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Phthalates – Targeted Search for Epidemiological Studies

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250 References Were Found:

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Preparation and Characterization of Tablet Formulation based on Solid Dispersion of Glimepiride and Poly(ester amide) Hyperbranched Polymer

Authors: Reven, S; Homar, M; Peternel, L; Kristl, J; Zagar, E (In Press) Pharm Dev Technol. HERO ID: 1249959

[Less] The feasibility of incorporating a solid dispersion containing poorly soluble antidiabetic drug glimepiride . . . [More] The feasibility of incorporating a solid dispersion containing poorly soluble antidiabetic drug glimepiride and poly(ester amide) hyperbranched polymer into a tablet using a direct-compression tabletting technique was investigated. Tablet cores were additionally coated with hydroxypropyl methylcellulose phthalate in order to protect the extremely hygroscopic solid dispersion from atmospheric moisture. Preliminary stability studies show that glimepiride, which is in amorphous form within solid dispersion, is chemically stable, even if tablets are exposed to elevated temperature and/or moisture. In-vitro dissolution studies show some impact of storage conditions on the tablet cores disintegration time and, consequently, drug release rate. Glimepiride solubility also deteriorates somewhat, most probably due to its partial recrystallization. Storage conditions much less affect the physical stability of coated tablets, which was ascribed to reduced tablet hygroscopicity due to the presence of protecting coating. The hyperbranched polymers are rather new and complex macromolecules. Therefore, we addressed also the biocompatibility of hyperbranched polymer, i.e., its impact on haemolysis of the red blood cells. The concentration required for the haemolytic effect on the red blood cells is around 100-times higher than its expected gastrointestinal luminal concentration, which makes the occurrence of hyperbranched polymer mediated cytotoxicity very unlikely.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Assessment of toxic metals and phthalates in children's toys and clays

Authors: Korfali, SI; Sabra, R; Jurdi, M; Taleb, RI (In Press) Archives of Environmental Contamination and Toxicology. HERO ID: 1677563

[Less] Toxic metals and phthalates are introduced in the manufacturing of plastic toys and modeling clays. . . . [More] Toxic metals and phthalates are introduced in the manufacturing of plastic toys and modeling clays. In Lebanon, inexpensive plastic toys and modeling clays (sold in dollar stores) are affordable and popular, and there is no legislation to monitor or regulate such toys. This study aimed to assess the quality of inexpensive plastic toys and modeling clays imported in Lebanon. Metal concentrations in toys, namely, zinc [not detectable (ND) to 3,708 μg/g], copper (ND to 140), chromium (ND to 75 μg/g), tin (ND to 39 μg/g), and cadmium (Cd) (ND to 20 μg/g), were lower than the European Union (EU) Directive limits, whereas lead (ND to 258 μg/g) in 10 % of samples and antimony (Sb) (ND to 195 μg/g) in 5 % of samples were greater than the EU limits. In modeling clays, most of the metals were lower than the EU Directive limits except for Cd and arsenic (As). Cd was detected in 83 % of samples, with a mean level of 9.1 μg/g, which is far greater than the EU Directive limit (1.9 μg/g). The As mean level of 4.5 μg/g was greater than the EU limit (4.0 μg/g) and was detected in 9 % of samples. Phthalic acid esters (PAEs) were found in 60 % of children's toys and 77 % of modeling clays. Phthalic acid butyl ester had the highest-level PAE encountered and was ≤59.1 % in one type of clay. However, among children's toys, di(4-octyl) ester terephthalic acid was the highest encountered phthalate at a concentration of 25.7 %. The community survey indicated that 82 % of households purchase their toys from inexpensive shops and that only 17 % of parents were aware of the health hazard of such toys. Consequently, an intervention plan was proposed for the provision of safe toys to children.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Effects of maternal exposure to di(2-ethylhexyl)phthalate (DEHP) during pregnancy on susceptibility to neonatal asthma

