Legacy Pollutants in Blood Linked to Inflammation Markers in French Women

A team of French and Italian researchers has uncovered fresh evidence that long-lived industrial chemicals lingering in human blood may leave a measurable imprint on the immune system. In a study published in the journal Environmental Health, scientists analyzing samples from the E3N-Generations cohort found that certain organochlorine pesticides were associated with elevated levels of a key inflammation marker, while a family of so-called forever chemicals showed an unexpected inverse relationship with another inflammatory signal. The findings add a new layer to the growing scientific debate over how the chemical mixtures we carry in our bodies shape long-term health.

Persistent organic pollutants, or POPs, are a diverse class of chemicals defined by three troubling properties: they resist degradation in the environment, they accumulate in the fatty tissues of living organisms, and they can be toxic to humans. Because they travel through food chains and persist for decades, compounds that were banned or restricted years ago still circulate in the blood of people who never directly handled them. The study focused on four major families: organochlorine pesticides such as dieldrin and heptachlor epoxide, polychlorinated biphenyls known as PCBs, polybrominated diphenyl ethers or PBDEs used as flame retardants, and per- and polyfluoroalkyl substances, the widely discussed PFAS.

The research team, led by Francesca Romana Mancini of Université Paris-Saclay, Inserm and Gustave Roussy, together with colleagues including German Cano-Sancho and Jean-Philippe Antignac of the LABERCA laboratory in Nantes and Gianluca Severi, drew on a cross-sectional sample of 468 women from the E3N-Generations cohort, a long-running French epidemiological project built on data from Inserm and supported by the Mutuelle Générale de l’Education Nationale, the Gustave Roussy Institute and the French League against Cancer. Blood samples were collected between 1994 and 1999, a period that gives researchers a window into body burdens accumulated during decades when many of these chemicals were still in active use.

What makes the study technically ambitious is its sheer analytical breadth. The researchers measured concentrations of 45 different POPs in each blood sample, alongside four circulating biomarkers of systemic inflammation: C-reactive protein, or CRP, interleukin-8, known as IL-8, monocyte chemoattractant protein-1, or MCP-1, and tumor necrosis factor-alpha, or TNF-alpha. These markers are the immune system’s chemical messengers and alarm bells. CRP, produced by the liver in response to inflammatory signals, is one of the most widely used clinical gauges of systemic inflammation, while IL-8, MCP-1 and TNF-alpha are signaling molecules involved in recruiting and activating immune cells. Chronically elevated levels of such markers have been linked in earlier research to a range of conditions, from cardiovascular disease to metabolic disorders, which is why toxicologists are keen to understand what drives them upward or downward.

The analytical strategy unfolded in two stages. First, the team applied logistic regression models to test whether individual POPs were associated with the inflammatory biomarkers, which were dichotomized, meaning participants were classified as having levels above or below a threshold. This compound-by-compound approach is the traditional way to scan for signals, but it has a well-known weakness: people are never exposed to one chemical at a time. POPs tend to travel together through food, water and the environment, so a person with high dieldrin likely carries elevated levels of related compounds too, making it hard to disentangle which agent is doing what.

To address that complexity, the researchers turned to principal component analysis, a statistical technique that compresses dozens of correlated pollutant measurements into a smaller number of composite exposure profiles. Each component represents a shared pattern of co-occurring chemicals, reflecting real-world exposure mixtures rather than isolated compounds. These derived profiles were then fed back into regression models to see whether the mixtures themselves, rather than any single pollutant, tracked with inflammation. This dual approach, examining both individual compounds and mixture-based components, is increasingly seen as the gold standard in modern exposure science, where the concept of the exposome demands that researchers grapple with chemical cocktails rather than single agents.

