Genotoxicity of radiofrequency electromagnetic fields on mammalian cells in vitro: A systematic

Abstract

Genotoxicity of radiofrequency electromagnetic fields on mammalian cells in vitro: A systematic review with narrative synthesis My note: This is not one the ten systematic reviews commissioned by the WHO. Nonetheless, this review of in vitro studies dismisses most evidence of adverse effects from RF-EMF. "Genotoxicity, a key characteristic of human carcinogens (Smith et al. 2016), is one of the most investigated outcomes in experimental studies on the effects of RF-EMF (SCHEER 2023). However, none of the ten systematic reviews commissioned by the World Health Organization (WHO) in the framework of an updated RF-EMF hazard and risk assessment, deals with this topic (Verbeek et al. 2021)." Romeo S, Sannino A, Scarfì MR, Lagorio S, Zeni O. Genotoxicity of radiofrequency electromagnetic fields on mammalian cells in vitro: A systematic review with narrative synthesis. Environment International, 2024, doi: 10.1016/j.envint.2024.109104. Abstract Background: Over the last decades, great concern has been raised about possible adverse effects to human health due to exposures to radiofrequency electromagnetic fields (RF-EMF, 100 kHz – 300 GHz) emitted by wireless communication technologies. In 2011 the International Agency for Research on Cancer classified RF-EMF as possibly carcinogenic to humans, highlighting that the evidence was weak and far from conclusive. Updated systematic reviews of the scientific literature on this topic are lacking, especially for mechanistic studies. Objectives: To perform a systematic review of the scientific literature on genotoxic effects induced by RF-EMF in in vitro experimental models. The overall aim is to assess the confidence and level of evidence of the induced effects in mammalian cell cultures. Methods: Full details regarding the eligibility criteria, information sources, and methods developed to assess risk of bias in the included study, are reported in our published protocol (Romeo et al. 2021). The databases NCBI PubMed, Web of Science, and EMF-Portal were used as information sources (last searched on 31st December 2022). In developing the systematic review, we followed the guidelines provided by the National Toxicology Program-Office of Health Assessment and Translation (NTP-OHAT), adapted to the evaluation of in vitro studies. A narrative synthesis of the body of evidence was performed by tabulating data classified according to meaningful groups (endpoints) and sub-groups (exposure parameters). This report, abstract included, conforms to the PRISMA 2020 (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Results: Out of 7750 unique records identified, 159 articles were eligible for inclusion. From the extracted data, we identified 1111 experiments (defined as independent specific combinations of diverse biological and electromagnetic parameters). The large majority (80%) of experiments reviewed did not show statistically significant genotoxic effects of RF-EMF exposures, and most “positive” studies were rated as of moderate to low quality, with negative ratings in the key bias domains. A qualitative evidence appraisal was conducted at the endpoint level, and then integrated across endpoints. Discussion: To the best of our knowledge, this is the first systematic review of the scientific literature on genotoxic effects in mammalian cell cultures in relation to RF-EMF exposure, which confirms and strengthens conclusions from previous syntheses of this specific topic thanks to the use of transparently reported methods, pre-defined inclusion criteria, and formal assessment of susceptibility to bias. Limitations of the evidence included were the frequent reporting of findings in graphical display only, and the large heterogeneity of experimental data, which precluded a meta-analysis. Conclusions: In the assessment restricted to studies reporting a significant effect of the exposure on the outcome, we reached an overall assessment of “low” confidence in the level of evidence that RF-EMF induce genotoxic effects in mammalian cells However, 80% of experiments reviewed showed no effect of RF exposure on the large majority of endpoints, especially the irreversible ones, independently of the exposure features, level, and duration (moderate evidence of no effect). Therefore, we conclude that the analysis of the papers included in this review, although only qualitative, suggests that RF exposure does not increase the occurrence of genotoxic effects in vitro. Framework and funding: This systematic review addresses one of the evidence streams considered in a larger systematic review of the scientific literature on the potential carcinogenicity of RF-EMF, performed by scientists from several Italian public research agencies. The project is supported by the Italian Workers’ Compensation Authority (INAIL) in the framework of the CRA with the Istituto Superiore di Sanità “BRiC 2018/06 – Scientific evidence on the carcinogenicity of electromagnetic fields”. Excerpt Conclusions The main conclusion of our systematic analysis is that the certainty of evidence for genotoxic effects of RF-EMF in mammalian cell cultures is weak. No genotoxic effects of RF exposure were observed in most experiments, especially those concerning irreversible endpoints, independently of the exposure features, level, and duration (moderate evidence of no effect). In the whole, we conclude that the analysis of the papers included in this review, although only qualitative, suggests that RF exposure does not increase the occurrence of genotoxic effects in vitro, also considering that the absence of significant effects prevails among the studies classified in tier-1 and tier-2 categories, whereas for the tier-3 studies the trend is reversed, highlighting how methodological quality affects the studies outcome (Simko et al. 2016). This systematic review may provide support to panels of experts involved in policy making regarding safety of exposure to RF-EMF. Furthermore, it is possible to state that, although the number of publications on this topic has considerably increased in recent years, this has not translated into an improvement of the experimental quality. Only a small number of the reviewed studies qualified for inclusion in the tier 1 category, while most of them, including those of moderate quality, still present considerable criticalities in key experimental features (use of sham samples, adequate dosimetry, exposure to a uniformly distributed electromagnetic field, appropriateness of biological methods, presence of positive control and outcome analysis blind to the exposure). It is evident that methodological quality is demanded for future research into this field, which will aim at producing sufficiently similar and unbiased data to be aggregated in meaningful categories. Open access paper: sciencedirect.com

