Annual progress reports

Systematic multidisciplinary approach to define impacts, molecular mechanisms, and ways to treat PFAS exposure (1185002)

  • Professor Graham Neely (Chief Investigator A)
  • University of Sydney
  • Budget: $2,539,080
  • Funding period: 2020 to 2025

Project Synopsis

A globally unique team will investigate the impacts of PFAS exposure on humans, from the population down to the molecular level. First, we will perform a series of innovative 'living' analysis on all published data to identify how PFAS exposure impacts human health, which we will then validate using stem cells differentiated into various human tissues. In parallel, we will use new genome editing technologies to define the precise mechanisms of action for how PFAS exert their toxic effects on human samples, information which will inform on disease mechanisms and ways to treat exposure. Finally, since PFAS exposure can lead to long lasting contamination, we will functionally identify safe strategies to remove PFAS from living animals, information that will lay the groundwork for helping at risk populations dealing with significant PFAS exposures. Our study will be performed in coordination with relevant consumers and stakeholders (Aboriginal community council, local and state government, professional organisations, media). We have already engaged with these entities and have established a framework for continued engagement over the course of this study. Most importantly, guided by our consumers specific interests we have defined the core biological mechanism of action for how one PFAS compound acts on human cells, and importantly have identified a new FDA-approved compound that can mitigate the effects of PFAS exposure in vivo and will continue these efforts in this study.

Progress report 30 April 2024

Since the previous reporting period we have used pooled CRISPR genome editing to identify human genes and pathways that PFAS use to hurt human cells. We have looked at blood cells and now also liver cells and have identified multiple pathways that teach us how PFAS hurts us, and importantly how we can block this damage. Moreover, we have treated human stem cell-derived brain tissue with PFAS and observed damage, which we are now characterising at the molecular level. The outcome of this work will be to inform the public on how PFAS and related compounds can potentially injure the public, and this can also inform on biomarkers to detect injury, or strategies to help people that have experienced significant PFAS exposure.

Publications and other resources

Ricolfi L, Vendl C, Bräunig J, Taylor MD, Hesselson D, Gregory Neely G, Lagisz M, Nakagawa S. A research synthesis of humans, animals, and environmental compartments exposed to PFAS: A systematic evidence map and bibliometric analysis of secondary literature. Environ Int. 2024 Aug;190:108860. doi: 10.1016/j.envint.2024.108860. Epub 2024 Jun 30. PMID: 38968830

Vendl, C., Taylor, M. D., Bräunig, J., Ricolfi, L., Ahmed, R., Chin, M., Gibson, M. J., Hesselson, D., Neely, G. G., Lagisz, M., & Nakagawa, S. (2024). Profiling research on PFAS in wildlife: Systematic evidence map and bibliometric analysis. Ecological Solutions and Evidence, 5, e12292. https://doi.org/10.1002/2688-8319.12292

Vendl, C., Taylor, M. D., Bräunig, J., Gibson, M. J., Hesselson, D., Neely, G. G., Lagisz, M., Nakagawa, S. PFAS exposure of humans, animals and the environment: Protocol of an evidence review map and bibliometric analysis, Environment International, Volume 158, 2022, 106973, ISSN 0160-4120, https://doi.org/10.1016/j.envint.2021.106973.

Vendl C, Pottier P, Taylor MD, Bräunig J, Gibson MJ, Hesselson D, Neely GG, Lagisz M, Nakagawa S. Thermal processing reduces PFAS concentrations in blue food - A systematic review and meta-analysis. Environ Pollut. 2022 Jul 1;304:119081. doi:10.1016/j.envpol.2022.119081. Epub 2022 Mar 30. PMID: 35367104

Vendl, C., Taylor, M. D., Bräunig, J., Gibson, M. J., Hesselson, D., Neely, G. G., Lagisz, M., & Nakagawa, S.. (2021). Profiling research on PFAS in wildlife: Protocol of a systematic evidence map and bibliometric analysis. Ecological Solutions and Evidence, 2, e12106. https://doi.org/10.1002/2688-8319.12106

Vendl, C., Taylor, M. D., Braeunig, J., Gibson, M. J., Hesselson, D., Neely, G. G., … Nakagawa, S. (2021, April 13). PFAS exposure of humans, animals and the environment: registration of the protocol of an evidence review map and bibliometric analysis. https://doi.org/10.17605/OSF.IO/7T4U2

 

Per- and poly-fluoroalkyl substance (PFAS) Exposure and Health Outcomes in Firefighters (1182022)

  • Associate Professor Deborah Glass (Chief Investigator A)
  • Monash University
  • Budget: $566,906.10
  • Funding period: 2020 to 2024

Project Synopsis

Firefighting foams containing PFAS have been used in Australia since 1970 but have been phased out over the last 10 years. Firefighters are likely to be the highest exposed occupation in Australia. PFAS are very persistent and can remain in the human body and the environment for many years.

