Biomonitoring

Human biomonitoring (HBM) is a tool for assessing exposure to environmental chemicals by measuring concentrations of substances, their metabolites, and biological markers at the cellular or molecular level, in biological fluids and in tissues such as urine, blood, breast milk, and hair. HBM has emerged as a powerful tool for assessing cumulative exposure to mixtures of chemicals; it can be used to assess environmental exposures of individuals and of population groups. HBM data can also be combined with environmental data to identify exposure pathways and with clinical data to find evidence of associations between exposure to chemicals and health outcomes.

HBM data have many uses in environmental and health research and in policymaking. They can be used to identify populations that are more exposed than others to environmental contaminants, support the formulation of policies designed to reduce exposure to contaminants, and assess policy effectiveness. Thus, many countries—including the U.S., Canada, Germany, France, Belgium, Spain, Italy, the Czech Republic, and South Korea—have developed national biomonitoring programs. In addition, twenty-eight countries, including Israel, are collaborating in the HBM4EU consortium, a project that promotes the use of HBM and the application of its results in policymaking in Europe.

Progress since 2017

The Environmental Health in Israel 2017 report defined challenges related to Human Biomonitoring. Progress achieved in this area during the past three years is outlined below. 

Israel’s involvement in the HBM4EU consortium includes sharing information on research and data from biomonitoring studies conducted in Israel. For example, Israel shared data on the exposure of women to bisphenol A (BPA) for a meta-analysis of sources of exposure to bisphenols among women in Europe. In addition, information on six HBM studies in Israel, including surveys by the Ministry of Health (MoH) and birth cohort studies, was uploaded to the International Platform for Chemical Monitoring (IPCHEM).¹ Israel is also participating in discussions on promoting the sustainability of HBM in Europe, including the use of biomonitoring data in risk assessment and advancement of environmental health policy.

HBM4EU’s activity was planned and funded for five years (2017–2021). As the end of the project approaches, the participants are weighing whether to create follow-up programs or join parallel programs. Either way, it is important that Israel continues to participate in such international projects.

The staff at MoH’s National Biomonitoring Laboratory validated protocols for measuring various environmental contaminants in human biological samples (Table 1). There is also a plan to validate analytical techniques for measuring per- and polyfluoroalkyl substances (PFAS) and flame retardants. 

Table 1: Analytical Capacity at the National Biomonitoring Laboratory*
Source: Israel Ministry of Health

In 2019 and 2020, the laboratory passed quality assurance tests conducted by an international quality assessment program for analyses in biological materials. During 2019, it conducted measurements of environmental contaminants in more than 400 biological samples. 

The National Biomonitoring Program, established with the support of the Environment and Health Fund (EHF), outlines a framework for the next decade including three rounds of collecting biological samples and measuring environmental contaminants. Contaminants of interest were chosen following preliminary prioritization, in which relevant experts ranked thirty-five chemicals and chemical groups under five criteria (such as indication of population exposure in Israel and potential regulatory use of data). The target populations and contaminants are displayed in Table 2. As part of the program, children (ages 4–11) and adults (ages 18–65) will be recruited from the general Jewish and Arab population in a nationwide convenience sample. The main objectives of the program are to provide data on trends of exposure to environmental contaminants, sources of exposure, and subpopulations at risk of high exposure. The program will also yield exposure data for use in quantitative risk assessment and environmental health policy analysis. 

Table 2: Outline of the National Biomonitoring Program in Israel, 2020–2030
Source: Israel ministry of Health

Using data on the concentration of urinary OP metabolites in 103 children, MoH researchers calculated the children’s estimated daily intakes (EDI) of OP pesticides. The urine samples were collected as part of the 2015–2016 National Health and Nutrition Survey (Rav-MABAT). The researchers compared the EDI with the acceptable daily intake (ADI)—a value expressing the level of exposure below which no adverse health effect is expected—as defined by the European Food Safety Authority (EFSA). According to this calculation, about 15% of the children were exposed to the pesticide chlorpyrifos at a level exceeding the ADI (Table 3).²

Table 3: Acceptable Daily Intake, Estimated Daily Intake, and Percentage of Children with Daily Intake Above Tolerated Dose—for Six OP Pesticides
Source: Berman et al., 2020²

The National Biomonitoring Program includes a plan to present the selection and prioritization of chemicals for HBM to representatives from academia, government, and the public, in order to improve the transparency of the process in Israel. It is essential to conduct a periodic reassessment of the prioritization and to consider including additional contaminants, such as OP flame retardants and PFAS.