Authors: Shin, IS; Lee, MY; Cho, ES; Choi, EY; Son, HY; Lee, KY (2014) Toxicology and Applied Pharmacology 274:402-407. HERO ID: 2231329

[Less] Di(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and is widely dispersed in the environment. . . . [More] Di(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and is widely dispersed in the environment. In this study, we investigated the effects of maternal exposure to DEHP during pregnancy on neonatal asthma susceptibility using a murine model of asthma induced by ovalbumin (OVA). Pregnant BALB/c mice received DEHP from gestation day 13 to lactation day 21. Their offspring were sensitized on postnatal days (PNDs) 9 and 15 by intraperitoneal injection of 0.5μg OVA with 200μg aluminum hydroxide. On PNDs 22, 23 and 24, live pups received an airway challenge of OVA for 30min. Offspring from pregnant mice that received DEHP showed reductions in inflammatory cell count, interleukin (IL)-4, IL-13, and eotaxin in their bronchoalveolar lavage fluid and in total immunoglobulin E and OVA-specific IgE in their plasma compared with offspring from pregnant mice that did not receive DEHP treatment. These results were consistent with histological analysis and immunoblotting. Maternal exposure to DEHP reduces airway inflammation and mucus production in offspring, with a decrease in inducible nitric oxide synthase (iNOS) in the lung tissue. This study suggests that maternal exposure to DEHP during pregnancy reduces asthmatic responses induced by OVA challenge in offspring. These effects were considered to be closely related to the suppression of Th2 immune responses and iNOS expression.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Exposure to widespread environmental toxicants and children's cognitive development and behavioral problems

Authors: Jurewicz, J; Polańska, K; Hanke, W (2013) International Journal of Occupational Medicine and Environmental Health 26:185-204. [Review] HERO ID: 1600103

[Less] Nowadays a special attention is focused on prenatal and childhood exposures to a variety of contaminants . . . [More] Nowadays a special attention is focused on prenatal and childhood exposures to a variety of contaminants in the environment, especially toxicants widely present in the environment and their impact on children's health and neurodevelopment. This article aims at evaluating the impact of exposure to several widespread toxicants including: polycyclic aromatic hydrocarbons (PAHs), phthalates, bisphenol A, brominated flame retardants and gas cooking on children's cognitive development and behavioral problems by reviewing most recent published literature. Epidemiological studies focusing on exposure to widespread toxicants and children's development for the last eleven years were identified by a search of the PubMed, Medline, Ebsco and Toxnet literature bases. The combination of following key words was used: 1) referring to the exposure: pregnancy, prenatal exposure, postnatal exposure, gas cooking, exposure to phthalates, bisphenol A, brominated flame retardants, PAHs and 2) referring to outcome: neurodevelopment, neurobehavior, psychomotor development, behavioral problems, cognitive development, mental health, school achievements, learning abilities. The results from the presented studies suggest that there are strong and rather consistent indications that the developing nervous system is particularly vulnerable to insult from low levels of exposure to widespread environmental contaminants such as: phthalates, bisphenol A, brominated flame retardants, polycyclic aromatic hydrocarbons, gas cooking. Considering the suggested health effects, more epidemiologic data is urgently needed and, in the meantime, precautionary policies must be implemented.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

New anticancer active and selective phenylene-bisbenzothiazoles: Synthesis, antiproliferative evaluation and DNA binding

Authors: Racané, L; Pavelić, SK; Nhili, R; Depauw, S; Paul-Constant, C; Ratkaj, I; David-Cordonnier, MH; Pavelić, K; Tralić-Kulenović, V; Karminski-Zamola, G (2013) European Journal of Medicinal Chemistry 63:882-891. HERO ID: 1600115

