Exposure to bisphenol A in European women from 2007 to 2014 using human biomonitoring data - The European Joint Programme HBM4EU.

BACKGROUND: Bisphenol A (BPA; or 4,4'-isopropylidenediphenol) is an endocrine disrupting chemical. It was widely used in a variety of plastic-based manufactured products for several years. The European Food Safety Authority (EFSA) recently reduced the Tolerable Daily Intake (TDI) for BPA by 20,000 times due to concerns about immune-toxicity. OBJECTIVE: We used human biomonitoring (HBM) data to investigate the general level of BPA exposure from 2007 to 2014 of European women aged 18-73 years (n = 4,226) and its determinants. METHODS: Fifteen studies from 12 countries (Austria, Belgium, Denmark, France, Germany, Greece, Israel, Luxembourg, Slovenia, Spain, Sweden, and the United Kingdom) were included in the BPA Study protocol developed within the European Joint Programme HBM4EU. Seventy variables related to the BPA exposure were collected through a rigorous post-harmonization process. Linear mixed regression models were used to investigate the determinants of total urine BPA in the combined population. RESULTS: Total BPA was quantified in 85-100 % of women in 14 out of 15 contributing studies. Only the Austrian PBAT study (Western Europe), which had a limit of quantification 2.5 to 25-fold higher than the other studies (LOQ=2.5 µg/L), found total BPA in less than 5 % of the urine samples analyzed. The geometric mean (GM) of total urine BPA ranged from 0.77 to 2.47 µg/L among the contributing studies. The lowest GM of total BPA was observed in France (Western Europe) from the ELFE subset (GM=0.77 µg/L (0.98 µg/g creatinine), n = 1741), and the highest levels were found in Belgium (Western Europe) and Greece (Southern Europe), from DEMOCOPHES (GM=2.47 µg/L (2.26 µg/g creatinine), n = 129) and HELIX-RHEA (GM=2.47 µg/L (2.44 µg/g creatinine), n = 194) subsets, respectively. One hundred percent of women in 14 out of 15 data collections in this study exceeded the health-based human biomonitoring guidance value for the general population (HBM-GVGenPop) of 0.0115 µg total BPA/L urine derived from the updated EFSA's BPA TDI. Variables related to the measurement of total urine BPA and those related to the main socio-demographic characteristics (age, height, weight, education, smoking status) were collected in almost all studies, while several variables related to BPA exposure factors were not gathered in most of the original studies (consumption of beverages contained in plastic bottles, consumption of canned food or beverages, consumption of food in contact with plastic packaging, use of plastic film or plastic containers for food, having a plastic floor covering in the house, use of thermal paper…). No clear determinants of total urine BPA concentrations among European women were found. A broader range of data planned for collection in the original questionnaires of the contributing studies would have resulted in a more thorough investigation of the determinants of BPA exposure in European women. CONCLUSION: This study highlights the urgent need for action to further reduce exposure to BPA to protect the population, as is already the case in the European Union. The study also underscores the importance of pre-harmonizing HBM design and data for producing comparable data and interpretable results at a European-wide level, and to increase HBM uptake by regulatory agencies.

Association between parental smoking and child exposure to environmental tobacco smoke in Israel.