We have an existing national cohort, of over 230,000 firefighters assembled in 2011 for a cancer and mortality study. The cohort is made up of 17,394 male and 641 female full-time firefighters, 12,663 male and 1,041 female part-time firefighters and 163,159 male and 37,973 female volunteer firefighters. It includes individualised data on the agency, jobs held and the incidents attended. An update of the mortality and cancer incidence of this cohort would be a cost-effective way of addressing the Expert Health Panel priority related to the long-term health of firefighters.

Subgroups of firefighters exposed to higher levels of PFAS or at higher frequency would be identified by:

  • consultations with fire agencies, trades unions and volunteer associations about when and where PFAS-containing foams were used, and the likely extent of exposure for specific subgroups such as those employed at training centres and airports, and
  • The use of Agency records of the use of the foams by individual firefighters

The cancer incidence and mortality of higher and lower PFAS-exposed firefighter groups would be compared. These analyses would look at long term health effects and within cohort comparisons to reduce confounding   variables by comparing similarly selected and recruited firefighters with likely similar, lifestyles, for example, socio-economic status, alcohol and tobacco consumption.

The association between PFAS exposure and cancer incidence, specifically testicular and kidney cancer, will be investigated. Other outcomes, such as thyroid, liver or kidney disease will be investigated by linkage to routinely collected health data sets, such as the Medical Benefits Scheme.

Progress report 30 April 2023

Delays to progress have been experienced due to difficulties engaging with stakeholders which is in part due to reorganisation of Victorian Fire Service. Recruitment has improved post June 2022 due to increased stakeholder support.

An Advisory Group has been established and exposure data collected from two fire agencies with three agencies actively preparing data for the study. Ethics approval is underway to enable linkage to hospital data.

Awaiting final report.

 

Assessing effectiveness of PFAS exposure control in individuals from exposed communities and occupationally exposed cohorts such as fire fighters (1179111)

  • Professor Jochen Mueller (Chief Investigator A)
  • University of Queensland
  • Budget: $2,208,009.60
  • Funding period: 2020 to 2024

Project Synopsis

Trends in serum concentrations of PFAS measured in cross-sectional pooled serum studies in Australia demonstrate that exposure to most routinely studied and bio-accumulative PFAS has substantially declined in the general population over the last 2 decades. This demonstrates that regulation of PFAS use in consumer products has been very effective. However, there are a number of communities and work cohorts that have experienced ‘above normal’ exposure. Our team has worked in/with these communities and with exposed firefighting cohorts and we have identified approximately 500 – 1000 individuals with elevated PFAS serum concentrations. We do not know whether the blood levels in these individuals have decreased over time, whether some individuals have faster reductions in levels than others, and what the predictors of rate of decline are. Hence, the aim of our proposed project is to identify and recruit individuals with elevated PFAS concentrations from various exposed communities and the firefighting cohorts, establish longitudinal trends in PFAS concentrations and, where available, relevant health biomarkers. We will use this information to identify individuals and associated factors that can be related to fast PFAS clearance versus slow clearance/lack of clearance/increase and determine ongoing exposure/exposure pathways for individuals for which clearance remains unsatisfactory. Furthermore, we will use the gained information to model (and date) individuals peak serum concentrations for relevant (elevated) PFAS. The models we develop will assist in other epidemiological studies.

Progress report 30 April 2024

We commenced the second sample collection. This sample collection is on-going and we have an approximately 87% retention rate of original study participants. Preliminary findings suggest that PFAS serum concentrations are decreasing on a group level.

Further data analysis will be conducted once second sampling round is completed.

In addition, we have assessed PFAS exposure in a subgroup of study participants following detection of PFAS contamination at their workplace. This assessment included an investigation of when the PFAS exposure started. Continued monitoring in these participants were conducted to ensure exposure control, as part of this assessment we found clear evidence showing that blood donation can speed up elimination of PFAS from the blood. This evidence has been particularly helpful for those who wish to reduce their PFAS levels.

