Consumers and Health

Landmark study confirms glyphosate–cancer link

June 13, 2025

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A landmark, long-term carcinogenicity study, conducted as part of the Global Glyphosate Study (GGS), provides the most comprehensive evidence to date linking prenatal and lifelong exposure to glyphosate and glyphosate-based herbicides (GBHs) with significant, dose-related increases in multiple tumors.

This pivotal investigation, led by the Ramazzini Institute and a consortium of international institutions, directly supports the International Agency for Research on Cancer’s (IARC) classification of glyphosate as a probable human carcinogen, offering crucial new data for public health and regulatory considerations worldwide.

Table of Contents

Study design and methodology

The research by Panzacchi and colleagues (2025) employed a robust experimental design involving 1,020 Sprague-Dawley rats (510 males and 510 females) exposed to three test substances: pure glyphosate, Roundup Bioflow (EU formulation), and RangerPro (US formulation). The prenatal exposure protocol began at gestational day 6, continuing through maternal exposure during pregnancy and lactation, with offspring exposure maintained until 104 weeks of age (Panzacchi et al., 2025).

Three glyphosate-equivalent doses were administered via drinking water:

0.5 mg/kg body weight/day (corresponding to the EU Acceptable Daily Intake)
5 mg/kg bw/day, and
50 mg/kg bw/day (the EU No-Observed-Adverse-Effect Level). This dose range enabled assessment of potential health effects at regulatory exposure limits currently considered safe for human consumption.

The study’s comprehensive histopathological evaluation examined all major organs and tissues, with particular attention to rare tumours (historical control incidence <1%). Statistical analyses included Cochran-Armitage trend tests, Fisher’s exact tests, and Poly-k survival-adjusted procedures to account for differential mortality rates between groups (Panzacchi et al., 2025).

Major findings

Haematological malignancies: unprecedented early onset

The study’s most alarming discovery was the early-life onset of leukaemia in treated animals, with 40% of leukaemia deaths occurring before 52 weeks of age — equivalent to less than 35-40 years in humans (Panzacchi et al., 2025). This contrasts starkly with historical controls from both the Ramazzini Institute (Gnudi et al., 2023) and the US National Toxicology Program (NTP, 2024), where no leukaemia deaths occurred before one year of age.

The dose-dependent mortality pattern was particularly pronounced: mean age at death decreased from 97 weeks in low-dose groups to 62 weeks in high-dose groups, suggesting that higher exposures accelerate disease progression (Panzacchi et al., 2025).

All three treatment substances induced statistically significant trends in leukaemia incidence, with lymphoblastic and monocytic subtypes predominating. Males showed greater susceptibility, though combined sex analyses strengthened statistical significance. Notably, no concurrent control animals developed leukaemia, whilst treated groups showed incidences ranging from 0.98% to 5.88%, exceeding historical control rates of 0.90% (NTP, 2024; Panzacchi et al., 2025).

Multi-organ carcinogenesis: rare tumours and treatment-related patterns

The investigation revealed treatment-related increases in both common and rare tumours across multiple organ systems. Skin tumours, absent in all control animals, showed significant dose-related trends in glyphosate-exposed males (p=0.0228), with squamous cell papillomas reaching 3.92% incidence at high doses — nearly four times the historical control rate of 1.02% (NTP, 2024; Panzacchi et al., 2025). Trichoepitheliomas, extraordinarily rare tumours with zero incidence in historical controls (NTP, 2024), appeared exclusively in high-dose females treated with Roundup Bioflow.

Hepatocellular carcinomas demonstrated concerning patterns of early mortality, with 60% of affected animals in the glyphosate group dying before 94 weeks — considerably younger than the 118-week average in historical controls (Panzacchi et al., 2025). Though not reaching statistical significance versus concurrent controls, the consistent appearance of multiple cases across dose groups and the early onset pattern suggest biological relevance. According to historical data, the incidence observed in control groups is as low as 0.17% in the National Toxicology Program (NTP) dataset and 0.82% in that of the Ramazzini Institute (NTP, 2024), confirming the rarity of the phenomenon in the absence of exposure.