BACKGROUND: Environmental tobacco smoke (ETS) exposure in children can cause delayed lung development and lifelong cardiovascular damage. The aim of this study was to measure ETS exposure in children in Israel in 2020-2021 using urinary cotinine (UC) measurements and to assess correlates of ETS exposure, including parental smoking. METHODS: In the framework of the National Human Biomonitoring Program, spot urine samples and questionnaire data were collected from 166 children aged 4-12 years, during the years 2020-2021. We collected urine samples in 233 adults, 69 of whom were parents of children included in the study. Parents of participating children were asked about parental smoking, child's exposure to ETS and smoking policy at home. Cotinine and creatinine were measured in urine. Creatinine-adjusted and unadjusted urine cotinine (UC) geometric means were calculated. Associations between potential correlates and UC concentrations were analyzed in univariate and multivariate analyses. For 69 child-parent pairs, correlation between child and parental UC was analyzed. RESULTS: Based on urinary cotinine measurement, 65.2% of children of smokers are exposed to ETS, compared to 20.7% of children in non-smoking families. Greater numbers of smokers living in the home (beta = 1.27, p < 0.01), and low maternal education (beta = - 2.32, p < 0.01) were associated with higher levels of UC in a multivariate analysis. Spearman correlations showed a positive moderate correlation between UC in 69 child-parent pairs (r = 0.52, p < 0.01). CONCLUSIONS: In order to reduce child exposure to ETS, smoking parents should be urgently targeted for smoking cessation and smoke-free home interventions. Further interventions are needed to protect all children from ETS.

Influence of exposure to pesticides on telomere length and pregnancy outcome: Diethylphosphates but not Dimethylphosphates are associated with accelerated telomere attrition in a Palestinian cohort.

Exposure to environmental pesticides during pregnancy is associated with adverse health outcomes such as low birth weight and impaired neuro-development. In this study, we assessed maternal leukocyte telomere lengths (TL) in Palestinian pregnant women and compared the data with urinary organophosphate concentrations, demographic, lifestyle and dietary factors, birth weight, body length, gestational age, and head circumference. Women with high urine levels of creatinine adjusted diethylphosphate(DE)derived pesticide metabolites DEP, DETP or DEDTP had shorter telomeres (p = 0.05). Women living in proximity to agricultural fields had shorter telomeres compared to women not living in proximity to agricultural fields (p = 0.011). Regular consumption of organic food was associated with shorter telomeres (p = 0.01), whereas the consumption of other vegetables such as artichokes was rather associated with longer telomeres. By contrast, urine levels of dimethylphosphate(DM)-derived pesticide metabolites DMTP and DMDTP were associated with lower birth weight (p = 0.05) but not with shrter telomeres. In conclusion organophosphate pesticides and living in proximity to agriculture are associated with shorter TL, likely due to higher consumption of contaminated fruits and vegetables and/or the transport of pesticides to non-treatment sites. DE and DM substituted pesticides seem to have different effects on telomeres and development.

Benzophenone-3: Comprehensive review of the toxicological and human evidence with meta-analysis of human biomonitoring studies.

BACKGROUND: Benzophenone-3 (BP-3) and its major metabolite benzophenone-1 (BP-1) are widely used as UV filters in sunscreens and cosmetics to prevent sunburn and skin damage, or as stabilizers to prevent photodegradation in many commercial products. As a result, their presence is ubiquitous in the environment, wildlife and humans. Based on endocrine disruption concerns, international regulatory agencies are performing a closer evaluation. OBJECTIVE AND METHODS: This work aimed to comprehensively review the available human relevant evidence for safety issues in MEDLINE/PubMed in order to create a structured database of studies, as well as to conduct an integrative analysis as part of the Human Biomonitoring for Europe (HBM4EU) Initiative. RESULTS: A total of 1,635 titles and abstracts were screened and 254 references were evaluated and tabulated in detail, and classified in different categories: i) exposure sources and predictors; ii) human biomonitoring (HBM) exposure levels to perform a meta-analysis; iii) toxicokinetic data in both experimental animals and humans; iv) in vitro and in vivo rodent toxicity studies; and v) human data on effect biomarkers and health outcomes. Our integrative analysis showed that internal peak BP-3 concentrations achieved after a single whole-body application of a commercially available sunscreen (4% w/w) may overlap with concentrations eliciting endocrine disrupting effects in vitro, and with internal concentrations causing in vivo adverse female reproductive effects in rodents that were supported by still limited human data. The adverse effects in rodents included prolonged estrous cycle, altered uterine estrogen receptor gene expression, endometrium hyperplasia and altered proliferation and histology of the mammary gland, while human data indicated menstrual cycle hormonal alterations and increased risk of uterine fibroids and endometriosis. Among the modes of action reported (estrogenic, anti-androgenic, thyroid, etc.), BP-3 and especially BP-1 showed estrogenic activity at human-relevant concentrations, in agreement with the observed alterations in female reproductive endpoints. The meta-analysis of HBM studies identified a higher concern for North Americans, showing urinary BP-3 concentrations on average 10 and 20 times higher than European and Asian populations, respectively. DISCUSSION AND CONCLUSIONS: Our work supports that these benzophenones present endocrine disrupting properties, endorsing recent European regulatory efforts to limit human exposure. The reproducible and comprehensive database generated may constitute a point of departure in future risk assessments to support regulatory initiatives. Meanwhile, individuals should not refrain from sunscreen use. Commercially available formulations using inorganic UV filters that are practically not absorbed into systemic circulation may be recommended to susceptible populations.

