Electronic Nicotine-Delivery Systems for Smoking Cessation.

BACKGROUND: Electronic nicotine-delivery systems - also called e-cigarettes - are used by some tobacco smokers to assist with quitting. Evidence regarding the efficacy and safety of these systems is needed. METHODS: In this open-label, controlled trial, we randomly assigned adults who were smoking at least five tobacco cigarettes per day and who wanted to set a quit date to an intervention group, which received free e-cigarettes and e-liquids, standard-of-care smoking-cessation counseling, and optional (not free) nicotine-replacement therapy, or to a control group, which received standard counseling and a voucher, which they could use for any purpose, including nicotine-replacement therapy. The primary outcome was biochemically validated, continuous abstinence from smoking at 6 months. Secondary outcomes included participant-reported abstinence from tobacco and from any nicotine (including smoking, e-cigarettes, and nicotine-replacement therapy) at 6 months, respiratory symptoms, and serious adverse events. RESULTS: A total of 1246 participants underwent randomization; 622 participants were assigned to the intervention group, and 624 to the control group. The percentage of participants with validated continuous abstinence from tobacco smoking was 28.9% in the intervention group and 16.3% in the control group (relative risk, 1.77; 95% confidence interval, 1.43 to 2.20). The percentage of participants who abstained from smoking in the 7 days before the 6-month visit was 59.6% in the intervention group and 38.5% in the control group, but the percentage who abstained from any nicotine use was 20.1% in the intervention group and 33.7% in the control group. Serious adverse events occurred in 25 participants (4.0%) in the intervention group and in 31 (5.0%) in the control group; adverse events occurred in 272 participants (43.7%) and 229 participants (36.7%), respectively. CONCLUSIONS: The addition of e-cigarettes to standard smoking-cessation counseling resulted in greater abstinence from tobacco use among smokers than smoking-cessation counseling alone. (Funded by the Swiss National Science Foundation and others; ESTxENDS ClinicalTrials.gov number, NCT03589989.).

Repeated Human Exposure to Semivolatile Organic Compounds by Inhalation: Novel Protocol for a Nonrandomized Study.

BACKGROUND: Semivolatile organic compounds (SVOCs) comprise several different chemical families used mainly as additives in many everyday products. SVOCs can be released into the air as aerosols and deposit on particulate matter during use by dispersion, evaporation, or abrasion. Phthalates are SVOCs of growing concern due to their endocrine-disrupting effects. Human data on the absorption, distribution, metabolism, and excretion (ADME) of these compounds upon inhalation are almost nonexistent. OBJECTIVE: The goal of this study is to develop a method for repeated inhalation exposures to SVOCs to characterize their ADME in humans. METHODS: We will use diethylhexyl phthalate (DEHP), a major indoor air pollutant, as a model SVOC in this novel protocol. The Swiss official Commission on Ethics in Human Research, Canton de Vaud, approved the study on October 14, 2020 (project-ID 2020-01095). Participants (n=10) will be repeatedly exposed (2 short daily exposures over 4 days) to isotope-labeled DEHP (DEHP-d4) to distinguish administered exposures from background exposures. DEHP-d4 aerosols will be generated with a small, portable, aerosol-generating device. Participants will inhale DEHP-d4-containing aerosols themselves with this device at home. Air concentrations of the airborne phthalates will be less than or equal to their occupational exposure limit (OEL). DEHP-d4 and its metabolites will be quantified in urine and blood before, during, and after exposure. RESULTS: Our developed device can generate DEHP-d4 aerosols with diameters of 2.5 µm or smaller and a mean DEHP-d4 mass of 1.4 (SD 0.2) µg per puff (n=6). As of May 2023, we have enrolled 5 participants. CONCLUSIONS: The portable device can be used to generate phthalate aerosols for repeated exposure in human studies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51020.

Quantitative risk assessment of skin sensitising pesticides: Clinical and toxicological considerations.