We have conducted several online community forums where we have presented study progress and preliminary results for the study participants.

Publications and other resources

Nilsson, S., Bräunig, J., Carey, R. N., Hui, J., Smurthwaite, K., Toms, L. M., Kirk, M. D., Mueller, J. F., & Fritschi, L. (2023). Longitudinal measurements of per- and poly-fluoroalkyl substances (PFAS) in archived human serum samples between 1975 and 1995 in Australia. Journal of hazardous materials, 443(Pt B), 130307. https://doi.org/10.1016/j.jhazmat.2022.130307

Conferences

Nilsson, S., Smurthwaite, K., Kay, M, Bräunig, J., Toms, L. M., Fielding, K., King, L., Marrington, S., McLachlan, M., Fritschi, L., Armstrong, B., Kirk, M. D., Mueller, J.F.,  “Effectiveness of Per- and Polyfluoroalkyl Substance (PFAS) Exposure Control in Exposed Communities in Australia”.Dioxin; 44th international Symposium on Halogenated Persistent Organic Pollutants (POPs), Singapore, 2025.

Nilsson, D. “Occupational Exposure of Firefighters to Per and Polyfluoroalkyl Substances (PFAS)” International conference of Occupational Exposure as a firefighter, health risks and mitigation strategies. Porto, Portugal. 2024.

 

Comprehensive characterisation of the PFAS exposome (1185347)

  • Professor Kevin Thomas (Chief Investigator A)
  • University of Queensland
  • Budget: $867,672
  • Funding period: 2020 to 2024

Project Synopsis

Per- and polyfluoroalkyl substances (PFAS) are environmentally ubiquitous and frequently detected in humans worldwide. The OECD has to date identified greater than 5,000 PFAS in use globally. Ninety percent of these have been identified as potential precursors to specific PFAS that bioaccumulates in humans (for example, perfluoroalkyl acids [PFAAs]). Transformation of PFAS precursors in the environment, or in humans (in vivo), can therefore lead to additional, indirect exposure pathways for bioaccumulative PFAS. Despite the high number of known PFAS to be in use, targeted biomonitoring typically looks for a limited number of approximately 30 analytes using tandem mass spectrometry (LC-MS/MS). Notably, current biomonitoring programs generally exclude precursors and to be effective, also need to reflect new fluorinated compounds released by industry to replace those phased out of production. In addition to the routinely monitored PFAS, up to 750 other PFASs have been reported to occur in the environment, identified using non-targeted high-resolution mass spectrometry (HRMS) techniques. Australians, and others elsewhere in the world, are therefore undoubtedly exposed to more PFAS compounds than those typically measured in human biomonitoring programs, either directly or through the transformation of precursors. Recognition of the PFAS exposome, such as, the totality of human environmental exposures to the numerous PFAS compounds, is therefore likely to be limited amongst stakeholders, for example, exposed individuals, the general population and public health regulators. The PFAS exposome unknowns represent a considerable source of uncertainty for ascertaining potential human health risks. With greater understanding and quantification of the PFAS exposome comes improved assessment of PFAS exposure that will facilitate increased understanding of any potential health effects. Alongside this, is an important task to communicate and contextualise what the PFAS exposome means for exposed individuals and the wider population.

Progress report 30 April 2024

The non-target high resolution mass spectrometry workflow for identifying novel PFAS has been applied to samples of pooled human serum from de-identified occupationally exposed people and from the general public. The workflow was demonstrated to be suitable and fit for purpose for use by successfully identifying several new and previously unidentified PFAS and has been published in a peer-reviewed journal. Analysis of the samples data have revealed the presence of several unknown PFAS in human serum and efforts are focused on identifying these compounds. Participants have been recruited to take part in a survey with the goal of enhancing health communication about PFAS exposure pathways. A manuscript on the readability of factsheets about PFAS has been submitted for peer-review.