Improving the Risk Assessment of Pesticides through the Integration of Human Biomonitoring and Food Monitoring Data: A Case Study for Chlorpyrifos.

The risk assessment of pesticide residues in food is a key priority in the area of food safety. Most jurisdictions have implemented pre-marketing authorization processes, which are supported by prospective risk assessments. These prospective assessments estimate the expected residue levels in food combining results from residue trials, resembling the pesticide use patterns, with food consumption patterns, according to internationally agreed procedures. In addition, jurisdictions such as the European Union (EU) have implemented large monitoring programs, measuring actual pesticide residue levels in food, and are supporting large-scale human biomonitoring programs for confirming the actual exposure levels and potential risk for consumers. The organophosphate insecticide chlorpyrifos offers an interesting case study, as in the last decade, its acceptable daily intake (ADI) has been reduced several times following risk assessments by the European Food Safety Authority (EFSA). This process has been linked to significant reductions in the use authorized in the EU, reducing consumers' exposure progressively, until the final ban in 2020, accompanied by setting all EU maximum residue levels (MRL) in food at the default value of 0.01 mg/kg. We present a comparison of estimates of the consumer's internal exposure to chlorpyrifos based on the urinary marker 3,5,6-trichloro-2-pyridinol (TCPy), using two sources of monitoring data: monitoring of the food chain from the EU program and biomonitoring of European citizens from the HB4EU project, supported by a literature search. Both methods confirmed a drastic reduction in exposure levels from 2016 onwards. The margin of exposure approach is then used for conducting retrospective risk assessments at different time points, considering the evolution of our understanding of chlorpyrifos toxicity, as well as of exposure levels in EU consumers following the regulatory decisions. Concerns are presented using a color code, and have been identified for almost all studies, particularly for the highest exposed group, but at different levels, reaching the maximum level, red code, for children in Cyprus and Israel. The assessment uncertainties are highlighted and integrated in the identification of levels of concern.

A hybrid model for evaluating exposure of the general population in Israel to air pollutants.

Exposure to air pollution is associated with a wide range of health effects, including increased respiratory symptoms, cancer, reproductive and birth defects, and premature death. Air quality measurements by standardized measuring equipment, although accurate, can only provide an estimate for part of the population, with decreasing accuracy further away from the monitoring sites. Estimating pollution levels over large geographical domains requires the use of air quality models which ideally incorporate air quality measurements. In order to estimate actual exposure of the population to air pollution (population-weighted concentrations of air pollutants), there is a need to combine data from air quality models with population density data. Here we present the results of exposure estimates for the entire population of Israel using a chemical transport model combined with measurements from the national monitoring network. We evaluated the individual exposure levels for the entire population to several air pollutants based on census tract units. Using this hybrid model, we found that the entire population of Israel is exposed to concentrations of PM10 and PM2.5 that exceed the target values but are below the environmental values according to the Israeli Clean Air Law. In addition, we found and that over 1.5 million residents are exposed to NOx at concentrations higher than the target values. This data may help decision makers develop targeted interventions to reduce the concentrations of specific pollutants, based on population-weighted exposure.

