Field-based environmental metabolomics offers a powerful tool for examining how organisms respond to complex mixtures of chemical and environmental stressors. When coupled with traditional ecotoxicology, metabolomics can help reveal mechanistic pathways; however, laboratory-based tests cannot fully replicate the dynamic, multifactorial conditions of natural ecosystems. This review synthesises current advances, challenges, and opportunities in applying metabolomics to ecotoxicology under real-world field conditions. We highlight the growing use of wild-caught organisms, caged exposures, mesocosms, and laboratory studies using field-collected samples to detect sub-lethal metabolic disruptions associated with contaminants such as PFAS, metals, organic pollutants, and wastewater-derived mixtures of compounds. Key themes include the sensitivity of metabolomics to early physiological changes, integration with complementary chemical and ecological data, the challenges in distinguishing natural variability from contaminant effects, the importance of establishing baselines and dose-response relationships, and the need for improved QA/QC and metadata reporting. As the methodological and logistical challenges are overcome, metabolomic profiles from field-exposed organisms are increasingly demonstrating value for environmental risk monitoring and forecasting. Environmental metabolomics has been successfully used for environmental monitoring, supporting regulatory frameworks, and identifying mechanistically grounded biomarkers of exposure and effects. However, to realise its full potential, coordinated efforts among current and future metabolomics practitioners are still needed to advance the current Metabolomics Standards Initiative (MSI) guidance. The MSI should, ideally, be expanded to include common standardised workflows, strengthen bioinformatics infrastructure, expand case studies, and fully embed and integrate metabolomics within routine environmental assessment and decision-making processes, thereby transitioning these 'academic' approaches into practical regulatory tools.

ABSTRACT Metal contamination is known to cause shifts in structure of freshwater assemblages where sensitive species do not survive and tolerant species thrive, and given their sensitivity, ubiquitous nature, and high abundances, microbes are ideal targets for biomonitoring assessments. However, the responses of diverse microbial communities to metal contamination in freshwater environments are currently understudied, particularly in the Southern hemisphere. Therefore, in this study we used environmental DNA metabarcoding to assess the influence of copper contamination events on an urban wetland. Laboratory‐based microcosms with clean and contaminated sediments were spiked with copper sulphate to assess microbial responses. We saw significant microbial variation both over time and between concentrations, with responses varying between the microbes from uncontaminated and contaminated sediments; outlining how the dynamics develop over a concentration and temporal gradient and how they vary with assemblages from contaminated and uncontaminated environments, with seven families identified as possible indicators of metal contamination.

Prenatal organophosphate (OP) pesticide exposure may be associated with reduced fetal growth, although studies are limited and have mixed results. We investigated associations between prenatal OP pesticide exposure and fetal size and modification by fetal sex. Maternal urinary concentrations of dialkyl phosphate (DAP) metabolites were measured at 3 time points. Fetal biometrics were obtained from ultrasounds in the second (n = 773) and third (n = 535) trimesters. Associations between pregnancy-averaged ΣDAP and fetal biometry z scores were determined through multiple linear regression. Modification by sex was investigated through stratification and interaction. In the second trimester, one ln-unit increase in ΣDAP was associated with lower estimated fetal weight (-0.15 SD; 95% CI, -0.29 to -0.01), head circumference (-0.11 SD; CI, -0.22 to 0.01), biparietal diameter (-0.14 SD; CI, -0.27 to -0.01), and abdominal circumference (-0.12 SD; CI, -0.26 to 0.01) in females. In the third trimester, one ln-unit increase in ΣDAP was associated with lower head circumference (-0.14 SD; CI, -0.28 to 0.00) and biparietal diameter (-0.12 SD; CI, -0.26 to 0.03) in males. Our results suggest that prenatal OP pesticide exposure is negatively associated with fetal growth in a sex-specific manner, with associations present for females in mid-gestation and males in late gestation. This article is part of a Special Collection on Environmental Epidemiology.

