Silicone Wristbands and Wearables to Assess Chemical Exposures
Holly M. Dixon, Carolyn M. Poutasse, and Kim A. Anderson
Oregon State University
Personal Chemical Exposures
Chemicals in our everyday environment may have unintended effects on human and environmental health. Increasing evidence indicates that environmental exposures impact the risk of disease (Advancing Science, Improving Health 2018), but researchers and community members often lack knowledge about the frequency and magnitude of personal exposures to many chemicals. In order to monitor such exposures, low-cost and easy-to-use technologies are critical tools that inform cutting-edge research in toxicology and environmental epidemiology. These exposure assessment tools will further complement recent research initiatives, such as understanding total exposures throughout a person’s lifespan (“exposome”) and pairing personal exposure data with genetic information (“total exposure health” and “precision medicine”).
Passive Sampling Background
Passive sampling devices (PSDs) for organic chemicals are lipophilic polymers that mimic biological cellular membranes (Figure 9.1) (Huckins et al. 2006, Anderson et al. 2008). Via simple diffusion, unbound chemicals in environmental media (e.g. air, sediment, soil, and water) are sequestered into PSD polymers (Anderson et al. 2008, O’Connell et al. 2014a). Researchers can then extract and quantify the chemicals in the polymer. PSDs do not sequester all chemicals in the environment, but rather the fraction biologically available to transport across cellular membranes (Forsberg et al. 2011, Booij et al. 2016, Paulik et al. 2016). A chemical’s bioavailability is not an inherent property. Rather, bioavailability is dependent upon
FIGURE 9.1 Simplified representation of a passive sampling device (PSD) membrane and biological cell membrane, illustrating functional similarities. Both membranes are lipophilic and have similar pore sizes (estimated 10 A for PSD membrane and 9.5 A for cell membrane) (Anderson et al. 2008). Chemicals are represented by spheres, with some chemicals able to cross the membranes (bioavailable fraction) and some chemicals unable to cross the membranes. (Adapted from Anderson and Hillwalker 2008.).
physiological uptake processes and physical-chemical properties (Bioavailability of Contaminants 2003, Anderson et al. 2008). When examining the relationship between chemical exposures and health effects, it is important to characterize the bioavailable fraction of chemicals.
Over 16,700 scientific publications have mentioned passive sampling since 1980, and over 45 percent of those papers were published between 2014 and 2018 (Google Scholar search; accessed January 4, 2019). Growing interest in passive sampling is partly attributed to low cost, ease of deployment, high sensitivity to low chemical concentrations, and ability to sequester a wide range of bioavailable chemicals (Bohlin et al. 2007, Lohmann 2011). In addition, PSD chemical concentrations represent an average chemical concentration over the study period (i.e. time-weighted average) (Bohlin et al. 2007, Booij et al. 2016, Bergmann et al. 2017b). A time- weighted average can be a benefit in comparison to conventional chemical assessment methods, such as taking water or soil grab samples. Grab samples, which represent a snapshot of chemicals at one time point, require repeated sampling campaigns to characterize long-term exposures, resulting in comparatively high costs (Anderson et al. 2008). For chemical monitoring programs, passive sampling is an effective long-term solution compared to grab sampling (O’Connell et al. 2014b).
Many different types of polymers, including silicone, have been optimized for use as PSDs. A novel application of PSDs are silicone wristbands, first described by O’Connell et al. in 2014. Wristbands are used to characterize personal exposure to organic chemicals. As of March 2019, wristband results have been included in 23 peer-reviewed manuscripts and have been worn by several thousand volunteers on six continents. To date, several different chemical classes including flame retardants, pesticides, polycyclic aromatic hydrocarbons (PAHs), phthalates, and consumer product-related chemicals, have been detected and quantified in silicone wristbands. The ability to concurrently monitor all these different chemical classes offers a unique opportunity to assess the effect of chemical mixtures on human health.