Newborn infant urinary cotinine and birth outcomes in the Jerusalem Environment Mother and Child Cohort Study.

BACKGROUND: Environmental tobacco smoke (ETS) exposure during pregnancy can cause preterm delivery and childhood cancer. The aim of this study was to measure ETS exposure in pregnant women and in newborn infants in Israel using urinary cotinine measurements, to assess predictors of ETS exposure in these vulnerable groups, and to assess associations with birth effects (birth weight, birth length, head circumference) in newborn infants. METHODS: We analyzed urinary cotinine and creatinine in 265 non-smoking pregnant women and 97 newborns, and analyzed associations with self-reported exposure to ETS, paternal smoking, sociodemographic variables and with birth outcomes (birth weight, birth length, head circumference). RESULTS: 37.7% of pregnant women and 29.0% of infants had urinary cotinine concentrations above the level of quantification (LOQ) of 1 µg/L, whereas 63.8% and 50.5%, respectively, had urinary cotinine concentrations above the level of detection (LOD) of 0.5 µg/L. Median unadjusted and creatinine adjusted urinary concentrations of cotinine in pregnant women were 0.7 µg/L, and 0.9 µg/g creatinine, respectively, and in newborn infants were 0.5 µg/L, and 1.3 µg/g creatinine, respectively. We did not find an association between maternal and infant urinary cotinine level. Maternal (but not infant) urinary cotinine was significantly associated with paternal smoking (p < 0.05). Infant (but not maternal) cotinine above the LOQ was negatively associated with birth weight (p < 0.05). CONCLUSIONS: In this high socioeconomic cohort, almost a third of newborn infants born to non-smoking mothers had quantifiable levels of urinary cotinine. This is the first study showing that newborns with quantifiable urinary cotinine levels have lower birth weight.

Socioeconomic inequalities in exposure to environmental tobacco smoke in children in Israel.

BACKGROUND: Environmental tobacco smoke (ETS) exposure in infants and children causes more frequent and severe asthma attacks, respiratory infections, ear infections, and sudden infant death syndrome. The aim of this study was to measure ETS exposure in children in Israel (ages 4-11 years) using urinary cotinine measurements, in order to compare exposure levels to other international populations, and to assess predictors of ETS exposure in children in Israel. METHODS: A subset of children who participated in the National Health and Nutrition Survey (RAV- MABAT) in 2015-2016 were invited to participate in the Second Israel Biomonitoring Survey. We analyzed urinary cotinine and creatinine concentrations in 103 children. Parents of study participants were interviewed in person on children's exposure to ETS at home and in other environments and on sociodemographic variables. We calculated creatinine-adjusted and unadjusted urinary cotinine geometric means in children and analyzed associations in univariable and multivariable analyses, between sociodemographic variables and parental - reported exposure, and urinary cotinine concentrations. RESULTS: Based on urinary creatinine measurement, over 60% of children are exposed to ETS (compared to <40% based on parental report). Linear regression showed a positive association between urinary cotinine concentration and reported ETS exposure (p = 0.001). Mean cotinine concentration among children whose parents reported that they are exposed to ETS at home (5.1 µg/l) was significantly higher than the concentration among children whose parents reported they are not exposed to ETS at home (1.6 µg/l, p < 0.001). There was an inverse relationship between total family income and urinary cotinine concentration (p < 0.05). In a multivariable model adjusted for ethnicity and other factors, family income was a significant predictor of urinary cotinine level (p = 0.04, slope = -0.49). Geometric mean creatinine adjusted concentrations in children in the current study were higher than in children in Canada and selected European countries. CONCLUSIONS: We found evidence of widespread exposure to ETS in children in the study. There is an urgent need to protect children in Israel from exposure to ETS.

Exposure to environmental tobacco smoke in non - smoking adults in Israel: results of the second Israel biomonitoring survey.

