Genotoxicity of radiofrequency electromagnetic fields on mammalian cells in vitro: A systematic review with narrative...

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.

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.

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.

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.

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 the frequent reporting of findings in graphical display only, and the large heterogeneity of experimental data, which precluded a meta-analysis.

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 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.

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".