Association between multiple sclerosis and urinary levels of toxic metals and organophosphates: A cross-sectional study in Israel.

BACKGROUND: Multiple sclerosis (MS) is a multifactorial disease of uncertain etiology damaging myelin sheaths around axons of the central nervous system. Myelin protects the axon from potentially harmful exogenous factors. The aetiological role of environmental exposure metals and organophosphates is unclear. OBJECTIVE: Identify whether urinary levels of metals and organophosphates differed in MS patients and controls. METHODS: We recruited MS patients from Ziv Medical Centre and healthy controls. MS patients were evaluated according to Expanded Disability Status Scale into mild and moderate-severe conditions. Each participant provided a urine sample and completed epidemiological questionnaires. The levels of six metal (Aluminum, Cadmium, Chromium, Lead, Mercury, Nickel) and one metalloid (Arsenic) and common organophosphates pesticide metabolites (6 dialkylphosphates, DAP) were measured in urine using inductively coupled plasma-mass spectrometry and gas-chromatography mass-spectrometry. We compared cases with controls in terms of urinary levels of these compounds using Mann-Whitney and Kruskall-Wallis tests. RESULTS: Urinary cadmium and mercury levels were higher in the 49 MS patients than the 37 controls (p < 0.01). Cadmium levels were higher in moderate-severe MS patients (n = 24) than mild MS patients (n = 25) (p = 0.003). CONCLUSION: Urinary cadmium and mercury levels were higher among MS patients than controls. Cadmium levels correlated with disease severity. Further studies are needed to explore potential causal pathways between these compounds and MS pathogenesis.

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.

Levels of PFAS concentrations in the placenta and pregnancy complications.

BACKGROUND: Recent research has raised concerns about the potential health effects of perfluoroalkyl and polyfluoroalkyl substances (PFAS) exposure, particularly during critical periods of development such as pregnancy. In this study, we sought to investigate the presence and potential impacts of PFAS in the placenta. METHODS: We measured 13 PFAS compounds in placental tissue samples among 50 women who gave birth at a tertiary medical center in southern Israel. The sample comprised of 10 women with pregnancy-related complications (preterm birth, preeclampsia, gestational diabetes or small-for-gestational age) and 40 women without complications individually matched to cases by age. RESULTS: For five (5) out of 13 PFAS compounds (Perfluorooctane Sulfonate (PFOS), perfluorooctanoic acid (PFOA), Perfluorohexanesulphonic acid (PFHxS), Perfluorononanoic acid (PFNA), Perfluorodecanoic acid (PFDA)) median concentrations were lower or comparable to placental measurements in different international populations. Geometric mean was estimated at 0.09 ng/g (90%CI:0.07;0.10) for PFOA, 0.05 ng/g for PFNA (90%CI:0.04;0.07), 0.03 ng/g for PFDA (90%CI:0.01;0.03), 0.06 ng/g for PFHxS (90%CI:0.05;0.07), 0.23 ng/g for PFOS linear measurement (90%CI:0.20;0.26) and 0.25 ng/g (90%CI:0.22;0.30) for PFOS summed concentrations that included non-linear isomers. Composite outcome of pregnancy-related complications was associated with elevated PFOA placental concentrations at an odds ratio (OR)= 1.82 (90%CI:1.06;3.13) for an increase of one quintile of PFOA value and adjusted to maternal gravidity in a conditional logistic regression. CONCLUSION: This pilot study indicates a widespread exposure to multiple PFAS compounds in placental tissue of pregnant women in Israel. These findings warrant further validation through comprehensive national human biomonitoring initiatives.

Linking between ambient pollution and metals concentration in blood. Nationwide study based on the national blood banking system.

This study was aimed to describe the chemical traces of air pollution in blood of residents and evaluate the association between ambient pollution and its dose absorbed internally by a human body. The national Magen David Adom Blood Services blood donation collection platform and the National Public Health Laboratory's testing services were utilized to conduct a human biomonitoring study among blood donors in Israel. The donors' residential addresses and donations sites' locations were geocoded and merged with the levels of pollutants recorded by the nearby monitoring stations. Pollutants included nitrogen dioxide (NO2), sulfate dioxide (SO2), ozone (O3), carbon monoxide (CO) and particulate matter of size <10 and 2.5 µm in diameter (PM10 & PM2.5). Metal concentrations were statistically analyzed by ratio t-test and a lognormal regression, and adjusted to age, gender and smoking (defined based on Cadmium values). The findings indicate an independent positive association between pollutants and metals' concentrations in blood. Specifically, an increase in interquartile range (IQR) of NO2 was associated with 9.5 % increase in As in blood. The increase in one IQR of PM10 and SO2 was associated with an increase in Pb, of 16.6 % and 12.4 %, respectively. SO2 was also adversely associated with Cd concentrations, by increasing its levels by 5.7 %. The donors' proximity to quarries was related to the Pb blood levels higher 1.47 times compared to donors without quarries close to their residence (p-value = 0.013). To conclude, ambient pollution levels are associated with internal metals' concentrations, reaffirming the link between the two in the pathological pathway from air pollution to morbidity.