The results split along chemical family lines in a striking way. Several organochlorine pesticides were positively associated with CRP levels, meaning women with higher blood concentrations of these legacy insecticides tended to show more of the inflammation marker. The finding held up when the mixture-based analysis was applied, lending it weight. After the researchers applied false discovery rate correction, a statistical safeguard that accounts for the many comparisons made when dozens of chemicals are tested simultaneously, two pesticides stood out as robust: cis-heptachlor epoxide, a breakdown product of the banned insecticide heptachlor, and dieldrin, another long-restricted pesticide. That these associations survived such stringent correction suggests they are unlikely to be statistical flukes, although the cross-sectional design of the study means it cannot prove that the pollutants caused the elevated inflammation.

Just as intriguing was the pattern on the other side of the ledger. Multiple PFAS compounds were inversely associated with IL-8 concentrations, both when tested individually and as part of a shared exposure component identified by the principal component analysis. Among them, PFDA, PFNA and PFOS showed the most robust associations after false discovery rate correction. In plain terms, women with higher blood levels of these fluorinated chemicals tended to have lower levels of the IL-8 inflammatory signal. The direction of this association is notable because PFAS, often called forever chemicals due to their extreme persistence, have been implicated in a wide range of health concerns in prior research, and an inverse link with an inflammatory marker does not necessarily indicate a protective effect. Biological relationships of this kind can reflect complex interactions, including the possibility that PFAS displace other compounds, alter immune signaling in unexpected ways, or correlate with other characteristics of the study participants that the models do not fully capture.

The authors are careful about what the study can and cannot say. As a cross-sectional analysis, it captures a snapshot of pollutant levels and inflammation markers at a single point in time, so reverse causation and confounding remain possibilities. Inflammation itself can change how chemicals are distributed and stored in the body, and the researchers note that immune and inflammatory dysregulation has been proposed as a key pathway underlying the adverse health effects of POPs, a hypothesis this study helps to refine rather than definitively confirm. Still, the convergence of individual-compound and mixture-based analyses on the same signals, reinforced by false discovery rate correction, gives the findings more credibility than a simple one-off association would carry.

The broader significance lies in the study’s demonstration that mixed exposures matter. By highlighting the importance of considering both individual compounds and exposure mixtures, the work aligns with a shift in environmental health research away from single-chemical risk assessment and toward methods that reflect the reality of simultaneous, low-dose, lifelong exposure. The E3N-Generations cohort, approved by the French National Commission for Data Protection and Privacy and by the Bicêtre ethics committee, with all participants giving written informed consent including for novel biomarker testing, provided the biological foundation, while the HBM platform of LABERCA, part of the France-Exposome and EIRENE research infrastructures, delivered the analytical muscle needed to quantify 45 pollutants with the precision such comparisons demand. As regulators worldwide confront mounting pressure to address PFAS contamination and as legacy pesticides continue to persist in soils and food chains, studies like this one offer a template for understanding not just whether these chemicals are present, but what they may be doing inside us. The open-access study, published on 28 September 2026, invites both replication in other populations and longitudinal follow-up to determine whether the inflammatory signatures observed here translate into tangible health outcomes over time.

Subject of Research: Associations between blood levels of persistent organic pollutants and systemic inflammation biomarkers in French women

Article Title: Blood levels of persistent organic pollutants and circulating biomarkers of systemic inflammation in French women: evidence from the E3N-generations cohort

Article References: Mancini, F. R., Frénoy, P., Cano-Sancho, G., Marques, C., Ren, X., Perrin, C., Perduca, V., Marchand, P., Le Bizec, B., Antignac, J.-P., & Severi, G. (2026). Blood levels of persistent organic pollutants and circulating biomarkers of systemic inflammation in French women: evidence from the E3N-generations cohort. Environmental Health. https://doi.org/10.1186/s12940-026-01340-5

Image Credits: AI Generated

DOI: 10.1186/s12940-026-01340-5

Keywords: persistent organic pollutants, PFAS, organochlorine pesticides, systemic inflammation, CRP, IL-8, E3N-Generations cohort, biomarkers, chemical mixtures, dieldrin, PCBs, environmental health