Publications and other resources

Pradeep Dewapriya, Sandra Nilsson, Sara Ghorbani Gorji, Jake W. O’Brien, Jennifer Bräunig, María José Gómez Ramos, Eric Donaldson, Saer Samanipour, Jonathan W. Martin, Jochen F. Mueller, Sarit L. Kaserzon, and Kevin V. Thomas. Novel Per- and Polyfluoroalkyl Substances Discovered in Cattle Exposed to AFFF-Impacted Groundwater. Environmental Science & Technology 2023 57 (36), 13635-13645. DOI: 10.1021/acs.est.3c03852

 

Utilising male fertility as a biomarker of health to understand the biological effects of PFAS (1189415)

  • Professor Brett Nixon (Chief Investigator A)
  • University of Newcastle
  • Budget: $1,301,122
  • Funding period: 2020 to 2024

Project Synopsis

Our multi-site multidisciplinary team of experts will harness the acute sensitivity and responsiveness of male fertility to environmental toxicant exposure, as a proven reliable biomarker of health, to deliver an evidence-based assessment of PFAS impacts in communities across Australia.

Aim 1: Study how blood PFAS profiles are associated with sperm parameters in three cohorts; a high-exposure group living in five contaminated ‘red zones’ near Department of Defence bases across Australia; a general population cohort from communities close to these red zones, and lastly; an occupationally-exposed cohort of firefighters.

Aim 2: Utilise a transgenerational animal model to determine the causal molecular mechanisms and direct effects, from exposure to drinking water contaminated with PFAS profiles of affected communities.

Aim 3: Assess the efficacy of an innovative remediation strategy in our animal model. Namely, to feed hemp protein extracts, which we have proven to be extremely effective in sequestering PFAS, to ameliorate adverse health sequelae associated with PFAS exposure. Ultimately, our research will be conducted in close collaboration with communities to fulfil their need for information and a long sought-after solution to PFAS contamination.

Progress report 30 April 2024

We have completed 3 major mouse studies assessing the direct impact of PFAS exposure on sperm biology: (i) in vitro study, (ii) 3-month whole animal PFAS exposure model and (iii) transgenerational study. The in vitro study revealed that direct PFAS exposure was not cytotoxic to spermatozoa and nor did it overtly influence their functional profile, with normal rates of in vitro fertilization recorded. PFAS treatment of spermatozoa did, however, result in a significant delay in the development of the preimplantation embryos they sired. Such development delays were not attributed to a loss of sperm DNA integrity or an elevated burden of oxidative lesions, thus raising the prospect that PFAS exposed spermatozoa may harbor alternative stress signal(s) that are conveyed to the embryo at the moment of syngamy. Similarly, our 2 in vivo studies have also shown that paternal PFAS exposure can lead to altered patterns of embryonic gene expression. Both of these studies are being prepared for publication. We are currently undertaking the studies of human cohorts described in Aim 1 and have commenced planning to assess the efficacy of hemp protein remediation strategy in our animal model as described in Aim 3. This project is therefore on track to deliver on the stated objectives.

Publications and other resources

Calvert et al., (2021) Assessment of the Emerging Threat Posed by Perfluoroalkyl and Polyfluoroalkyl Substances to Male Reproduction in Humans. Front Endocrinol. 12:799043. doi: 10.3389/fendo.2021.799043
Calvert et al., (2024) Assessment of the impact of direct in vitro PFAS treatment on mouse spermatozoa. Reproduction and Fertility. 5:e230087. doi: 10.1530/RAF-23-0087

Green et al., (2024) The perils of per- and polyfluorinated chemicals on the reproductive health of humans, livestock, and wildlife. Reproduction, Fertility and Development (accepted: in press)

Conference abstracts and presentations

B. Nixon (2024) How the sperm epigenome can aid our understanding of pathology and infertility. 7th Annual Meeting of the Australian Reproduction Update, Melbourne, Australia. Invited Plenary Speaker

B. Nixon (2023) Which environmental factors disturb testicular and epididymal physiology? 3rd Virtual Mini Symposium on Male Reproductive Immunology “At the Interface of Tolerance and Defense” Munich, Germany. Invited Keynote Speaker

B. Nixon (2023) Working towards improved understanding of the causes of male infertility. Hunter Medical Research Institute, Newcastle, Australia. Invited Keynote Speaker

B. Nixon (2023) Making heads or tails of male infertility. Hunter Medical Research Institute, Newcastle, Australia. Invited Keynote Speaker

B. Nixon (2023) What makes the best swimmers. 15th Network for Young Researchers in Andrology (NYRA) Meeting: Palace de Caux, Switzerland. Invited Keynote Speaker