The nervous system showed particular vulnerability, with malignant granular cell tumours of the brain occurring at 3.92% incidence in high-dose glyphosate males — over 20 times the historical rate of 0.17% in NTP controls (NTP, 2024; Panzacchi et al., 2025). Peripheral nervous system effects included malignant Schwannomas in multiple organs, with two cases causing death at 34 and 67 weeks of age in Roundup Bioflow-treated males. These exceptionally rare tumours (0.82% historical incidence in Ramazzini controls, zero in NTP controls) suggest specific neurotoxic mechanisms (NTP, 2024; Panzacchi et al., 2025).

Endocrine system disruption: sex-specific vulnerabilities

Endocrine-sensitive tissues demonstrated pronounced treatment effects, particularly in reproductive organs:

male mammary gland tumours, virtually non-existent in SD rats with only 0.17% incidence in NTP historical controls (NTP, 2024), showed statistically significant increases with glyphosate and Roundup Bioflow exposure (p=0.0071) (Panzacchi et al., 2025). This finding gains significance considering the hormone-dependent nature of mammary tissue and recent increases in male breast cancer incidence;
female rats exhibited ovarian granulosa cell tumours at young ages, with one Roundup Bioflow case occurring at just 43 weeks. These tumours are rare, with only 0.85% incidence in NTP historical controls (NTP, 2024);
thyroid effects showed sex-specific patterns: follicular carcinomas in males and C-cell carcinomas in females (Panzacchi et al., 2025);
the adrenal cortex proved particularly sensitive to GBH formulations, with cortical carcinomas reaching 3.92% incidence in RangerPro males—over 16 times the historical rate of 0.24% (NTP, 2024; Panzacchi et al., 2025).

Epidemiological correlations

The experimental findings gain substantial weight when considered alongside accumulating human epidemiological evidence. Recent meta-analyses have documented concerning associations between glyphosate exposure and cancer risk in occupational and environmental settings. The timing and patterns of tumour development in this rat study mirror several key epidemiological observations.

Haematological malignancies in humans show particularly strong correlations with glyphosate exposure. Multiple case-control studies have reported elevated risks of non-Hodgkin lymphoma, with highly exposed individuals facing 41% increased risk. The Agricultural Health Study’s extended follow-up identified significant associations with acute myeloid leukaemia among pesticide applicators with highest cumulative exposures. Critically, the early-onset leukaemia observed in prenatally exposed rats parallels emerging evidence of childhood leukaemia clusters in agricultural communities.

Geographical correlation studies have revealed disturbing patterns linking glyphosate use expansion to cancer incidence. Brazilian researchers documented temporal and spatial relationships between genetically modified soy cultivation — requiring intensive glyphosate application — and childhood acute lymphoblastic leukaemia deaths ( Skidmore et al., 2023. See also Karalexi et al., 2021). Similar associations have emerged from Italian fenceline exposure studies (Malagoli et al., 2016), where children living near treated crops showed elevated leukaemia risk from pesticide mixtures containing glyphosate.

The developmental vulnerability demonstrated in this rat study aligns with epidemiological findings on parental occupational exposure. Children of agricultural workers exposed to glyphosate-containing pesticide mixtures show increased risks of brain tumours, leukaemia, and other malignancies. These human data support the biological plausibility of the prenatal programming effects observed experimentally.

Mechanistic considerations

The diverse tumour spectrum observed suggests glyphosate and GBHs operate through multiple carcinogenic pathways, consistent with their classification as multi-site carcinogens. The predominance of haematological, nervous system, and endocrine-related tumours points to systemic mechanisms affecting cellular differentiation and proliferation control.

Genotoxic mechanisms likely contribute to the observed carcinogenicity, particularly for leukaemias and nervous system tumours. Glyphosate exposure induces DNA damage markers, chromosomal aberrations, and oxidative stress in multiple experimental systems. The early onset of tumours in prenatally exposed animals suggests these genotoxic effects may be particularly damaging during rapid cellular division in developing tissues. Recent molecular profiling studies have demonstrated p53 activation and altered DNA repair pathways following glyphosate exposure.