BACKGROUND: Exposure to environmental tobacco smoke (ETS) increases the risk of heart and respiratory disease, cancer, and premature mortality in non-smoking individuals. Results from the first Israel Biomonitoring Study in 2011 showed that over 60% of non-smoking adults are exposed to ETS. The purpose of the current study was to assess whether policies to restrict smoking in public places have been associated with reductions in exposure to ETS, and to examine predictors of exposure. METHODS: We analyzed urinary cotinine and creatinine concentrations in 194 adult participants in the National Health and Nutrition (RAV MABAT) Survey in 2015-2016. Study participants were interviewed in person on smoking status and exposure to ETS. We calculated creatinine-adjusted and unadjusted urinary cotinine geometric means and medians among smokers and non-smokers. We analyzed associations in univariable analyses, between socio-demographic variables and self - reported exposure, and urinary cotinine concentrations. RESULTS: There was no reduction in geometric mean urinary cotinine levels in non-smokers in the current study (1.7 µg/g) compared to that in 2011 (1.6 µg/g). Median cotinine levels among the non - smoking Arab participants were higher in comparison to the Jewish and other participants (2.97 versus 1.56 µg/l, p = 0.035). Participants who reported that they were exposed to ETS at home had significantly higher median levels of creatinine adjusted urinary cotinine than those reporting they were not exposed at home (4.19 µg/g versus 2.9 µg/g, p = 0.0039). CONCLUSIONS: Despite additional restrictions on smoking in public places in 2012-2016, over 60% of non-smoking adults in Israel continue to be exposed to ETS. Urinary cotinine levels in non-smokers have not decreased compared to 2011. Results indicate higher exposure to ETS in Arab study participants and those reporting ETS exposure at home. There is an urgent need: (1) to increase enforcement on the ban on smoking in work and public places; (2) for public health educational programs and campaigns about the adverse health effects of ETS; and (3) to develop and disseminate effective interventions to promote smoke free homes. Periodic surveys using objective measures of ETS exposure (cotinine) are an important tool for monitoring progress, or lack thereof, of policies to reduce exposure to tobacco smoke in non-smokers.

Decreasing urinary organophosphate pesticide metabolites among pregnant women and their offspring in Jerusalem: Impact of regulatory restrictions on agricultural organophosphate pesticides use?

INTRODUCTION: Maternal urinary levels of dialkyl phosphate (DAP) metabolites of organophosphate pesticides (OP) during pregnancy are associated with adverse outcomes in the offspring. Between 2012 and 2014, eighteen active OP ingredients were restricted or banned in Israel for agricultural use. AIM: We aimed to study trends of urinary DAP metabolites among pregnant women and their offspring in the era of the new regulations. METHODS: Pregnant women were recruited at 11-18 weeks of gestation and provided spot urine samples (n = 273). Soon after birth, neonatal urine samples were collected (n = 107). All urine specimens analyzed for DAP metabolites. Trends in DAP metabolites were tested using Mann-Kendall trend statistic (M-K S) and linear regression models were constructed to estimate the association between calendar period and DAP levels between September 2012 and March 2016. RESULTS: Over the study period, median maternal ∑DAP levels decreased from 248 nmol/L to 148 nmol/L. Time of recruitment was associated with a statistically significant decrease in DAP metabolites, which remained significant after multivariate adjustment. Overall, the results for the analysis of before and after June 2014 showed a significant decrease in ∑DAP of -0.198 log10 nmol/L (95%CI: -0.311,-0.084) which corresponds with a decrease of 36.6% in ∑DAP. A similar trend was found for DAP metabolites in neonatal urine. Compared to other studies, pregnant women in Jerusalem had higher ∑DAP levels, even at the end of the study period. CONCLUSION: We observed significant reductions in maternal and neonatal DAP urinary levels during the period of 2012-2016. Regulations restricting agricultural use of OP seem to be effective in reducing population exposure to OP, in an era when residential use of OP is banned.

Human biomonitoring in Israel: Recent results and lessons learned.

