Human Excretion of Bisphenol A: Blood, Urine, and Sweat (BUS) Study

Background. Bisphenol A (BPA) is an ubiquitous chemical contaminant that has recently been associated with adverse effects on human health. There is incomplete understanding of BPA toxicokinetics, and there are no established interventions to eliminate this compound from the human body. Using 20 study participants, this study was designed to assess the relative concentration of BPA in three body fluids—blood, urine, and sweat—and to determine whether induced sweating may be a therapeutic intervention with potential to facilitate elimination of this compound. Methods. Blood, urine, and sweat were collected from 20 individuals (10 healthy participants and 10 participants with assorted health problems) and analyzed for various environmental toxicants including BPA. Results. BPA was found to differing degrees in each of blood, urine, and sweat. In 16 of 20 participants, BPA was identified in sweat, even in some individuals with no BPA detected in their serum or urine samples. Conclusions. Biomonitoring of BPA through blood and/or urine testing may underestimate the total body burden of this potential toxicant. Sweat analysis should be considered as an additional method for monitoring bioaccumulation of BPA in humans. Induced sweating appears to be a potential method for elimination of BPA

Understanding implementation context and social processes through integrating Normalization Process Theory (NPT) and the Consolidated Framework for Implementation Research (CFIR)

Background For successful implementation of an innovation within a complex adaptive system, we need to understand the ways that implementation processes and their contexts shape each other. To do this, we need to explore the work people do to make sense of an innovation and integrate it into their workflow and the contextual elements that impact implementation. Combining Normalization Process Theory (NPT) with the Consolidated Framework for Implementation Research (CFIR) offers an approach to achieve this. NPT is an implementation process theory that explains how changes in the way people think about and use an innovation occurs, while CFIR is a framework that categorizes and describes contextual determinants across five domains that influence implementation. We demonstrate through a case example from our prior research how we integrated NPT and CFIR to inform the development of the interview guide, coding manual, and analysis of the findings. Methods In collaboration with our stakeholders, we selected NPT and CFIR to study the implementation process and co-developed an interview guide to elicit responses that would illuminate concepts from both. We conducted, audio-recorded, and transcribed 28 interviews with various professionals involved with the implementation. Based on independent coding of select transcripts and team discussion comparing, clarifying, and crystallizing codes, we developed a coding manual integrating CFIR and NPT constructs. We applied the integrated codes to all interview transcripts. Results Our findings highlight how integrating CFIR domains with NPT mechanisms adds explanatory strength to the analysis of implementation processes, with particular implications for practical strategies to facilitate implementation. Multiple coding across both theoretical frames captured the entanglement of process and context. Integrating NPT and CFIR enriched understandings of how interactions between implementation processes and contextual determinants shaped each other during implementation. Conclusion The integration of NPT and CFIR provides guidance to identify and explore complex entangled interactions between agents, processes, and contextual conditions within and beyond organizations to embed innovations into routine practices. Nuanced understandings gained through this approach moves understandings beyond descriptions of determinants to explain how change occurs or not during implementation. Mechanism-based explanations illuminate concrete practical strategies to support implementation

Isomer Profiles of Perfluorochemicals in Matched Maternal, Cord, and House Dust Samples: Manufacturing Sources and Transplacental Transfer

Background: Perfluorochemicals (PFCs) are detectable in the general population and in the human environment, including house dust. Sources are not well characterized, but isomer patterns should enable differentiation of historical and contemporary manufacturing sources. Isomer-specific maternal–fetal transfer of PFCs has not been examined despite known developmental toxicity of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in rodents

Isomer-Specific Binding Affinity of Perfluorooctanesulfonate (PFOS) and Perfluorooctanoate (PFOA) to Serum Proteins

Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are among the most prominent contaminants in human serum, and these were historically manufactured as technical mixtures of linear and branched isomers. The isomers display unique pharmacokinetics in humans and in animal models, but molecular mechanisms underlying isomer-specific PFOS and PFOA disposition have not previously been studied. Here, ultrafiltration devices were used to examine (i) the dissociation constants (<i>K</i>_d) of individual PFOS and PFOA isomers with human serum albumin (HSA) and (ii) relative binding affinity of isomers in technical mixtures spiked to whole calf serum and human serum. Measurement of HSA <i>K</i>_d’s demonstrated that linear PFOS (<i>K</i>_d = 8(±4) × 10^–8 M) was much more tightly bound than branched PFOS isomers (<i>K</i>_d range from 8(±1) × 10^–5 M to 4(±2) × 10^–4 M). Similarly, linear PFOA (<i>K</i>_d = 1(±0.9) × 10^–4 M) was more strongly bound to HSA compared to branched PFOA isomers (<i>K</i>_d range from 4(±2) × 10^–4 M to 3(±2) × 10^–4 M). The higher binding affinities of linear PFOS and PFOA to total serum protein were confirmed when both calf serum and human serum were spiked with technical mixtures. Overall, these data provide a mechanistic explanation for the longer biological half-life of PFOS in humans, compared to PFOA, and for the higher transplacental transfer efficiencies and renal clearance of branched PFOS and PFOA isomers, compared to the respective linear isomer

Human Elimination of Phthalate Compounds: Blood, Urine, and Sweat (BUS) Study

Background. Individual members of the phthalate family of chemical compounds are components of innumerable everyday consumer products, resulting in a high exposure scenario for some individuals and population groups. Multiple epidemiological studies have demonstrated statistically significant exposure-disease relationships involving phthalates and toxicological studies have shown estrogenic effects in vitro. Data is lacking in the medical literature, however, on effective means to facilitate phthalate excretion. Methods. Blood, urine, and sweat were collected from 20 individuals (10 healthy participants and 10 participants with assorted health problems) and analyzed for parent phthalate compounds as well as phthalate metabolites using high performance liquid chromatography-tandem mass spectrometry. Results. Some parent phthalates as well as their metabolites were excreted into sweat. All patients had MEHP (mono(2-ethylhexyl) phthalate) in their blood, sweat, and urine samples, suggesting widespread phthalate exposure. In several individuals, DEHP (di (2-ethylhexl) phthalate) was found in sweat but not in serum, suggesting the possibility of phthalate retention and bioaccumulation. On average, MEHP concentration in sweat was more than twice as high as urine levels. Conclusions. Induced perspiration may be useful to facilitate elimination of some potentially toxic phthalate compounds including DEHP and MEHP. Sweat analysis may be helpful in establishing the existence of accrued DEHP in the human body

Biomonitoring of Perfluoroalkyl Acids in Human Urine and Estimates of Biological Half-Life

Perfluoroalkyl acids (PFAAs) are persistent and bioaccumulative compounds that have been associated with adverse health outcomes. In human blood, PFAAs exist as both linear and branched isomers, yet for most linear homologues, and for all branched isomers, elimination rates are unknown. Paired blood and urine samples (<i>n</i> = 86) were collected from adults in China. They were analyzed by a sensitive isomer-specific method that permitted the detection of many PFAAs in human urine for the first time. For all PFAAs except perfluoroundecanoate (PFUnA), levels in urine correlated positively with levels in blood. Perfluoroalkyl carboxylates (PFCAs) were excreted more efficiently than perfluoroalkane sulfonates (PFSAs) of the same carbon chain-length. In general, shorter PFCAs were excreted more efficiently than longer ones, but for PFSAs, perfluorooctanesulfonate (PFOS, a C8 compound) was excreted more efficiently than perfluorohexanesulfonate (PFHxS, a C6 compound). Among PFOS and perfluorooctanoate (PFOA) isomers, major branched isomers were more efficiently excreted than the corresponding linear isomer. A one-compartment model was used to estimate the biological elimination half-lives of PFAAs. Among all PFAAs, the estimated arithmetic mean elimination half-lives ranged from 0.5 ± 0.1 years (for one branched PFOA isomer, 5<i>m</i>-PFOA) to 90 ± 11 years (for one branched PFOS isomer, 1<i>m</i>-PFOS). Urinary excretion was the major elimination route for short PFCAs (C ≤ 8), but for longer PFCAs, PFOS and PFHxS, other routes of excretion likely contribute to overall elimination. Urinary concentrations are good biomarkers of the internal dose, and this less invasive strategy can therefore be used in future epidemiological and biomonitoring studies. The very long half-lives of long-chain PFCAs, PFHxS, and PFOS isomers in humans stress the importance of global and domestic exposure mitigation strategies