Environmental pollution is regarded as one of the most substantial threats facing freshwater ecosystems. Two contaminant types in particular, metals and pesticides, represent both long-term and widespread hazards to aquatic environments. Contamination negatively affects the health of aquatic flora and fauna. Constructed wetlands are an important mitigation measure for managing stormwater in urban landscapes. Given that constructed wetlands are designed to capture and retain contaminants from stormwater in sediments, the resulting chemical profiles are largely representative of contamination in the surrounding local catchment and aquatic environments. Environmental DNA is expanding the field of aquatic monitoring, introducing the ability to assess biological profiles quickly and reliably, and expanding the knowledge of how contamination affects ecosystems down to a microbial level. Here, we used environmental DNA (eDNA) metabarcoding to characterize the sedimentary microbial profiles of nine urban stormwater wetlands and one rural wetland with low levels of contamination and assess the variation in community structures between sites as well as between the inlet and outlet within each site. We found significant variation in microbial communities between the rural (reference) wetland and stormwater wetlands, variation between some stormwater wetlands, and between over half of the inlets to outlets. The bacterial phyla Cyanobacteria and Proteobacteria were mostly driving this variation, along with Planctomycetota and Bacteroidota. We also found correlations between microbial community structure and chemical occurrences, particularly zinc and barium, with the latter not previously reported to be associated with microbial dynamics in freshwater environments. Our study validates the ability of eDNA metabarcoding to reliably evaluate sedimentary microbial profiles in stormwater wetlands and highlights its value in the assessment and prediction of contamination in these environments.

Assessing the harm caused by pollutants in urban ecosystems remains a significant challenge. Traditional ecotoxicological endpoints are often not sensitive enough to detect the effects of toxicants at environmentally relevant concentrations (≤ng/L). A potential solution is using molecular biology methods to look at small biochemical changes caused by exposure to ng/L concentrations of contaminants. This has been tested in the lab but not conclusively demonstrated in the field. We exposed the freshwater amphipod (Austrochiltonia subtenuis) to water from an urban wetland containing known concentrations of per-and polyfluoroalkyl substances (as well as very low concentrations of pesticides) for 14 days and analyzed their metabolite profiles. Mannose, Myo-inositol, and Isopropyl propionate were found to change in PFAS exposed amphipods, a similar response to that previously observed in laboratory exposures to the same PFAS, but not pesticides. The results give a better understanding of PFAS toxicity at environmentally relevant concentrations and conditions.

Abstract Background Research consistently finds poorer health and educational outcomes for children who have experienced out-of-home care relative to the general population. Few studies have explored differences between those in care and those in receipt of intervention from social services but not in care. Children receiving social services interventions often experience Adverse Childhood Experiences (ACEs), and deprivation, which are known to negatively impact outcomes. We aimed to estimate the association of different social services interventions with educational outcomes and hospital admissions, while adjusting for ACEs and deprivation. Methods We linked retrospective, routinely collected administrative records from health, education, and social care to create a cohort via the Secure Anonymised Information Linkage (SAIL) databank in Wales, UK. We analysed data for children and household members (N = 30,439) across four different groups: [1] no social care intervention; [2] children in need but not in care (CIN); [3] children on the Child Protection Register but not in care (CPR); [4] children in care - i.e. removed from the family home and looked after by the local authority (CLA). Our primary outcome was education outcomes at age 16 years. Secondary outcomes were all cause emergency hospital admissions, and emergency admissions for external causes/injuries. Results Children in receipt of social services intervention were more likely to not attain the expected level upon leaving statutory education at age 16 after adjusting for ACEs and other characteristics (for children who had been in out-of-home care (conditional OR: 1·76, (95%CI) 1·25 − 2·48), in need (2·51, 2·00–3·15) and those at risk (i.e., on the child protection register) (4·04, 2·44 − 6·68). For all-cause emergency admissions, all social care groups were at greater risk compared to children in the general population (children in care (conditional HR: 1·31, 1·01–1·68), children in need (1·62, 1·38 − 1·90), and children at risk (1·51, 1·11 − 2·04). Conclusions All groups receiving social service intervention experience poorer educational and health outcomes than peers in the general population. Children who remain with their home parents or caregivers but are identified as ‘in need’ or ‘at risk’ by social care practitioners require further research. Integrated support is needed from multiple sectors, including health, educational and social care.