National blood bank services as a platform for national human biomonitoring - A proof-of-concept study.

BACKGROUND: Human biomonitoring (HBM) is crucial for identifying potential risks to human health from exposure to environmental hazards. However, it is an expensive and labor-intensive endeavor. To save on samples' collection process we suggested using a national blood banking system as a platform for a national HBM program. For the case study, we used a comparison of blood donors from heavily industrialized Haifa Bay region, northern Israel, with donors from the rest of the country. METHODS: The study population comprised a random sample of blood donors donating blood all over Israel. Samples of whole blood were tested for arsenic (As), cadmium (Cd), chromium (Cr) and lead (Pb). Donors' donations sites and residential locations were geocoded. Smoking status was verified based on Cd levels, after calibrating their concentrations vs Cotinine in a sub-sample of 45 subjects. Metal concentrations were compared between regions using a lognormal regression, while controlling for age, gender, and predicted probability of smoking. RESULTS: During Mar 2020-Feb 2022, we collected 6230 and tested 911 samples. Concentrations of most of the metals were modified by age, gender, and smoking. Cr and Pb appeared to be 1.08-1.10 times higher among Haifa Bay residents than in the rest of the country (although with borderline significance of 0.069 for Cr). Cr and Pb were 1.13-1.15 times higher for those who donated blood in the Haifa Bay region, but not necessarily resided in the area. Donors from Haifa Bay had lower levels of As and Cd as compared to other donors in Israel. CONCLUSIONS: Using a national blood banking system for HBM proved to be feasible and efficient. Blood donors from Haifa Bay area were characterized by elevated levels of Cr and Pb and lower levels of As and Cd. An extensive investigation of industries in the area is warranted.

Prenatal exposure to heavy metal mixtures and anthropometric birth outcomes: a cross-sectional study.

BACKGROUND: Numerous studies have suggested significant associations between prenatal exposure to heavy metals and newborn anthropometric measures. However, little is known about the effect of various heavy metal mixtures at relatively low concentrations. Hence, this study aimed to investigate associations between prenatal exposures to a wide range of individual heavy metals and heavy metal mixtures with anthropometric measures of newborns. METHODS: We recruited 975 mother-term infant pairs from two major hospitals in Israel. Associations between eight heavy metals (arsenic, cadmium, chromium, mercury, nickel, lead, selenium, and thallium) detected in maternal urine samples on the day of delivery with weight, length, and head circumference at birth were estimated using linear and Bayesian kernel machine regression (BKMR) models. RESULTS: Most heavy metals examined in our study were observed in lower concentrations than in other studies, except for selenium. In the linear as well as the BKMR models, birth weight and length were negatively associated with levels of chromium. Birth weight was found to be negatively associated with thallium and positively associated with nickel. CONCLUSION: By using a large sample size and advanced statistical models, we could examine the association between prenatal exposure to metals in relatively low concentrations and anthropometric measures of newborns. Chromium was suggested to be the most influential metal in the mixture, and its associations with birth weight and length were found negative. Head circumference was neither associated with any of the metals, yet the levels of metals detected in our sample were relatively low. The suggested associations should be further investigated and could shed light on complex biochemical processes involved in intrauterine fetal development.

Human biologic monitoring based on blood donations to the National Blood Services.

BACKGROUND: The ambient exposure does not always reflect the internal levels of pollution absorbed in the body. While human biomonitoring (HBM) could provide a valid estimate of exposure extent, it is usually an expensive and a heavily manpowered enterprise. Using samples collected during blood donations for HMB may provide a more efficient platform for a routine biomonitoring. METHODS: The current study is aimed to explore the feasibility of using the national blood banking system for the purposes of HBM, to compare between residents of a suspected polluted area in northern Israel (Haifa Bay) to the rest of the country. Specifically, we will assemble a geographically representative sample of blood donors residing in the study area and of the general population, to test for four industry and traffic-related metals: lead (Pb), cadmium (Cd), arsenic (As) and chromium (Cr). Samples of whole blood from donors will be tested in the Laboratory of Public Health Services managed by the Ministry of Health. The information on donors' biomarkers levels will be further linked with the air pollution and meteorological data assessed at the location of the blood collection sites (short-term exposure) and donors' permanent address (long-term exposure), as recorded by the monitoring stations spread throughout Israel and the satellite-based exposure models. The association between biomarkers and ambient environmental exposures will be assessed. The samples' collection is planned for 2 years of 2020-2021. DISCUSSION: The information collected in this study could lead to environmental regulations within Haifa Bay area aimed to prevent exposure to high levels of hazardous chemicals.