[Less] Novel amidino-derivatives of phenylene-bisbenzothiazoles were synthesized and tested for their antiproliferative . . . [More] Novel amidino-derivatives of phenylene-bisbenzothiazoles were synthesized and tested for their antiproliferative activity against several human cancer cell lines, as well as DNA-binding properties. The synthetic approach used for preparation of isomeric amidino substituted-phenylene-bis-benzothyazoles 3a-3f was achieved by condensation reaction of isophthaloyl dichloride 1a and terephthaloyl dichloride 1b or with phthalic acid 1c with 5-amidinium-2-aminobenzothiolate 2a and 5-(imidazolinium-2-yl)-2-aminobenzothiolate 2b in good yields. The targeted compounds were converted in the desired water soluble dihydrochloride salts by reaction of appropriate free base with concd HCl in ethanol or acetic acid. All tested compounds (3a-3f) showed antiproliferative effects on tumour cells in a concentration-dependant manner. The strongest activity and cytotoxicity was observed for diimidazolinyl substituted phenylene-bisbenzothiazole compound 3b. These effects were shown to be related to DNA-binding properties, topoisomerase I and II poisoning effects and apoptosis induction. The highest tested selectivity towards tumour cells was observed for the imidazolyl substituted phenylene-benzothiazole 3d that showed no cytotoxic effects on normal fibroblasts making it an excellent candidate for further chemical optimization and preclinical evaluation.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Bisphenol A and other phenols in urine from Danish children and adolescents analyzed by isotope diluted TurboFlow-LC-MS/MS

Authors: Frederiksen, H; Aksglaede, L; Sorensen, K; Nielsen, O; Main, KM; Skakkebaek, NE; Juul, A; Andersson, AM (2013) International Journal of Hygiene and Environmental Health. HERO ID: 1804934

[Less] Bisphenol A (BPA), triclosan (TCS), benzophenone-3 (BP-3), dichoro- and phenyl phenols are industrial . . . [More] Bisphenol A (BPA), triclosan (TCS), benzophenone-3 (BP-3), dichoro- and phenyl phenols are industrial chemicals present in numerous consumer products such as polycarbonate plastics, preservatives in personal care products, sun screens, pesticides and fungicides, respectively, and they are all suspected endocrine disrupters. In this study the urinary excretion of eight phenols in Danish children recruited from the general population were investigated. One 24h urine and two consecutive first morning samples were collected from each of 129 healthy Danish children and adolescents (6-21 years). The concentrations of urinary phenols were analyzed by a new on-line TurboFlow-liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Most of the analyzed phenols were detectable in more than 80% of the 24h urine samples and the median concentration of BPA, TCS, BP-3, 2,4-dichorophenol and 2,5-dichorophenol (analyzed as ∑DCP), 2-phenylphenol and 4-phenylphenol were 1.37, 1.45, 1.41, 0.65, 0.36 and 0.53ng/mL, respectively. The ranges of the excreted TCS and BP-3 were wide; from below limit of detection to maximum levels of 955ng/mL and 162ng/mL, respectively, while the other phenols were excreted in a more narrow range with maximum levels below 25ng/mL. Concentrations in first morning urine were in general higher than in 24h urine and comprised 30-47% of the absolute amount excreted during 24h. The youngest children aged 6-10 years had a significantly higher urinary BPA concentration (ng/mL) and also a relatively higher daily BPA excretion (ng/kg bw/24h) than the older children and adolescents. The opposite pattern was observed for TCS, BP-3 and ∑DCP for which urinary levels increased significantly with age. No gender difference or associations to pubertal development were observed. In conclusion, our study showed that Danish children were exposed to multiple phenols simultaneously. Small children were relatively more exposed to BPA than older children, while higher exposures to TCS, BP-3 and ∑DCP were seen among adolescents.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Migration of plasticisers from Tritan (TM) and polycarbonate bottles and toxicological evaluation

Authors: Guart, A; Wagner, M; Mezquida, A; Lacorte, S; Oehlmann, J; Borrell, A (2013) Food Chemistry 141:373-380. HERO ID: 1935996