Human Biomonitoring Research in Israel 

• In a pilot study, researchers from Ben-Gurion University of the Negev quantified environmental contaminants in pooled urine samples of pregnant women from the Negev. They found heavy metals in all urine samples and metabolites of OP pesticides and OP flame retardants in some. No significant differences between Bedouin women and Jewish women were found.³ 
• Researchers from Shamir Medical Center (Assaf Harofeh), Tel Aviv University, Dana-Dwek Children’s Hospital, Kimron Veterinary Institute, and Columbia University studied the association between intrauterine exposure to polychlorinated biphenyls (PCBs) and 1) thyroid hormone levels (TSH) in pregnant women and newborns and 2) anogenital distance (AGD) in newborns. The mean maternal serum concentrations were 2.95 ng/g, 4.62 ng/g, 7.67 ng/g and 5.10 ng/g for congeners 118, 138, 153 and 180, respectively. The researchers found no association between PCB exposure and TSH levels in pregnant women in the study. Among women with a low weight-to-height ratio, however, a significant association between PCB exposure and TSH was reported.⁴ Higher maternal concentrations of PCBs were found to be associated with reduced AGD in male infants.⁵
• The Ministry of Environmental Protection is funding several studies on epidemiological aspects of exposure to air pollution in the Haifa Bay population, including research with an emphasis on HBM (including biomonitoring of heavy metals and organic contaminants in pregnant women, and heavy metals in blood donors⁶).

Exposure to Chemicals in Consumer Products

• Researchers from Tel Aviv University, Sheba Medical Center at Tel Hashomer, and MoH, in collaboration with colleagues from Columbia University, Harvard University, and the U.S. Centers for Disease Control and Prevention (CDC), measured concentrations of thirty-one chemicals including phthalates and phenols in the urine of fifty pregnant women. Fourteen chemicals, including BPA, various parabens, and benzophenone-3 were found in the urine of over 90% of the participants. Other chemicals, including bisphenol S (BPS) and DINCH (a phthalate substitute), were detected in the urine of 30%–63% of the participants. Concentrations of benzophenone-3, a component in sunscreen, were low in comparison with populations in other countries, even though most of the adult population in Israel reports using sunscreen.⁷
• Researchers from Sheba Medical Center, in collaboration with colleagues from Harvard University, Columbia University, and the University of Milan, measured concentrations of phenols and phthalates in the urine of 130 women who underwent in vitro fertilization (IVF) and analyzed miRNA molecules found in follicular fluid. They found an association between concentrations of eight miRNA molecules that play a role in the development of ovarian follicles and oocytes, and concentrations of phenols and phthalates. They concluded that exposure to chemicals from consumer products may change the concentrations of cellular regulatory molecules that play a role in female fertility.⁸ 
• Researchers from Sheba Medical Center, in collaboration with colleagues from Harvard University, Columbia University, and the CDC, measured urinary concentrations of phthalates and DINCH in the same cohort of women who underwent IVF. They found several phthalates of which concentrations were inversely associated with several IVF outcomes: total number of retrieved oocytes, number of mature oocytes, number of fertilized oocytes, and number of top quality embryos. Conversely, no association between concentrations of DINCH and IVF outcomes was found.⁹

Exposure to Pesticides

• Researchers from MoH, measuring urinary OP levels in children during 2015–2016, found higher concentrations of several metabolites in children’s urine in Israel than in other Western countries. They also found associations between fruit consumption and concentrations of several OP metabolites (DMP, DMTP and DETP) and between cucumber consumption and concentrations of DEP and DETP.²
• MoH researchers, measuring urinary OP levels in adults in Israel in 2015–2016, found a statistically significant decrease in concentrations of most urinary OP metabolites relative to the findings of a survey conducted in 2011. The average concentrations, however, were still high relative to populations in the U.S., Denmark, and Canada.^{10, 11} 
• Researchers from the Hebrew University-Hadassah Braun School of Public Health and Community Medicine measured concentrations of urinary OP metabolites in 273 pregnant women and 109 newborns. The urine samples were collected during a four-year period (2012–2016) in which stricter regulations were imposed on the use of OPs in Israel. The researchers found that average concentrations of dialkyl phosphates (DAPs) in the women decreased by about 40% during those years (from 248 nM/L to 148 nM/L). A similar trend was observed among the newborns.¹²