The use of human biomonitoring (HBM) as a tool for environmental health policy and research is developing rapidly in Israel. Despite challenges in securing political and financial support for HBM, the Ministry of Health has initiated national HBM studies and has utilized HBM data in environmental health policy decision making. Currently, the Ministry of Health is collecting urine samples from children and adults in the framework of the National Health and Nutrition Study (MABAT), with the goal of ongoing surveillance of population exposure to pesticides and environmental tobacco smoke, and of combining HBM data with data on diet and health behavior. In academic research studies in Israel, biomarkers are used increasingly in environmental epidemiology, including in three active birth cohort studies on adverse health effects of phthalates, brominated flame retardants, and organophosphate pesticides. Future Ministry of Health goals include establishing HBM analytical capabilities, developing a long term national HBM plan for Israel and participating in the proposed HBM4EU project in order to improve data harmonization. One of the lessons learned in Israel is that even in the absence of a formal HBM program, it is possible to collect meaningful HBM data and use it in an ad hoc fashion to support environmental health policy.

Exposure to endocrine disrupting chemicals among residents of a rural vegetarian/vegan community.

BACKGROUND & AIMS: Endocrine-disrupting chemicals (EDCs) are increasingly thought to be involved in the rising prevalence of disorders such as obesity, diabetes, and some hormone-dependent cancers. Several lines of evidence have indicated that vegetarian and vegan diets may offer some protection from such diseases. We hypothesized that exposure to selected EDCs among residents of the unique vegetarian/vegan community of Amirim would be lower than what has recently been reported for the omnivorous population in the first Israel Biomonitoring Study (IBMS). METHODS: We studied 42 Amirim residents (29 vegetarians/13 vegans; 24 women/18men, aged 50.7±13.7y). Subjects answered detailed lifestyle, and multipass, memory-based 24-hr dietary recall questionnaires. Concentrations of bisphenol A (BPA), 11 phthalate metabolites, and the isoflavone phytoestrogens (genistein and daidzein) were determined by GC or LC tandem mass-spectrometry on a spot urine sample. The results were compared to those obtained following the same methodology in the Jewish subgroup of the IBMS (n=184). RESULTS: While a vegetarian/vegan nutritional pattern had no effect on exposure to BPA, it seemed to confer a modest protection (~21%) from exposure to high molecular weight phthalates. Furthermore, the summed metabolites of the high molecular weight phthalate DiNP were 36% lower in vegans compared to vegetarians (P<0.05). In contrast, Amirim residents exhibited a level of exposure to isoflavone phytoestrogens about an order of magnitude higher than in the IBMS (P<0.001). CONCLUSIONS: In Israel, a country whose inhabitants demonstrate exposure to EDCs comparable to that of the US and Canada, a voluntary lifestyle of vegetarianism and preference for organic food has a modest, but possibly valuable, impact on exposure to phthalates, while it is associated with a very steep increase in the exposure to phytoestrogens. Major reduction in exposure to EDCs will require regulatory actions.

Urinary concentrations of polycyclic aromatic hydrocarbons in Israeli adults: demographic and life-style predictors.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants associated with adverse health outcomes, including cancer, asthma, and reduced fertility. Because data on exposure to these contaminants in Israel and the Middle East are very limited this study was conducted to measure urinary levels of PAHs in the general adult population in Israel and to identify demographic and life-style predictors of exposure. We measured concentrations of five PAH metabolites: 1-hydroxypyrene (1OH_pyrene) and four different hydroxyphenanthrenes (1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, 4-hydroxyphenanthrene), as well as cotinine in urine samples collected from 243 Israeli adults from the general population. We interviewed participants using structured questionnaires to collect detailed demographic, smoking and dietary data. For over 99% of the study participants, urinary concentration of at least one of the PAHs was above both the limit of detection (LOD) and the limit of quantification (LOQ). All PAHs were significantly correlated (rho=0.67-0.92). Urinary concentration of hydroxyphenanthrenes, but not 1OH_pyrene, was significantly higher among Arabs and Druze study participants (N=56) compared to Jewish participants (N=183). For 4-hydroxyphenanthrene, concentration in Arabs and Druze was 1.95 (95% CI 1.50-2.52) that of Jews, after controlling for creatinine, age and cotinine levels. Urinary concentrations of all PAHs were significantly higher among current smokers or participants with higher cotinine levels and increased significantly with smoking frequency. While PAHs concentrations were not associated with cotinine concentrations in nonsmokers in the overall study population, PAHs concentration was significantly higher among nonsmoking Jews with cotinine ≥LOQ (1µg/L), which represents exposure to environmental tobacco smoking, compared to nonsmoking Jews with cotinine concentrations