[Less] This study is aimed to compare Tritan™ and polycarbonate (PC) from a point of view of migration of monomers . . . [More] This study is aimed to compare Tritan™ and polycarbonate (PC) from a point of view of migration of monomers and additives and toxicological evaluation. Migration assays were performed according with Commission Regulation (UE) No. 10/2011. Samples were incubated at 40°C for three consecutive periods of 10 days. Identification and quantification of the compounds intended to migrate was done using solid phase extraction (SPE) followed by gas chromatography coupled to mass spectrometry (GC-MS) in scan mode. Compounds identified in Tritan™ were 2-phenoxyethanol (2-PE), 4-nonylphenol (4-NP), bisphenol A (BPA), benzylbuthyl phthalate (BBP) and dimethyl isophthalate (DMIP) at levels from 0.027 ± 0.002 to 0.961 ± 0.092 μg/kg, although in the 3rd migration period, BBP and DMIP were the only compounds detected well below the specific migration limit. On the other hand, BPA was the only compound detected in PC polymers at a mean concentration of 0.748 μg/kg. In vitro bioassays for (anti)estrogenic, (anti)androgenic as well as retinoic acid- and vitamin D-like activity were negative for Tritan™ and PC migrates. BPA and DMIP were estrogenic in high concentrations. Exposure of the estrogen-sensitive molluskan sentinel Potamopyrgus antipodarum confirmed the estrogenic activity of BPA in vivo at 30 μg/L.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Disconcordance in statistical models of bisphenol A and chronic disease outcomes in NHANES 2003-08

Authors: Casey, MF; Neidell, M (2013) PLoS ONE 8:e79944. HERO ID: 2215393

[Less] BACKGROUND: Bisphenol A (BPA), a high production chemical commonly found in plastics, . . . [More] BACKGROUND: Bisphenol A (BPA), a high production chemical commonly found in plastics, has drawn great attention from researchers due to the substance's potential toxicity. Using data from three National Health and Nutrition Examination Survey (NHANES) cycles, we explored the consistency and robustness of BPA's reported effects on coronary heart disease and diabetes.

METHODS AND FINDINGS: We report the use of three different statistical models in the analysis of BPA: (1) logistic regression, (2) log-linear regression, and (3) dose-response logistic regression. In each variation, confounders were added in six blocks to account for demographics, urinary creatinine, source of BPA exposure, healthy behaviours, and phthalate exposure. Results were sensitive to the variations in functional form of our statistical models, but no single model yielded consistent results across NHANES cycles. Reported ORs were also found to be sensitive to inclusion/exclusion criteria. Further, observed effects, which were most pronounced in NHANES 2003-04, could not be explained away by confounding.

CONCLUSIONS: Limitations in the NHANES data and a poor understanding of the mode of action of BPA have made it difficult to develop informative statistical models. Given the sensitivity of effect estimates to functional form, researchers should report results using multiple specifications with different assumptions about BPA measurement, thus allowing for the identification of potential discrepancies in the data.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Within-person reproducibility of urinary bisphenol A and phthalate metabolites over a 1 to 3 year period among women in the Nurses' Health Studies: a prospective cohort study

Authors: Townsend, MK; Franke, AA; Li, X; Hu, FB; Eliassen, AH (2013) Environmental Health: A Global Access Science Source 12:80. HERO ID: 2215422

[Less] BACKGROUND: Associations of bisphenol A and phthalates with chronic disease health . . . [More] BACKGROUND: Associations of bisphenol A and phthalates with chronic disease health outcomes are increasingly being investigated in epidemiologic studies. The majority of previous studies of within-person variability in urinary bisphenol A and phthalate metabolite concentrations have focused on reproducibility over short time periods. Long-term reproducibility data are needed to assess the potential usefulness of these biomarkers for prospective studies, particularly those examining risk of diseases with long latency periods. Low within-person reproducibility may attenuate relative risk estimates and reduce statistical power to detect associations with disease. Therefore, we assessed within-person reproducibility of bisphenol A, eight phthalate metabolites, and phthalic acid in spot urine samples over 1 to 3 years among women enrolled in two large cohort studies.