Purpose Using a mixed methodology comprising interviews, case file analysis and descriptive statistics, this study aims to examine the experiences of all 43 young people in Wales subject to secure accommodation orders between 1st April 2016 and 31st March 2018. Design/methodology/approach Children in the UK aged 10–17 years who are deemed to be at a significant level of risk to themselves or others may be subject to a secure accommodation order, leading to time spent in a secure children’s home (SCH) on welfare grounds. Following a rise in the number of children in Wales referred to SCHs for welfare reasons, this paper describes these young people’s journeys into, through and out of SCHs, giving insight into their experiences and highlighting areas for policy and practice improvements. Findings Findings indicate that improvements in mental health support and placement availability are key in improving the experiences of this particularly vulnerable group of young people throughout their childhood. Practical implications Other practical implications of the study’s findings, such as improvements in secure transport arrangements, are also discussed. Originality/value While the findings are limited by the reliance on self-report methods and the size of the study, namely, the small number of young people with experience of SCHs who were able to participate, the findings build on the existing knowledge base around children’s residential accommodation and provide new insights into how best to support these children.

The aim was to investigate the concentrations of some per- and polyfluoroalkyl substances (PFAS) in patients with pancreatic cancer from New York, and to compare them with a group of controls from the general population of the United States. We selected 50 cases of pancreatic cancer from donors to the New York University Pancreatic Biorepository. Controls were selected from the 2017–18 National Health and Examination Survey sample (n = 167), matched to cases on age, sex, and race and ethnicity. Six PFAS were analyzed in serum samples using high performance liquid chromatography in conjunction with mass spectrometry. PFAS concentrations were categorized into tertiles to explore non-linear associations, and odds ratios (OR) were estimated using conditional logistic regression, adjusting by BMI. Most PFAS were not associated with pancreatic cancer risk. Serum perfluorohexane sulfonic acid (PFHxS) was associated with a decreased risk (OR for upper tertile = 0.24, 95

BACKGROUND:Children receive care and support from social services due to the risk of harm or impeded development or because of disability. This study aimed to identify typologies of adversity experienced by children receiving care and support from social services and to explore how typologies differ by sociodemographic characteristics. METHODS:This is a cross-sectional study of 'Children Receiving Care and Support' (N = 12 792) during 2017/2018 in Wales, UK. We sought to (1) examine the prevalence of household adversities experienced by children in receipt of care and support from social services; (2) identify typologies of household adversities; and (3) explore how typologies of household adversities differ by family characteristics (demographics, measures of social disadvantage, perinatal and care factors). RESULTS:We found evidence for multiple risk factor constellations. The four-class solution suggested four distinct classes of adversities: child disability (50.0%), low adversities (20.3%), family poor health (6.7%) and multiple risks (23.0%). Children in the 'multiple risk' class were significantly more likely to be younger, more deprived and 'looked after' by the local authority compared with those in the 'low adversities' class. CONCLUSIONS:Given the presence of different constellations of household adversities, policies and interventions that address multiple risk factors simultaneously may be more effective and have longer-lasting benefits.