Like many other consumer and occupational products, pesticide formulations may contain active ingredients or co-formulants which have the potential to cause skin sensitisation. Currently, there is little evidence they do, but that could just reflect lack of clinical investigation. Consequently, it is necessary to carry out a safety evaluation process, quantifying risks so that they can be properly managed. A workshop on this topic in 2022 discussed how best to undertake quantitative risk assessment (QRA) for pesticide products, including learning from the experience of industries, notably cosmetics, that already undertake such a process routinely. It also addressed ways to remedy the matter of clinical investigation, even if only to demonstrate the absence of a problem. Workshop participants concluded that QRA for skin sensitisers in pesticide formulations was possible, but required careful justification of any safety factors applied, as well as improvements to the estimation of skin exposure. The need for regulations to stay abreast of the science was also noted. Ultimately, the success of any risk assessment/management for skin sensitisers must be judged by the clinical picture. Accordingly, the workshop participants encouraged the development of more active skin health monitoring amongst groups most exposed to the products.

Determinants of Pesticide Exposure in Occupational Studies: A Meta-Analysis.

Few epidemiological studies use exposure determinants specifically tailored to assess pesticide or plant protection product (PPP) exposures when assessing presumed association between occupational exposure and health outcomes among agricultural workers. This lack of exposure specificity could lead to results that fail to detect an association. It could be related to the lack of consensus on exposure assessment methods and the choice of exposure determinants. We conducted a meta-analysis following the PRISMA checklist to identify PPP exposure determinants used in occupational studies and identified exposure determinants that best characterized agricultural exposures to PPPs. Out of 1436 studies identified, 71 were included. The exposure determinants identified were active ingredients, chemical classes, types of PPP, crops, tasks, frequencies, duration, lifetime exposure days, and intensity-weighted exposure days. Only six over 17 associations between exposure determinants and health outcomes were found with moderate quality of evidence. Overall, epidemiological studies had difficulty defining relevant determinants to characterize PPP exposures for agricultural workers. We recommend that a standardized list of determinants for PPP exposures in occupational exposure studies should include information on formulations, intensity, duration, and frequency of PPP exposure. Harmonized data collection on exposure and health outcomes are required as well as standard units for each exposure determinant.

Dosimetry in the lungs of α-particles (210Po) and ß-particles (210Pb) present in the tobacco smoke of conventional cigarettes and heated tobacco products.

Tobacco products contain radioactive 210Pb and 210Po which can be transferred from the filler to the mainstream smoke. When inhaled, they can contribute to the radioactive dose to the lungs and are suspected to significantly contribute to lung cancer from smoking. Currently, no data are available on the radioactive risk of the heated tobacco products (HTP). However, due to the relatively high heat involved in some of these devices, there are concerns about the volatility of polonium particles. Here we used data on the 210Po and 210Pb content in tobacco smoke along with biokinetic and dosimetric models to compute the effective dose induced by conventional smoking and by using an HTP device (PMI IQOS system). Results show that conventional smoking of one pack per day induces a dose to the lung of about 0.3 mSv/year. This dose decreases by a factor of ten (0.03 mSv/year) for the IQOS system. However, this dose reduction is not obtained by specific countermeasures but by the fact that the IQOS system heats only 15% of the tobacco filler to the target temperature of 330 °C. When heated homogeneously to 300 °C, both conventional and Heets (IQOS) cigarettes release about 80% of the 210Po from the tobacco, leading to similar doses to lungs.

Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) soil contamination in Lausanne, Switzerland: Combining pollution mapping and human exposure assessment for targeted risk management.

