Dermal uptake of nicotine from air and clothing: Experimental verification.

This study aims to elucidate in greater detail the dermal uptake of nicotine from air or from nicotine-exposed clothes, which was demonstrated recently in a preliminary study. Six non-smoking participants were exposed to gaseous nicotine (between 236 and 304 µg/m3 ) over 5 hours while breathing clean air through a hood. Four of the participants wore only shorts and 2 wore a set of clean clothes. One week later, 2 of the bare-skinned participants were again exposed in the chamber, but they showered immediately after exposure instead of the following morning. The 2 participants who wore clean clothes on week 1 were now exposed wearing a set of clothes that had been exposed to nicotine. All urine was collected for 84 hours after exposure and analyzed for nicotine and its metabolites, cotinine and 3OH-cotinine. All participants except those wearing fresh clothes excreted substantial amounts of biomarkers, comparable to levels expected from inhalation intake. Uptake for 1 participant wearing exposed clothes exceeded estimated intake via inhalation by >50%. Biomarker excretion continued during the entire urine collection period, indicating that nicotine accumulates in the skin and is released over several days. Absorbed nicotine was significantly lower after showering in 1 subject but not the other. Differences in the normalized uptakes and in the excretion patterns were observed among the participants. The observed cotinine half-lives suggest that non-smokers exposed to airborne nicotine may receive a substantial fraction through the dermal pathway. Washing skin and clothes exposed to nicotine may meaningfully decrease exposure.

Measurements of dermal uptake of nicotine directly from air and clothing.

In this preliminary study, we have investigated whether dermal uptake of nicotine directly from air or indirectly from clothing can be a meaningful exposure pathway. Two participants wearing only shorts and a third participant wearing clean cotton clothes were exposed to environmental tobacco smoke (ETS), generated by mechanically "smoking" cigarettes, for three hours in a chamber while breathing clean air from head-enveloping hoods. The average nicotine concentration (420 µg/m3 ) was comparable to the highest levels reported for smoking sections of pubs. Urine samples were collected immediately before exposure and 60 hour post-exposure for bare-skinned participants. For the clothed participant, post-exposure urine samples were collected for 24 hour. This participant then entered the chamber for another three-hour exposure wearing a hood and clothes, including a shirt that had been exposed for five days to elevated nicotine levels. The urine samples were analyzed for nicotine and two metabolites-cotinine and 3OH-cotinine. Peak urinary cotinine and 3OH-cotinine concentrations for the bare-skinned participants were comparable to levels measured among non-smokers in hospitality environments before smoking bans. The amount of dermally absorbed nicotine for each bare-skinned participant was conservatively estimated at 570 µg, but may have been larger. For the participant wearing clean clothes, uptake was ~20 µg, and while wearing a shirt previously exposed to nicotine, uptake was ~80 µg. This study demonstrates meaningful dermal uptake of nicotine directly from air or from nicotine-exposed clothes. The findings are especially relevant for children in homes with smoking or vaping.

Dermal uptake of phthalates from clothing: Comparison of model to human participant results.

In this research, we extend a model of transdermal uptake of phthalates to include a layer of clothing. When compared with experimental results, this model better estimates dermal uptake of diethylphthalate and di-n-butylphthalate (DnBP) than a previous model. The model predictions are consistent with the observation that previously exposed clothing can increase dermal uptake over that observed in bare-skin participants for the same exposure air concentrations. The model predicts that dermal uptake from clothing of DnBP is a substantial fraction of total uptake from all sources of exposure. For compounds that have high dermal permeability coefficients, dermal uptake is increased for (i) thinner clothing, (ii) a narrower gap between clothing and skin, and (iii) longer time intervals between laundering and wearing. Enhanced dermal uptake is most pronounced for compounds with clothing-air partition coefficients between 104 and 107 . In the absence of direct measurements of cotton cloth-air partition coefficients, dermal exposure may be predicted using equilibrium data for compounds in equilibrium with cellulose and water, in combination with computational methods of predicting partition coefficients.

Dermal uptake directly from air under transient conditions: advances in modeling and comparisons with experimental results for human subjects.