B. Nixon (2023) Epididymis and Epididymosome Contributions to Sperm Epigenome. American Society of Andrology, Boston, Massachusetts. Invited Symposium Speaker

B. Nixon (2023) Post-testicular influences on programming of sperm function. Society for the Study of Reproduction, Ottawa Canada. Invited Symposium Speaker

B. Nixon (2023) Post-testicular influences on male reproductive health and fertility. Fertility Society of Australia and NZ (FSANZ): Gold Coast, Australia. Invited Keynote Speaker

B. Nixon (2023) Utilising male fertility as a biomarker of health to understand the biological effects of PFAS. New Frontiers for a Healthy Start to Life - ‘Planetary Health’. Adelaide, SA. Invited Keynote Speaker
 

 

Impact of exposure pathway and source on PFAS absorption and bioavailability (1186337)

  • Professor Albert Juhasz (Chief Investigator A)
  • University of South Australia
  • Budget: $1,398,763.20
  • Funding period: 2020 to 2024

Project Synopsis

A fundamental knowledge gap when assessing PFAS health effects is an understanding of exposure; the extent of PFAS absorption (i.e. bioavailability) following ingestion, inhalation or dermal contact with PFAS-contaminated media. As bioavailability influences the dose available to exert a toxicological effect, understanding bioavailability is critical for assessing the risk of exposure to PFAS sources.

This project leverages UniSA’s recognised strengths and world class reputation in contaminant exposure assessment through collaboration with public health researchers, medical researchers, environmental chemists, environmental regulators, risk assessors and the community. The multidisciplinary approach allows a fundamental understanding of PFAS bioavailability from oral, inhalation and dermal pathways and applied outcomes from the assessment of contaminated soil, dust, fruit, vegetables, meat and fish. By understanding factors influencing PFAS absorption from environmental media, this may lead to future development and application of physicochemical and / or nutritional strategies for PFAS exposure minimisation.

Progress report 30 April 2024

The relative bioavailability of key compounds was determined in a range of PFAS impacted soils. Different endpoints were utilised (urinary excretion, liver accumulation) for the quantification of the relative bioavailability of perfluorooctane sulfonate (PFOS), Perfluorooctanoic acid (PFOA) and Perfluorohexane sulfonate (PFHxS). In addition, the influence of sorptive phases (i.e. activated carbon) on changes in PFAS relative bioavailability was also assessed. Initial experiments were undertaken to assess the relative bioavailability of PFAS in edible plants. Hydroponically grown lettuce (with 10 ug/l PFHxA) and lettuce grown in PFAS impacted soil (predominantly PFOS) were utilised to test the experimental approach for dose administration in addition to assessing levels of quantification. Outcomes from these experiments were the establishment of a dosing strategy (different to impacted soil) and a low dose threshold. A request to extend the end date of the project was submitted to allocate additional research time to assess PFAS exposure from food (vegetable) consumption.

Publications and other Resources

Juhasz, A. L., Keith, A., Jones, R., Kastury, F. (2023). Impact of precursors and bioaccessibility on childhood PFAS exposure from house dust. Science of the Total Environment 889, 164306.

Cáceres, T., Jones, R., Kastury, F., Juhasz, Al. L. (2024). Soil amendments reduce PFAS bioaccumulation in Eisenia fetida following exposure to AFFF-impacted soil. Environmental Pollution 358, 124489 (partially funded by project 1186337).

Conference Presentations

Juhasz, A. L., Seeborun, M., Jones, R., Kastury, F., Herde, C., Cavallaro, M. (2024). Immobilization of PFAS in AFFF-contaminated soil: Impact on ecological and human exposure. Battelle 2024 Chlorinated Conference. June 2-7, 2024, Denver, Colorado.

Juhasz, A. L. (2024). Understanding the importance of legacy and emerging contaminant bioavailability for human health exposure assessment. Society for Environmental Toxicology and Chemistry Asia-Pacific 14th Biennial Meeting. 21-25 September, 2024.

 

Human exposure to PFAS and their precursors in the environment and their biotransformation processes (1189660)

  • Professor Xianyu Wang (Chief Investigator A)
  • University of Queensland
  • Budget: $509,160
  • Funding period: 2020 to 2024

Project Synopsis

Aims: To identify PFAS profiles in the environment for exposed cohorts, characterise the biotransformation processes of PFAS precursors and identify their products, and evaluate the contribution from exposure pathways of air inhalation, dust ingestion and dermal contact to the total human burden of PFAS.