Silicone Wristband Characterization
Silicone wristbands are a robust, simple technology used to characterize an individual’s chemical exposures from dermal, inhalation, and limited ingestion exposure pathways. Due to their small size and mass (less than five grams), wristbands are comfortable, rugged, and do not interfere with daily activities (Figure 9.2). Wristbands also do not require a battery or maintenance, allowing an individual to continuously wear the sampler. Finally, as a noninvasive chemical monitor, wristbands studies have high volunteer compliance (Donald et al. 2016, Kile et al. 2016, Bergmann et al. 2017a, Vidi et al. 2017, Harley et al. 2019).
Silicone wristbands sequester a wide range of chemicals, including volatile organic chemicals (VOCs) and semi-volatile organic chemicals (SVOCs). Depending
FIGURE 9.2 Silicone wristbands can be worn during normal daily activities, such as showering, driving, smoking, sleeping, swimming, and interacting with animals.
on physical-chemical properties, different chemicals will sequester at different rates into the wristband, which can be characterized by chemical partition coefficients (e.g. octanol-air partition coefficient, log Koa) (Anderson et al. 2017, Bergmann et al. 2018, Hammel et al. 2018). Wristbands can sample chemicals that span over twelve orders of magnitude for octanol-air partition coefficients, with log Koa ranging from
3.3 to 16 (toluene to di(2-ethylhexyl)tetrabromophthalate) (Bergmann et al. 2018). As an analogy for several orders of magnitude, the temperature of water freezing at 0°C (log 0) and the temperature at the sun center is 15,000,000°C (log 7). This wide range enables the PSD to function as a broad, nonspecific organic chemical sampler.
Uptake into the silicone wristband, or other silicone wearable, is unique to each chemical based on its physical-chemical properties, environmental concentrations, and exposure time. The uptake of organic chemicals into the wristband over time includes linear, curvilinear, and equilibrium phases (Figure 9.3) (Shoeib and Harner 2002, Huckins et al. 2006, Bohlin et al. 2007). In the linear phase, a chemical’s concentration in the wristband is lower than in the environment and the uptake rate is constant. In the curvilinear phase, a chemical’s concentration in the wristband increases and the uptake rate is reduced. In the next phase, the wristband is in equilibrium with the surrounding environment; the chemical concentration in the wristband becomes constant if the environmental concentration is not changing.
FIGURE 9.3 Theoretical chemical uptake curve for silicone wearables over time. Each chemical will have a different uptake curve.
Regardless of whether a chemical is in the linear, curvilinear, or equilibrium phase, chemical uptake is dynamic and chemicals are actively moving in and out of the silicone wristband during the entire sampling period.
Some chemicals will reach equilibrium between the wristband and the environment, representing the estimated average concentration of the chemical over the time worn. This is the case for small, volatile chemicals (e.g. naphthalene). Saturation of the wristbands is not a concern at equilibrium; the wristbands have been tested in highly contaminated environments for long deployment times with no evidence of saturation. At equilibrium, wristbands can detect changes in a chemical’s concentration and will accurately reflect the average concentrations over the period worn. The chemicals are sequestered within the silicone polymer via simple diffusion (Figure 9.1), but the polymer pores do not behave like enzymatic binding sites (e.g. lock-and-key mechanism). Wristbands do not fill up nor stop sequestering chemicals during uptake; rather, chemicals can move freely between the environment and silicone wristband, resulting in relevant chemical concentrations.
Although the process of chemical uptake depends on several factors, researchers have tools to determine chemical uptake rates in wristbands. Performance reference compounds (PRCs) can be added to wristbands prior to deployment and they allow researchers to calculate a chemical’s uptake rate and phase specific to each sampler’s environment (Booij et al. 2002). There is significant precedence for using PRCs with PSDs (Shoeib and Harner 2002, Bohlin et al. 2007, Lohmann 2011, Anderson et al. 2017).