Amphipods are ideal indicators for biomonitoring and ecotoxicological studies of environmental contaminants because they are extensively distributed in aquatic environments, are easy to collect and are important in nutrient cycling. Marine amphipods (Allorchestes compressa) were exposed to two concentrations of copper and pyrene, and their mixtures, for 24 and 48 h. Changes in polar metabolites were assessed using Gas Chroma-tography Mass Spectrometry (GC-MS)-based untargeted metabolomics. Generally, limited metabolite changes were observed for copper and pyrene single exposures (eight and two significant metabolites, respectively), while 28 metabolites had changed following exposures to mixtures. Furthermore, changes were mainly observed after 24 h but had seemingly returned to control levels after 48 h. Multiple types of metabolites were affected including amino acids, Tricarboxylic acid (TCA) cycle intermediates, sugars, fatty acids, and hormones. This study highlights the sensitivity of metabolomics in assessing the impacts of low concentrations of chemicals compared to traditional ecotoxicological endpoints.

It is crucial to understand the effects caused by experimental parameters such as temperature, light, and food type on lab and field-based ecotoxicology experiments, as these variables, and combinations thereof, can affect results. The type of substrate used in exposure experiments, however, is generally assumed to have no effect. This may not always be correct. The metabolic changes in the freshwater crustacean, Austrochiltonia subtenuis exposed to copper, using three common substrates, gauze; toilet paper; and cellulose were investigated. Substrate alone did not affect survival, but each substrate elicited a different metabolic response and adult and juvenile amphipods had different substrate preferences. Several classes of metabolites were shown to change in response to different substrates and toxicant. These included disaccharides, monosaccharides, fatty acids, and tricarboxylic acid cycle intermediates. The results illustrate that metabolomic responses can differ in response to experimental factors that were previously thought not to be significant. In fact, our data indicate that substrate should be viewed as an experimental factor as important to control for as more well-known confounders such as temperature or food, thus challenging the current paradigm. Assuming substrate type has no effect on the experiment could potentially lead to errors in contaminant toxicity assessments. We propose that ideal good practise would be that all experimental factors should be evaluated for their potential influence on metabolomic profiles prior to contaminant response experiments being undertaken.

A survey of 111 urban constructed stormwater wetlands (median watershed area = 86.8 ha) was conducted to identify the major pesticides present and to determine their major catchment sources (residential, industrial, commercial, sporting ovals) and associations with catchment imperviousness. Melbourne, Australia, has separate stormwater and sewerage systems and these wetlands are designed to treat urban stormwater. To maximise the pesticides that could be detected, three types of passive samplers (POCIS, Chemcatcher® SDB-XC and Chemcatcher® C18) were deployed, along with collection of fine sediments. A total of 231 pesticides were screened using these methods. Pesticides that were detected in >5 % of wetlands were checked to determine their registered use in urban areas using an Australian government database (PubCris). Twenty-five pesticides were detected in >5 % of wetlands: 4 pesticides were associated with non-urban land uses (agriculture and forests), another 4 pesticides had no known registered use in urban areas and 17 were associated with urban areas. The pesticides associated with urban areas were the herbicides simazine, diuron, metolachlor, bromacil, propyzamide and paclobutrazol, the fungicides tebuconazole, propiconazole, metalaxyl, trifloxystrobin, iprodione and carbendazim and the insecticides fipronil, bifenthrin, chlorantraniliprole, thiamethoxam and permethrin. Atrazine was also detected in 59 % of wetlands but has not been registered for urban uses in Australia since 2010. It's presence in Melbourne may be due to legacy issues or aerial transportation from rural areas where it's still widely used in crop cultivation. Generally, the major urban catchment source of pesticides is from residential areas (particularly fipronil and simazine), most likely in wood preservatives, paints and from weed or insect control. Many of these widely used pesticides were correlated with increased catchment imperviousness. Some pesticides (bromacil and imidacloprid) were correlated with commercial premises and chlorantraniliprole was correlated with the presence of sporting ovals in the catchment. No pesticides were specifically correlated with industrial areas. The use of passive samplers and fine sediments, in conjunction with detailed land use mapping of stormwater wetland catchments is very effective and efficient in monitoring and sourcing pesticide contamination in urban environments.