In December 2020, high soil concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) were discovered across large parts of Lausanne, Switzerland. Concentrations reached up to 640 ng TEQWHO-2005/kg dry weight. The most likely source was a former municipal waste incinerator. A three-step, multidisciplinary approach to human health risk assessment was conducted to determine the potential population exposure to PCDD/Fs and identify appropriate preventive measures. First, exposure scenarios were developed based on contaminated land uses. Second, the toxicological risks of different scenarios were evaluated using a toxicokinetic model estimating increases in blood serum PCDD/F concentrations over background concentrations from the general population's food consumption. Third, a detailed geostatistical mapping of PCDD/F soil contamination was performed. Stochastic simulations with an external drift and an anisotropic model of the variogram were generated to incorporate the effects of distance from emission source, topography, and main wind directions on the spatial distribution of PCDD/Fs in topsoil. Three main scenarios were assessed: i) direct ingestion of soil by children in playgrounds; ii) consumption of vegetables from private gardens by children and adults; and iii) consumption of food from livestock and poultry raised on contaminated soil. The worst exposure scenario involved the consumption of eggs from private hen houses, resulting in PCDD/F concentrations in serum an order of magnitude higher than might normally be expected. No relevant increases in serum concentrations were calculated for direct soil ingestion and vegetable consumption, except for cucurbitaceous vegetables. Combining mapping and exposure scenario assessment resulted in targeted protective measures for land users, especially concerning food consumption. The results also raised concerns about the potential unsafe consumption of products derived from animals raised on land with PCDD/F concentrations only moderately over environmental background levels.

Associations between urinary biomarkers of oxidative stress and biomarkers of tobacco smoke exposure in smokers.

Oxidative stress can contribute to the development of diseases, and may originate from exposures to toxicants commonly found in air pollution and cigarette smoke such as polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs). Yet, associations between these exposures and oxidative stress biomarkers are poorly characterized. We report here novel associations between 14 exposure biomarkers of PAHs and VOCs, and two oxidative stress biomarkers; 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-isoprostaglandin F2α (8-isoprostane) in urine obtained from smokers participating in an ongoing clinical study (ESTxENDS, NCT03589989). We also assessed associations between six biomarkers of tobacco smoke exposure (metabolites of nicotine and tobacco-specific nitrosamines (TSNAs)) and both oxidative stress biomarkers. We then quantified the relative importance of each family of the 20 exposure biomarkers on oxidative stress. Participating smokers (153 men and 117 women, median age 44 years) had on average smoked 25 [2-62] years and smoked about 17 [5-40] cigarettes per day at the time of the study. Multiple linear regression results showed an association between 8-oxodG concentrations and the following metabolites in decreasing relative importance: PAHs (beta coefficient ß = 0.105, p-value <0.001, partial R2 = 0.15) > VOCs (ß = 0.028, p < 0.001, partial R2 = 0.09) > nicotine (ß = 0.226, p < 0.001, partial R2 = 0.08); and between 8-isoprostane concentrations and metabolites of PAHs (ß = 0.117, p < 0.001, partial R2 = 0.14) > VOCs (ß = 0.040, p < 0.001, partial R2 = 0.14) > TSNAs (ß = 0.202, p = 0.003, partial R2 = 0.09) > nicotine (ß = 0.266, p < 0.001, partial R2 = 0.08). Behavioral factors known to contribute to oxidative stress, including sleep quality, physical activity, and alcohol consumption, did not play a significant role. Exposures to PAHs and VOCs among smokers were significantly associated with oxidative stress.

210Po and 210Pb content in the smoke of Heated Tobacco Products versus Conventional Cigarette smoking.

210Po is a radioactive component of conventional cigarette tobacco smoke and is a recognized carcinogen. Despite the expanding market of heated tobacco products, no data are available on the activity of 210Po in the smoke of IQOS Heets cigarette. We determined the 210Po activity in the mainstream smoke of thirteen cigarette brands available on the Swiss market using a smoking machine and compared the results to the 210Po activity measured in the mainstream smoke of the IQOS system. In addition, we measured the 210Po and 210Pb loss on heating after uniform heating from 50 to 600 °C for several cigarette brands and the Heets cigarettes. 13.6 ± 4.1% of 210Po activity was found in the mainstream smoke in conventional cigarette smoking (7% for 210Pb). This dropped to 1.8 ± 0.3% in the mainstream smoke of IQOS Heets. Conversely, when the tobacco was heated uniformly at 330 °C, a loss of 210Po of more than 80% was observed for all type of cigarettes. Apparently, IQOS significantly reduced the 210Po and 210Pb activities in the mainstream smoke. However, our results show that only 15% of the Heets tobacco reaches 330 °C with IQOS. While IQOS reduces the 210Po and 210Pb activities in the mainstream smoke compared to conventional cigarettes, it only heats a marginal fraction of the tobacco present in the Heets cigarette. Because smoking is an addiction (mostly due to nicotine), IQOS could possibly deliver an unsatisfactory dose of nicotine to a Heets cigarette smoker, as most of the tobacco is left unaltered.