Exposure to tobacco smoke based on urinary cotinine levels among Israeli smoking and nonsmoking adults: a cross-sectional analysis of the first Israeli human biomonitoring study.

BACKGROUND: Cotinine levels provide a valid measure of exposure to environmental tobacco smoke (ETS). The goal of this study was to examine exposure to tobacco smoke among smoking and nonsmoking Israeli adults and to identify differences in ETS exposure among nonsmokers by socio-demographic factors. METHODS: We analyzed urinary cotinine data from the first Israeli human biomonitoring study conducted in 2011. In-person questionnaires included data on socio-demographic and active smoking status. Cotinine levels were measured using a gas chromatography-mass spectrometry procedure. We calculated creatinine-adjusted urinary cotinine geometric means (GM) among smokers and nonsmokers, and by socio-demographic, smoking habits and dietary factors. We analyzed associations, in a univariable and multivariable analysis, between socio-demographic variables and proportions of urinary cotinine ≥1 µg/l (Limit of Quantification = LOQ) or ≥4 µg/l. RESULTS: Cotinine levels were significantly higher among 91 smokers (GM = 89.7 µg/g creatinine; 95% confidence interval [CI]: 47.4-169.6) than among 148 nonsmokers (GM = 1.3; 1.1-1.7). Among exclusive waterpipe smokers, cotinine levels were relatively high (GM = 53.4; 95% CI 12.3-232.7). ETS exposure was widespread as 62.2% of nonsmokers had levels ≥ LOQ, and was higher in males (75.8%) than in females (52.3%). In a multivariable model, urinary cotinine ≥ LOQ was higher in males (Prevalence ratio [PR] = 1.30; 95% CI: 1.02-1.64, p = 0.032) and in those with lower educational status (PR = 1.58; 1.04-2.38, p = 0.031) and decreased with age (PR = 0.99; 0.98-1.00, p = 0.020, per one additional year). There were no significant differences by ethnicity, residence type or country of birth. CONCLUSIONS: Our findings indicate widespread ETS exposure in the nonsmoking Israeli adult population, especially among males, and younger and less educated participants. These findings demonstrate the importance of human biomonitoring, were instrumental in expanding smoke-free legislation implemented in Israel on July 2012 and will serve as a baseline to measure the impact of the new legislation.

Trends in reproductive health in Israel: implications for environmental health policy.

Nearly two decades ago, researchers first reported that endocrine disrupting chemicals in the environment were affecting reproductive health in the general population. The purpose of this article is to examine the evidence of adverse reproductive health trends in Israel and to explore implications for environmental health policy in Israel. We reviewed studies and data in Israel regarding trends in reproductive health indices, specifically: breast and testis cancer, hypospadias, sperm quality, male factor infertility, and age at menarche. The data provide some evidence of adverse reproductive trends in the Israeli population: an increase in testicular cancer from 1990 to 2007, a decrease in age at menarche from 1986 to 2000, an increase in the prevalence of male factor infertility, and some evidence of decreasing sperm counts. However, we note that much of the evidence is limited.The policy implications of reported adverse reproductive health trends possibly related to environmental exposure have been radically different in Europe and the United States. In Europe, such reports led the Parliament of the European Community to adopt a resolution on endocrine disruptors, which emphasizes the application of the Precautionary Principle. U.S. Environmental Protection Agency policy is focused on screening chemicals for endocrine disrupting properties and does not specifically refer to the Precautionary Principle. To date, there has been no formal governmental policy or strategy in Israel regarding endocrine disrupting chemicals. Environmental health policy on endocrine disruptors requires integrating evidence on human reproductive health trends, evidence on adverse reproductive outcomes in wildlife and experimental systems, and data from biomonitoring studies. Despite gaps in evidence and current data, we support a precautionary approach to regulating potential endocrine disrupting chemicals and reducing public exposures, especially in sensitive groups such as children and pregnant women.