Trace metals are major environmental contaminants, and the accumulation of trace metals could cause changes to the metabolism of marine organisms. In order to understand trends in bioaccumulation and changes in metabolic pathways in marine mussels during short-term and long-term exposure to trace metal mixtures, wild Mediterranean mussels (Mytilus galloprovincialis) were exposed to natural seawater spiked with two sub lethal concentrations of a mixture of copper (Cu), zinc (Zn), and lead (Pb) for 30 days. Mussels were collected every 5 days and trace metal levels in the whole bodies were measured. The gills of mussels collected on day 5 and day 30 were sampled separately. Trace metal levels in whole bodies of these samples were measured and metabolites in the gill tissue extracted, profiled, identified, and compared between groups with different exposure time and trace metal levels. The results showed continuous increase in body burdens of Cu and Pb in mussels throughout the exposure period, while Zn accumulation reached a plateau after day 10 in the whole body and gills. The metabolomics analysis demonstrated that multiple metabolites were down-regulated and multiple metabolic pathways possibly interrupted by exposure to the mixture of trace metals. This study provides extensive knowledge that the effects of Cu, Zn, and Pb exposure on the metabolic pathways have the potential to result in reduced fitness of Mediterranean mussels and demonstrates potential of GC-MS based untargeted metabolomics to be used as a part of trace metal pollution evaluation and ecosystem health monitoring.

Abstract Background falls are common in older people, but associations between falls, dementia and frailty are relatively unknown. The impact of the COVID-19 pandemic on falls admissions has not been studied. Aim to investigate the impact of dementia, frailty, deprivation, previous falls and the differences between years for falls resulting in an emergency department (ED) or hospital admission. Study Design longitudinal cross-sectional observational study. Setting older people (aged 65+) resident in Wales between 1 January 2010 and 31 December 2020. Methods we created a binary (yes/no) indicator for a fall resulting in an attendance to an ED, hospital or both, per person, per year. We analysed the outcomes using multilevel logistic and multinomial models. Results we analysed a total of 5,141,244 person years of data from 781,081 individuals. Fall admission rates were highest in 2012 (4.27%) and lowest in 2020 (4.27%). We found an increased odds ratio (OR [95% confidence interval]) of a fall admission for age (1.05 [1.05, 1.05] per year of age), people with dementia (2.03 [2.00, 2.06]) and people who had a previous fall (2.55 [2.51, 2.60]). Compared with fit individuals, those with frailty had ORs of 1.60 [1.58, 1.62], 2.24 [2.21, 2.28] and 2.94 [2.89, 3.00] for mild, moderate and severe frailty respectively. Reduced odds were observed for males (0.73 [0.73, 0.74]) and less deprived areas; most deprived compared with least OR 0.75 [0.74, 0.76]. Conclusions falls prevention should be targeted to those at highest risk, and investigations into the reduction in admissions in 2020 is warranted.