Monitoring of pesticides in ambient air: Prioritization of substances.

Despite the richness of data collected on pesticide concentrations in ambient air in France, knowledge on this topic remains partial and heterogeneous in the absence of specific regulations. The population exposure remains thus difficult to estimate; therefore it was necessary to define modalities for implementing national monitoring of pesticides in ambient air in metropolitan France and in the overseas territories. The objective of this work was to identify which active substances (a.s.) have to be monitored in priority. As part of a collective expertise, a group of multidisciplinary experts has developed a method to rank active substances authorised as plant protection products, biocides and antiparasitic agents, which were available on the French market in 2015. A 3-steps approach has been developed. The first step consisted of a theoretical approach based on a hierarchy of substances according to four criteria: (a) national uses, (b) emission potential to the air, (c) persistence in the air, and (d) chronic toxicity. The three first criteria give information on their potential to be present in the atmosphere, and the fourth criterion allows to consider their potential of hazard. The second step was an observational approach based on existing database on pesticide air measurements in France. In the third step, both approaches were combined using decision trees to select priority pesticides. Among the 1316 a.s. first identified from the EU Pesticides database, 90 were selected, among which 43 required metrological and/or analytical development. The experts recommended confirming the relevance of performing a longer term monitoring of these a. s. after a one-year exploratory campaign. The proposed method is reproduceable, transparent, easy to update (e.g. in the light of a change in product authorization), and can be adapted to other agricultural and geographical conditions, and objectives (e.g. monitoring of the ecotoxicological effects of pesticides).

Levels of the oxidative stress biomarker malondialdehyde in tears of patients with central serous chorioretinopathy relate to disease activity.

Purpose: Central serous chorioretinopathy (CSCR) has been associated with oxidative stress-related risk factors. The objective of this study was to optimize an analytical method for evaluating the oxidative stress biomarker malondialdehyde (MDA) in human tears and determine its level in the tears of patients with CSCR. Methods: In this pilot study, tear samples were obtained from 34 healthy donors and 31 treatment-naïve CSCR male patients (eight with acute CSCR and 23 with chronic CSCR). Two analytical methods based on high-performance liquid chromatography followed by fluorescence detection were evaluated, with either 2-thiobarbituric derivative (TBA) or 2-aminoacridone (2-AA). Activity of CSCR was defined by the serous retinal detachment (SRD) height, which was measured by two independent observers on spectral-domain optical coherence tomography. Results: The 2-AA method showed higher sensitivity and precision compared to the TBA method. When the 2-AA method was applied to tears from healthy donors, the levels of MDA were statistically significantly higher in men compared to women (mean ± standard deviation, SD: 9,914 nM ± 6,126 versus 4,635 nM ± 1,173, p = 0.006). No difference was found in tear MDA levels between male patients with CSCR and age-matched control men (p = 0.17). However, MDA levels were statistically significantly higher in acute compared to chronic CSCR cases (mean ± SD: 12,295 nM ± 8,495 versus 6,790 ± 3,969 nM, p = 0.03). Additionally, there was a correlation between MDA levels and RPE leakage, quantified by the height of the serous retinal detachment (p = 0.02, r = 0.40). Conclusions: Levels of MDA in tears, measured with an optimized analytical method, correlate with RPE leakage in CSCR.