Endocrine disruption (Muñoz et al., 2020) emerges as a critical mechanism, particularly given the spectrum of hormone-sensitive tumours observed. Glyphosate interferes with steroid hormone synthesis, disrupts thyroid function, and alters hypothalamic-pituitary-adrenal axis regulation. The appearance of male mammary tumours — extremely rare in normal rats — strongly implicates oestrogenic or anti-androgenic activity. Mechanistic studies have shown glyphosate can bind hormone receptors and alter gene expression in endocrine tissues.

The differential effects between pure glyphosate and GBH formulations suggest important toxicological interactions. Co-formulants may enhance glyphosate bioavailability, disrupt cellular membranes, or contribute independent toxic effects. The appearance of kidney mesenchymal tumours, urinary bladder carcinomas, and hemangiosarcomas exclusively with GBH exposure indicates formulation-specific carcinogenic mechanisms beyond glyphosate alone.

Neurotoxic pathways deserve particular attention, as already highlighted by Professor Alberto Mantovani in an interview with Food Times. This is especially relevant given the unprecedented incidence of tumours affecting the nervous system. Glyphosate accumulates in neural tissue, disrupts neurotransmitter systems, and induces neuroinflammation. The S100B protein alterations and white matter changes documented in developmental neurotoxicity studies provide mechanistic links to the granular cell tumours and Schwannomas observed.

Regulatory implications

These findings fundamentally challenge the adequacy of current safety standards for glyphosate and GBHs. The observation of multiple tumour types at the EU Acceptable Daily Intake (0.5 mg/kg bw/day) indicates that exposure limits established to protect public health may fail to prevent cancer development, particularly when exposure begins during vulnerable developmental windows.

A substantial and urgent revision of current risk assessment paradigms is essential in order to incorporate the principles of developmental toxicology:

traditional approaches, which initiate exposure in adult animals, fail to capture critical windows of susceptibility during organogenesis and early postnatal development;
the dramatic differences in tumour incidence and latency between prenatal and adult-onset exposure studies underscore this regulatory blind spot;
risk assessment agencies must adopt comprehensive lifecycle testing for pesticides, particularly those with widespread environmental presence.

The formulation testing gap represents another critical regulatory failure. Most safety assessments focus on active ingredients whilst ignoring commercial formulation effects. This study’s demonstration of formulation-specific tumours — including rare kidney, bladder, and vascular malignancies — highlights the inadequacy of single-compound testing. Regulatory frameworks must require testing of complete commercial products as sold and used, not just technical-grade active ingredients.

Cumulative risk assessment approaches gain urgency given the ubiquitous nature of glyphosate exposure through food, water, and environmental contamination. Current regulations consider pesticides in isolation, ignoring real-world multiple exposure scenarios. The early-onset tumours observed with low-dose chronic exposure suggest that aggregate exposure from multiple sources – including the so-called cocktail effect (Mesnage et al., 2020) – may pose greater risks than previously recognised.

International harmonisation of safety standards becomes imperative given global food trade and environmental persistence. The substantial differences between regulatory positions — from the IARC’s probable carcinogen classification to some agencies’ continued approval — create confusion and potential public health risks. This comprehensive dataset should inform evidence-based regulatory convergence prioritising precautionary protection.

Conclusions

This landmark study provides robust experimental evidence that glyphosate and GBHs cause dose-related increases in multiple tumour types when exposure begins during prenatal development. The findings support IARC’s classification of glyphosate as a probable human carcinogen and highlight the critical importance of early-life exposure windows in carcinogenesis.

The observation of tumour development at doses corresponding to current regulatory limits raises significant public health concerns. Combined with consistent epidemiological evidence and mechanistic plausibility, these results underscore the urgent need for comprehensive re-evaluation of glyphosate safety standards, particularly regarding prenatal and early-life exposures.

Future research should focus on elucidating specific mechanisms of carcinogenesis, identifying biomarkers of early effects, and developing protective strategies for vulnerable populations. The integration of developmental toxicology principles into regulatory frameworks represents a critical step toward more comprehensive chemical safety assessment.

Dario Dongo

References

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