Minorities and underserved populations disproportionately experience adverse pregnancy outcomes (APO). The CDC's Social Vulnerability Index (SVI) is a validated measure of area-level social vulnerability assigned to every US Census tract based on social factors. Higher SVI scores indicate greater area-level social vulnerability. We investigate the association between the SVI and a composite measure of APO, including preterm birth, hypertensive disorders of pregnancy, stillbirth and small for gestational age in a diverse New York City (NYC) cohort. We analyzed data from pregnant participants in the longitudinal New York University (NYU) Children's Health and Environment Study (2016-17). Individual level sociodemographic and lifestyle factors were collected through questionnaires and electronic medical records. A census tract was assigned to participants based on geocoded residential address. SVI scores were considered continuously and in quartiles. The primary outcome was APO. We analyzed bivariate associations, and then fit multivariable logistic regression models. We included 1363 patients with one geocoded address who delivered at NYU and its affiliates. Higher SVI tracts were mainly located outside of Manhattan (Figure). Our population was 49% Hispanic and 48% reported less than a college education. Sociodemographic factors differed with increasing SVI quartile. (Table) Approximately one-fifth of women had an APO (20.1%). Participants from census tracts with higher SVI had higher odds of developing APO but the associations were not significant in unadjusted or adjusted analyses [OR 1.37 (95% CI: 0.82-2.28); aOR 1.23 (95% CI: 0.67, 2.24)]. Similarly, we did not observe a dose-response relationship with increasing SVI quartiles. (Table) In NYC, the SVI may not appreciably increase our ability to predict which individuals are at highest risk of APO. This may be due the high correlation of individual and area-level socioeconomic status. Further research is needed to understand how SVI is associated with APO in highly segregated areas of the country.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Measuring biological responses in resident biota is a commonly used approach for monitoring disturbed habitats. Ideally, these responses will be stressor-specific, so they can be used diagnostically, and sensitive, so they are early warning indicators of environmental stress. Previous studies have shown the capability of metabolomics approaches to detect changes in metabolite abundance in organisms exposed to low concentrations of pollutants. This study investigated the effects of 24-h exposure to zinc on the Australian aquatic invertebrate, Chironomis tepperi. A multiplatform metabolomics approach (gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS)) was used to identify potential biomarkers of zinc exposure. Exposure to zinc resulted in changes in the abundance of metabolites involved in energy metabolism and intermediates of the transsulfuration pathway. Further research is required to ascertain if these changes in metabolite abundance are specific to zinc. This study demonstrates the potential of using metabolomics alongside other measures of environmental conditions to assess ecosystem health.

Fetal exposure to environmental chemicals has been associated with adverse health outcomes in children and later into adulthood. While several studies have examined correlations and variability of non-persistent chemical exposures throughout pregnancy, many do not capture more recent exposures, particularly in New York City. Our goal was to characterize exposure to phthalates, bisphenols, polycyclic aromatic hydrocarbons, and organo-phosphate pesticides among pregnant women residing in New York City who enrolled in the New York University Children's Health and Environment Study (NYU CHES) between 2016 and 2018. We measured urinary chemical metabolite concentrations in 671 women at early, mid, and late pregnancy (median 10.8, 20.8, and 29.3 weeks, respectively). We calculated Spearman correlation coefficients among chemical concentrations at each mea-surement time point. We compared changes in population-level urinary metabolites at each stage using paired Wilcoxon signed-rank tests and calculated intraclass correlation coefficients (ICCs) to quantify intra-individual variability of metabolites across pregnancy. Geometric means and ICCs were compared to nine other preg-nancy cohorts that recruited women in 2011 or later as well as nationally reported levels from women of child-bearing age. Compared with existing cohorts, women in NYU CHES had higher geometric means of organo-phosphate pesticides (Ediethylphosphates = 28.7 nmol/g cr, Edimethylphosphates = 57.3 nmol/g cr, Edialkyl phosphates = 95.9 nmol/g cr), bisphenol S (0.56 mu g/g cr), and 2-naphthalene (8.98 mu g/g cr). Five PAH me-tabolites and two phthalate metabolites increased between early to mid and early to late pregnancy at the population level. Spearman correlation coefficients for chemical metabolites were generally below 0.50. Intra-individual exposures varied over time, as indicated by low ICCs (0.22-0.88, median = 0.38). However, these ICCs were often higher than those observed in other pregnancy cohorts. These results provide a general overview of the chemical metabolites measured in NYU CHES in comparison to other contemporary pregnancy cohorts and highlight directions for future studies.