Human skin permeation rates ex vivo following exposures to mixtures of glycol ethers.

Skin exposure to cleaning products in the general and occupational population are a public health concern. Among the most frequently identified amphiphilic organic solvents in cleaning products are propylene glycol monomethyl ether (PGME) and propylene glycol n-butyl ether (PGBE). Internal dose from skin exposure may be efficiently evaluated using in vitro flow-through diffusion cells with excised human skin. Our aim in this study was two-fold; 1) characterize the permeation rates (J), time lag (Tlag), and permeation coefficients (Kp) of PGME and PGBE in human ex-vivo skin permeation assays, and 2) determine a possible mixture effect on skin permeation characteristics when applied together. Our results showed a short Tlag for PGME and was reduced further depending on the amount of PGBE in the mixture (Tlag was reduced from 2 h to 1-1.7 h) for fresh skin. PGBE Tlag slightly increased when mixed with 50 % or more PGME. Permeation rate decreased to half for both PGME and PGBE in mixture at any concentration. This substantial permeation was greater with previously frozen skin. This mixture effect could favor permeation of other compounds through human skin.

Parental occupational exposure to pesticides and risk of childhood cancer in Switzerland: a census-based cohort study.

BACKGROUND: Pesticide exposure is a suspected risk factor for childhood cancer. We investigated the risk of developing childhood cancer in relation to parental occupational exposure to pesticides in Switzerland for the period 1990-2015. METHODS: From a nationwide census-based cohort study in Switzerland, we included children aged < 16 years at national censuses of 1990 and 2000 and followed them until 2015. We extracted parental occupations reported at the census closest to the birth year of the child and estimated exposure to pesticides using a job exposure matrix. Cox proportional hazards models, adjusted for potential confounders, were fitted for the following outcomes: any cancer, leukaemia, central nervous system tumours (CNST), lymphoma, non-CNS solid tumours. RESULTS: Analyses of maternal (paternal) exposure were based on approximately 15.9 (15.1) million-person years at risk and included 1891 (1808) cases of cancer, of which 532 (503) were leukaemia, 348 (337) lymphomas, 423 (399) CNST, and 588 (569) non-CNS solid tumours. The prevalence of high likelihood of exposure was 2.9% for mothers and 6.7% for fathers. No evidence of an association was found with maternal or paternal exposure for any of the outcomes, except for "non-CNS solid tumours" (High versus None; Father: adjusted HR [95%CI] =1.84 [1.31-2.58]; Mother: 1.79 [1.13-2.84]). No evidence of an association was found for main subtypes of leukaemia and lymphoma. A post-hoc analysis on frequent subtypes of "non-CNS solid tumours" showed positive associations with wide CIs for some cancers. CONCLUSION: Our study suggests an increased risk for solid tumours other than in the CNS among children whose parents were occupationally exposed to pesticides; however, the small numbers of cases limited a closer investigation of cancer subtypes. Better exposure assessment and pooled studies are needed to further explore a possible link between specific childhood cancers types and parental occupational exposure to pesticides.

Tolylfluanid permeates human skin slowly and as dimethylamino sulfotoluidid (DMST).

Tolylfluanid (TF) is a sensitizing biocide used in antifouling products and wood preservatives. Paint application is associated with skin exposure; however, the importance of this exposure route is uncertain as TF skin permeation rates are lacking in the peer-reviewed scientific literature. TF is a lipophilic powder that hydrolyses rapidly in contact with water to dimethylamino sulfotoluidid (DMST). DMST is also a TF metabolite. We characterized TF and DMST skin permeation using an ex vivo flow-through diffusion system with viable and frozen human skin. TF permeated as DMST with a low permeation rate (0.18 ± 0.05 µg/cm2/h) and a moderate time lag (7.1 ± 1.4 h) in viable human skin. Applying DMST gave a 3.5-fold lower permeation rate (0.05 ± 0.01 µg/cm2/h) compared to TF under a similar experimental setting. We simulated paint activities in an exposure chamber to understand a possible skin exposure from airborne TF concentrations. Although, paint can deposit onto the skin during work activities, TF permeation when paint was applied to human skin ex vivo was very low (as TF: 0.004 ± 0.005 µg/cm2/h, and as DMST: 0.02 ± 0.001 µg/cm2/h). Our results show that TF can permeate skin, and consequently, can contribute to sensitization, which support previous reports on sensitization in TF exposed workers.