Wristband Data Applications
Understanding the process of chemical uptake is essential when making conclusions about chemical exposure. Wristband results are often used to make comparisons between different groups of study volunteers. For exposure comparisons, chemical concentrations can be reported as ng/wristband, ng/g wristband, or pmol/g wristband (Donald et al. 2016, Poutasse et al. 2019). Even if specific uptake rates are not known, the uptake rate of a given chemical will be approximately equivalent for all samplers, enabling comparisons of the given chemical between samplers. Because different chemicals have unique uptake curves, researchers have to be cautious when making comparisons between different chemicals (e.g. toluene compared to benzo[a]pyrene), either within a wristband or between different wristbands (Donald et al. 2016). Screening for the presence and absence of a large number of chemicals can also be an efficient way to make comparisons between groups of volunteers and inform future toxicology and exposure science studies (Bergmann et al. 2017a, Dixon et al. 2019).
Current research is addressing how environmental concentrations can be calculated from silicone wristbands via partition coefficients (Anderson et al. 2017). For PAHs, partition coefficients between wristbands and air have been reported from two paired studies: one using wristbands and active air samplers (Anderson et al. 2017) and one using wristbands and low-density polyethylene, another common PSD (Donald et al. 2019).
Another application of wristband data sets is to predict chemical concentrations in biological matrices. This is similar to other research that has used PSD data to predict chemical concentrations in organisms such as crayfish, clams, mussels, and aquatic worms (Muijs et al. 2012, Fernandez et al. 2015, Joyce et al. 2015, Paulik et al. 2016). Data from Dixon et al. (2018) was used to generate a linear regression model of phenanthrene in wristbands and associated metabolites in urine from participants in an urban environment (Figure 9.4). When looking at the sum of
FIGURE 9.4 Linear regression model of phenanthrene in wristbands and associated phenanthrene metabolites in urine from data in Dixon et al. (2018). (aSum of 1-OH-phenanthrene, 2-OH- and 3-OH-phenanthrene, 4-OH-phenanthrene concentrations.) phenanthrene urinary metabolites, the associated R-squared value for the line of best fit was 0.62 (Figure 9.4). This type of approach could be used with other chemicals and types of biological matrices (e.g. blood and breast milk) to predict internal biomarker concentrations.
Silicone Wristband Limitations and Additional Considerations
While wristbands and other silicone wearables offer many opportunities to examine personal chemical exposures, wristbands are not real-time samplers (e.g. do not change color nor notify the wearer when chemical exposure occurs). A sampler must be sent back to a laboratory for chemical analysis. Wristband extracts from either liquid extraction or thermal desorption methods can be stored and reanalyzed later with other analytical methods after sampling has occurred.
Additionally, when worn on the wrist, chemical concentrations in wristbands represent a combination of several exposure routes (e.g. dermal and inhalation) (Weschler et al. 2012, Aerts et al. 2018, Dixon et al. 2019). Although determining the contribution from specific exposure routes may be difficult, it can be advantageous to evaluate chemical exposures from multiple routes to address human health questions.
There are other types of methodologies beyond silicone wristbands that are currently available to monitor personal organic chemical exposures (O’Connell 2017). Stakeholders (e.g. researchers, communities, non-government organizations) need to consider which method aligns best with their objectives. For example, biomonitoring samples are traditionally analyzed to monitor chemical exposures (Ospina et al. 2018). However, biomarker concentrations can vary due to several factors, such as individual variability in metabolism, gender, age, and health status (Aylward et al. 2014, Koch et al. 2014). Additionally, some chemicals remain in the body for a long time or lack a clear link to an internal biomarker (Forsberg et al. 2011). These factors complicate efforts to evaluate chemical exposures, assess intervention strategies, and set regulatory limits via biomonitoring samples. The characteristics of any chemical exposure assessment method must be fit-for-purpose to best address stakeholder questions.