Hypothesis: Air, dust and hand wipe samples are detected with both PFAS and Pre-FAS that are available for human exposure.

Precursors are transformed in vitro to end products such as PFAAs. Concentrations of PFAAs in the air, dust and wipe samples increase during the biotransformation reaction. Exposure risk via air inhalation is higher for more volatile PFAS such as Pre-FAS and the risk of dust ingestion is more important for young children. Some PFAS can be absorbed through dermal contact due to their diverse physicochemical properties. Daily intake of PFAS from the environment is a non-negligible exposure pathway when evaluating the overall human exposure risk.

Significance: Outcomes from this project are expected to contribute to quantifying human exposure to PFAS with a comprehensive understanding of exposure pathways, advancing the understanding of results from human biomonitoring studies for translating the body fluid concentration to human exposure profiling. Eventually this project will contribute to the development of risk mitigation methods for Australian affected communities.

Expected outcomes include:

  1. characterisation of PFAS in the environment, for Australian affected communities
  2. identification and quantification of PFAS that are produced from precursors during in-vitro reaction using human liver microsomes and cytosol
  3. evaluation of the contribution from so far under-recognised exposure pathways
  4. recommendations to the individuals in the affected communities on how to understand and/or reduce exposure to PFAS.

Progress report 30 April 2024

For firefighting stations, we have recruited an additional site which brings the total number of participating stations to four. The sample analysis and data processing are in progress.

For residential homes, environmental sample (floor dust, air, wipes) collection is now completed. Chemical analysis of the collected samples has been also completed and data processing is in progress.

A series of skin permeation experiments for PFAS have been conducted and data have been obtained. Comprehensive data analysis is in progress.

Publications and other resources

A scientific paper has been submitted to the Journal of Chemosphere and is currently under review.

Another 2 scientific papers are in preparation, one based on the data from firefighting stations and the other based on the data from community homes.

The fourth scientific paper is in preparation as well, focusing on PFAS permeation through skin and estimating the permeation factor for risk assessment via dermal contact pathway.

 

Human biomonitoring of PFAS: assessing reliability and validity (1180109)

  • Dr Leisa-Maree Toms (Chief Investigator A)
  • Queensland University of Technology
  • Budget: $415,316
  • Funding period: 2020 to 2024

Project Synopsis

Our human biomonitoring program involves collection and analysis of de-identified, surplus pathology samples collected in South East Queensland which are stratified and pooled from 6 age groups (0–4; 5–15; 16–30; 31–45; 46–60; and >60 years) and sex; undertaken every two years since 2002. Limitations of this established methodology are: the inability to determine individual exposures based on pooled samples; issues of representativeness due to use of de-identified pathology “sick” samples; and concerns of spatial variation across the population of Australia since samples are sourced from South East Queensland only.

This project will evaluate and advance the reliability of biomonitoring of human PFAS exposure in Australia through the assessment of these limitations to provide new data on variance and representativeness of biomonitoring in Australia. Specifically, we will:

  • evaluate the representativeness of pooled pathology samples for assessing exposure risk
  • determine chemical concentration data by age/sex from 2020 to 2024
  • investigate both traditional and emerging PFAS.

Progress report 30 April 2024

We have collected samples for temporal trend analysis and interpretation suggests a plateau of PFAS concentrations over time in the general population in Australia. Samples from children have been collected and currently being analysed. Samples from all States and Territories of Australia have been collected and analysed and a paper is being prepared for publication. Samples from areas of known PFAS contamination (compared with controls) have been collected and analysed and a paper is submitted for publication. The suite of PFAS analysed has been increased and interpretation of these is underway. Assessment of optimal human biomonitoring methodology is underway following collection and analysis of blood serum pools of smaller age brackets, 'sick' and 'not sick' pathology samples and investigation of pool size. We have sought and had approved a 6-month extension for this project.