Rapid Liquid Chromatography-Tandem Mass Spectrometry Analysis of Two Urinary Oxidative Stress Biomarkers: 8-oxodG and 8-isoprostane.

Human biomonitoring of oxidative stress relies on urinary effect biomarkers such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and 8-iso-prostaglandin F2α (8-isoprostane); however, their levels reported for similar populations are inconsistent in the scientific literature. One of the reasons is the multitude of analytical methods with varying degrees of selectivity used to quantify these biomarkers. Single-analyte methods are often used, requiring multiple injections that increase both time and cost. We developed a rapid ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to quantify both urinary biomarkers simultaneously. A reversed-phase column using a gradient consisting of 0.1% acetic acid in water and 0.1% acetic acid in methanol/acetonitrile (70:30) was used for separation. The MS detection was by positive (8-oxodG) and negative (8-isoprostane) ion-mode by multiple reaction monitoring. Very low limit of detection (<20 pg/mL), excellent linearity (R2 > 0.999), accuracy (near 100%), and precision (CV < 10%) both for intra-day and inter-day experiments were achieved, as well as high recovery rates (>91%). Matrix effects were observed but were compensated by using internal standards. Our newly developed method is applicable for biomonitoring studies as well as large epidemiological studies investigating the effect of oxidative damage, as it requires only minimal clean up using solid phase extraction.

Ethanolamines permeate slowly across human skin ex vivo, but cause severe skin irritation at low concentrations.

Skin exposures are common during cleaning activities, and may contribute to the overall body burden. Cleaning products may contain irritants such as monoethanolamine (MEA) and diethanol amine (DEA). The significance of the skin exposure route is unknown, as no estimates for MEA skin permeation are available. We used in vitro flow-through diffusion cells with excised fresh human skin to measure skin permeation, and assessed skin damage with histological methods. MEA(aq) by itself (2%) or as a constituent in cleaning products (0.25% working solution) did not permeate after 1 h or 24 h of exposure. MEA(aq) (10%) did not permeate skin after 1 h but after 24 h with a delay (Tlag; 7 h) and a moderate permeation rate (J; 26.6 µg/cm2/h). MEA permeation rate was 20-fold greater (544 µg/cm2/h) and » of the time lag (1.5 h) when applied as undiluted cleaning product (13% MEA) compared to 10% MEA(aq). DEA in cleaning products did not permeate skin after 24 h. MEA and DEA produced skin irritations at low concentrations (1% MEA) and severe skin irritations when tested as a constituent in cleaning products. Absorption increased from 0 to 3% after 24 h to 14-29% after 88 h of MEA exposure, and is likely explained by the increased damage of the skin barrier. Limitations of this study are the low number of skin donors (N = 5) available. Our results demonstrate that topically applied MEA permeates across human skin relatively slowly and not below 5% while relatively extensively as a constituent of a commercial cleaning product.

[« Heated ¼ tobacco products : what do you need to know ?] / Produits du tabac «chauffé¼ : que faut­il savoir ?

With the decline of conventional cigarette sales, tobacco companies developed and began marketing a new type of product that does not burn tobacco in 2015. These products, called « heated tobacco products ¼ (HTP), are marketed as potentially reduced risk products because their technology limits combustion and the generation of toxic compounds. However, the principal harmful compounds commonly measured in conventional cigarette smoke are also present in HTP emissions. Currently, few independent studies have verified the level of risk of these HTP, which raises important questions for the population and public health actors. This article aims to describes the current situation with regards to HTP.