AI evidence extraction

Main findings

The majority (80%) of experiments showed no statistically significant genotoxic effects from RF-EMF exposure in mammalian cell cultures. Positive findings were mostly from studies with moderate to low quality and risk of bias. Overall, there is low confidence in evidence that RF-EMF induces genotoxic effects in vitro, with moderate evidence supporting no effect.

Outcomes measured

• genotoxic effects

Limitations

• Heterogeneity of experimental data prevented meta-analysis
• Frequent reporting of findings only in graphical form
• Most studies had moderate to low methodological quality
• Limited number of high-quality (tier 1) studies

Suggested hubs

• who-icnirp (0.9)
  Systematic review relevant to WHO and ICNIRP assessments on RF-EMF health effects
• occupational-exposure (0.5)
  Study supported by Italian Workers’ Compensation Authority and relevant for occupational safety

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    "study_type": "systematic_review",
    "exposure": {
        "band": "RF",
        "source": null,
        "frequency_mhz": null,
        "sar_wkg": null,
        "duration": null
    },
    "population": "mammalian cells in vitro",
    "sample_size": 159,
    "outcomes": [
        "genotoxic effects"
    ],
    "main_findings": "The majority (80%) of experiments showed no statistically significant genotoxic effects from RF-EMF exposure in mammalian cell cultures. Positive findings were mostly from studies with moderate to low quality and risk of bias. Overall, there is low confidence in evidence that RF-EMF induces genotoxic effects in vitro, with moderate evidence supporting no effect.",
    "effect_direction": "no_effect",
    "limitations": [
        "Heterogeneity of experimental data prevented meta-analysis",
        "Frequent reporting of findings only in graphical form",
        "Most studies had moderate to low methodological quality",
        "Limited number of high-quality (tier 1) studies"
    ],
    "evidence_strength": "moderate",
    "confidence": 0.6999999999999999555910790149937383830547332763671875,
    "peer_reviewed_likely": "yes",
    "keywords": [
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        "in vitro",
        "systematic review",
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        "carcinogenicity",
        "dosimetry",
        "methodological quality"
    ],
    "suggested_hubs": [
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            "reason": "Systematic review relevant to WHO and ICNIRP assessments on RF-EMF health effects"
        },
        {
            "slug": "occupational-exposure",
            "weight": 0.5,
            "reason": "Study supported by Italian Workers’ Compensation Authority and relevant for occupational safety"
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}

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