Cancer risks in naval divers with multiple exposures to carcinogens.

We investigated risks for cancer and the case for a cause-effect relationship in five successive cohorts of naval commando divers (n = 682) with prolonged underwater exposures (skin, gastrointestinal tract, and airways) to many toxic compounds in the Kishon River, Israel's most polluted waterway, from 1948 to 1995. Releases of industrial, ship, and agricultural effluents in the river increased substantially, fish yields decreased, and toxic damage to marine organisms increased. Among the divers (16,343 person-years follow-up from 18 years of age to year 2000), the observed/expected ratio for all tumors was 2.29 (p<0.01). Risks increased in cohorts first diving after 1960 compared to risks in earlier cohorts, notably for hematolymphopoietic, central nervous system, gastrointestinal, and skin cancer; induction periods were often brief. The findings suggest that the increases in risk for cancer and short induction periods resulted from direct contact with and absorption of multiple toxic compounds. Early toxic effects in marine life predicted later risks for cancer in divers.

Brain cancer with induction periods of less than 10 years in young military radar workers.

The authors have reported on 5 young patients who had brain tumors that appeared within 10 yr of initial occupational exposures to radar. Four of the patients were less than 30 yr of age when the diagnoses were initially made. Brief induction periods that follow high exposures in individual sentinel patients are a recognized indicator of impending group risk, and these periods call attention to the need for precautionary measures. Similarly, reports of short induction periods for brain cancer on the side of the head in which there has been prior use of cell phones may also indicate increased risk.

Environmental and occupational medicine and injury prevention: education and impact, classroom and community.

The core value guiding the work of physicians and health workers, including those in Environmental and Occupational Epidemiology and Medicine and Injury Prevention, is to protect the health of the public, especially its most vulnerable individuals. In these fields, we emphasize teaching the use of epidemiology, the core discipline of public health, as a tool for early detection and prevention of disease and injury, as well as an instrument for hypothesis testing. The classic core topics are toxic and physical exposures and their effects, and strategies for their prevention; emerging issues are child labor, mass violence, and democide. In environmental health, students need to be prepared for the reality that the most important and severe problems are often the most difficult to investigate, solve, and evaluate. The following are some recommendations for producing graduates who are effective in protecting communities from environmental hazards and risks: (1) Teach the precautionary principle and its application; (2) Evaluate programs for teaching environmental and occupational health, medicine and epidemiology in schools of public health by their impact on the WHO health indicators and their impact on measures of ecosystem sustainability; (3) Develop problem-oriented projects and give academic credit for projects with definable public health impact and redefine the role of the health officer as the chief resident for Schools of Public Health and Community Medicine; (4) Teach the abuses of child labor and working conditions of women in the workplace and how to prevent the hazards and risks from the more common types of child work; (5) Upgrade teaching of injury prevention and prevention of deaths from external causes; (6) Teach students to recognize the insensitivity of epidemiology as a tool for early detection of true risk; (7) Teach the importance of context in the use of tests of statistical significance; (8) Teach the epidemiologic importance of short latency periods from high exposures as sentinel events for later group risk for cancer and stating the case for action; (9) Protect students and colleagues who are whistleblowers in environmental health from harassment and punishment; (10) Develop curricula and workshops that promote the use of epidemiologic tools for preventing genocide, democide, and their precursors. Schools of Public Health and Community Medicine are at the interface between the resources of academic power and the major problems of community health. Implementing the above recommendations will strengthen academic investigation and impact.