To better understand the dermal exposure pathway, we enhance an existing mechanistic model of transdermal uptake by including skin surface lipids (SSL) and consider the impact of clothing. Addition of SSL increases the overall resistance to uptake of SVOCs from air but also allows for rapid transfer of SVOCs to sinks like clothing or clean air. We test the model by simulating di-ethyl phthalate (DEP) and di-n-butyl phthalate (DnBP) exposures of six bare-skinned (Weschler et al. 2015, Environ. Health Perspect., 123, 928) and one clothed participant (Morrison et al. 2016, J. Expo. Sci. Environ. Epidemiol., 26, 113). The model predicts total uptake values that are consistent with the measured values. For bare-skinned participants, the model predicts a normalized mass uptake of DEP of 3.1 (µg/m2 )/(µg/m3 ), whereas the experimental results range from 1.0 to 4.3 (µg/m2 )/(µg/m3 ); uptake of DnBP is somewhat overpredicted: 4.6 (µg/m2 )/(µg/m3 ) vs. the experimental range of 0.5-3.2 (µg/m2 )/(µg/m3 ). For the clothed participant, the model predicts higher than observed uptake for both species. Uncertainty in model inputs, including convective mass transfer coefficients, partition coefficients, and diffusion coefficients, could account for overpredictions. Simulations that include transfer of skin oil to clothing improve model predictions. A dynamic model that includes SSL is more sensitive to changes that impact external mass transfer such as putting on and removing clothes and bathing.

Associations between selected allergens, phthalates, nicotine, polycyclic aromatic hydrocarbons, and bedroom ventilation and clinically confirmed asthma, rhinoconjunctivitis, and atopic dermatitis in preschool children.

Previous studies, often using data from questionnaires, have reported associations between various characteristics of indoor environments and allergic disease. The aim of this study has been to investigate possible associations between objectively assessed indoor environmental factors and clinically confirmed asthma, rhinoconjunctivitis, and atopic dermatitis. The study is a cross-sectional case-control study of 500 children aged 3-5 years from Odense, Denmark. The 200 cases had at least two parentally reported allergic diseases, while the 300 controls were randomly selected from 2835 participating families. A single physician conducted clinical examinations of all 500 children. Children from the initially random control group with clinically confirmed allergic disease were subsequently excluded from the control group and admitted in the case group, leaving 242 in the healthy control group. For most children, specific IgE's against various allergens were determined. In parallel, dust samples were collected and air change rates were measured in the children's bedrooms. The dust samples were analyzed for phthalate esters, polycyclic aromatic hydrocarbons (PAH), nicotine, and various allergens. Among children diagnosed with asthma, concentrations of nicotine were higher (P < 0.05) and cat allergens were lower (P < 0.05) compared with the healthy controls; air change rates were lower for those sensitized (specific IgE+) compared with those not sensitized (specific IgE-, P < 0.05); and dust mite allergens were higher for specific IgE+ cases compared with healthy controls (P < 0.05). When disease status was based solely on questionnaire responses (as opposed to physician diagnosis), significant associations were found between di(2-ethylhexyl) phthalate (DEHP) and dog allergens in dust and current wheeze.

Children's health and its association with indoor environments in Danish homes and daycare centres - methods.

UNLABELLED: The principle objective of the Danish research program 'Indoor Environment and Children's Health' (IECH) was to explore associations between various exposures that children experience in their indoor environments (specifically their homes and daycare centers) and their well-being and health. The targeted health endpoints were allergy, asthma, and certain respiratory symptoms. The study was designed with two stages. In the first stage, a questionnaire survey was distributed to more than 17,000 families with children between the ages of 1 and 5. The questionnaire focused on the children's health and the environments within the homes they inhabited and daycare facilities they attended. More than 11,000 questionnaires were returned. In the second stage, a subsample of 500 children was selected for more detailed studies, including an extensive set of measurements in their homes and daycare centers and a clinical examination; all clinical examinations were carried out by the same physician. In this study, the methods used for data collection within the IECH research program are presented and discussed. Furthermore, initial findings are presented regarding descriptors of the study population and selected characteristics of the children's dwellings and daycare centers. PRACTICAL IMPLICATIONS: This study outlines methods that might be followed by future investigators conducting large-scale field studies of potential connections between various indoor environmental factors and selected health endpoints. Of particular note are (i) the two-stage design - a broad questionnaire-based survey followed by a more intensive set of measurements among a subset of participants who have been selected based on their responses to the questionnaire; (ii) the case-base approach utilized in the stage 2 in contrast to the more commonly used case-control approach; (iii) the inclusion of the children's daycare environment when conducting intensive sampling to more fully capture the children's total indoor exposure; and (iv) all clinical examinations conducted by the same physician. We recognize that future investigators are unlikely to fully duplicate the methods outlined in this study, but we hope that it provides a useful starting point in terms of factors that might be considered when designing such a study.

