for the significant digits (1 through 9) of a randomly occurring number is not equally distributed but follows a distribution where 1 occurs more frequently than 2, 2 more than 3, and so on. Use of the NBL has frequently been used to identify fraudulent or manipulated data in the political, economic, and natural sciences. However, few studies have used the NBL to identify underlying mechanisms in toxicokinetic and toxicodynamic analyses. We applied NBL to five different exposure data sets with the aim of understanding how toxicokinetics and toxicodynamics (TK-TD) of essential, beneficial, and nonessential elements may influence conformity to the Newcomb-Benford distribution (NBD) in mammalian biosamples. Data sets were collected for observational and experimental studies and measured a range of concentrations of essential, beneficial, and nonessential elements in human adults and children as well as mice. Findings suggest that underlying physiological mechanisms, such as preferential uptake of essential elements, may lead to violations of the NBD and that in these cases, the violation appeared to follow a characteristic rotated sigmoidal curve. Findings also indicate that competitive co-exposure to a beneficial and nonessential element results in a violation without a characteristic trend. Therefore, the use of the NBL in exposure data to detect data manipulation may be flawed