Face à la diminution constante des ventes de cigarettes conventionnelles, l'industrie du tabac a développé et mis sur le marché depuis 2015 un nouveau type de produits qui ne « brûlent ¼ pas le tabac, dits produits du tabac « chauffé ¼ (heated tobacco products ou HTP). Ils sont vendus comme des produits à risques potentiellement réduits, du fait de leur capacité technique à limiter le processus de combustion et la génération de composés toxiques. Toutefois, les principaux composés toxiques émis par la fumée de cigarette conventionnelle sont aussi présents. Actuellement, très peu de recherches indépendantes existent pour vérifier le niveau de risque des HTP, ce qui soulève d'importantes questions parmi la population et les acteurs de santé publique. Cet article fait le point sur ces produits.

Occupational exposure to plant protection products and health effects in Switzerland: what do we know and what do we need to do?

AIMS: There is currently no centralised database on workers' exposures to plant protection products (PPPs) in Switzerland, nor a national register for negative health effects linking them to occupational PPP exposure. This lack of basic data makes it difficult to implement either epidemiological research or prevention campaigns for the agricultural sector. The first objective was to understand the level of information and flow of data on occupational PPP exposures and health effects in the Canton of Vaud, Switzerland. Then, to apply this information to develop recommendations for improving a vigilance system for occupational health effects related to PPP exposure. METHODS: A mapping study and semistructured stakeholder interviews were conducted to better understand the flow of data on occupational PPP exposures and health effects. A clinical records investigation of workers occupationally exposed to PPPs was undertaken to understand the magnitude of this potential problem. Finally, a workshop brought together relevant stakeholders to discuss recommendations for the way forwards. RESULTS: A lack of data on PPP exposures and associated health effects was revealed. This highlighted important knowledge gaps at different levels of the current institutional information flow system. We found that although there were numerous stakeholders that worked efficiently in their own mandate, there was a clear need for increased collaboration and coordination in order to make use of existing data to promote safer PPP use among agricultural workers in Switzerland. CONCLUSIONS: Due to increasing evidence of an association between PPP exposure and health effects, increased collaboration between stakeholders is necessary to develop links between the data sources that already exist. Our study was the first to investigate the health effects linked to PPP exposure among the Swiss agricultural population. The recommendations presented in this paper would help promote a safer and healthier agricultural workforce in Switzerland, as well as the population at large.

Polycyclic aromatic hydrocarbons (PAHs) skin permeation rates change with simultaneous exposures to solar ultraviolet radiation (UV-S).

Road construction workers are simultaneously exposed to two carcinogens; solar ultraviolet (UV-S) radiation and polycyclic aromatic hydrocarbons (PAHs) in bitumen emissions. The combined exposure may lead to photogenotoxicity and enhanced PAH skin permeation rates. Skin permeation rates (J) for selected PAHs in a mixture (PAH-mix) or in bitumen fume condensate (BFC) with and without UV-S co-exposures were measured with in vitro flow-through diffusion cells mounted with human viable skin and results compared. Possible biomarkers were explored. Js were greater with UV-S for naphthalene, anthracene, and pyrene in BFC (0.08-0.1 ng/cm2/h) compared to without (0.02-0.26 ng/cm2/h). This was true for anthracene, pyrene, and chrysene in the PAH-mix. Naphthalene and benzo(a)pyrene (BaP) in the PAH-mix had greater Js without (0.97-13.01 ng/cm2/h) compared to with UV-S (0.40-6.35 ng/cm2/h). Time until permeation (Tlags) in the PAH-mix were generally shorter compared to the BFC, and they ranged from 1 to 13 h. The vehicle matrix could potentially be the reason for this discrepancy as BFC contains additional not identified substances. Qualitative interpretation of p53 suggested a dose-response with UV-S, and somewhat with the co-exposures. MMP1, p65 and cKIT were not exploitable. Although not statistically different, PAHs permeate human viable skin faster with simultaneous exposures to UV.