Reflections on the state of research: indoor environmental quality.

UNLABELLED: More than 30 years after the First International Indoor Climate Symposium, ten researchers from the USA, Slovakia, Sweden, and Denmark gathered to review the current status of indoor environmental research. We initiated our review with discussions during the 1-day meeting and followed that with parallel research and writing efforts culminating with internal review and revision cycles. In this paper, we present our choices for the most important research findings on indoor environmental quality from the past three decades followed by a discussion of the most important research questions in our field today. We then continue with a discussion on whether there are research areas for which we can 'close the book' and say that we already know what is needed. Finally, we discuss whether we can maintain our identity in the future or it is time to team up with new partners. PRACTICAL IMPLICATIONS: In the early years of this field, the accumulated knowledge was small and it was possible for any researcher to acquire a complete understanding. To do so has become impossible today as what we know has grown to exceed the learning capacity of any person. These circumstances challenge us to work collectively to synthesize what we do know and to define clearly what remains to be learned. If we fail to do these things well, we risk repeating research without memory, an inefficiency that we cannot afford.

Small difference in international normalized ratio may yield a significant impact on prioritizing patients listed for liver transplantation.

Priority for liver transplantation is currently based on the Model for End-stage Liver Disease (MELD) score. The aim of our study was to assess in detail the contribution of international normalized ratio (INR) differences for MELD scores because of interlaboratory variability. The samples from 92 cirrhotic patients were measured on different systems combining three coagulometers and three thromboplastin products to determine variations in INR and MELD score. The INR differences among the first four systems varied between 0 and 0.2, resulting in MELD differences of 0 to 2. The MELD scores of 92 patients changed only among 10 possible integers so that normally 2 to 10 patients shared the same MELD value. In some cases, one MELD score difference resulted in a 10 superpositioning on the waiting list. Including one more system (mechanical vs optical) into our investigations achieved a five MELD difference. Supposing an extreme situation where one patient competes with his or her lowest, all the other with their highest possible score (and visa versa), the difference may be even 20 positions, overturning the complete waiting list. In conclusion substantial interlaboratory differences in MELD score have profound clinical consequences.

Maternal cytokine balance on the third postpartum day is not affected by the mode of delivery after healthy pregnancies.

Previous reports have suggested that delivery is associated with the induction of inflammatory cytokines. The present study was designed to investigate whether increased cytokine production was present on postpartum day 3 after a normal pregnancy and whether any changes were associated with the mode of delivery. In total, 33 pregnant women were enrolled; 18 delivered vaginally and 15 underwent an elective caesarean section (C-section). The levels of 17 cytokines and growth hormones were measured at the beginning of delivery or before anaesthesia and on postpartum day 3. While interleukin (IL)-6 and IL-8 levels decreased significantly postpartum, other cytokine concentrations were comparable before and after delivery. Only IL-7 levels were significantly increased in the C-section patients compared with the vaginal birth patients postpartum. In conclusion, there was no risk of a prolonged maternal inflammatory reaction after an uncomplicated vaginal birth or elective C-section, so it is probably not necessary to consider this as an issue when making a decision on the mode of delivery following uncomplicated pregnancy.

Sensory pollution from bag filters, carbon filters and combinations.