Exposure to Environmental Tobacco Smoke

• MoH researchers, measuring urinary cotinine concentrations in children in 2015–2016, found cotinine in the urine of over 60% of the children even though only 40% of parents reported that their children were exposed to environmental tobacco smoke (ETS). These concentrations are much higher than corresponding concentrations among children in several Western countries.¹³ 
• Researchers from the Hebrew University-Hadassah Braun School of Public Health and Community Medicine and MoH measured urinary cotinine levels in 265 non-smoking pregnant women and ninety-seven newborns. Most of the participants were of high socioeconomic status. The researchers found cotinine in the urine of 37.7% of the women and 29% of the newborns. No association was found between the maternal and infant cotinine levels. The researchers found an inverse association between cotinine levels in the newborns and their birth weight.¹⁴
• MoH researchers, measuring urinary cotinine concentrations in urine samples collected from adults in 2015–2016, found cotinine in the urine of over 60% of non-smoking participants. Urinary cotinine levels were higher among Arab participants than among Jewish participants and higher among non-smoking participants who reported exposure to ETS at home than among non-smoking participants who reported no exposure to ETS at home.¹⁵
• Researchers from Sheba Medical Center, the Hebrew University of Jerusalem, and MoH examined the association between self-reported smoking among 125 fertility patients and cotinine levels in their urine. The research population comprised eighty-three women who self-reported as non-smokers and forty-two who self-reported as smokers. Importantly, the sample does not represent the percentage of smokers among women who underwent IVF at Sheba (18%, according to polling). High urinary cotinine values (>150 µg/L) were found in 4.8% of the eighty-three women who defined themselves as non-smokers.

Future Challenges

The establishment of the National Biomonitoring Laboratory and the development of the National Biomonitoring Program are significant milestones in advancing the field of HBM in Israel. Full implementation of the program—including regular collection of biological samples, analysis of the samples in the national laboratory, and publication of the data and their application in shaping policy in Israel—are the main challenges for the coming years. Within the framework of the program, it is also important to improve collaboration between researchers in academia and the government personnel who collect HBM data and to utilize the data appropriately in planning, management, and budgeting. 

While the National Biomonitoring Program focuses on exposure to harmful environmental chemicals, it is also important to note the centrality of HBM in assessing beneficial dietary metabolic exposures (for example, folates, vitamins, iodine, and magnesium). There is currently no national system for regular monitoring of the nutritional status of the population in Israel, and no coordination between the system that monitors chemical exposures and that which monitors nutritional exposures. Nutritional HBM should be conducted in coordination with the National Biomonitoring Program.

Public interest in HBM results has grown in recent years. An MoH conference in 2019 on exposure to ETS focused on HBM data and analytical techniques for measuring exposure to ETS. Increasing public interest in the HBM findings and publishing data in a way that is accessible to the public is key. For this purpose, a strategy for reporting National Biomonitoring Program data to the public and to decision-makers should be developed. In addition, it is vital to develop a strategy for providing access to HBM data and using HBM data to advance environmental health policy. 

Beyond their use by decision-makers, HBM data may influence ordinary individuals’ behavior, as in the context of reducing childern’s exposure to ETS. It is important to examine the clinical use of HBM (for example, in asthma or well-baby clinics) as a tool for identifying infants or children who are exposed to ETS. 

Potential public exposure to PFAS—in water, consumer products, and food—raises the need to incorporate tests for these contaminants into the National Biomonitoring Program. A combination of environmental analyses and HBM analyses can facilitate research on the primary sources of exposure to these contaminants. 

This chapter and all other chapters in the report was written by a team of scientists and professionals from the Ministry of Health, in collaboration with Environment and Health Fund.