METHODS: Women in the Nurses' Health Study and Nurses' Health Study II provided two spot urine samples, 1 to 3 years apart (n = 80 women for analyses of bisphenol A; n = 40 women for analyses of phthalate metabolites; n = 34 women for analyses of phthalic acid). To measure within-person reproducibility, we calculated Spearman rank correlation coefficients and intraclass correlation coefficients for creatinine-adjusted concentrations of bisphenol A, phthalate metabolites, and phthalic acid.

RESULTS: Over 1 to 3 years, within-person variability of bisphenol A was high relative to total variability (intraclass correlation coefficient = 0.14) and rankings of bisphenol A levels between time-points were weakly correlated (Spearman correlation = 0.19). Seven of the eight phthalate metabolites and phthalic acid demonstrated moderate within-person stability over time (Spearman correlation or intraclass correlation coefficient = 0.39-0.55). Restricting analyses to first-morning urine samples did not alter results.

CONCLUSIONS: Single measurements of bisphenol A in spot urine samples were highly variable within women over 1 to 3 years, indicating that investigation of associations between a single urinary bisphenol A measurement and disease risk may be challenging in epidemiologic studies. The majority of urinary phthalate metabolites and phthalic acid appeared moderately reproducible within women over time, suggesting single measurements may be useful in epidemiologic studies, although observed relative risks can be substantially attenuated.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Urinary concentrations of environmental contaminants and phytoestrogens in adults in Israel

Authors: Berman, T; Goldsmith, R; Göen, T; Spungen, J; Novack, L; Levine, H; Amitai, Y; Shohat, T; Grotto, I (2013) Environment International 59:478-484. HERO ID: 2215430

[Less] BACKGROUND: The Ministry of Health Biomonitoring Study estimated exposure of individuals . . . [More] BACKGROUND: The Ministry of Health Biomonitoring Study estimated exposure of individuals in the Israeli population to bisphenol A (BPA), organophosphate (OP) pesticides, phthalates, cotinine, polycyclic aromatic hydrocarbons (PAHs), and the phytoestrogenic compounds genistein and daidzein.

METHODS: In 2011, 250 individuals (ages 20-74) were recruited from five different regions in Israel. Urine samples were collected and questionnaire data were obtained, including detailed dietary data (food frequency questionnaire and 24hour recall). Urinary samples were analyzed for BPA, OP metabolites (dialkyl phosphates), phthalate metabolites, cotinine, PAH metabolites, genistein, and daidzein.

RESULTS AND DISCUSSION: BPA urinary concentrations were above the limit of quantification (LOQ) in 89% of the samples whereas urinary concentrations of phthalate metabolites were above the LOQ in 92-100% of the samples. PAH metabolites were above the LOQ in 63-99% of the samples whereas OP metabolites were above the LOQ in 44-100% of the samples. All non-smoking participants had detectable levels of cotinine in their urine; 63% had levels above the LOQ, and the rate of quantification was high compared to the general non-smoking population in Canada. Median creatinine adjusted concentrations of several OP metabolites (dimethyl phosphate, dimethyl thiophosphate) were high in our study population compared to the general US and Canadian populations. Median creatinine adjusted urinary BPA concentrations in the study population were comparable to those in Belgium and Korea; higher than those reported for the general US, German, and Canadian populations; and very low compared to health-based threshold values. Phthalate concentrations were higher in our study population compared to the general US population but values were very low compared to health-based threshold values. Median creatinine adjusted PAH concentrations were generally comparable to those reported for the general US population; median creatinine adjusted daidzein concentrations were high in our population compared to the general US population whereas genistein concentrations were comparable.

CONCLUSIONS: We interpreted observed urinary contaminant levels observed in our study by comparing values with health-based threshold values and/or values from international human biomonitoring studies. Using this data interpretation scheme, we identified two contaminants as being of potential public health concern and high priority for public health policy intervention: environmental tobacco smoke (ETS) and OP pesticides. We used the data collected in this study to support public health policy interventions. We plan to conduct a follow-up biomonitoring study in 2015 to measure ETS and OP exposure in the general population in Israel, to evaluate the effectiveness of relevant policy interventions.