Effects of radiofrequency electromagnetic field exposure on cancer in laboratory animal studies, a systematic review

Abstract

Volume 199, May 2025, 109482 Environment International Abstract Background More than ten years ago, the World Health Organization’s (WHO) International Agency for Research on Cancer (IARC) published a monograph concluding there was limited evidence in experimental animals for carcinogenicity of Radio Frequency Electromagnetic Field (RF EMF). Objective The objective of this review was to systematically evaluate the effects of RF EMF exposure on cancer in experimental animals. Methods Eligibility criteria: Based on pre-established Populations, Exposures, Comparators, Outcomes, and Study Type (PECOS) criteria, studies in experimental animals of the following study types were included: chronic cancer bioassays, initiation-(co–)promotion studies, and studies with tumor-prone animals. Information sources: MEDLINE (PubMed), Science Citation Index Expanded and Emerging Sources Citation Index (Web of Science), and the EMF Portal. Data abstraction and synthesis: Data are publicly available online as interactive visuals with downloadable metadata. We adapted the risk-of-bias (RoB) tool developed by Office of Health Assessment and Translation (OHAT) to include considerations pertinent to the evaluation of RF EMF exposure and cancer bioassays. Study sensitivity was assessed with a tool adopted from the Report on Carcinogens (RoC). We synthesized studies using a narrative approach. Effect size was calculated as the 1% Bayesian Average benchmark dose (BMD) of a respective study when dose–response or a trend was identified (see BMDAnalysisSupplementaryMaterial) (Supplement 1). Evidence Assessment: Certainty of the evidence (CoE) was assessed using the Grading of Recommendations, Assessment, Developing and Evaluations (GRADE) approach, as refined by OHAT. Evidence from chronic cancer bioassays was considered the most directly applicable to evaluation of carcinogenicity. Results We included 52 studies with 20 chronic bioassays No studies were excluded based on risk of bias concerns. Studies were not considered suitable for meta-analysis due to heterogeneity in study design, species, strain, sex, exposure characteristics, and cancer outcome. No or minimal evidence of RF EMF exposure-related cancer outcomes was found in most systems or organs in any study (these included gastrointestinal/digestive, kidney, mammary gland, urinary, endocrine, musculoskeletal, reproductive, and auditory). For lymphoma (18 studies), with 6 chronic bioassays (1,120 mice, 1,780 rats) inconsistency between two chronic bioassays was not plausibly explainable, and the CoE for lymphoma was rated ‘moderate’. For brain tumors (20 studies), including 5 chronic bioassays (1,902 mice, 6,011 rats), an increase in glial cell-derived neoplasms was reported in two chronic bioassays in male rats. The CoE for an increased risk in glioma was judged as high. The BMD analysis was statistically significant for only one study and the BMD was 4.25 (95% CI 2.70, 10.24). For neoplasms of the heart (4 chronic bioassays with 6 experiments), 3 studies were performed in rats (∼2,165 animals), and 1 in mice (∼720 animals). Based on 2 bioassays, statistically significant increases in malignant schwannomas was judged as high CoE for an increase in heart schwannomas in male rats. The BMDs from the two positive studies were 1.92 (95 %CI 0.71, 4.15) and 0.177 (95 %CI 0.125, 0.241), respectively. Twelve studies reported neoplasms in the adrenal gland (5 chronic bioassays). The CoE for an increased risk in pheochromocytoma was judged as moderate. None of these findings were dose-dependent when compared to the sham controls. Sixteen studies investigated tumors of the liver with 5 of these being chronic bioassays. The CoE was evaluated as moderate for hepatoblastomas. For neoplasms of the lung (3 chronic bioassays), 8 studies were conducted in rats (∼1,296 animals) and 23 studies in mice (∼2,800 animals). In one chronic bioassay, a statistically significant positive trend was reported for bronchoalveolar adenoma or carcinoma (combined), which was rated as moderate CoE for an increase in lung neoplasms with some evidence from 2 initiation-(co–)promotion studies. Discussion Meta-analysis was considered inappropriate due to the heterogeneity in study methods. The GRADE/OHAT CoE framework has not been frequently applied to animal studies and experience to date suggests refinements are needed. We referred to standard methods in environmental health where CoE is fram Mevissen et al. (2025) Full Title: Effects of radiofrequency electromagnetic field exposure on cancer in laboratory animal studies, a systematic review Journal: Environment International Direct Link: sciencedirect.com PubMed: pubmed.ncbi.nlm.nih.gov DOI: 10.1016/j.envint.2025.109482 This is the flagship WHO-commissioned cancer review. It evaluated 52 animal studies — including the large U.S. National Toxicology Program (NTP) bioassay and the Ramazzini Institute far-field study. Conclusions: The review concluded high certainty of evidence that RF-EMF exposure causes: Malignant heart schwannomas in male rats Brain gliomas in male rats These are the exact tumor types found in the NTP study. The review also reported moderate certainty evidence for: Lymphoma Adrenal pheochromocytomas Liver hepatoblastomas Lung tumors This is a substantial upgrade from the 2011 IARC classification of “limited evidence.” High-certainty evidence in animal carcinogenicity studies is not a minor classification shift. It means: Results are consistent Risk of bias is low Dose-response relationships are credible Replication exists Critics — including the International Commission on the Biological Effects of EMF (ICBE-EMF) — have described this as the strongest animal cancer evidence ever assembled for cell-phone-level RF exposure.

AI evidence extraction

Main findings

The review of 52 animal studies found high certainty evidence that RF-EMF exposure causes malignant heart schwannomas and brain gliomas in male rats. Moderate certainty evidence was found for lymphoma, adrenal pheochromocytomas, liver hepatoblastomas, and lung tumors. These findings represent a substantial upgrade from previous classifications of limited evidence.

Outcomes measured

• malignant heart schwannomas in male rats
• brain gliomas in male rats
• lymphoma
• adrenal pheochromocytomas
• liver hepatoblastomas
• lung tumors

Limitations

• Heterogeneity in study design, species, strain, sex, exposure characteristics, and cancer outcomes prevented meta-analysis
• GRADE/OHAT certainty of evidence framework requires refinement for animal studies

Suggested hubs

• who-icnirp (0.9)
  WHO-commissioned review on RF-EMF carcinogenicity
• occupational-exposure (0.3)
  Animal studies relevant to RF exposure risk assessment

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    "exposure": {
        "band": "RF",
        "source": null,
        "frequency_mhz": null,
        "sar_wkg": null,
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    },
    "population": "laboratory animals (rats and mice)",
    "sample_size": null,
    "outcomes": [
        "malignant heart schwannomas in male rats",
        "brain gliomas in male rats",
        "lymphoma",
        "adrenal pheochromocytomas",
        "liver hepatoblastomas",
        "lung tumors"
    ],
    "main_findings": "The review of 52 animal studies found high certainty evidence that RF-EMF exposure causes malignant heart schwannomas and brain gliomas in male rats. Moderate certainty evidence was found for lymphoma, adrenal pheochromocytomas, liver hepatoblastomas, and lung tumors. These findings represent a substantial upgrade from previous classifications of limited evidence.",
    "effect_direction": "harm",
    "limitations": [
        "Heterogeneity in study design, species, strain, sex, exposure characteristics, and cancer outcomes prevented meta-analysis",
        "GRADE/OHAT certainty of evidence framework requires refinement for animal studies"
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    "peer_reviewed_likely": "yes",
    "keywords": [
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        "hepatoblastoma",
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    ],
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