Publications and other resources

Taucare, G., Chan, G., Nilsson, S., Toms, L. L., Zhang, X., Mueller, J. F., & Jolliet, O. (2024). Temporal trends of per- and polyfluoroalkyl substances concentrations: Insights from Australian human biomonitoring 2002-2021 and the U.S. NHANES programs 2003-2018. Environ Res, 262(Pt 1), 119777. https://doi.org/10.1016/j.envres.2024.119777

Nilsson, S., Kucharski, N., Orr, J., Bräunig, J., Thompson, K., Jolliet, O., Langguth, D., Kennedy, C., Hobson, P., Thomas, K.V., Mueller, J.F., Toms, L.M. Serum Concentrations of PFAS Across Australian States and Territories (submitted to International Journal of Hygiene and Environmental Health September 2024).

Orr, J.J., Toms, L.M., Hobson, P , Kennedy, C., Langguth, D., Kucharski, N., Santivanez Olazoa, A., Mueller, J.F., Nilsson, S. Spatial Variations in Per- and Polyfluoroalkyl Substance Concentrations in Pooled Sera from Inland, Coastal, and Island Populations (submitted to Environmental Research September 2024).

Nilsson, S., Bräunig, J., Mueller, A., Sontag, N.J., Langguth, D., Kennedy, C., Hobson, P., Thomas, K.V., Mueller, J.F., Toms, L.M. Identifying Populations with Elevated PFAS Exposure by Targeted Serum Sample Pooling (submitted to Journal of Hazardous Materials September 2024).

 

Using advanced technologies to investigate the impact of PFAS exposure on the human mucosal barrier and interaction with pre-existing medical conditions (1186216)

  • Dr Gerard Kaiko (Chief Investigator A)
  • University of Newcastle
  • Budget: $910,060
  • Funding period: 2020 to 2024

Project Synopsis

Epidemiological research has associated increased PFAS levels with inflammatory bowel disease (IBD) and asthma. Furthermore, traditional toxicology screening, although limited, indicates that PFAS may have deleterious effects (for example, kidney/endocrine function). A major concern of the Australian Department of Health’s Expert Panel Review on PFAS and consumers, is the unknown effects of chronic exposure, dose level, and risk of an impact on human health. In this proposal we aim to identify potencies and related exposure risks (range of pathophysiological readouts) of PFAS (and combinations thereof) on human mucosal epithelial barrier (HMEB) surfaces of the intestinal tract and lung (healthy, IBD and asthmatic). These are the sites most frequently exposed to PFAS. We will employ state-of-the-art three-dimensional cellular models of human organoids (including ‘mini-guts’) to re-capitulate the function of HMEB, as this is now the gold standard for determining the potential toxic effects of chemicals/environmental compounds on human cells. The long-term impact of PFAS on the intestinal and airway barrier cells will be assessed through analysis of genomic methylation using single cell sequencing. Preclinical models of IBD and asthma will be used to assess the potential of PFAS to exacerbate disease, and if pre-existing barrier dysregulation in these disorders increases systemic transit of PFAS from the environment.

Outcomes: Identification of the pathophysiological impact of PFAS on the HMEB will establish a frame-work to inform community and the government on exposure risk and health policy, especially with regard to pre-existing IBD or asthma.

Progress report 30 April 2024

We are close to completion of organoid testing with Perfluorononanoic acid (PFNA) and Perfluorohexanesulfonic acid (PFHxS), which are less abundant chemicals in the environment, water supply, and household and consumer items compared to perfluorooctane sulfonate (PFOS) and Perfluorooctanoic acid (PFOA) but remain significant contaminants that persist long term.

We tested the impact of PFNA and PFHxS at doses ranging from what each molecules is found to be present in the environment in contaminated areas, normal uncontaminated water, and found to be present in human blood in both contaminated and non-contaminated locations. This includes a 1000-fold dose range. We tested both acute short term, and chronic longer-term exposure in our lab systems. We have measured the impact on mucosal epithelial barrier function in our in vitro humanized models in terms of its permeability to substances, its capacity to repair after injury as in disease, and its cell turnover with PFNA and PFHxS to compare to our previous PFOS and PFOA findings. We have so far found no significant impact for either chronic longer term or acute short-term exposure to PFNA or PFHxS across the full dose range relevant to human exposure and blood concentration. We are now proceeding to test these findings using in vivo preclinical models of disease and healthy states to determine impact across environmentally relevant exposure ranges in a non-perturbed (healthy) and perturbed (disease context) mucosal barrier.

Based on feedback we will be combining our results for PFNA and PFHxS into a larger scientific publication with PFOS and PFOA for more impact so that they can be compared in the same assays and functional readouts with what we have already identified from findings with PFOA and PFOS.