Environment & Exposome

Endocrine-disrupting chemicals (EDCs) are exogenous substances that interfere with hormone synthesis, transport, receptor binding or metabolism; bisphenol A (BPA) and its structural analogues (BPS, BPF) act primarily as agonists or antagonists at oestrogen receptors (ERα, ERβ) and also interact with androgen and thyroid hormone pathways, while phthalates — plasticisers used widely in food packaging, medical devices and personal-care products — reduce androgen biosynthesis by inhibiting steroidogenic enzymes. Epidemiological associations include earlier puberty onset, reduced sperm quality, polycystic ovary syndrome, type 2 diabetes and obesity, though establishing causality in observational data is complicated by ubiquitous co-exposure and the non-monotonic dose-response curves characteristic of many EDCs. The EU has banned BPA from polycarbonate baby bottles (2011) and is progressively restricting it from other food-contact materials under ongoing regulatory action, and applies a group tolerable daily intake for phthalates, but regulatory thresholds remain contested; cumulative mixture risk assessment is not yet standard practice in most jurisdictions.

Lead, cadmium and inorganic mercury are the heavy metals most consistently associated with chronic low-level human exposure and adverse health outcomes in epidemiological research. Lead enters via ageing drinking-water infrastructure and legacy paint; cadmium accumulates through cigarette smoke, contaminated soil and certain foods; methylmercury is concentrated in large predatory fish through bioaccumulation. Mechanistically, these metals displace essential ions, inhibit enzymatic activity, generate reactive oxygen species and alter DNA methylation patterns — epigenetic effects linked to accelerated biological ageing. NHANES blood-lead studies have reported a continuous dose-response relationship between blood lead levels and all-cause and cardiovascular mortality even at concentrations previously considered safe, contributing to successive downward revisions of reference values.

Artificial light at night (ALAN) — from street lighting, screens and indoor illumination — suppresses melatonin secretion via intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing melanopsin, which are maximally sensitive to short-wavelength (~480 nm) blue light, thereby delaying or blunting the nocturnal melatonin surge and phase-shifting the master circadian clock in the suprachiasmatic nucleus. Chronic circadian misalignment is linked to impaired immune function, metabolic dysregulation, cardiovascular risk and accelerated epigenetic ageing. Epidemiological research by Erren and colleagues, along with multiple large cohort studies, has identified associations between ALAN exposure and elevated incidence of breast and prostate cancer, possibly through melatonin-mediated effects on cell proliferation. Urbanisation trajectories project continued increases in global ALAN intensity, making the biological effects of outdoor and indoor light environment increasingly relevant to public health.

Microplastics are solid plastic particles smaller than 5 mm, encompassing nanoplastics at the sub-micron scale, originating from the fragmentation of larger plastic debris, synthetic textiles, tyre wear and personal-care products. They have been detected in human blood, placental tissue, breast milk and, in a 2024 NEJM study by Marfella and colleagues, within carotid artery atheromas — patients with detectable plaque microplastics had a significantly higher risk of myocardial infarction, stroke and death over a median 34-month follow-up. Proposed mechanisms of harm include local inflammatory responses, endocrine disruption via adsorbed chemical additives such as phthalates and bisphenols, and oxidative stress, though dose-response relationships in humans remain poorly characterised. Clinical significance and safe threshold levels have not yet been established, and no validated reduction strategy exists beyond minimising dietary and inhalation exposure.

Per- and polyfluoroalkyl substances (PFAS) are a class of more than 10,000 synthetic chemicals characterised by extremely stable carbon-fluorine bonds, resulting in environmental persistence and, for long-chain variants such as PFOA and PFOS, serum half-lives in humans of several years. Exposure routes include contaminated drinking water, food packaging, non-stick cookware and occupational contact; PFAS have been detected in blood and tissue globally, including in remote Arctic populations. Epidemiological evidence links PFAS exposure to suppressed antibody responses to vaccines, dyslipidaemia, thyroid hormone disruption, reduced birthweight and increased risk of kidney and testicular cancers, with mechanistic pathways involving PPAR-alpha activation and nuclear receptor interference. In 2024 the US EPA set enforceable maximum contaminant levels for PFOA and PFOS at 4 parts per trillion in drinking water; the EU is pursuing a restriction under REACH covering entire PFAS groups.

PM2.5 refers to airborne particles with an aerodynamic diameter of 2.5 micrometres or less, arising predominantly from combustion sources — vehicle exhaust, power generation, wood burning and industrial processes — as well as secondary formation from gaseous precursors such as sulphur dioxide and nitrogen oxides. Their small size allows deep deposition in the alveolar region and translocation into systemic circulation, where they trigger oxidative stress, endothelial dysfunction and inflammatory cytokine release; carriers of the APOE ε4 allele may face heightened neurological risk through blood-brain barrier penetration. Dose-response analyses by Pope, Burnett and colleagues in large American cohorts have demonstrated continuous associations between long-term PM2.5 exposure and all-cause, cardiovascular and lung-cancer mortality without an apparent safe threshold. The WHO 2021 Air Quality Guidelines tightened the recommended annual mean limit to 5 µg/m³ — a level most European and North American cities still exceed.