Background COVID-19 vaccinations have been prioritised for high risk individuals. Aim Determine individual-level risk factors for care home residents testing positive for SARS-CoV-2. Study design Longitudinal observational cohort study using individual-level linked data from the Secure Anonymised Information Linkage (SAIL) databank. Setting Fourteen thousand seven hundred and eighty-six older care home residents (aged 65+) living in Wales between 1 September 2020 and 1 May 2021. Our dataset consisted of 2,613,341 individual-level daily observations within 697 care homes. Methods We estimated odds ratios (ORs [95% confidence interval]) using multilevel logistic regression models. Our outcome of interest was a positive SARS-CoV-2 PCR test. We included time-dependent covariates for the estimated community positive test rate of COVID-19, hospital inpatient status, vaccination status and frailty. Additional covariates were included for age, sex and specialist care home services. Results The multivariable regression model indicated an increase in age (OR 1.01 [1.00,1.01] per year), community positive test rate (OR 1.13 [1.12,1.13] per percent increase), hospital inpatients (OR 7.40 [6.54,8.36]), and residents in care homes with non-specialist dementia care (OR 1.42 [1.01,1.99]) had an increased odds of a positive test. Having a positive test prior to the observation period (OR 0.58 [0.49,0.68]) and either one or two doses of a vaccine (0.21 [0.17,0.25] and 0.05 [0.02,0.09], respectively) were associated with a decreased odds. Conclusions Care providers need to remain vigilant despite the vaccination rollout, and extra precautions should be taken when caring for the most vulnerable. Minimising potential COVID-19 infection for care home residents when admitted to hospital should be prioritised.

Per and polyfluoroalkyl substances (PFAS) are of concern to environmental regulators due to their widespread occurrence, persistence and reported toxicity. However, little data exist on the effects of PFAS at environmentally relevant concentrations. The development of molecular markers for PFAS exposure would therefore be useful to better understand the environmental risks of these compounds. In this study, we assessed if such markers could be developed using Gas Chromatography–Mass Spectrometry-based metabolomics. We exposed the freshwater amphipod Austrochiltonia subtenuis to a range of environmentally relevant concentrations of perfluoro-octane sulfonic acid (PFOS), hexafluoropropylene oxide dimer acid (GenX) and perfluorohexanesulphonic acid (PFHxS) for 7 days at five concentrations. A metabolic response was detected in all concentrations and treatments even though the survival rates only differed significantly at the highest exposure levels. The metabolic response differed between compounds but all three PFAS induced changes in the levels of amino acids, fatty acids, and cholesterol, in line with the literature. PFOS was found to bioaccumulate. Both GenX and PFHxS were eliminated from the amphipods, but PFHxS was eliminated at a slower rate than GenX. This information improves our understanding of the sublethal effects of PFAS as well as their environmental fate and behaviour.

Per and Polyfluoroalkyl Substances (PFAS) are a diverse group of man-made chemicals with a range of industrial applications and which are widespread in the environment. They are structurally diverse but comprise a common chemical feature of at least one (though usually more) perfluorocarbon moiety (-CnF2n-) attached to a functional group such as a carboxylic or sulphonic acid. The strength of the Carbon-Fluorine bond means the compounds do not break down easily and can thus bioaccumulate. PFAS are of high concern to regulators and the public due to their potential toxicity and high persistence. At high exposure levels, PFAS have been implicated in a range of harmful effects on human and environmental health, particularly problems in/with development, cholesterol and endocrine disruption, immune system function, and oncogenesis. However, most environmental toxicology studies use far higher levels of PFAS than are generally found in the environment. Additionally, since the type of exposure, the PFAS used, and the organisms tested all vary between studies, so do the results. Traditional ecotoxicology studies may thus not identify PFAS effects at environmentally relevant exposures. Here we conduct a review of omics-based PFAS exposure studies using laboratory ecotoxicological methodologies and environmentally relevant exposure levels and show that common biochemical response pathways are identified in multiple studies. A major pathway identified was the pentose phosphate shunt pathway. Such molecular markers of sublethal PFAS exposure will greatly benefit accurate and effective risk assessments to ensure that new PFAS regulations can consider the full effects of PFAS exposure on environmental and human health receptors.