UNLABELLED: Used ventilation filters are a major source of sensory pollutants in air handling systems. The objective of the present study was to evaluate the net effect that different combinations of filters had on perceived air quality after 5 months of continuous filtration of outdoor suburban air. A panel of 32 subjects assessed different sets of used filters and identical sets consisting of new filters. Additionally, filter weights and pressure drops were measured at the beginning and end of the operation period. The filter sets included single EU5 and EU7 fiberglass filters, an EU7 filter protected by an upstream pre-filter (changed monthly), an EU7 filter protected by an upstream activated carbon (AC) filter, and EU7 filters with an AC filter either downstream or both upstream and downstream. In addition, two types of stand-alone combination filters were evaluated: a bag-type fiberglass filter that contained AC and a synthetic fiber cartridge filter that contained AC. Air that had passed through used filters was most acceptable for those sets in which an AC filter was used downstream of the particle filter. Comparable air quality was achieved with the stand-alone bag filter that contained AC. Furthermore, its pressure drop changed very little during the 5 months of service, and it had the added benefit of removing a large fraction of ozone from the airstream. If similar results are obtained over a wider variety of soiling conditions, such filters may be a viable solution to a long recognized problem. PRACTICAL IMPLICATIONS: The present study was designed to address the emission of sensory offending pollutants from loaded ventilation filters. The goal was to find a low-polluting solution from commercially available products. The results indicate that the use of activated carbon (AC) filters downstream of fiberglass bag filters can reduce the degradation of air quality that occurs with increasing particle loading. A more practical solution, yet comparably effective, is a stand-alone particle filter that incorporates AC. In either case, further testing under a variety of conditions is recommended before making design decisions regarding the type of filters best suited to efficient building operation.

Anemia is associated with mortality in kidney-transplanted patients--a prospective cohort study.

Although anemia is a known risk factor of mortality in several patient populations, no prospective study to date has demonstrated association between anemia and mortality in kidney-transplanted patients. In our prospective cohort study (TransQol-HU Study), we tested the hypothesis that anemia is associated with mortality and graft failure (return to dialysis) in transplanted patients. Data from 938 transplanted patients, followed at a single outpatient transplant center, were analyzed. Sociodemographic parameters, laboratory data, medical history and information on comorbidity were collected at baseline. Data on 4-year outcome (graft failure, mortality or combination of both) were collected prospectively from the patients' charts. Both mortality and graft failure rate during the 4-year follow-up was significantly higher in patients who were anemic at baseline (for anemic vs nonanemic patients, respectively: mortality 18% vs. 10%; p < 0.001; graft failure 17% vs 6%; p < 0.001). In multivariate Cox proportional hazard models the presence of anemia significantly predicted mortality (HR = 1.690; 95% CI: 1.115-2.560) and also graft failure (HR = 2.465; 95% CI: 1.485-4.090) after adjustment for several covariables. Anemia, which is a treatable complication, is significantly and independently associated with mortality and graft failure in kidney-transplanted patients.

Initial studies of oxidation processes on filter surfaces and their impact on perceived air quality.

Used filters can be a strong sensory pollutant source. Oxidation processes, especially those initiated by ozone, may contribute to the pollutants emitted from such filters. In the present study, ozone was added to the airstream passing through used ventilation filters. Two flow rates were examined. While the upstream ozone concentration was approximately 75 ppb, the concentrations downstream of the filter were initially 35-50% lower. However, within an hour downstream concentrations were only 5-10% lower than those upstream. These filter samples were then placed for 48 h in nitrogen, ambient air containing less than 5 ppb ozone, or ambient air at an elevated temperature. This resulted in partial regeneration of the ozone removal capability of the filter. In analogous experiments, lower ozone removal occurred when the filter samples were first ventilated for 24 h with ozone-free air before making the measurements. Samples from a new filter removed <10% of the ozone in the airstream, and removal remained relatively constant over time. In companion studies, human subjects assessed the air passing through various used filter samples. In the initial evaluation each of the four filter samples, taken from the same filter and ventilated for 24 h, were assessed to be equivalent. The next evaluation was immediately after the samples had been kept for 24 h in either nitrogen, air, air at an elevated temperature or ozone. The nitrogen-treated filter was assessed to be best, while the ozone-treated filter was assessed to be the worst. The final evaluation occurred after ambient air had passed through the 'treated' filters for 2 h. All such ventilated filters were assessed to be more acceptable than immediately after the 24-h treatments; the ozonized and air-treated filters were the most polluting of the four. Practical Implications The present paper supports previous findings that loaded ventilation filters can be significant sources of sensory pollution. Replacing a loaded filter with a new filter temporarily removes this source of pollution. However, the present study does not provide an answer to how frequently changes are needed under different conditions. The results indicate that in cases of intermittent operation of ventilation systems, the airflow through the polluted filters should be restarted in sufficient time prior to occupancy to purge odorous pollutants that have accumulated on the filter surface. Removal of ozone upstream of the particle filters may further improve perceived air quality in the space downstream of the filter bank. Future efforts related to the development and application of low-polluting filtration systems are warranted.